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Optimization of Hematology/ Oncology E-Consult Ordering Process
Background
Multiple responses or repeat e-consults were observed by Hematology/Oncology Department. Root cause analysis uncovered that 60% of e-consults ordered required multiple responses or repeat econsults for the same clinical situation, often due to the need for additional lab testing before the e-consult question could be addressed. Hematology/Oncology econsult ordering process did not have an order design menu to provide guidance on appropriate questions, simplified ordering of relevant tests, or ways to identify patients that were either already established in the Hem/Onc clinic or patients that would be better managed with a more urgent or in-person consultation. This quality improvement project was created to improve the appropriateness and efficiency of hematology/oncology e-consult ordering process.
Methods
Using Plan-Do-Study-Act (PDSA) quality improvement methodology, a project team lead by Hematology/Oncology, Clinical Informatics, Clinical Application Coordinator and the Systems Redesign Coordinator, rebuilt menus to navigate referring providers to the appropriate e-consults. This would improve the process flow and enhance clear communication. The primary process improvement goals were 1) to decrease the number of e-consults that were better suited for inperson evaluation; 2) decrease the number of Hem/Onc e-consults that lack adequate clinical lab information and 3) decrease the number of e-consults for patients that are already established with a Hematology/Oncology provider.
Results
Baseline sample data (7-1-23-11-30-22)-revealed only 60% of e-consults placed were deemed appropriate. 13% required certain minimum lab testing, 11% were already established patients and 11% were better managed through in-person consultation. After the first PDSA cycle, from 9/21/23-3/29/24, 72% of econsults were deemed appropriate (114/158), a 12% improvement.
Conclusions
The success of the project supports the use of existing VA hospital-based program resources such as clinical informatics and utilizing frontline physician input. This input was critical to the redesigned ordering process. Ultimately, our process improvement efforts helped facilitate communication and information flow which improved our ability to better coordinate our Veteran’s care.
Background
Multiple responses or repeat e-consults were observed by Hematology/Oncology Department. Root cause analysis uncovered that 60% of e-consults ordered required multiple responses or repeat econsults for the same clinical situation, often due to the need for additional lab testing before the e-consult question could be addressed. Hematology/Oncology econsult ordering process did not have an order design menu to provide guidance on appropriate questions, simplified ordering of relevant tests, or ways to identify patients that were either already established in the Hem/Onc clinic or patients that would be better managed with a more urgent or in-person consultation. This quality improvement project was created to improve the appropriateness and efficiency of hematology/oncology e-consult ordering process.
Methods
Using Plan-Do-Study-Act (PDSA) quality improvement methodology, a project team lead by Hematology/Oncology, Clinical Informatics, Clinical Application Coordinator and the Systems Redesign Coordinator, rebuilt menus to navigate referring providers to the appropriate e-consults. This would improve the process flow and enhance clear communication. The primary process improvement goals were 1) to decrease the number of e-consults that were better suited for inperson evaluation; 2) decrease the number of Hem/Onc e-consults that lack adequate clinical lab information and 3) decrease the number of e-consults for patients that are already established with a Hematology/Oncology provider.
Results
Baseline sample data (7-1-23-11-30-22)-revealed only 60% of e-consults placed were deemed appropriate. 13% required certain minimum lab testing, 11% were already established patients and 11% were better managed through in-person consultation. After the first PDSA cycle, from 9/21/23-3/29/24, 72% of econsults were deemed appropriate (114/158), a 12% improvement.
Conclusions
The success of the project supports the use of existing VA hospital-based program resources such as clinical informatics and utilizing frontline physician input. This input was critical to the redesigned ordering process. Ultimately, our process improvement efforts helped facilitate communication and information flow which improved our ability to better coordinate our Veteran’s care.
Background
Multiple responses or repeat e-consults were observed by Hematology/Oncology Department. Root cause analysis uncovered that 60% of e-consults ordered required multiple responses or repeat econsults for the same clinical situation, often due to the need for additional lab testing before the e-consult question could be addressed. Hematology/Oncology econsult ordering process did not have an order design menu to provide guidance on appropriate questions, simplified ordering of relevant tests, or ways to identify patients that were either already established in the Hem/Onc clinic or patients that would be better managed with a more urgent or in-person consultation. This quality improvement project was created to improve the appropriateness and efficiency of hematology/oncology e-consult ordering process.
Methods
Using Plan-Do-Study-Act (PDSA) quality improvement methodology, a project team lead by Hematology/Oncology, Clinical Informatics, Clinical Application Coordinator and the Systems Redesign Coordinator, rebuilt menus to navigate referring providers to the appropriate e-consults. This would improve the process flow and enhance clear communication. The primary process improvement goals were 1) to decrease the number of e-consults that were better suited for inperson evaluation; 2) decrease the number of Hem/Onc e-consults that lack adequate clinical lab information and 3) decrease the number of e-consults for patients that are already established with a Hematology/Oncology provider.
Results
Baseline sample data (7-1-23-11-30-22)-revealed only 60% of e-consults placed were deemed appropriate. 13% required certain minimum lab testing, 11% were already established patients and 11% were better managed through in-person consultation. After the first PDSA cycle, from 9/21/23-3/29/24, 72% of econsults were deemed appropriate (114/158), a 12% improvement.
Conclusions
The success of the project supports the use of existing VA hospital-based program resources such as clinical informatics and utilizing frontline physician input. This input was critical to the redesigned ordering process. Ultimately, our process improvement efforts helped facilitate communication and information flow which improved our ability to better coordinate our Veteran’s care.
Standardization of the Discharge Process for Inpatient Hematology and Oncology Using Plan-Do-Study-Act Methodology Improves Follow-Up and Patient Hand-Off
Hematology and oncology patients are a complex patient population that requires timely follow-up to prevent clinical decompensation and delays in treatment. Previous reports have demonstrated that outpatient follow-up within 14 days is associated with decreased 30-day readmissions. The magnitude of this effect is greater for higher-risk patients.1 Therefore, patients being discharged from the hematology and oncology inpatient service should be seen by a hematology and oncology provider within 14 days of discharge. Patients who do not require close oncologic follow-up should be seen by a primary care provider (PCP) within this timeframe.
Background
The Institute of Medicine (IOM) identified the need to focus on quality improvement and patient safety with a 1999 report, To Err Is Human.2 Tremendous strides have been made in the areas of quality improvement and patient safety over the past 2 decades. In a 2013 report, the IOM further identified hematology and oncology care as an area of need due to a combination of growing demand, complexity of cancer and cancer treatment, shrinking workforce, and rising costs. The report concluded that cancer care is not as patient-centered, accessible, coordinated, or evidence based as it could be, with detrimental impacts on patients.3 Patients with cancer have been identified as a high-risk population for hospital readmissions.4,5 Lack of timely follow-up and failed hand-offs have been identified as factors contributing to poor outcomes at time of discharge.6-10
Upon internal review of baseline performance data, we identified areas needing improvement in the discharge process. These included time to hematology and oncology follow-up appointment, percent of patients with PCP appointments scheduled at time of discharge, and electronically alerts for the outpatient hematologist/oncologist to discharge summaries. It was determined that patients discharged from the inpatient service were seen a mean 17 days later by their outpatient hematology and oncology provider and the time to the follow-up appointment varied substantially, with some patients being seen several weeks to months after discharge. Furthermore, only 68% of patients had a primary care appointment scheduled at the time of discharge. These data along with review of data reported in the medical literature supported our initiative for improvement in the transition from inpatient to outpatient care for our hematology and oncology patients.
Plan-Do-Study-Act (PDSA) quality improvement methodology was used to create and implement several interventions to standardize the discharge process for this patient population, with the primary goal of decreasing the mean time to hematology and oncology follow-up from 17 days by 12% to fewer than 14 days. Patients who do not require close oncologic follow-up should be seen by a PCP within this timeframe. Otherwise, PCP follow-up within at least 6 months should be made. Secondary aims included (1) an increase in scheduled PCP visits at time of discharge from 68% to > 90%; and (2) an increase in communication of the discharge summary via electronic alerting of the outpatient hematology and oncology physician from 20% to > 90%. Herein, we report our experience and results of this quality improvement initiative
Methods
The Institutional Review Board at Edward Hines Veteran Affairs Hospital in Hines, Illinois reviewed this single-center study and deemed it to be exempt from oversight. Using PDSA quality improvement methodology, a multidisciplinary team of hematology and oncology staff developed and implemented a standardized discharge process. The multidisciplinary team included a robust representation of inpatient and outpatient staff caring for the hematology and oncology patient population, including attending physicians, fellows, residents, advanced practice nurses, registered nurses, clinical pharmacists, patient care coordinators, clinic schedulers, clinical applications coordinators, quality support staff, and a systems redesign coach. Hospital leadership including chief of staff, chief of medicine, and chief of nursing participated as the management guidance team. Several interviews and group meetings were conducted and a multidisciplinary team collaboratively developed and implemented the interventions and monitored the results.
Outcome measures were identified, including time to hematology and oncology clinic visit, primary care follow-up scheduling, and communication of discharge to the outpatient hematology and oncology physician. Baseline data were collected and reviewed. The multidisciplinary team developed a process flow map to understand the steps and resources involved with the transition from inpatient to outpatient care. Gap analysis and root cause analysis were performed. A solutions approach was applied to develop interventions. Table 1 shows a summary of the identified problems, symptoms, associated causes, the interventions aimed to address the problems, and expected outcomes. Rotating resident physicians were trained through online and in-person education. The multidisciplinary team met intermittently to monitor outcomes, provide feedback, further refine interventions, and develop additional interventions.
PDSA Cycle 1
A standardized discharge process was developed in the form of guidelines and expectations. These include an explanation of unique features of the hematology and oncology service and expectations of medication reconciliation with emphasis placed on antiemetics, antimicrobial prophylaxis, and bowel regimen when appropriate, outpatient hematology and oncology follow-up within 14 days, primary care follow-up, communication with the outpatient hematology and oncology physician, written discharge instructions, and bedside teaching when appropriate.
PDSA Cycle 2
Based on team member feedback and further discussions, a discharge checklist was developed. This checklist was available online, reviewed in person, and posted in the team room for rotating residents to use for discharge planning and when discharging patients (Figure 1).
PDSA Cycle 3
Based on ongoing user feedback, group discussions, and data monitoring, the discharge checklist was further refined and updated. An electronic clinical decision support tool was developed and integrated into the electronic medical record (EMR) in the form of a discharge checklist note template directly linked to orders. The tool is a computerized patient record system (CPRS) note template that prompts users to select whether medications or return to clinic orders are needed and offers a menu of frequently used medications. If any of the selections are chosen within the note template, an order is generated automatically in the chart that requires only the user’s signature. Furthermore, the patient care coordinator reviews the prescribed follow-up and works with the medical support assistant to make these appointments. The physician is contacted only when an appointment cannot be made. Therefore, this tool allows many additional actions to be bypassed such as generating medication and return to clinic orders individually and calling schedulers to make follow-up appointments (Figure 2).
Data Analysis
All patients discharged during the 2-month period prior to and discharged after the implementation of the standardized process were reviewed. Patients who followed up with hematology and oncology at another facility, enrolled in hospice, or died during admission were excluded. Follow-up appointment scheduling data and communication between inpatient and outpatient providers were reviewed. Data were analyzed using XmR statistical process control chart and Fisher’s Exact Test using GraphPad. Control limits were calculated for each PDSA cycle as the mean ± the average of the moving range multiplied by 2.66. All data were included in the analysis.
Results
A total of 142 consecutive patients were reviewed from May 1, 2018 to August 31, 2018 and January 1, 2019 to April 30, 2019, including 58 patients prior to the intervention and 84 patients during PDSA cycles. There was a gap in data collection between September 1, 2018 and December 31, 2018 due to limited team member availability. All data were collected by 2 reviewers—a postgraduate year (PGY)-4 chief resident and a PGY-2 internal medicine resident. The median age of patients in the preintervention group was 72 years and 69 years in the postintervention group. All patients were men. Baseline data revealed a mean 17 days to hematology and oncology follow-up. Primary care visits were scheduled for 68% of patients at the time of discharge. The outpatient hematology and oncology physician was alerted electronically to the discharge summary for 20% of the patients (Table 2).
The primary endpoint of time to hematology and oncology follow-up appointment improved to 13 days in PDSA cycles 1 and 2 and 10 days in PDSA cycle 3. The target of mean 14 days to follow-up was achieved. The statistical process control chart shows 5 shifts with clusters of ≥ 7 points below the mean revealing a true signal or change in the data and demonstrating that an improvement was seen (Figure 3). Furthermore, the statistical process control chart demonstrates upper control limit decreased from 58 days at baseline to 21 days in PDSA cycle 3, suggesting a decrease in variation.
Regarding secondary endpoints, the outpatient hematology and oncology attending physician and/or fellow was alerted electronically to the discharge summary for 62% of patients compared with 20% at baseline (P = .01), and primary care appointments were scheduled for 77% of patients after the intervention compared with 68% at baseline (P = .88) (Table 2).
Through ongoing meetings, discussions, and feedback, we identified additional objectives unique to this patient population that had no performance measurement. These included peripherally inserted central catheter (PICC) care nursing visits scheduled 1 week after discharge and port care nursing visits scheduled 4 weeks after discharge. These visits allow nursing staff to dress and flush these catheters for routine maintenance per institutional policy. The implementation of the discharge checklist note creates a mechanism of tracking performance in meeting this goal moving forward, whereas no method was in place to track this metric.
Discussion
The 2013 IOM report Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis found that that cancer care is not as patient-centered, accessible, coordinated, or evidence-based as it could be, with detrimental impacts on patients.3 The document offered a conceptual framework to improve quality of cancer care that includes the translation of evidence into clinical practice, quality measurement, and performance improvement, as well as using advances in information technology to enhance quality measurement and performance improvement. Our quality initiative uses this framework to work toward the goal as stated by the IOM report: to deliver “comprehensive, patient-centered, evidence-based, high-quality cancer care that is accessible and affordable.”3
Two large studies that evaluated risk factors for 15-day and 30-day hospital readmissions identified cancer diagnosis as a risk factor for increased hospital readmission, highlighting the need to identify strategies to improve the discharge process for these patients.4,5 Timely outpatient follow-up and better patient hand-off may improve clinical outcomes among this high-risk patient population after hospital discharge. Multiple studies have demonstrated that timely follow-up is associated with fewer readmissions.1,8-10 A study by Forster and colleagues that evaluated postdischarge adverse events (AEs) revealed a 23% incidence of AEs with 12% of these identified as preventable. Postdischarge monitoring was deemed inadequate among these patients, with closer follow-up and improved hand-offs between inpatient and outpatient medical teams identified as possible interventions to improve postdischarge patient monitoring and to prevent AEs.7
The present quality initiative to standardize the discharge process for the hematology and oncology service decreased time to hematology and oncology follow-up appointment, improved communication between inpatient and outpatient teams, and decreased process variation. Timelier follow-up for this complex patient population likely will prevent clinical decompensation, delays in treatment, and directly improve patient access to care.
The multidisciplinary nature of this effort was instrumental to successful completion. In a complex health care system, it is challenging to truly understand a problem and identify possible solutions without the perspective of all members of the care team. The involvement of team members with training in quality improvement methodology was important to evaluate and develop interventions in a systematic way. Furthermore, the support and involvement of leadership is important in order to allocate resources appropriately to achieve system changes that improve care. Using quality improvement methodology, the team was able to map our processes and perform gap and root cause analyses. Strategies were identified to improve our performance using a solutions approach. Changes were implemented with continued intermittent meetings for monitoring of progression and discussion of how interventions could be made more efficient, effective, and user friendly. The primary goal was ultimately achieved.
Integration of intervention into the EMR embodies the IOM’s call to use advances in information technology to enhance the quality and delivery of care, quality measurement, and performance improvement.3 This intervention offered the strongest system changes as an electronic clinical decision support tool was developed and embedded into the EMR in the form of a Discharge Checklist Note that is linked to associated orders. This intervention was the most robust, as it provided objective data regarding utilization of the checklist, offered a more efficient way to communicate with team members regarding discharge needs, and streamlined the workflow for the discharging provider. Furthermore, this electronic tool created the ability to measure other important aspects in the care of this patient population that we previously had no mechanism of measuring: timely nursing appointments for routine care of PICC lines and ports.
Limitations
The absence of clinical endpoints was a limitation of this study. The present study was unable to evaluate the effect of the intervention on readmission rates, emergency department visits, hospital length of stay, cost, or mortality. Coordinating this multidisciplinary effort required much time and planning, and additional resources were not available to evaluate these clinical endpoints. Further studies are needed to evaluate whether the increased patient access and closer follow-up would result in improvement in these clinical endpoints. Another consideration for future improvement projects would be to include patients in the multidisciplinary team. The patient perspective would be invaluable in identifying gaps in care delivery and strategies aimed at improving care delivery.
Conclusions
This quality initiative to standardize the discharge process for the hematology and oncology service decreased time to the initial hematology and oncology follow-up appointment, improved communication between inpatient and outpatient teams, and decreased process variation. Timelier follow-up for this complex patient population likely will prevent clinical decompensation, delays in treatment, and directly improve patient access to care.
Acknowledgments
We thank our patients for whom we hope our process improvement efforts will ultimately benefit. We thank all the hematology and oncology staff at Edward Hines Jr. VA Hospital and Loyola University Medical Center residents and fellows who care for our patients and participated in the multidisciplinary team to improve care for our patients. We thank the following professionals for their uncompensated assistance in the coordination and execution of this initiative: Robert Kutter, MS, and Meghan O’Halloran, MD.
1. Jackson C, Shahsahebi M, Wedlake T, DuBard CA. Timeliness of outpatient follow-up: an evidence-based approach for planning after hospital discharge. Ann Fam Med. 2015;13(2):115-122. doi:10.1370/afm.1753
2. Kohn LT, Corrigan J, Donaldson MS, eds. To Err Is Human: Building a Safer Health System. Washington, DC: National Academy Press; 2000.
3. Levit LA, Balogh E, Nass SJ, Ganz P, Institute of Medicine (U.S.), eds. Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis. Washington, DC: National Academies Press; 2013.
4. Allaudeen N, Vidyarthi A, Maselli J, Auerbach A. Redefining readmission risk factors for general medicine patients. J Hosp Med. 2011;6(2):54-60. doi:10.1002/jhm.805
5. Dorajoo SR, See V, Chan CT, et al. Identifying potentially avoidable readmissions: a medication-based 15-day readmission risk stratification algorithm. Pharmacotherapy. 2017;37(3):268-277. doi:10.1002/phar.1896
6. Kripalani S, LeFevre F, Phillips CO, Williams MV, Basaviah P, Baker DW. Deficits in communication and information transfer between hospital-based and primary care physicians: implications for patient safety and continuity of care. JAMA. 2007;297(8):831-841. doi:10.1001/jama.297.8.831
7. Forster AJ, Clark HD, Menard A, et al. Adverse events among medical patients after discharge from hospital [published correction appears in CMAJ. 2004 March 2;170(5):771]. CMAJ. 2004;170(3):345-349.
8. Hernandez AF, Greiner MA, Fonarow GC, et al. Relationship between early physician follow-up and 30-day readmission among Medicare beneficiaries hospitalized for heart failure. JAMA. 2010;303(17):1716-1722. doi:10.1001/jama.2010.533
9. Misky GJ, Wald HL, Coleman EA. Post-hospitalization transitions: examining the effects of timing of primary care provider follow-up. J Hosp Med. 2010;5(7):392-397. doi:10.1002/jhm.666
10. Sharma G, Kuo YF, Freeman JL, Zhang DD, Goodwin JS. Outpatient follow-up visit and 30-day emergency department visit and readmission in patients hospitalized for chronic obstructive pulmonary disease. Arch Intern Med. 2010;170(18):1664-1670. doi:10.1001/archinternmed.2010.345
Hematology and oncology patients are a complex patient population that requires timely follow-up to prevent clinical decompensation and delays in treatment. Previous reports have demonstrated that outpatient follow-up within 14 days is associated with decreased 30-day readmissions. The magnitude of this effect is greater for higher-risk patients.1 Therefore, patients being discharged from the hematology and oncology inpatient service should be seen by a hematology and oncology provider within 14 days of discharge. Patients who do not require close oncologic follow-up should be seen by a primary care provider (PCP) within this timeframe.
Background
The Institute of Medicine (IOM) identified the need to focus on quality improvement and patient safety with a 1999 report, To Err Is Human.2 Tremendous strides have been made in the areas of quality improvement and patient safety over the past 2 decades. In a 2013 report, the IOM further identified hematology and oncology care as an area of need due to a combination of growing demand, complexity of cancer and cancer treatment, shrinking workforce, and rising costs. The report concluded that cancer care is not as patient-centered, accessible, coordinated, or evidence based as it could be, with detrimental impacts on patients.3 Patients with cancer have been identified as a high-risk population for hospital readmissions.4,5 Lack of timely follow-up and failed hand-offs have been identified as factors contributing to poor outcomes at time of discharge.6-10
Upon internal review of baseline performance data, we identified areas needing improvement in the discharge process. These included time to hematology and oncology follow-up appointment, percent of patients with PCP appointments scheduled at time of discharge, and electronically alerts for the outpatient hematologist/oncologist to discharge summaries. It was determined that patients discharged from the inpatient service were seen a mean 17 days later by their outpatient hematology and oncology provider and the time to the follow-up appointment varied substantially, with some patients being seen several weeks to months after discharge. Furthermore, only 68% of patients had a primary care appointment scheduled at the time of discharge. These data along with review of data reported in the medical literature supported our initiative for improvement in the transition from inpatient to outpatient care for our hematology and oncology patients.
Plan-Do-Study-Act (PDSA) quality improvement methodology was used to create and implement several interventions to standardize the discharge process for this patient population, with the primary goal of decreasing the mean time to hematology and oncology follow-up from 17 days by 12% to fewer than 14 days. Patients who do not require close oncologic follow-up should be seen by a PCP within this timeframe. Otherwise, PCP follow-up within at least 6 months should be made. Secondary aims included (1) an increase in scheduled PCP visits at time of discharge from 68% to > 90%; and (2) an increase in communication of the discharge summary via electronic alerting of the outpatient hematology and oncology physician from 20% to > 90%. Herein, we report our experience and results of this quality improvement initiative
Methods
The Institutional Review Board at Edward Hines Veteran Affairs Hospital in Hines, Illinois reviewed this single-center study and deemed it to be exempt from oversight. Using PDSA quality improvement methodology, a multidisciplinary team of hematology and oncology staff developed and implemented a standardized discharge process. The multidisciplinary team included a robust representation of inpatient and outpatient staff caring for the hematology and oncology patient population, including attending physicians, fellows, residents, advanced practice nurses, registered nurses, clinical pharmacists, patient care coordinators, clinic schedulers, clinical applications coordinators, quality support staff, and a systems redesign coach. Hospital leadership including chief of staff, chief of medicine, and chief of nursing participated as the management guidance team. Several interviews and group meetings were conducted and a multidisciplinary team collaboratively developed and implemented the interventions and monitored the results.
Outcome measures were identified, including time to hematology and oncology clinic visit, primary care follow-up scheduling, and communication of discharge to the outpatient hematology and oncology physician. Baseline data were collected and reviewed. The multidisciplinary team developed a process flow map to understand the steps and resources involved with the transition from inpatient to outpatient care. Gap analysis and root cause analysis were performed. A solutions approach was applied to develop interventions. Table 1 shows a summary of the identified problems, symptoms, associated causes, the interventions aimed to address the problems, and expected outcomes. Rotating resident physicians were trained through online and in-person education. The multidisciplinary team met intermittently to monitor outcomes, provide feedback, further refine interventions, and develop additional interventions.
PDSA Cycle 1
A standardized discharge process was developed in the form of guidelines and expectations. These include an explanation of unique features of the hematology and oncology service and expectations of medication reconciliation with emphasis placed on antiemetics, antimicrobial prophylaxis, and bowel regimen when appropriate, outpatient hematology and oncology follow-up within 14 days, primary care follow-up, communication with the outpatient hematology and oncology physician, written discharge instructions, and bedside teaching when appropriate.
PDSA Cycle 2
Based on team member feedback and further discussions, a discharge checklist was developed. This checklist was available online, reviewed in person, and posted in the team room for rotating residents to use for discharge planning and when discharging patients (Figure 1).
PDSA Cycle 3
Based on ongoing user feedback, group discussions, and data monitoring, the discharge checklist was further refined and updated. An electronic clinical decision support tool was developed and integrated into the electronic medical record (EMR) in the form of a discharge checklist note template directly linked to orders. The tool is a computerized patient record system (CPRS) note template that prompts users to select whether medications or return to clinic orders are needed and offers a menu of frequently used medications. If any of the selections are chosen within the note template, an order is generated automatically in the chart that requires only the user’s signature. Furthermore, the patient care coordinator reviews the prescribed follow-up and works with the medical support assistant to make these appointments. The physician is contacted only when an appointment cannot be made. Therefore, this tool allows many additional actions to be bypassed such as generating medication and return to clinic orders individually and calling schedulers to make follow-up appointments (Figure 2).
Data Analysis
All patients discharged during the 2-month period prior to and discharged after the implementation of the standardized process were reviewed. Patients who followed up with hematology and oncology at another facility, enrolled in hospice, or died during admission were excluded. Follow-up appointment scheduling data and communication between inpatient and outpatient providers were reviewed. Data were analyzed using XmR statistical process control chart and Fisher’s Exact Test using GraphPad. Control limits were calculated for each PDSA cycle as the mean ± the average of the moving range multiplied by 2.66. All data were included in the analysis.
Results
A total of 142 consecutive patients were reviewed from May 1, 2018 to August 31, 2018 and January 1, 2019 to April 30, 2019, including 58 patients prior to the intervention and 84 patients during PDSA cycles. There was a gap in data collection between September 1, 2018 and December 31, 2018 due to limited team member availability. All data were collected by 2 reviewers—a postgraduate year (PGY)-4 chief resident and a PGY-2 internal medicine resident. The median age of patients in the preintervention group was 72 years and 69 years in the postintervention group. All patients were men. Baseline data revealed a mean 17 days to hematology and oncology follow-up. Primary care visits were scheduled for 68% of patients at the time of discharge. The outpatient hematology and oncology physician was alerted electronically to the discharge summary for 20% of the patients (Table 2).
The primary endpoint of time to hematology and oncology follow-up appointment improved to 13 days in PDSA cycles 1 and 2 and 10 days in PDSA cycle 3. The target of mean 14 days to follow-up was achieved. The statistical process control chart shows 5 shifts with clusters of ≥ 7 points below the mean revealing a true signal or change in the data and demonstrating that an improvement was seen (Figure 3). Furthermore, the statistical process control chart demonstrates upper control limit decreased from 58 days at baseline to 21 days in PDSA cycle 3, suggesting a decrease in variation.
Regarding secondary endpoints, the outpatient hematology and oncology attending physician and/or fellow was alerted electronically to the discharge summary for 62% of patients compared with 20% at baseline (P = .01), and primary care appointments were scheduled for 77% of patients after the intervention compared with 68% at baseline (P = .88) (Table 2).
Through ongoing meetings, discussions, and feedback, we identified additional objectives unique to this patient population that had no performance measurement. These included peripherally inserted central catheter (PICC) care nursing visits scheduled 1 week after discharge and port care nursing visits scheduled 4 weeks after discharge. These visits allow nursing staff to dress and flush these catheters for routine maintenance per institutional policy. The implementation of the discharge checklist note creates a mechanism of tracking performance in meeting this goal moving forward, whereas no method was in place to track this metric.
Discussion
The 2013 IOM report Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis found that that cancer care is not as patient-centered, accessible, coordinated, or evidence-based as it could be, with detrimental impacts on patients.3 The document offered a conceptual framework to improve quality of cancer care that includes the translation of evidence into clinical practice, quality measurement, and performance improvement, as well as using advances in information technology to enhance quality measurement and performance improvement. Our quality initiative uses this framework to work toward the goal as stated by the IOM report: to deliver “comprehensive, patient-centered, evidence-based, high-quality cancer care that is accessible and affordable.”3
Two large studies that evaluated risk factors for 15-day and 30-day hospital readmissions identified cancer diagnosis as a risk factor for increased hospital readmission, highlighting the need to identify strategies to improve the discharge process for these patients.4,5 Timely outpatient follow-up and better patient hand-off may improve clinical outcomes among this high-risk patient population after hospital discharge. Multiple studies have demonstrated that timely follow-up is associated with fewer readmissions.1,8-10 A study by Forster and colleagues that evaluated postdischarge adverse events (AEs) revealed a 23% incidence of AEs with 12% of these identified as preventable. Postdischarge monitoring was deemed inadequate among these patients, with closer follow-up and improved hand-offs between inpatient and outpatient medical teams identified as possible interventions to improve postdischarge patient monitoring and to prevent AEs.7
The present quality initiative to standardize the discharge process for the hematology and oncology service decreased time to hematology and oncology follow-up appointment, improved communication between inpatient and outpatient teams, and decreased process variation. Timelier follow-up for this complex patient population likely will prevent clinical decompensation, delays in treatment, and directly improve patient access to care.
The multidisciplinary nature of this effort was instrumental to successful completion. In a complex health care system, it is challenging to truly understand a problem and identify possible solutions without the perspective of all members of the care team. The involvement of team members with training in quality improvement methodology was important to evaluate and develop interventions in a systematic way. Furthermore, the support and involvement of leadership is important in order to allocate resources appropriately to achieve system changes that improve care. Using quality improvement methodology, the team was able to map our processes and perform gap and root cause analyses. Strategies were identified to improve our performance using a solutions approach. Changes were implemented with continued intermittent meetings for monitoring of progression and discussion of how interventions could be made more efficient, effective, and user friendly. The primary goal was ultimately achieved.
Integration of intervention into the EMR embodies the IOM’s call to use advances in information technology to enhance the quality and delivery of care, quality measurement, and performance improvement.3 This intervention offered the strongest system changes as an electronic clinical decision support tool was developed and embedded into the EMR in the form of a Discharge Checklist Note that is linked to associated orders. This intervention was the most robust, as it provided objective data regarding utilization of the checklist, offered a more efficient way to communicate with team members regarding discharge needs, and streamlined the workflow for the discharging provider. Furthermore, this electronic tool created the ability to measure other important aspects in the care of this patient population that we previously had no mechanism of measuring: timely nursing appointments for routine care of PICC lines and ports.
Limitations
The absence of clinical endpoints was a limitation of this study. The present study was unable to evaluate the effect of the intervention on readmission rates, emergency department visits, hospital length of stay, cost, or mortality. Coordinating this multidisciplinary effort required much time and planning, and additional resources were not available to evaluate these clinical endpoints. Further studies are needed to evaluate whether the increased patient access and closer follow-up would result in improvement in these clinical endpoints. Another consideration for future improvement projects would be to include patients in the multidisciplinary team. The patient perspective would be invaluable in identifying gaps in care delivery and strategies aimed at improving care delivery.
Conclusions
This quality initiative to standardize the discharge process for the hematology and oncology service decreased time to the initial hematology and oncology follow-up appointment, improved communication between inpatient and outpatient teams, and decreased process variation. Timelier follow-up for this complex patient population likely will prevent clinical decompensation, delays in treatment, and directly improve patient access to care.
Acknowledgments
We thank our patients for whom we hope our process improvement efforts will ultimately benefit. We thank all the hematology and oncology staff at Edward Hines Jr. VA Hospital and Loyola University Medical Center residents and fellows who care for our patients and participated in the multidisciplinary team to improve care for our patients. We thank the following professionals for their uncompensated assistance in the coordination and execution of this initiative: Robert Kutter, MS, and Meghan O’Halloran, MD.
Hematology and oncology patients are a complex patient population that requires timely follow-up to prevent clinical decompensation and delays in treatment. Previous reports have demonstrated that outpatient follow-up within 14 days is associated with decreased 30-day readmissions. The magnitude of this effect is greater for higher-risk patients.1 Therefore, patients being discharged from the hematology and oncology inpatient service should be seen by a hematology and oncology provider within 14 days of discharge. Patients who do not require close oncologic follow-up should be seen by a primary care provider (PCP) within this timeframe.
Background
The Institute of Medicine (IOM) identified the need to focus on quality improvement and patient safety with a 1999 report, To Err Is Human.2 Tremendous strides have been made in the areas of quality improvement and patient safety over the past 2 decades. In a 2013 report, the IOM further identified hematology and oncology care as an area of need due to a combination of growing demand, complexity of cancer and cancer treatment, shrinking workforce, and rising costs. The report concluded that cancer care is not as patient-centered, accessible, coordinated, or evidence based as it could be, with detrimental impacts on patients.3 Patients with cancer have been identified as a high-risk population for hospital readmissions.4,5 Lack of timely follow-up and failed hand-offs have been identified as factors contributing to poor outcomes at time of discharge.6-10
Upon internal review of baseline performance data, we identified areas needing improvement in the discharge process. These included time to hematology and oncology follow-up appointment, percent of patients with PCP appointments scheduled at time of discharge, and electronically alerts for the outpatient hematologist/oncologist to discharge summaries. It was determined that patients discharged from the inpatient service were seen a mean 17 days later by their outpatient hematology and oncology provider and the time to the follow-up appointment varied substantially, with some patients being seen several weeks to months after discharge. Furthermore, only 68% of patients had a primary care appointment scheduled at the time of discharge. These data along with review of data reported in the medical literature supported our initiative for improvement in the transition from inpatient to outpatient care for our hematology and oncology patients.
Plan-Do-Study-Act (PDSA) quality improvement methodology was used to create and implement several interventions to standardize the discharge process for this patient population, with the primary goal of decreasing the mean time to hematology and oncology follow-up from 17 days by 12% to fewer than 14 days. Patients who do not require close oncologic follow-up should be seen by a PCP within this timeframe. Otherwise, PCP follow-up within at least 6 months should be made. Secondary aims included (1) an increase in scheduled PCP visits at time of discharge from 68% to > 90%; and (2) an increase in communication of the discharge summary via electronic alerting of the outpatient hematology and oncology physician from 20% to > 90%. Herein, we report our experience and results of this quality improvement initiative
Methods
The Institutional Review Board at Edward Hines Veteran Affairs Hospital in Hines, Illinois reviewed this single-center study and deemed it to be exempt from oversight. Using PDSA quality improvement methodology, a multidisciplinary team of hematology and oncology staff developed and implemented a standardized discharge process. The multidisciplinary team included a robust representation of inpatient and outpatient staff caring for the hematology and oncology patient population, including attending physicians, fellows, residents, advanced practice nurses, registered nurses, clinical pharmacists, patient care coordinators, clinic schedulers, clinical applications coordinators, quality support staff, and a systems redesign coach. Hospital leadership including chief of staff, chief of medicine, and chief of nursing participated as the management guidance team. Several interviews and group meetings were conducted and a multidisciplinary team collaboratively developed and implemented the interventions and monitored the results.
Outcome measures were identified, including time to hematology and oncology clinic visit, primary care follow-up scheduling, and communication of discharge to the outpatient hematology and oncology physician. Baseline data were collected and reviewed. The multidisciplinary team developed a process flow map to understand the steps and resources involved with the transition from inpatient to outpatient care. Gap analysis and root cause analysis were performed. A solutions approach was applied to develop interventions. Table 1 shows a summary of the identified problems, symptoms, associated causes, the interventions aimed to address the problems, and expected outcomes. Rotating resident physicians were trained through online and in-person education. The multidisciplinary team met intermittently to monitor outcomes, provide feedback, further refine interventions, and develop additional interventions.
PDSA Cycle 1
A standardized discharge process was developed in the form of guidelines and expectations. These include an explanation of unique features of the hematology and oncology service and expectations of medication reconciliation with emphasis placed on antiemetics, antimicrobial prophylaxis, and bowel regimen when appropriate, outpatient hematology and oncology follow-up within 14 days, primary care follow-up, communication with the outpatient hematology and oncology physician, written discharge instructions, and bedside teaching when appropriate.
PDSA Cycle 2
Based on team member feedback and further discussions, a discharge checklist was developed. This checklist was available online, reviewed in person, and posted in the team room for rotating residents to use for discharge planning and when discharging patients (Figure 1).
PDSA Cycle 3
Based on ongoing user feedback, group discussions, and data monitoring, the discharge checklist was further refined and updated. An electronic clinical decision support tool was developed and integrated into the electronic medical record (EMR) in the form of a discharge checklist note template directly linked to orders. The tool is a computerized patient record system (CPRS) note template that prompts users to select whether medications or return to clinic orders are needed and offers a menu of frequently used medications. If any of the selections are chosen within the note template, an order is generated automatically in the chart that requires only the user’s signature. Furthermore, the patient care coordinator reviews the prescribed follow-up and works with the medical support assistant to make these appointments. The physician is contacted only when an appointment cannot be made. Therefore, this tool allows many additional actions to be bypassed such as generating medication and return to clinic orders individually and calling schedulers to make follow-up appointments (Figure 2).
Data Analysis
All patients discharged during the 2-month period prior to and discharged after the implementation of the standardized process were reviewed. Patients who followed up with hematology and oncology at another facility, enrolled in hospice, or died during admission were excluded. Follow-up appointment scheduling data and communication between inpatient and outpatient providers were reviewed. Data were analyzed using XmR statistical process control chart and Fisher’s Exact Test using GraphPad. Control limits were calculated for each PDSA cycle as the mean ± the average of the moving range multiplied by 2.66. All data were included in the analysis.
Results
A total of 142 consecutive patients were reviewed from May 1, 2018 to August 31, 2018 and January 1, 2019 to April 30, 2019, including 58 patients prior to the intervention and 84 patients during PDSA cycles. There was a gap in data collection between September 1, 2018 and December 31, 2018 due to limited team member availability. All data were collected by 2 reviewers—a postgraduate year (PGY)-4 chief resident and a PGY-2 internal medicine resident. The median age of patients in the preintervention group was 72 years and 69 years in the postintervention group. All patients were men. Baseline data revealed a mean 17 days to hematology and oncology follow-up. Primary care visits were scheduled for 68% of patients at the time of discharge. The outpatient hematology and oncology physician was alerted electronically to the discharge summary for 20% of the patients (Table 2).
The primary endpoint of time to hematology and oncology follow-up appointment improved to 13 days in PDSA cycles 1 and 2 and 10 days in PDSA cycle 3. The target of mean 14 days to follow-up was achieved. The statistical process control chart shows 5 shifts with clusters of ≥ 7 points below the mean revealing a true signal or change in the data and demonstrating that an improvement was seen (Figure 3). Furthermore, the statistical process control chart demonstrates upper control limit decreased from 58 days at baseline to 21 days in PDSA cycle 3, suggesting a decrease in variation.
Regarding secondary endpoints, the outpatient hematology and oncology attending physician and/or fellow was alerted electronically to the discharge summary for 62% of patients compared with 20% at baseline (P = .01), and primary care appointments were scheduled for 77% of patients after the intervention compared with 68% at baseline (P = .88) (Table 2).
Through ongoing meetings, discussions, and feedback, we identified additional objectives unique to this patient population that had no performance measurement. These included peripherally inserted central catheter (PICC) care nursing visits scheduled 1 week after discharge and port care nursing visits scheduled 4 weeks after discharge. These visits allow nursing staff to dress and flush these catheters for routine maintenance per institutional policy. The implementation of the discharge checklist note creates a mechanism of tracking performance in meeting this goal moving forward, whereas no method was in place to track this metric.
Discussion
The 2013 IOM report Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis found that that cancer care is not as patient-centered, accessible, coordinated, or evidence-based as it could be, with detrimental impacts on patients.3 The document offered a conceptual framework to improve quality of cancer care that includes the translation of evidence into clinical practice, quality measurement, and performance improvement, as well as using advances in information technology to enhance quality measurement and performance improvement. Our quality initiative uses this framework to work toward the goal as stated by the IOM report: to deliver “comprehensive, patient-centered, evidence-based, high-quality cancer care that is accessible and affordable.”3
Two large studies that evaluated risk factors for 15-day and 30-day hospital readmissions identified cancer diagnosis as a risk factor for increased hospital readmission, highlighting the need to identify strategies to improve the discharge process for these patients.4,5 Timely outpatient follow-up and better patient hand-off may improve clinical outcomes among this high-risk patient population after hospital discharge. Multiple studies have demonstrated that timely follow-up is associated with fewer readmissions.1,8-10 A study by Forster and colleagues that evaluated postdischarge adverse events (AEs) revealed a 23% incidence of AEs with 12% of these identified as preventable. Postdischarge monitoring was deemed inadequate among these patients, with closer follow-up and improved hand-offs between inpatient and outpatient medical teams identified as possible interventions to improve postdischarge patient monitoring and to prevent AEs.7
The present quality initiative to standardize the discharge process for the hematology and oncology service decreased time to hematology and oncology follow-up appointment, improved communication between inpatient and outpatient teams, and decreased process variation. Timelier follow-up for this complex patient population likely will prevent clinical decompensation, delays in treatment, and directly improve patient access to care.
The multidisciplinary nature of this effort was instrumental to successful completion. In a complex health care system, it is challenging to truly understand a problem and identify possible solutions without the perspective of all members of the care team. The involvement of team members with training in quality improvement methodology was important to evaluate and develop interventions in a systematic way. Furthermore, the support and involvement of leadership is important in order to allocate resources appropriately to achieve system changes that improve care. Using quality improvement methodology, the team was able to map our processes and perform gap and root cause analyses. Strategies were identified to improve our performance using a solutions approach. Changes were implemented with continued intermittent meetings for monitoring of progression and discussion of how interventions could be made more efficient, effective, and user friendly. The primary goal was ultimately achieved.
Integration of intervention into the EMR embodies the IOM’s call to use advances in information technology to enhance the quality and delivery of care, quality measurement, and performance improvement.3 This intervention offered the strongest system changes as an electronic clinical decision support tool was developed and embedded into the EMR in the form of a Discharge Checklist Note that is linked to associated orders. This intervention was the most robust, as it provided objective data regarding utilization of the checklist, offered a more efficient way to communicate with team members regarding discharge needs, and streamlined the workflow for the discharging provider. Furthermore, this electronic tool created the ability to measure other important aspects in the care of this patient population that we previously had no mechanism of measuring: timely nursing appointments for routine care of PICC lines and ports.
Limitations
The absence of clinical endpoints was a limitation of this study. The present study was unable to evaluate the effect of the intervention on readmission rates, emergency department visits, hospital length of stay, cost, or mortality. Coordinating this multidisciplinary effort required much time and planning, and additional resources were not available to evaluate these clinical endpoints. Further studies are needed to evaluate whether the increased patient access and closer follow-up would result in improvement in these clinical endpoints. Another consideration for future improvement projects would be to include patients in the multidisciplinary team. The patient perspective would be invaluable in identifying gaps in care delivery and strategies aimed at improving care delivery.
Conclusions
This quality initiative to standardize the discharge process for the hematology and oncology service decreased time to the initial hematology and oncology follow-up appointment, improved communication between inpatient and outpatient teams, and decreased process variation. Timelier follow-up for this complex patient population likely will prevent clinical decompensation, delays in treatment, and directly improve patient access to care.
Acknowledgments
We thank our patients for whom we hope our process improvement efforts will ultimately benefit. We thank all the hematology and oncology staff at Edward Hines Jr. VA Hospital and Loyola University Medical Center residents and fellows who care for our patients and participated in the multidisciplinary team to improve care for our patients. We thank the following professionals for their uncompensated assistance in the coordination and execution of this initiative: Robert Kutter, MS, and Meghan O’Halloran, MD.
1. Jackson C, Shahsahebi M, Wedlake T, DuBard CA. Timeliness of outpatient follow-up: an evidence-based approach for planning after hospital discharge. Ann Fam Med. 2015;13(2):115-122. doi:10.1370/afm.1753
2. Kohn LT, Corrigan J, Donaldson MS, eds. To Err Is Human: Building a Safer Health System. Washington, DC: National Academy Press; 2000.
3. Levit LA, Balogh E, Nass SJ, Ganz P, Institute of Medicine (U.S.), eds. Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis. Washington, DC: National Academies Press; 2013.
4. Allaudeen N, Vidyarthi A, Maselli J, Auerbach A. Redefining readmission risk factors for general medicine patients. J Hosp Med. 2011;6(2):54-60. doi:10.1002/jhm.805
5. Dorajoo SR, See V, Chan CT, et al. Identifying potentially avoidable readmissions: a medication-based 15-day readmission risk stratification algorithm. Pharmacotherapy. 2017;37(3):268-277. doi:10.1002/phar.1896
6. Kripalani S, LeFevre F, Phillips CO, Williams MV, Basaviah P, Baker DW. Deficits in communication and information transfer between hospital-based and primary care physicians: implications for patient safety and continuity of care. JAMA. 2007;297(8):831-841. doi:10.1001/jama.297.8.831
7. Forster AJ, Clark HD, Menard A, et al. Adverse events among medical patients after discharge from hospital [published correction appears in CMAJ. 2004 March 2;170(5):771]. CMAJ. 2004;170(3):345-349.
8. Hernandez AF, Greiner MA, Fonarow GC, et al. Relationship between early physician follow-up and 30-day readmission among Medicare beneficiaries hospitalized for heart failure. JAMA. 2010;303(17):1716-1722. doi:10.1001/jama.2010.533
9. Misky GJ, Wald HL, Coleman EA. Post-hospitalization transitions: examining the effects of timing of primary care provider follow-up. J Hosp Med. 2010;5(7):392-397. doi:10.1002/jhm.666
10. Sharma G, Kuo YF, Freeman JL, Zhang DD, Goodwin JS. Outpatient follow-up visit and 30-day emergency department visit and readmission in patients hospitalized for chronic obstructive pulmonary disease. Arch Intern Med. 2010;170(18):1664-1670. doi:10.1001/archinternmed.2010.345
1. Jackson C, Shahsahebi M, Wedlake T, DuBard CA. Timeliness of outpatient follow-up: an evidence-based approach for planning after hospital discharge. Ann Fam Med. 2015;13(2):115-122. doi:10.1370/afm.1753
2. Kohn LT, Corrigan J, Donaldson MS, eds. To Err Is Human: Building a Safer Health System. Washington, DC: National Academy Press; 2000.
3. Levit LA, Balogh E, Nass SJ, Ganz P, Institute of Medicine (U.S.), eds. Delivering High-Quality Cancer Care: Charting a New Course for a System in Crisis. Washington, DC: National Academies Press; 2013.
4. Allaudeen N, Vidyarthi A, Maselli J, Auerbach A. Redefining readmission risk factors for general medicine patients. J Hosp Med. 2011;6(2):54-60. doi:10.1002/jhm.805
5. Dorajoo SR, See V, Chan CT, et al. Identifying potentially avoidable readmissions: a medication-based 15-day readmission risk stratification algorithm. Pharmacotherapy. 2017;37(3):268-277. doi:10.1002/phar.1896
6. Kripalani S, LeFevre F, Phillips CO, Williams MV, Basaviah P, Baker DW. Deficits in communication and information transfer between hospital-based and primary care physicians: implications for patient safety and continuity of care. JAMA. 2007;297(8):831-841. doi:10.1001/jama.297.8.831
7. Forster AJ, Clark HD, Menard A, et al. Adverse events among medical patients after discharge from hospital [published correction appears in CMAJ. 2004 March 2;170(5):771]. CMAJ. 2004;170(3):345-349.
8. Hernandez AF, Greiner MA, Fonarow GC, et al. Relationship between early physician follow-up and 30-day readmission among Medicare beneficiaries hospitalized for heart failure. JAMA. 2010;303(17):1716-1722. doi:10.1001/jama.2010.533
9. Misky GJ, Wald HL, Coleman EA. Post-hospitalization transitions: examining the effects of timing of primary care provider follow-up. J Hosp Med. 2010;5(7):392-397. doi:10.1002/jhm.666
10. Sharma G, Kuo YF, Freeman JL, Zhang DD, Goodwin JS. Outpatient follow-up visit and 30-day emergency department visit and readmission in patients hospitalized for chronic obstructive pulmonary disease. Arch Intern Med. 2010;170(18):1664-1670. doi:10.1001/archinternmed.2010.345
Use of Fluorodeoxyglucose-Positron Emission Tomography in the Diagnosis of Intravascular Diffuse Large B-Cell Lymphoma
Patient 1
A white man aged 67 years, with diastolic heart failure and chronic obstructive pulmonary disease, presented to the emergency department (ED) with shortness of breath. The initial laboratory results were significant for a newly elevated creatinine level of 2.06 mg/dL and a brain natriuretic peptide level of 648 pg/mL.
Imaging studies included a chest radiograph, a ventilation/perfusion scan, and an echocardiogram, as well as a right heart catheterization. All were nondiagnostic. 
The patient's shortness of breath persisted despite treatment with diuretics, antibiotics, and steroids. Further laboratory workup revealed an elevated lactate dehydrogenase (LDH) level of 1,338 IU/L. A bone marrow biopsy performed because of concern about malignancy was unremarkable. Flow cytometry of the bone marrow aspirate did not reveal clonal B- or T-cell populations. Immunohistochemical staining was not performed. During this hospitalization for shortness of breath, the patient's mental staus began to decline, and his oxygen requirements increased. The patient was intubated but expired 48 hours after mechanical ventilation was initiated.
Patient 2
A white woman aged 67 years presented to the ED with generalized weakness, fatigue, and nausea. The patient’s medical history was significant for a diagnosis of stage IIIa ovarian cancer. She was treated with surgical resection and completed 6 cycles of adjuvant carboplatin and paclitaxel 3 months prior to this presentation. She had good response to treatment with normalization of CA-125. 
After completion of chemotherapy, the patient was found to have persistent anemia and thrombocytopenia. Admission laboratory results were significant for a hemoglobin level of 8.4 g/dL, a platelet count of 20,000/μL, and an LDH level of 1,220 IU/L.
Chest, abdomen, and pelvis CT scans showed mesenteric adenopathy and splenomegaly (Figures 3A, 3B, and 3C) compared with prior imaging. Bone marrow biopsy revealed large lymphoid cells with scant cytoplasm and irregular nuclei, primarily within blood vessels and sinusoids consistent with IVLBCL (Figure 4). Flow cytometry of the bone marrow specimen showed an abnormal B-cell population with expression CD20, CD19, FMC-7, and dim κ light chain restriction. The cells were negative for CD5 and CD10. Immunohistochemical staining was positive for CD20, CD79a, PAX5, BCL-2 , and MUM1.
The patient was treated with 4 cycles of cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab, plus intrathecal methotrexate. The chemotherapy dose was reduced in the final cycle because of neuropathy in the hands and feet. The patient had undergone autologous stem-cell transplantation to allow high-dose chemotherapy. She was doing well more than 5 months after her transplant without evidence of recurrent disease.
Patient 3
A white man aged 76 years presented to the ED with cutaneous nodules, weight loss, fatigue, fevers, and epigastric pain. The patient’s medical history was significant for asymptomatic lymphoplasmacytic lymphoma diagnosed 2 months earlier, which had not required treatment. Laboratory results on admission revealed transaminitis, mild anemia with a hemoglobin level of 11 g/dL, and LDH level of 497 IU/L.
Chest, abdomen, and pelvis CT scans showed a 1.7cm hepatic lesion and mesenteric adenopathy. A bone marrow biopsy was unchanged from prior studies and showed minimal involvement (5%) of marrow space by low grade B-cell lymphoma.
Fluorodeoxyglucose-positron emission tomography (FDG-PET) scans showed multiple areas of uptake in the neck, chest, abdomen, and pelvis (Figures 5 and 6). No increased uptake in the subcutaneous nodules was noted on examination. Laparoscopic biopsy of FDG-avid mesenteric nodes showed clusters of atypical large lymphoid cells resulting in distention of the vascular lumina, resulting in the diagnosis of IVLBCL (Figure 7).
Immunohistochemical stains showed that the intravascular lymphocytes were strongly positive for CD20 and BCL-2 and negative for CD5 and CD10. Flow cytometry on the sample was limited by a low cell count and could not be assessed for clonality. The patient completed 6 cycles of rituximab as well as intrathecal methotrexate. Restaging studies showed a complete remission.
Two months later, the patient developed a skin nodule on the right shoulder. A repeat FDG-PET scan showed increased uptake, and fine-needle biopsy confirmed recurrent disease. The patient is undergoing treatment with ifosfamide, carboplatin, etoposide, and rituximab, as well as workup for autologous stem-cell transplant.
Discussion
Intravascular large B-cell lymphoma, a subtype of diffuse large B-cell lymphoma, is unique because it is primarily extranodal and typically without significant tumor burden.1-4 Standard imaging modalities, therefore, are often nonspecific and do not aid clinicians in establishing a diagnosis. Fluorodeoxyglucose-positron emission tomography has a known role in the assessment of diffuse large B-cell lymphoma, both at time of diagnosis and in monitoring response to treatment.5 However, the use of FDGPET in the diagnosis and management of IVLBCL has not been clearly established.
In a review of the literature, 26 English-language case reports and small case series reporting individual centers’ experience with the use of this imaging modality in the diagnosis of IVLBCL were identified. Two cases were eliminated from review because they did not discuss the use of FDG-PET in relationship to diagnosis. Of the remaining 24 cases, 21 underwent initial imaging with 1 or more of the following imaging modalities: CT, magnetic resonance, ultrasound, bone scan, and gallium scintigraphy, all of which were nonspecific and did not lead to a definitive diagnosis.3,6-25 Each of the 21 cases was followed up by FDG-PET; in 19, the FDG-PET scan was positive and resulted in a diagnosis of IVLBCL. In 2 cases, the FDG-PET scan was nonrevealing and was not considered helpful in diagnosis.11,18 In 3 of the 21 cases, the FDG-PET scan was the primary imaging modality.6,14,25
In this review, all 3 patients had initial imaging with CT scans of anatomic locations that were largely unrevealing, although later histologic examination showed them to be locations of active disease either by biopsy or on autopsy. One patient who underwent early FDG-PET was found to have increased uptake in the mesenteric lymph nodes, which were later biopsied, as well as uptake in the bilateral adrenal glands, lungs, and bone.
Several characteristic FDG-PET findings that have been described in the literature have been identified in patients with IVLBCL, including diffuse accumulation in bilateral lung fields, accumulation in the renal cortex or adrenal glands, diffuse bony involvement, and hypometabolism in the brain.7,10,12,13,17,23,25 These findings show that organs with the richest blood supply, specifically the lungs and kidneys, often are affected. The brain, an obligate glucose metabolizer, would be expected to have high uptake; however, with tumor thrombi occluding small intracranial vessels, micro infarcts ensue and are evidenced by areas of low uptake on FDG-PET scans in patients with IVLBCL.7 These characteristic patterns seen on FDG-PET scans can help to support a diagnosis of IVLBCL when clinical suspicion is high. Further, clinicians may be able to use imaging results to guide an appropriate site for biopsy to confirm diagnosis.
Conclusion
Intravascular large B-cell lymphoma remains a diagnostic challenge for clinicians. Prognosis is generally poor and likely related to frequent delays in diagnosis.1 Clinicians continue to work toward improving their ability to diagnose this disease in its early stages. New diagnostic algorithms and the use of random skin biopsies have shown some promise in improving diagnostic efficiency.26-28 Based on the authors’ experience and review of the literature, FDG-PET may be another promising tool to aid early diagnosis. Characteristic FDG-PET findings have been well described and may help to support the diagnosis of IVLBCL and guide an appropriate biopsy site when clinical suspicion for IVLBCL exists.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
Click here to read the digital edition.
Patient 1
A white man aged 67 years, with diastolic heart failure and chronic obstructive pulmonary disease, presented to the emergency department (ED) with shortness of breath. The initial laboratory results were significant for a newly elevated creatinine level of 2.06 mg/dL and a brain natriuretic peptide level of 648 pg/mL.
Imaging studies included a chest radiograph, a ventilation/perfusion scan, and an echocardiogram, as well as a right heart catheterization. All were nondiagnostic.
The patient's shortness of breath persisted despite treatment with diuretics, antibiotics, and steroids. Further laboratory workup revealed an elevated lactate dehydrogenase (LDH) level of 1,338 IU/L. A bone marrow biopsy performed because of concern about malignancy was unremarkable. Flow cytometry of the bone marrow aspirate did not reveal clonal B- or T-cell populations. Immunohistochemical staining was not performed. During this hospitalization for shortness of breath, the patient's mental staus began to decline, and his oxygen requirements increased. The patient was intubated but expired 48 hours after mechanical ventilation was initiated.
Patient 2
A white woman aged 67 years presented to the ED with generalized weakness, fatigue, and nausea. The patient’s medical history was significant for a diagnosis of stage IIIa ovarian cancer. She was treated with surgical resection and completed 6 cycles of adjuvant carboplatin and paclitaxel 3 months prior to this presentation. She had good response to treatment with normalization of CA-125.
After completion of chemotherapy, the patient was found to have persistent anemia and thrombocytopenia. Admission laboratory results were significant for a hemoglobin level of 8.4 g/dL, a platelet count of 20,000/μL, and an LDH level of 1,220 IU/L.
Chest, abdomen, and pelvis CT scans showed mesenteric adenopathy and splenomegaly (Figures 3A, 3B, and 3C) compared with prior imaging. Bone marrow biopsy revealed large lymphoid cells with scant cytoplasm and irregular nuclei, primarily within blood vessels and sinusoids consistent with IVLBCL (Figure 4). Flow cytometry of the bone marrow specimen showed an abnormal B-cell population with expression CD20, CD19, FMC-7, and dim κ light chain restriction. The cells were negative for CD5 and CD10. Immunohistochemical staining was positive for CD20, CD79a, PAX5, BCL-2 , and MUM1.
The patient was treated with 4 cycles of cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab, plus intrathecal methotrexate. The chemotherapy dose was reduced in the final cycle because of neuropathy in the hands and feet. The patient had undergone autologous stem-cell transplantation to allow high-dose chemotherapy. She was doing well more than 5 months after her transplant without evidence of recurrent disease.
Patient 3
A white man aged 76 years presented to the ED with cutaneous nodules, weight loss, fatigue, fevers, and epigastric pain. The patient’s medical history was significant for asymptomatic lymphoplasmacytic lymphoma diagnosed 2 months earlier, which had not required treatment. Laboratory results on admission revealed transaminitis, mild anemia with a hemoglobin level of 11 g/dL, and LDH level of 497 IU/L.
Chest, abdomen, and pelvis CT scans showed a 1.7cm hepatic lesion and mesenteric adenopathy. A bone marrow biopsy was unchanged from prior studies and showed minimal involvement (5%) of marrow space by low grade B-cell lymphoma.
Fluorodeoxyglucose-positron emission tomography (FDG-PET) scans showed multiple areas of uptake in the neck, chest, abdomen, and pelvis (Figures 5 and 6). No increased uptake in the subcutaneous nodules was noted on examination. Laparoscopic biopsy of FDG-avid mesenteric nodes showed clusters of atypical large lymphoid cells resulting in distention of the vascular lumina, resulting in the diagnosis of IVLBCL (Figure 7).
Immunohistochemical stains showed that the intravascular lymphocytes were strongly positive for CD20 and BCL-2 and negative for CD5 and CD10. Flow cytometry on the sample was limited by a low cell count and could not be assessed for clonality. The patient completed 6 cycles of rituximab as well as intrathecal methotrexate. Restaging studies showed a complete remission.
Two months later, the patient developed a skin nodule on the right shoulder. A repeat FDG-PET scan showed increased uptake, and fine-needle biopsy confirmed recurrent disease. The patient is undergoing treatment with ifosfamide, carboplatin, etoposide, and rituximab, as well as workup for autologous stem-cell transplant.
Discussion
Intravascular large B-cell lymphoma, a subtype of diffuse large B-cell lymphoma, is unique because it is primarily extranodal and typically without significant tumor burden.1-4 Standard imaging modalities, therefore, are often nonspecific and do not aid clinicians in establishing a diagnosis. Fluorodeoxyglucose-positron emission tomography has a known role in the assessment of diffuse large B-cell lymphoma, both at time of diagnosis and in monitoring response to treatment.5 However, the use of FDGPET in the diagnosis and management of IVLBCL has not been clearly established.
In a review of the literature, 26 English-language case reports and small case series reporting individual centers’ experience with the use of this imaging modality in the diagnosis of IVLBCL were identified. Two cases were eliminated from review because they did not discuss the use of FDG-PET in relationship to diagnosis. Of the remaining 24 cases, 21 underwent initial imaging with 1 or more of the following imaging modalities: CT, magnetic resonance, ultrasound, bone scan, and gallium scintigraphy, all of which were nonspecific and did not lead to a definitive diagnosis.3,6-25 Each of the 21 cases was followed up by FDG-PET; in 19, the FDG-PET scan was positive and resulted in a diagnosis of IVLBCL. In 2 cases, the FDG-PET scan was nonrevealing and was not considered helpful in diagnosis.11,18 In 3 of the 21 cases, the FDG-PET scan was the primary imaging modality.6,14,25
In this review, all 3 patients had initial imaging with CT scans of anatomic locations that were largely unrevealing, although later histologic examination showed them to be locations of active disease either by biopsy or on autopsy. One patient who underwent early FDG-PET was found to have increased uptake in the mesenteric lymph nodes, which were later biopsied, as well as uptake in the bilateral adrenal glands, lungs, and bone.
Several characteristic FDG-PET findings that have been described in the literature have been identified in patients with IVLBCL, including diffuse accumulation in bilateral lung fields, accumulation in the renal cortex or adrenal glands, diffuse bony involvement, and hypometabolism in the brain.7,10,12,13,17,23,25 These findings show that organs with the richest blood supply, specifically the lungs and kidneys, often are affected. The brain, an obligate glucose metabolizer, would be expected to have high uptake; however, with tumor thrombi occluding small intracranial vessels, micro infarcts ensue and are evidenced by areas of low uptake on FDG-PET scans in patients with IVLBCL.7 These characteristic patterns seen on FDG-PET scans can help to support a diagnosis of IVLBCL when clinical suspicion is high. Further, clinicians may be able to use imaging results to guide an appropriate site for biopsy to confirm diagnosis.
Conclusion
Intravascular large B-cell lymphoma remains a diagnostic challenge for clinicians. Prognosis is generally poor and likely related to frequent delays in diagnosis.1 Clinicians continue to work toward improving their ability to diagnose this disease in its early stages. New diagnostic algorithms and the use of random skin biopsies have shown some promise in improving diagnostic efficiency.26-28 Based on the authors’ experience and review of the literature, FDG-PET may be another promising tool to aid early diagnosis. Characteristic FDG-PET findings have been well described and may help to support the diagnosis of IVLBCL and guide an appropriate biopsy site when clinical suspicion for IVLBCL exists.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
Click here to read the digital edition.
Patient 1
A white man aged 67 years, with diastolic heart failure and chronic obstructive pulmonary disease, presented to the emergency department (ED) with shortness of breath. The initial laboratory results were significant for a newly elevated creatinine level of 2.06 mg/dL and a brain natriuretic peptide level of 648 pg/mL.
Imaging studies included a chest radiograph, a ventilation/perfusion scan, and an echocardiogram, as well as a right heart catheterization. All were nondiagnostic.
The patient's shortness of breath persisted despite treatment with diuretics, antibiotics, and steroids. Further laboratory workup revealed an elevated lactate dehydrogenase (LDH) level of 1,338 IU/L. A bone marrow biopsy performed because of concern about malignancy was unremarkable. Flow cytometry of the bone marrow aspirate did not reveal clonal B- or T-cell populations. Immunohistochemical staining was not performed. During this hospitalization for shortness of breath, the patient's mental staus began to decline, and his oxygen requirements increased. The patient was intubated but expired 48 hours after mechanical ventilation was initiated.
Patient 2
A white woman aged 67 years presented to the ED with generalized weakness, fatigue, and nausea. The patient’s medical history was significant for a diagnosis of stage IIIa ovarian cancer. She was treated with surgical resection and completed 6 cycles of adjuvant carboplatin and paclitaxel 3 months prior to this presentation. She had good response to treatment with normalization of CA-125.
After completion of chemotherapy, the patient was found to have persistent anemia and thrombocytopenia. Admission laboratory results were significant for a hemoglobin level of 8.4 g/dL, a platelet count of 20,000/μL, and an LDH level of 1,220 IU/L.
Chest, abdomen, and pelvis CT scans showed mesenteric adenopathy and splenomegaly (Figures 3A, 3B, and 3C) compared with prior imaging. Bone marrow biopsy revealed large lymphoid cells with scant cytoplasm and irregular nuclei, primarily within blood vessels and sinusoids consistent with IVLBCL (Figure 4). Flow cytometry of the bone marrow specimen showed an abnormal B-cell population with expression CD20, CD19, FMC-7, and dim κ light chain restriction. The cells were negative for CD5 and CD10. Immunohistochemical staining was positive for CD20, CD79a, PAX5, BCL-2 , and MUM1.
The patient was treated with 4 cycles of cyclophosphamide, doxorubicin, vincristine, prednisone, and rituximab, plus intrathecal methotrexate. The chemotherapy dose was reduced in the final cycle because of neuropathy in the hands and feet. The patient had undergone autologous stem-cell transplantation to allow high-dose chemotherapy. She was doing well more than 5 months after her transplant without evidence of recurrent disease.
Patient 3
A white man aged 76 years presented to the ED with cutaneous nodules, weight loss, fatigue, fevers, and epigastric pain. The patient’s medical history was significant for asymptomatic lymphoplasmacytic lymphoma diagnosed 2 months earlier, which had not required treatment. Laboratory results on admission revealed transaminitis, mild anemia with a hemoglobin level of 11 g/dL, and LDH level of 497 IU/L.
Chest, abdomen, and pelvis CT scans showed a 1.7cm hepatic lesion and mesenteric adenopathy. A bone marrow biopsy was unchanged from prior studies and showed minimal involvement (5%) of marrow space by low grade B-cell lymphoma.
Fluorodeoxyglucose-positron emission tomography (FDG-PET) scans showed multiple areas of uptake in the neck, chest, abdomen, and pelvis (Figures 5 and 6). No increased uptake in the subcutaneous nodules was noted on examination. Laparoscopic biopsy of FDG-avid mesenteric nodes showed clusters of atypical large lymphoid cells resulting in distention of the vascular lumina, resulting in the diagnosis of IVLBCL (Figure 7).
Immunohistochemical stains showed that the intravascular lymphocytes were strongly positive for CD20 and BCL-2 and negative for CD5 and CD10. Flow cytometry on the sample was limited by a low cell count and could not be assessed for clonality. The patient completed 6 cycles of rituximab as well as intrathecal methotrexate. Restaging studies showed a complete remission.
Two months later, the patient developed a skin nodule on the right shoulder. A repeat FDG-PET scan showed increased uptake, and fine-needle biopsy confirmed recurrent disease. The patient is undergoing treatment with ifosfamide, carboplatin, etoposide, and rituximab, as well as workup for autologous stem-cell transplant.
Discussion
Intravascular large B-cell lymphoma, a subtype of diffuse large B-cell lymphoma, is unique because it is primarily extranodal and typically without significant tumor burden.1-4 Standard imaging modalities, therefore, are often nonspecific and do not aid clinicians in establishing a diagnosis. Fluorodeoxyglucose-positron emission tomography has a known role in the assessment of diffuse large B-cell lymphoma, both at time of diagnosis and in monitoring response to treatment.5 However, the use of FDGPET in the diagnosis and management of IVLBCL has not been clearly established.
In a review of the literature, 26 English-language case reports and small case series reporting individual centers’ experience with the use of this imaging modality in the diagnosis of IVLBCL were identified. Two cases were eliminated from review because they did not discuss the use of FDG-PET in relationship to diagnosis. Of the remaining 24 cases, 21 underwent initial imaging with 1 or more of the following imaging modalities: CT, magnetic resonance, ultrasound, bone scan, and gallium scintigraphy, all of which were nonspecific and did not lead to a definitive diagnosis.3,6-25 Each of the 21 cases was followed up by FDG-PET; in 19, the FDG-PET scan was positive and resulted in a diagnosis of IVLBCL. In 2 cases, the FDG-PET scan was nonrevealing and was not considered helpful in diagnosis.11,18 In 3 of the 21 cases, the FDG-PET scan was the primary imaging modality.6,14,25
In this review, all 3 patients had initial imaging with CT scans of anatomic locations that were largely unrevealing, although later histologic examination showed them to be locations of active disease either by biopsy or on autopsy. One patient who underwent early FDG-PET was found to have increased uptake in the mesenteric lymph nodes, which were later biopsied, as well as uptake in the bilateral adrenal glands, lungs, and bone.
Several characteristic FDG-PET findings that have been described in the literature have been identified in patients with IVLBCL, including diffuse accumulation in bilateral lung fields, accumulation in the renal cortex or adrenal glands, diffuse bony involvement, and hypometabolism in the brain.7,10,12,13,17,23,25 These findings show that organs with the richest blood supply, specifically the lungs and kidneys, often are affected. The brain, an obligate glucose metabolizer, would be expected to have high uptake; however, with tumor thrombi occluding small intracranial vessels, micro infarcts ensue and are evidenced by areas of low uptake on FDG-PET scans in patients with IVLBCL.7 These characteristic patterns seen on FDG-PET scans can help to support a diagnosis of IVLBCL when clinical suspicion is high. Further, clinicians may be able to use imaging results to guide an appropriate site for biopsy to confirm diagnosis.
Conclusion
Intravascular large B-cell lymphoma remains a diagnostic challenge for clinicians. Prognosis is generally poor and likely related to frequent delays in diagnosis.1 Clinicians continue to work toward improving their ability to diagnose this disease in its early stages. New diagnostic algorithms and the use of random skin biopsies have shown some promise in improving diagnostic efficiency.26-28 Based on the authors’ experience and review of the literature, FDG-PET may be another promising tool to aid early diagnosis. Characteristic FDG-PET findings have been well described and may help to support the diagnosis of IVLBCL and guide an appropriate biopsy site when clinical suspicion for IVLBCL exists.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
Click here to read the digital edition.
Pneumatic Tube-Induced Reverse Pseudohyperkalemia in a Patient With Chronic Lymphocytic Leukemia
Pseudohyperkalemia is a potentially dangerous phenomenon where falsely reported elevated potassium levels result in potentially unwarranted correction of potassium by sodium polystyrene or by dialysis in extreme cases. Overcorrection of potassium in a patient whose potassium is normal or low can lead to hypokalemia and potentially life-threatening consequences. Typical pseudohyperkalemia is thought to be a result of platelet-mediated release of potassium that occurs from the clotting process of a serum sample where no anticoagulant is present. As a result, pseudohyperkalemia is typically corrected when potassium is measured with a plasma sample where heparin and other preservatives are present in the collection tube.1
Reverse pseudohyperkalemia is seen in patients with leukemia and lymphoma with significant lymphocytosis when laboratory studies demonstrate falsely elevated potassium. In reverse pseudohyperkalemia the potassium level from a plasma sample is falsely elevated despite the presence of an anticoagulant, as the process is independent of platelet activation and occurs as a result of white blood cell (WBC) breakdown.2
For several decades, it has been suggested that the presence of heparin in tubes used to collect plasma is the cause of lysis of WBCs, presumably due to possible membrane fragility of these cells. Correction was recommended with the use of low-heparin-coated tubes.3 The other proposed theory for reverse pseudohyperkalemia is that lysis of WBCs is primarily due to procedural handling: Several case reports suggest that pneumatic tube transport likely plays a strong role, as well as other factors, such as the length of time to the laboratory.4-6
The authors report a case of a patient with chronic lymphocytic leukemia (CLL) who presented with significant reverse pseudohyperkalemia that later was determined to be dependent on pneumatic tube transport and independent of heparin.
Case Presentation
The patient, an 83-year-old man with a long history of asymptomatic CLL, was noted to have rapid WBC doubling time. His WBC counts had increased from 45 × 103/μL to 95 x 103/μL over the year preceding admission, then further increased to 300 x 103/μL in the month before admission.
A computed tomography (CT) scan of the chest, abdomen, and pelvis showed significant lymphadenopathy and splenomegaly. The patient presented to the hospital for treatment with a planned first cycle of bendamustine alone and subsequent cycles of bendamustine and rituximab. His medical history included Prinzmetal angina, coronary artery disease, wet macular degeneration, and benign prostatic hyperplasia. Notably, he had a documented history of hyperkalemia with potassium levels ranging from 4.7 mEq/L to 4.9 mEq/L over the previous year and was placed on a potassium-restricted diet.
On presentation, he reported no recent history of B symptoms of fever, night sweats, weight loss, and malaise. His labs oratory results showed an elevated potassium level of 6.1 mEq/L with repeated whole blood potassium of 8.2 mEq/L. An electrocardiogram (ECG) showed sinus rhythm, no noted T-wave abnormalities, and no conduction abnormalities. A physical exam was significant for normal muscle strength, cervical lymphadenopathy, and splenomegaly.
The patient was initially treated for hyperkalemia with insulin plus glucose and sodium polystyrene. He responded with mild improvement of his potassium level to 6.3 mEq/L, 5.6 mEq/L, and 5.1 mEq/L after receiving 5 doses of 30 g of polystyrene over multiple checks during a 24-hour period. Hemolysis results drawn at that time were unremarkable. It was noted that the patient had an elevated lactate dehydrogenase (LDH) level of 328 IU/L.
The following morning, his potassium level remained elevated at 6.2 mEq/L, but because the treatment team suspected pseudohyperkalemia, the decision at the time was to proceed with chemotherapy.
To evaluate this possibility, the authors attempted to correct for procedural handling resulting in unwanted WBC lysis. They reduced the lithium heparin in the collection from 81 IU of lithium heparin found in the green-mint collection tube and instead used an arterial blood gas (ABG) syringe that contained 23.5 IU of heparin and hand-carried the sample to the lab. The potassium value was 3.4 mEq/L in the sample collected in the ABG syringe, and a concurrent value collected by the standard method was 7.4 mEq/L. A repeated ECG was negative for any cardiac arrhythmias or conduction abnormalities. The subsequent 2 sets of potassium values were 3.9 mEq/L for the ABG syringe and 6.4 mEq/L for the standard heparinized tube, and 3.5 mEq/L and 5.8 mEq/L, respectively. The patient received the remainder of his chemotherapy, and there was no evidence of tumor lysis syndrome (TLS).
The following day, tumor lysis labs were collected in a low-heparin ABG syringe and a regular green-mint collection tube. Both samples were manually brought to the lab without pneumatic tube transport. Interestingly, the patient’s repeat potassium levels were 3.3 mEq/L and 3.1 mEq/L, respectively. Therefore, it was determined that the potassium level was not dependent on the presence of an anticoagulant. The following day the patient remained asymptomatic with normal potassium levels, and he was discharged on a normal cardiac diet. When he was evaluated in an outpatient setting a month later, the patient was found to have a normal potassium level at 4.3 mEq/L on a normal potassium diet.
Conclusion
In the hospital setting, pseudohyperkalemia is a potentially dangerous situation. Because the patient discussed here initially presented with potassium values as high as 8.2 mEq/L, treatment was warranted. However, given the presence of CLL with extreme leukocytosis and otherwise
normal clinical findings, suspicion for pseudohyperkalemia was high. Initial treatment of the elevated potassium levels, which were revealed to be borderline low later in his clinical course, may have had detrimental effects on his cardiac function if hypokalemia had been inadvertently exacerbated to a significant level. The authors bring this case to the attention of health care providers of patients with CLL because this patient had been chronically managed for hyperkalemia with a lowpotassium diet.
Further, this case confirms the importance of avoiding the use of pneumatic tubes to prevent WBC lysis in patients with significant malignant leukocytosis. Importantly, the authors were able to differentiate between postulated heparin-mediated lysis and pneumatictube usage. As the literature has suggested, the authors speculated that mechanical stress on chronic lymphocytic leukemia cells is the primary cause of pseudo-hyperkalemia.
Pneumatic tube use or mechanical manipulation seemed to cause unwanted WBC lysis in this case, as values in the standard 81 IU heparin tubes used in this case study could be corrected by manually transporting the tube to the lab. This suggests that the process is heparin-independent, although initial investigations on that effect focused on the use of low-heparin vials. The potassium correction also was supported by the correction of likely falsely elevated LDH, which normalized when samples were manually transported. This supports the mechanism of WBC lysis. The authors’ observations are in line with several recent reports where pneumatic tube use was suspected as the cause of reverse pseudohyperkalemia.4,5,7,8
During the authors’ monitoring of the patient for TLS, comparison of repeat values for potassium showed a significant difference of about 2.7 mEq/L between samples transported manually and samples sent via pneumatic tube (Figure). Similar elevations of values have been described in other case reports.1
Reverse pseudohyperkalemia is a phenomenon that should not be overlooked in the medical management of patients with CLL with leukocytosis, especially in asymptomatic chronic patients. Although initially the differences can be benign, as the tumor burden increases, the degree of falsely elevated potassium can increase to thresholds that lead to inappropriate management in an acute setting. To prevent mismanagement, the authors recommend placing precautionary flags with hospital laboratories so that if a patient with CLL has a high potassium draw, lab values are rechecked with hand-delivered samples. The authors hope that this case will highlight the importance of suspecting this diagnosis in patients with CLL and provide guidance on obtaining accurate labs to better manage these patients.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
Click here to read the digital edition.
1. Avelar T. Reverse pseudohyperkalemia in a patient with chronic lymphocytic leukemia. Perm J. 2014;18(4):e150-e152.
2. Abraham B, Fakhar I, Tikaria A, et al. Reverse pseudohyperkalemia in a leukemic patient. Clin Chem. 2008;54(2):449-451.
3. Singh PJ, Zawada ET, Santella RN. A case of “reverse” pseudohyperkalemia. Miner Electrolyte Metab. 1997;23(1):58-61.
4. Garwicz D, Karlman M. Early recognition of reverse pseudohyperkalemia in heparin plasma samples during leukemic hyperleukocytosis can prevent iatrogenic hypokalemia. Clin Biochem. 2012;45(18):1700-1702.
5. Garwicz D, Karlman M, Øra I. Reverse pseudohyperkalemia in heparin plasma samples from a child with T cell acute lymphoblastic leukemia with hyperleukocytosis. Clin Chim Acta. 2011;412(3-4):396-397.
6. Kintzel PE, Scott WL. Pseudohyperkalemia in a patient with chronic lymphoblastic leukemia and tumor lysis syndrome. J Oncol Pharm Pract. 2012;18(4):432-435.
7. Sindhu SK, Hix JK, Fricke W. Pseudohyperkalemia in chronic lymphocytic leukemia: phlebotomy sites and pneumatic tubes. Am J Kidney Dis. 2011;57(2):354-355.
8. Kellerman PS, Thornbery JM. Pseudohyperkalemia due to pneumatic tube transport in a leukemic patient. Am J Kidney Dis. 2005;46(4):746-748
Note: Page numbers differ between the print issue and digital edition.
Pseudohyperkalemia is a potentially dangerous phenomenon where falsely reported elevated potassium levels result in potentially unwarranted correction of potassium by sodium polystyrene or by dialysis in extreme cases. Overcorrection of potassium in a patient whose potassium is normal or low can lead to hypokalemia and potentially life-threatening consequences. Typical pseudohyperkalemia is thought to be a result of platelet-mediated release of potassium that occurs from the clotting process of a serum sample where no anticoagulant is present. As a result, pseudohyperkalemia is typically corrected when potassium is measured with a plasma sample where heparin and other preservatives are present in the collection tube.1
Reverse pseudohyperkalemia is seen in patients with leukemia and lymphoma with significant lymphocytosis when laboratory studies demonstrate falsely elevated potassium. In reverse pseudohyperkalemia the potassium level from a plasma sample is falsely elevated despite the presence of an anticoagulant, as the process is independent of platelet activation and occurs as a result of white blood cell (WBC) breakdown.2
For several decades, it has been suggested that the presence of heparin in tubes used to collect plasma is the cause of lysis of WBCs, presumably due to possible membrane fragility of these cells. Correction was recommended with the use of low-heparin-coated tubes.3 The other proposed theory for reverse pseudohyperkalemia is that lysis of WBCs is primarily due to procedural handling: Several case reports suggest that pneumatic tube transport likely plays a strong role, as well as other factors, such as the length of time to the laboratory.4-6
The authors report a case of a patient with chronic lymphocytic leukemia (CLL) who presented with significant reverse pseudohyperkalemia that later was determined to be dependent on pneumatic tube transport and independent of heparin.
Case Presentation
The patient, an 83-year-old man with a long history of asymptomatic CLL, was noted to have rapid WBC doubling time. His WBC counts had increased from 45 × 103/μL to 95 x 103/μL over the year preceding admission, then further increased to 300 x 103/μL in the month before admission.
A computed tomography (CT) scan of the chest, abdomen, and pelvis showed significant lymphadenopathy and splenomegaly. The patient presented to the hospital for treatment with a planned first cycle of bendamustine alone and subsequent cycles of bendamustine and rituximab. His medical history included Prinzmetal angina, coronary artery disease, wet macular degeneration, and benign prostatic hyperplasia. Notably, he had a documented history of hyperkalemia with potassium levels ranging from 4.7 mEq/L to 4.9 mEq/L over the previous year and was placed on a potassium-restricted diet.
On presentation, he reported no recent history of B symptoms of fever, night sweats, weight loss, and malaise. His labs oratory results showed an elevated potassium level of 6.1 mEq/L with repeated whole blood potassium of 8.2 mEq/L. An electrocardiogram (ECG) showed sinus rhythm, no noted T-wave abnormalities, and no conduction abnormalities. A physical exam was significant for normal muscle strength, cervical lymphadenopathy, and splenomegaly.
The patient was initially treated for hyperkalemia with insulin plus glucose and sodium polystyrene. He responded with mild improvement of his potassium level to 6.3 mEq/L, 5.6 mEq/L, and 5.1 mEq/L after receiving 5 doses of 30 g of polystyrene over multiple checks during a 24-hour period. Hemolysis results drawn at that time were unremarkable. It was noted that the patient had an elevated lactate dehydrogenase (LDH) level of 328 IU/L.
The following morning, his potassium level remained elevated at 6.2 mEq/L, but because the treatment team suspected pseudohyperkalemia, the decision at the time was to proceed with chemotherapy.
To evaluate this possibility, the authors attempted to correct for procedural handling resulting in unwanted WBC lysis. They reduced the lithium heparin in the collection from 81 IU of lithium heparin found in the green-mint collection tube and instead used an arterial blood gas (ABG) syringe that contained 23.5 IU of heparin and hand-carried the sample to the lab. The potassium value was 3.4 mEq/L in the sample collected in the ABG syringe, and a concurrent value collected by the standard method was 7.4 mEq/L. A repeated ECG was negative for any cardiac arrhythmias or conduction abnormalities. The subsequent 2 sets of potassium values were 3.9 mEq/L for the ABG syringe and 6.4 mEq/L for the standard heparinized tube, and 3.5 mEq/L and 5.8 mEq/L, respectively. The patient received the remainder of his chemotherapy, and there was no evidence of tumor lysis syndrome (TLS).
The following day, tumor lysis labs were collected in a low-heparin ABG syringe and a regular green-mint collection tube. Both samples were manually brought to the lab without pneumatic tube transport. Interestingly, the patient’s repeat potassium levels were 3.3 mEq/L and 3.1 mEq/L, respectively. Therefore, it was determined that the potassium level was not dependent on the presence of an anticoagulant. The following day the patient remained asymptomatic with normal potassium levels, and he was discharged on a normal cardiac diet. When he was evaluated in an outpatient setting a month later, the patient was found to have a normal potassium level at 4.3 mEq/L on a normal potassium diet.
Conclusion
In the hospital setting, pseudohyperkalemia is a potentially dangerous situation. Because the patient discussed here initially presented with potassium values as high as 8.2 mEq/L, treatment was warranted. However, given the presence of CLL with extreme leukocytosis and otherwise
normal clinical findings, suspicion for pseudohyperkalemia was high. Initial treatment of the elevated potassium levels, which were revealed to be borderline low later in his clinical course, may have had detrimental effects on his cardiac function if hypokalemia had been inadvertently exacerbated to a significant level. The authors bring this case to the attention of health care providers of patients with CLL because this patient had been chronically managed for hyperkalemia with a lowpotassium diet.
Further, this case confirms the importance of avoiding the use of pneumatic tubes to prevent WBC lysis in patients with significant malignant leukocytosis. Importantly, the authors were able to differentiate between postulated heparin-mediated lysis and pneumatictube usage. As the literature has suggested, the authors speculated that mechanical stress on chronic lymphocytic leukemia cells is the primary cause of pseudo-hyperkalemia.
Pneumatic tube use or mechanical manipulation seemed to cause unwanted WBC lysis in this case, as values in the standard 81 IU heparin tubes used in this case study could be corrected by manually transporting the tube to the lab. This suggests that the process is heparin-independent, although initial investigations on that effect focused on the use of low-heparin vials. The potassium correction also was supported by the correction of likely falsely elevated LDH, which normalized when samples were manually transported. This supports the mechanism of WBC lysis. The authors’ observations are in line with several recent reports where pneumatic tube use was suspected as the cause of reverse pseudohyperkalemia.4,5,7,8
During the authors’ monitoring of the patient for TLS, comparison of repeat values for potassium showed a significant difference of about 2.7 mEq/L between samples transported manually and samples sent via pneumatic tube (Figure). Similar elevations of values have been described in other case reports.1
Reverse pseudohyperkalemia is a phenomenon that should not be overlooked in the medical management of patients with CLL with leukocytosis, especially in asymptomatic chronic patients. Although initially the differences can be benign, as the tumor burden increases, the degree of falsely elevated potassium can increase to thresholds that lead to inappropriate management in an acute setting. To prevent mismanagement, the authors recommend placing precautionary flags with hospital laboratories so that if a patient with CLL has a high potassium draw, lab values are rechecked with hand-delivered samples. The authors hope that this case will highlight the importance of suspecting this diagnosis in patients with CLL and provide guidance on obtaining accurate labs to better manage these patients.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
Click here to read the digital edition.
Pseudohyperkalemia is a potentially dangerous phenomenon where falsely reported elevated potassium levels result in potentially unwarranted correction of potassium by sodium polystyrene or by dialysis in extreme cases. Overcorrection of potassium in a patient whose potassium is normal or low can lead to hypokalemia and potentially life-threatening consequences. Typical pseudohyperkalemia is thought to be a result of platelet-mediated release of potassium that occurs from the clotting process of a serum sample where no anticoagulant is present. As a result, pseudohyperkalemia is typically corrected when potassium is measured with a plasma sample where heparin and other preservatives are present in the collection tube.1
Reverse pseudohyperkalemia is seen in patients with leukemia and lymphoma with significant lymphocytosis when laboratory studies demonstrate falsely elevated potassium. In reverse pseudohyperkalemia the potassium level from a plasma sample is falsely elevated despite the presence of an anticoagulant, as the process is independent of platelet activation and occurs as a result of white blood cell (WBC) breakdown.2
For several decades, it has been suggested that the presence of heparin in tubes used to collect plasma is the cause of lysis of WBCs, presumably due to possible membrane fragility of these cells. Correction was recommended with the use of low-heparin-coated tubes.3 The other proposed theory for reverse pseudohyperkalemia is that lysis of WBCs is primarily due to procedural handling: Several case reports suggest that pneumatic tube transport likely plays a strong role, as well as other factors, such as the length of time to the laboratory.4-6
The authors report a case of a patient with chronic lymphocytic leukemia (CLL) who presented with significant reverse pseudohyperkalemia that later was determined to be dependent on pneumatic tube transport and independent of heparin.
Case Presentation
The patient, an 83-year-old man with a long history of asymptomatic CLL, was noted to have rapid WBC doubling time. His WBC counts had increased from 45 × 103/μL to 95 x 103/μL over the year preceding admission, then further increased to 300 x 103/μL in the month before admission.
A computed tomography (CT) scan of the chest, abdomen, and pelvis showed significant lymphadenopathy and splenomegaly. The patient presented to the hospital for treatment with a planned first cycle of bendamustine alone and subsequent cycles of bendamustine and rituximab. His medical history included Prinzmetal angina, coronary artery disease, wet macular degeneration, and benign prostatic hyperplasia. Notably, he had a documented history of hyperkalemia with potassium levels ranging from 4.7 mEq/L to 4.9 mEq/L over the previous year and was placed on a potassium-restricted diet.
On presentation, he reported no recent history of B symptoms of fever, night sweats, weight loss, and malaise. His labs oratory results showed an elevated potassium level of 6.1 mEq/L with repeated whole blood potassium of 8.2 mEq/L. An electrocardiogram (ECG) showed sinus rhythm, no noted T-wave abnormalities, and no conduction abnormalities. A physical exam was significant for normal muscle strength, cervical lymphadenopathy, and splenomegaly.
The patient was initially treated for hyperkalemia with insulin plus glucose and sodium polystyrene. He responded with mild improvement of his potassium level to 6.3 mEq/L, 5.6 mEq/L, and 5.1 mEq/L after receiving 5 doses of 30 g of polystyrene over multiple checks during a 24-hour period. Hemolysis results drawn at that time were unremarkable. It was noted that the patient had an elevated lactate dehydrogenase (LDH) level of 328 IU/L.
The following morning, his potassium level remained elevated at 6.2 mEq/L, but because the treatment team suspected pseudohyperkalemia, the decision at the time was to proceed with chemotherapy.
To evaluate this possibility, the authors attempted to correct for procedural handling resulting in unwanted WBC lysis. They reduced the lithium heparin in the collection from 81 IU of lithium heparin found in the green-mint collection tube and instead used an arterial blood gas (ABG) syringe that contained 23.5 IU of heparin and hand-carried the sample to the lab. The potassium value was 3.4 mEq/L in the sample collected in the ABG syringe, and a concurrent value collected by the standard method was 7.4 mEq/L. A repeated ECG was negative for any cardiac arrhythmias or conduction abnormalities. The subsequent 2 sets of potassium values were 3.9 mEq/L for the ABG syringe and 6.4 mEq/L for the standard heparinized tube, and 3.5 mEq/L and 5.8 mEq/L, respectively. The patient received the remainder of his chemotherapy, and there was no evidence of tumor lysis syndrome (TLS).
The following day, tumor lysis labs were collected in a low-heparin ABG syringe and a regular green-mint collection tube. Both samples were manually brought to the lab without pneumatic tube transport. Interestingly, the patient’s repeat potassium levels were 3.3 mEq/L and 3.1 mEq/L, respectively. Therefore, it was determined that the potassium level was not dependent on the presence of an anticoagulant. The following day the patient remained asymptomatic with normal potassium levels, and he was discharged on a normal cardiac diet. When he was evaluated in an outpatient setting a month later, the patient was found to have a normal potassium level at 4.3 mEq/L on a normal potassium diet.
Conclusion
In the hospital setting, pseudohyperkalemia is a potentially dangerous situation. Because the patient discussed here initially presented with potassium values as high as 8.2 mEq/L, treatment was warranted. However, given the presence of CLL with extreme leukocytosis and otherwise
normal clinical findings, suspicion for pseudohyperkalemia was high. Initial treatment of the elevated potassium levels, which were revealed to be borderline low later in his clinical course, may have had detrimental effects on his cardiac function if hypokalemia had been inadvertently exacerbated to a significant level. The authors bring this case to the attention of health care providers of patients with CLL because this patient had been chronically managed for hyperkalemia with a lowpotassium diet.
Further, this case confirms the importance of avoiding the use of pneumatic tubes to prevent WBC lysis in patients with significant malignant leukocytosis. Importantly, the authors were able to differentiate between postulated heparin-mediated lysis and pneumatictube usage. As the literature has suggested, the authors speculated that mechanical stress on chronic lymphocytic leukemia cells is the primary cause of pseudo-hyperkalemia.
Pneumatic tube use or mechanical manipulation seemed to cause unwanted WBC lysis in this case, as values in the standard 81 IU heparin tubes used in this case study could be corrected by manually transporting the tube to the lab. This suggests that the process is heparin-independent, although initial investigations on that effect focused on the use of low-heparin vials. The potassium correction also was supported by the correction of likely falsely elevated LDH, which normalized when samples were manually transported. This supports the mechanism of WBC lysis. The authors’ observations are in line with several recent reports where pneumatic tube use was suspected as the cause of reverse pseudohyperkalemia.4,5,7,8
During the authors’ monitoring of the patient for TLS, comparison of repeat values for potassium showed a significant difference of about 2.7 mEq/L between samples transported manually and samples sent via pneumatic tube (Figure). Similar elevations of values have been described in other case reports.1
Reverse pseudohyperkalemia is a phenomenon that should not be overlooked in the medical management of patients with CLL with leukocytosis, especially in asymptomatic chronic patients. Although initially the differences can be benign, as the tumor burden increases, the degree of falsely elevated potassium can increase to thresholds that lead to inappropriate management in an acute setting. To prevent mismanagement, the authors recommend placing precautionary flags with hospital laboratories so that if a patient with CLL has a high potassium draw, lab values are rechecked with hand-delivered samples. The authors hope that this case will highlight the importance of suspecting this diagnosis in patients with CLL and provide guidance on obtaining accurate labs to better manage these patients.
Author disclosures
The authors report no actual or potential conflicts of interest with regard to this article.
Disclaimer
The opinions expressed herein are those of the authors and do not necessarily reflect those of Federal Practitioner, Frontline Medical Communications Inc., the U.S. Government, or any of its agencies. This article may discuss unlabeled or investigational use of certain drugs. Please review complete prescribing information for specific drugs or drug combinations—including indications, contraindications, warnings, and adverse effects—before administering pharmacologic therapy to patients.
Click here to read the digital edition.
1. Avelar T. Reverse pseudohyperkalemia in a patient with chronic lymphocytic leukemia. Perm J. 2014;18(4):e150-e152.
2. Abraham B, Fakhar I, Tikaria A, et al. Reverse pseudohyperkalemia in a leukemic patient. Clin Chem. 2008;54(2):449-451.
3. Singh PJ, Zawada ET, Santella RN. A case of “reverse” pseudohyperkalemia. Miner Electrolyte Metab. 1997;23(1):58-61.
4. Garwicz D, Karlman M. Early recognition of reverse pseudohyperkalemia in heparin plasma samples during leukemic hyperleukocytosis can prevent iatrogenic hypokalemia. Clin Biochem. 2012;45(18):1700-1702.
5. Garwicz D, Karlman M, Øra I. Reverse pseudohyperkalemia in heparin plasma samples from a child with T cell acute lymphoblastic leukemia with hyperleukocytosis. Clin Chim Acta. 2011;412(3-4):396-397.
6. Kintzel PE, Scott WL. Pseudohyperkalemia in a patient with chronic lymphoblastic leukemia and tumor lysis syndrome. J Oncol Pharm Pract. 2012;18(4):432-435.
7. Sindhu SK, Hix JK, Fricke W. Pseudohyperkalemia in chronic lymphocytic leukemia: phlebotomy sites and pneumatic tubes. Am J Kidney Dis. 2011;57(2):354-355.
8. Kellerman PS, Thornbery JM. Pseudohyperkalemia due to pneumatic tube transport in a leukemic patient. Am J Kidney Dis. 2005;46(4):746-748
Note: Page numbers differ between the print issue and digital edition.
1. Avelar T. Reverse pseudohyperkalemia in a patient with chronic lymphocytic leukemia. Perm J. 2014;18(4):e150-e152.
2. Abraham B, Fakhar I, Tikaria A, et al. Reverse pseudohyperkalemia in a leukemic patient. Clin Chem. 2008;54(2):449-451.
3. Singh PJ, Zawada ET, Santella RN. A case of “reverse” pseudohyperkalemia. Miner Electrolyte Metab. 1997;23(1):58-61.
4. Garwicz D, Karlman M. Early recognition of reverse pseudohyperkalemia in heparin plasma samples during leukemic hyperleukocytosis can prevent iatrogenic hypokalemia. Clin Biochem. 2012;45(18):1700-1702.
5. Garwicz D, Karlman M, Øra I. Reverse pseudohyperkalemia in heparin plasma samples from a child with T cell acute lymphoblastic leukemia with hyperleukocytosis. Clin Chim Acta. 2011;412(3-4):396-397.
6. Kintzel PE, Scott WL. Pseudohyperkalemia in a patient with chronic lymphoblastic leukemia and tumor lysis syndrome. J Oncol Pharm Pract. 2012;18(4):432-435.
7. Sindhu SK, Hix JK, Fricke W. Pseudohyperkalemia in chronic lymphocytic leukemia: phlebotomy sites and pneumatic tubes. Am J Kidney Dis. 2011;57(2):354-355.
8. Kellerman PS, Thornbery JM. Pseudohyperkalemia due to pneumatic tube transport in a leukemic patient. Am J Kidney Dis. 2005;46(4):746-748
Note: Page numbers differ between the print issue and digital edition.