Kenneth M. Jarman, PharmD

Increasingly, there is a focus on prevention of hospital‐acquired conditions including venous thromboembolism (VTE). Many studies have evaluated pulmonary embolism (PE) and lower extremity deep vein thrombosis (LEDVT), but despite increasing recognition of upper extremity deep vein thrombosis (UEDVT),[1, 2, 3, 4] less is known about this condition in hospitalized patients.

UEDVTs may be classified as primary, including disorders such as Paget‐Schroetter syndrome or other structural abnormality, or may be idiopathic; the majority are secondary clots.[5] Conventional risk factors for LEDVT including older age and obesity have been found to be less commonly associated,[1, 2, 5, 6, 7] and patients with UEDVT are generally younger, leaner, and a higher proportion are men. They are more likely to have malignancy or history of VTE and have undergone recent surgery or intensive care unit stay.[1, 2, 6] Central venous catheters (CVCs), often used in hospitalized patients, remain among the biggest known risks for UEDVT[1, 2, 3, 7, 8, 9, 10]; concomitant malignancy, VTE history, severe infection, surgery lasting >1 hour, and length of stay (LOS) >10 days confer additional risks with CVCs.[6, 7, 8, 11]

UEDVTs, once thought to be relatively benign, are now recognized to result in complications including PE, progression, recurrence, and post‐thrombotic syndrome.[2, 4, 12, 13] Despite extensive efforts to increase appropriate VTE prophylaxis in inpatients,[14] the role of chemoprophylaxis to prevent UEDVT remains undefined. Current guidelines recommend anticoagulation for treatment and complication prevention,[13, 15] but to date the evidence derives largely from observational studies or is extrapolated from the LEDVT literature.[2, 13]

To improve understanding of UEDVT at our institution, we set out to (1) determine UEDVT incidence in hospitalized patients, (2) describe associated risks and outcomes, and (3) assess management during hospitalization and at discharge.

METHODS

We identified all consecutive adult patients diagnosed with Doppler ultrasound‐confirmed UEDVT during hospitalization at Harborview Medical Center between September 2011 and November 2012. For patients who were readmitted during the study period, the first of their hospitalizations was used to describe associated factors, management, and outcomes. We present characteristics of all other hospitalizations during this time period for comparison. Harborview is a 413‐bed academic tertiary referral center and the only level 1 trauma center in a 5‐state area. Patients with UEDVT were identified using an information technology (IT) tool (the Harborview VTE tool) (Figure 1), which captures VTE events from vascular laboratory and radiology studies using natural language processing. Doppler ultrasound to assess for deep vein thrombosis (DVT) and computed tomographic scans to diagnose PE were ordered by inpatient physicians for symptomatic patients. The reason for obtaining the study is included in the ultrasound reports. We do not routinely screen for UEDVT at our institution. UEDVT included clots in the deep veins of the upper extremities including internal jugular, subclavian, axillary, and brachial veins. Superficial thrombosis and thrombophlebitis were excluded. We previously compared VTE events captured by this tool with administrative billing data and found that all VTE events that were coded were captured with the tool.

Figure 1

The VTE tool (Figure 1) displays imaging results together with demographic, clinical, and medication data and links this information with admission, discharge, and death summaries as well as CVC insertion procedure notes from the electronic health record (EHR). Additional data, including comorbid conditions, primary reason for hospitalization, past medical history such as prior VTE events, and cause of death (if not available in the admission note or discharge/death summaries), were obtained from EHR abstraction by 1 of the investigators. A 10% random sample of charts was rereviewed by another investigator with complete concordance. Supplementary data about date of CVC insertion if placed at an outside facility, date of CVC removal if applicable, clinical assessments regarding whether a clot was CVC‐associated, and contraindications to therapeutic anticoagulation were also abstracted directly from the EHR. Administrative data were used to identify the case mix index, an indicator of severity of illness.

Pharmacologic VTE prophylaxis included all chemical prophylaxis specified on our institutional guideline, most commonly subcutaneous unfractionated heparin 5000 units every 8 hours or low molecular weight heparin (LMWH), either enoxaparin 40 mg every 12 or 24 hours or dalteparin 5000 units every 24 hours. Mechanical prophylaxis was defined as use of sequential compression devices (SCDs) when pharmacologic prophylaxis was contraindicated. Prophylaxis was considered to be appropriate if it was applied according to our guideline for >90% of hospital days prior to UEDVT diagnosis. Therapeutic anticoagulation included heparin bridging (most commonly continuous heparin infusion, LMWH 1 mg/kg or dalteparin) as well as oral vitamin K antagonists. The VTE tool (Figure 1) allows identification of pharmacologic prophylaxis and therapy that is actually administered (not just ordered) directly from our pharmacy IT system. SCD application (not just ordered SCDs) is electronically integrated into the tool from nursing documentation.

CVCs included internal jugular or subclavian triple lumen catheters, tunneled dialysis catheters, or peripherally inserted central catheters (PICCs), single or double lumen. Criteria used to identify that a UEDVT was CVC‐associated included temporal relationship (CVC was placed prior to clot diagnosis), plausibility (ipsilateral clot), evidence of clot surrounding CVC on ultrasound, and physician designation of association (as documented in progress notes or discharge summary).

Simple percentages of patient characteristics, associated factors, management, and outcomes were calculated using counts as the numerator and number of patients as the denominator. For information about UEDVTs, we used total number of UEDVTs as the denominator. Line days were day counts from insertion until removal if applicable. The CVC placement date was available in our mandated central line placement procedure notes (directly accessed from the VTE tool) for all lines placed at our institution; date of removal (if applicable) was determined from chart abstraction. For the vast majority of patients whose CVCs were placed at outside facilities, date of placement was available in the EHR (often in the admission note or in the ultrasound report/reason for study). If date of line placement at an outside facility was not known, date of admission was used. The University of Washington Human Subjects Board approved this review.

RESULTS

DISCUSSION

UEDVT is increasingly recognized in hospitalized patients.[3, 9] At our medical center, 0.2% of symptomatic inpatients were diagnosed with UEDVT over 14 months. These patients were predominantly men with high rates of CVCs, malignancy, VTE history, severe infection, and renal disease. Interestingly, although the literature suggests that some proportion of patients with UEDVT have anatomic abnormalities, such as Paget‐Schroetter syndrome,[15] none of the patients in our study were found to have these anomalies. In our review, hospitalized patients with UEDVT were critically ill, with a long LOS and high morbidity and mortality, suggesting that in addition to just being a complication of hospitalization,[1, 6] UEDVT may be a marker of severe illness.

In our institution, clinical presentation was consistent with what has been described with the majority of patients presenting with upper extremity swelling.[1, 3] The internal jugular veins were the most common anatomic UEDVT site, followed by brachial then axillary veins. In other series including both in‐ and outpatients, subclavian clots were most commonly diagnosed, reflecting in part higher rates of CVC association and CVC location in those studies.[3, 9] Concurrent DVT and PE rates were similar to those reported.[1, 3, 10]

Although many studies have focused on prevention of LEDVT and PE, few trials have specifically targeted UEDVT. Among our patients with UEDVTs that were not present on admission, VTE prophylaxis rates were considerably higher than what has been reported,[1, 6] suggesting that in these critically ill patients' prophylaxis may not prevent symptomatic UEDVT. It is unknown how many UEDVTs were prevented with prophylaxis, as only patients with symptomatic UEDVT were included. Adequacy of prophylaxis at outside hospitals for patients transferred in could not be assessed. Nonetheless, low numbers of UEDVT at a trauma referral center with many high‐risk patients raise the question of whether prophylaxis makes a difference. Additional study is needed to further define the role of chemoprophylaxis to prevent UEDVT in hospitalized patients.

In our inpatient group, 84% required CVCs; 44% of patients were thought to have CVC‐associated UEDVTs. Careful patient selection and attention to potentially modifiable risks, such as insertion site, catheter type, and tip position, may need further examination in this population.[3, 11, 16] Catheter duration was long; focus on removing CVCs when no longer necessary is important. Interestingly, almost 10% in our study underwent diagnostic ultrasound because a new CVC could not be successfully placed suggesting that UEDVT may develop in critically ill patients regardless of CVCs.

In our study, there were high rates of guideline‐recommended pharmacologic treatment; surprisingly the majority of CVCs with associated clot were removed. Guidelines currently support 3 months of anticoagulation for treatment of UEDVT[2, 13, 17]; evidence derives from observational trials or is largely extrapolated from LEDVT literature.[2, 13] Routine CVC removal is not specifically recommended for CVC‐associated UEDVT, particularly if lines remain functional and medically necessary; systemic anticoagulation should be provided.[13]

In our review, no hospitalized patients with UEDVT developed complications or were readmitted to our medical center within 30 days for clot progression, new PE, or post‐thrombotic syndrome, which is lower than rates reported over longer time periods.[2, 6, 10, 12] Ten percent died during hospitalization, all from their primary disease rather than from complications of VTE or VTE treatment, and no additional patients died at our institution within 30 days. Although these rates are lower than have been otherwise reported,[2, 10] the inpatient mortality rate is similar to a recent study that included inpatients; however, all patients who died in that study had cancer and CVCs.[3] In the latter study, 6.4% died within 30 days of discharge.

CONCLUSIONS

Among hospitalized patients, UEDVT is increasingly recognized. In our medical center, hospitalized patients diagnosed with UEDVT were more likely to have CVCs, malignancy, renal disease, and severe infection. Many of these patients were transferred critically ill, had prolonged LOS, and had high in‐hospital mortality. Most developed UEDVT despite prophylaxis, and the majority of UEDVTs were treated even in the absence of concurrent LEDVT or PE. As we move toward an era of increasing accountability, with a focus on preventing hospital‐acquired conditions including VTE, additional research is needed to identify modifiable risks, explore opportunities for effective prevention, and optimize outcomes such as prevention of complications or readmissions, particularly in critically ill patients with UEDVT.

Increasingly, there is a focus on prevention of hospital‐acquired conditions including venous thromboembolism (VTE). Many studies have evaluated pulmonary embolism (PE) and lower extremity deep vein thrombosis (LEDVT), but despite increasing recognition of upper extremity deep vein thrombosis (UEDVT),[1, 2, 3, 4] less is known about this condition in hospitalized patients.

UEDVTs may be classified as primary, including disorders such as Paget‐Schroetter syndrome or other structural abnormality, or may be idiopathic; the majority are secondary clots.[5] Conventional risk factors for LEDVT including older age and obesity have been found to be less commonly associated,[1, 2, 5, 6, 7] and patients with UEDVT are generally younger, leaner, and a higher proportion are men. They are more likely to have malignancy or history of VTE and have undergone recent surgery or intensive care unit stay.[1, 2, 6] Central venous catheters (CVCs), often used in hospitalized patients, remain among the biggest known risks for UEDVT[1, 2, 3, 7, 8, 9, 10]; concomitant malignancy, VTE history, severe infection, surgery lasting >1 hour, and length of stay (LOS) >10 days confer additional risks with CVCs.[6, 7, 8, 11]

UEDVTs, once thought to be relatively benign, are now recognized to result in complications including PE, progression, recurrence, and post‐thrombotic syndrome.[2, 4, 12, 13] Despite extensive efforts to increase appropriate VTE prophylaxis in inpatients,[14] the role of chemoprophylaxis to prevent UEDVT remains undefined. Current guidelines recommend anticoagulation for treatment and complication prevention,[13, 15] but to date the evidence derives largely from observational studies or is extrapolated from the LEDVT literature.[2, 13]

To improve understanding of UEDVT at our institution, we set out to (1) determine UEDVT incidence in hospitalized patients, (2) describe associated risks and outcomes, and (3) assess management during hospitalization and at discharge.

METHODS

We identified all consecutive adult patients diagnosed with Doppler ultrasound‐confirmed UEDVT during hospitalization at Harborview Medical Center between September 2011 and November 2012. For patients who were readmitted during the study period, the first of their hospitalizations was used to describe associated factors, management, and outcomes. We present characteristics of all other hospitalizations during this time period for comparison. Harborview is a 413‐bed academic tertiary referral center and the only level 1 trauma center in a 5‐state area. Patients with UEDVT were identified using an information technology (IT) tool (the Harborview VTE tool) (Figure 1), which captures VTE events from vascular laboratory and radiology studies using natural language processing. Doppler ultrasound to assess for deep vein thrombosis (DVT) and computed tomographic scans to diagnose PE were ordered by inpatient physicians for symptomatic patients. The reason for obtaining the study is included in the ultrasound reports. We do not routinely screen for UEDVT at our institution. UEDVT included clots in the deep veins of the upper extremities including internal jugular, subclavian, axillary, and brachial veins. Superficial thrombosis and thrombophlebitis were excluded. We previously compared VTE events captured by this tool with administrative billing data and found that all VTE events that were coded were captured with the tool.

Figure 1

The VTE tool (Figure 1) displays imaging results together with demographic, clinical, and medication data and links this information with admission, discharge, and death summaries as well as CVC insertion procedure notes from the electronic health record (EHR). Additional data, including comorbid conditions, primary reason for hospitalization, past medical history such as prior VTE events, and cause of death (if not available in the admission note or discharge/death summaries), were obtained from EHR abstraction by 1 of the investigators. A 10% random sample of charts was rereviewed by another investigator with complete concordance. Supplementary data about date of CVC insertion if placed at an outside facility, date of CVC removal if applicable, clinical assessments regarding whether a clot was CVC‐associated, and contraindications to therapeutic anticoagulation were also abstracted directly from the EHR. Administrative data were used to identify the case mix index, an indicator of severity of illness.

Pharmacologic VTE prophylaxis included all chemical prophylaxis specified on our institutional guideline, most commonly subcutaneous unfractionated heparin 5000 units every 8 hours or low molecular weight heparin (LMWH), either enoxaparin 40 mg every 12 or 24 hours or dalteparin 5000 units every 24 hours. Mechanical prophylaxis was defined as use of sequential compression devices (SCDs) when pharmacologic prophylaxis was contraindicated. Prophylaxis was considered to be appropriate if it was applied according to our guideline for >90% of hospital days prior to UEDVT diagnosis. Therapeutic anticoagulation included heparin bridging (most commonly continuous heparin infusion, LMWH 1 mg/kg or dalteparin) as well as oral vitamin K antagonists. The VTE tool (Figure 1) allows identification of pharmacologic prophylaxis and therapy that is actually administered (not just ordered) directly from our pharmacy IT system. SCD application (not just ordered SCDs) is electronically integrated into the tool from nursing documentation.

CVCs included internal jugular or subclavian triple lumen catheters, tunneled dialysis catheters, or peripherally inserted central catheters (PICCs), single or double lumen. Criteria used to identify that a UEDVT was CVC‐associated included temporal relationship (CVC was placed prior to clot diagnosis), plausibility (ipsilateral clot), evidence of clot surrounding CVC on ultrasound, and physician designation of association (as documented in progress notes or discharge summary).

Simple percentages of patient characteristics, associated factors, management, and outcomes were calculated using counts as the numerator and number of patients as the denominator. For information about UEDVTs, we used total number of UEDVTs as the denominator. Line days were day counts from insertion until removal if applicable. The CVC placement date was available in our mandated central line placement procedure notes (directly accessed from the VTE tool) for all lines placed at our institution; date of removal (if applicable) was determined from chart abstraction. For the vast majority of patients whose CVCs were placed at outside facilities, date of placement was available in the EHR (often in the admission note or in the ultrasound report/reason for study). If date of line placement at an outside facility was not known, date of admission was used. The University of Washington Human Subjects Board approved this review.

RESULTS

DISCUSSION

UEDVT is increasingly recognized in hospitalized patients.[3, 9] At our medical center, 0.2% of symptomatic inpatients were diagnosed with UEDVT over 14 months. These patients were predominantly men with high rates of CVCs, malignancy, VTE history, severe infection, and renal disease. Interestingly, although the literature suggests that some proportion of patients with UEDVT have anatomic abnormalities, such as Paget‐Schroetter syndrome,[15] none of the patients in our study were found to have these anomalies. In our review, hospitalized patients with UEDVT were critically ill, with a long LOS and high morbidity and mortality, suggesting that in addition to just being a complication of hospitalization,[1, 6] UEDVT may be a marker of severe illness.

In our institution, clinical presentation was consistent with what has been described with the majority of patients presenting with upper extremity swelling.[1, 3] The internal jugular veins were the most common anatomic UEDVT site, followed by brachial then axillary veins. In other series including both in‐ and outpatients, subclavian clots were most commonly diagnosed, reflecting in part higher rates of CVC association and CVC location in those studies.[3, 9] Concurrent DVT and PE rates were similar to those reported.[1, 3, 10]

Although many studies have focused on prevention of LEDVT and PE, few trials have specifically targeted UEDVT. Among our patients with UEDVTs that were not present on admission, VTE prophylaxis rates were considerably higher than what has been reported,[1, 6] suggesting that in these critically ill patients' prophylaxis may not prevent symptomatic UEDVT. It is unknown how many UEDVTs were prevented with prophylaxis, as only patients with symptomatic UEDVT were included. Adequacy of prophylaxis at outside hospitals for patients transferred in could not be assessed. Nonetheless, low numbers of UEDVT at a trauma referral center with many high‐risk patients raise the question of whether prophylaxis makes a difference. Additional study is needed to further define the role of chemoprophylaxis to prevent UEDVT in hospitalized patients.

In our inpatient group, 84% required CVCs; 44% of patients were thought to have CVC‐associated UEDVTs. Careful patient selection and attention to potentially modifiable risks, such as insertion site, catheter type, and tip position, may need further examination in this population.[3, 11, 16] Catheter duration was long; focus on removing CVCs when no longer necessary is important. Interestingly, almost 10% in our study underwent diagnostic ultrasound because a new CVC could not be successfully placed suggesting that UEDVT may develop in critically ill patients regardless of CVCs.

In our study, there were high rates of guideline‐recommended pharmacologic treatment; surprisingly the majority of CVCs with associated clot were removed. Guidelines currently support 3 months of anticoagulation for treatment of UEDVT[2, 13, 17]; evidence derives from observational trials or is largely extrapolated from LEDVT literature.[2, 13] Routine CVC removal is not specifically recommended for CVC‐associated UEDVT, particularly if lines remain functional and medically necessary; systemic anticoagulation should be provided.[13]

In our review, no hospitalized patients with UEDVT developed complications or were readmitted to our medical center within 30 days for clot progression, new PE, or post‐thrombotic syndrome, which is lower than rates reported over longer time periods.[2, 6, 10, 12] Ten percent died during hospitalization, all from their primary disease rather than from complications of VTE or VTE treatment, and no additional patients died at our institution within 30 days. Although these rates are lower than have been otherwise reported,[2, 10] the inpatient mortality rate is similar to a recent study that included inpatients; however, all patients who died in that study had cancer and CVCs.[3] In the latter study, 6.4% died within 30 days of discharge.

CONCLUSIONS

Among hospitalized patients, UEDVT is increasingly recognized. In our medical center, hospitalized patients diagnosed with UEDVT were more likely to have CVCs, malignancy, renal disease, and severe infection. Many of these patients were transferred critically ill, had prolonged LOS, and had high in‐hospital mortality. Most developed UEDVT despite prophylaxis, and the majority of UEDVTs were treated even in the absence of concurrent LEDVT or PE. As we move toward an era of increasing accountability, with a focus on preventing hospital‐acquired conditions including VTE, additional research is needed to identify modifiable risks, explore opportunities for effective prevention, and optimize outcomes such as prevention of complications or readmissions, particularly in critically ill patients with UEDVT.

Increasingly, there is a focus on prevention of hospital‐acquired conditions including venous thromboembolism (VTE). Many studies have evaluated pulmonary embolism (PE) and lower extremity deep vein thrombosis (LEDVT), but despite increasing recognition of upper extremity deep vein thrombosis (UEDVT),[1, 2, 3, 4] less is known about this condition in hospitalized patients.

UEDVTs may be classified as primary, including disorders such as Paget‐Schroetter syndrome or other structural abnormality, or may be idiopathic; the majority are secondary clots.[5] Conventional risk factors for LEDVT including older age and obesity have been found to be less commonly associated,[1, 2, 5, 6, 7] and patients with UEDVT are generally younger, leaner, and a higher proportion are men. They are more likely to have malignancy or history of VTE and have undergone recent surgery or intensive care unit stay.[1, 2, 6] Central venous catheters (CVCs), often used in hospitalized patients, remain among the biggest known risks for UEDVT[1, 2, 3, 7, 8, 9, 10]; concomitant malignancy, VTE history, severe infection, surgery lasting >1 hour, and length of stay (LOS) >10 days confer additional risks with CVCs.[6, 7, 8, 11]

UEDVTs, once thought to be relatively benign, are now recognized to result in complications including PE, progression, recurrence, and post‐thrombotic syndrome.[2, 4, 12, 13] Despite extensive efforts to increase appropriate VTE prophylaxis in inpatients,[14] the role of chemoprophylaxis to prevent UEDVT remains undefined. Current guidelines recommend anticoagulation for treatment and complication prevention,[13, 15] but to date the evidence derives largely from observational studies or is extrapolated from the LEDVT literature.[2, 13]

To improve understanding of UEDVT at our institution, we set out to (1) determine UEDVT incidence in hospitalized patients, (2) describe associated risks and outcomes, and (3) assess management during hospitalization and at discharge.

METHODS

We identified all consecutive adult patients diagnosed with Doppler ultrasound‐confirmed UEDVT during hospitalization at Harborview Medical Center between September 2011 and November 2012. For patients who were readmitted during the study period, the first of their hospitalizations was used to describe associated factors, management, and outcomes. We present characteristics of all other hospitalizations during this time period for comparison. Harborview is a 413‐bed academic tertiary referral center and the only level 1 trauma center in a 5‐state area. Patients with UEDVT were identified using an information technology (IT) tool (the Harborview VTE tool) (Figure 1), which captures VTE events from vascular laboratory and radiology studies using natural language processing. Doppler ultrasound to assess for deep vein thrombosis (DVT) and computed tomographic scans to diagnose PE were ordered by inpatient physicians for symptomatic patients. The reason for obtaining the study is included in the ultrasound reports. We do not routinely screen for UEDVT at our institution. UEDVT included clots in the deep veins of the upper extremities including internal jugular, subclavian, axillary, and brachial veins. Superficial thrombosis and thrombophlebitis were excluded. We previously compared VTE events captured by this tool with administrative billing data and found that all VTE events that were coded were captured with the tool.

Figure 1

The VTE tool (Figure 1) displays imaging results together with demographic, clinical, and medication data and links this information with admission, discharge, and death summaries as well as CVC insertion procedure notes from the electronic health record (EHR). Additional data, including comorbid conditions, primary reason for hospitalization, past medical history such as prior VTE events, and cause of death (if not available in the admission note or discharge/death summaries), were obtained from EHR abstraction by 1 of the investigators. A 10% random sample of charts was rereviewed by another investigator with complete concordance. Supplementary data about date of CVC insertion if placed at an outside facility, date of CVC removal if applicable, clinical assessments regarding whether a clot was CVC‐associated, and contraindications to therapeutic anticoagulation were also abstracted directly from the EHR. Administrative data were used to identify the case mix index, an indicator of severity of illness.

Pharmacologic VTE prophylaxis included all chemical prophylaxis specified on our institutional guideline, most commonly subcutaneous unfractionated heparin 5000 units every 8 hours or low molecular weight heparin (LMWH), either enoxaparin 40 mg every 12 or 24 hours or dalteparin 5000 units every 24 hours. Mechanical prophylaxis was defined as use of sequential compression devices (SCDs) when pharmacologic prophylaxis was contraindicated. Prophylaxis was considered to be appropriate if it was applied according to our guideline for >90% of hospital days prior to UEDVT diagnosis. Therapeutic anticoagulation included heparin bridging (most commonly continuous heparin infusion, LMWH 1 mg/kg or dalteparin) as well as oral vitamin K antagonists. The VTE tool (Figure 1) allows identification of pharmacologic prophylaxis and therapy that is actually administered (not just ordered) directly from our pharmacy IT system. SCD application (not just ordered SCDs) is electronically integrated into the tool from nursing documentation.

CVCs included internal jugular or subclavian triple lumen catheters, tunneled dialysis catheters, or peripherally inserted central catheters (PICCs), single or double lumen. Criteria used to identify that a UEDVT was CVC‐associated included temporal relationship (CVC was placed prior to clot diagnosis), plausibility (ipsilateral clot), evidence of clot surrounding CVC on ultrasound, and physician designation of association (as documented in progress notes or discharge summary).

Simple percentages of patient characteristics, associated factors, management, and outcomes were calculated using counts as the numerator and number of patients as the denominator. For information about UEDVTs, we used total number of UEDVTs as the denominator. Line days were day counts from insertion until removal if applicable. The CVC placement date was available in our mandated central line placement procedure notes (directly accessed from the VTE tool) for all lines placed at our institution; date of removal (if applicable) was determined from chart abstraction. For the vast majority of patients whose CVCs were placed at outside facilities, date of placement was available in the EHR (often in the admission note or in the ultrasound report/reason for study). If date of line placement at an outside facility was not known, date of admission was used. The University of Washington Human Subjects Board approved this review.

RESULTS

DISCUSSION

UEDVT is increasingly recognized in hospitalized patients.[3, 9] At our medical center, 0.2% of symptomatic inpatients were diagnosed with UEDVT over 14 months. These patients were predominantly men with high rates of CVCs, malignancy, VTE history, severe infection, and renal disease. Interestingly, although the literature suggests that some proportion of patients with UEDVT have anatomic abnormalities, such as Paget‐Schroetter syndrome,[15] none of the patients in our study were found to have these anomalies. In our review, hospitalized patients with UEDVT were critically ill, with a long LOS and high morbidity and mortality, suggesting that in addition to just being a complication of hospitalization,[1, 6] UEDVT may be a marker of severe illness.

In our institution, clinical presentation was consistent with what has been described with the majority of patients presenting with upper extremity swelling.[1, 3] The internal jugular veins were the most common anatomic UEDVT site, followed by brachial then axillary veins. In other series including both in‐ and outpatients, subclavian clots were most commonly diagnosed, reflecting in part higher rates of CVC association and CVC location in those studies.[3, 9] Concurrent DVT and PE rates were similar to those reported.[1, 3, 10]

Although many studies have focused on prevention of LEDVT and PE, few trials have specifically targeted UEDVT. Among our patients with UEDVTs that were not present on admission, VTE prophylaxis rates were considerably higher than what has been reported,[1, 6] suggesting that in these critically ill patients' prophylaxis may not prevent symptomatic UEDVT. It is unknown how many UEDVTs were prevented with prophylaxis, as only patients with symptomatic UEDVT were included. Adequacy of prophylaxis at outside hospitals for patients transferred in could not be assessed. Nonetheless, low numbers of UEDVT at a trauma referral center with many high‐risk patients raise the question of whether prophylaxis makes a difference. Additional study is needed to further define the role of chemoprophylaxis to prevent UEDVT in hospitalized patients.

In our inpatient group, 84% required CVCs; 44% of patients were thought to have CVC‐associated UEDVTs. Careful patient selection and attention to potentially modifiable risks, such as insertion site, catheter type, and tip position, may need further examination in this population.[3, 11, 16] Catheter duration was long; focus on removing CVCs when no longer necessary is important. Interestingly, almost 10% in our study underwent diagnostic ultrasound because a new CVC could not be successfully placed suggesting that UEDVT may develop in critically ill patients regardless of CVCs.

In our study, there were high rates of guideline‐recommended pharmacologic treatment; surprisingly the majority of CVCs with associated clot were removed. Guidelines currently support 3 months of anticoagulation for treatment of UEDVT[2, 13, 17]; evidence derives from observational trials or is largely extrapolated from LEDVT literature.[2, 13] Routine CVC removal is not specifically recommended for CVC‐associated UEDVT, particularly if lines remain functional and medically necessary; systemic anticoagulation should be provided.[13]

In our review, no hospitalized patients with UEDVT developed complications or were readmitted to our medical center within 30 days for clot progression, new PE, or post‐thrombotic syndrome, which is lower than rates reported over longer time periods.[2, 6, 10, 12] Ten percent died during hospitalization, all from their primary disease rather than from complications of VTE or VTE treatment, and no additional patients died at our institution within 30 days. Although these rates are lower than have been otherwise reported,[2, 10] the inpatient mortality rate is similar to a recent study that included inpatients; however, all patients who died in that study had cancer and CVCs.[3] In the latter study, 6.4% died within 30 days of discharge.

CONCLUSIONS

Among hospitalized patients, UEDVT is increasingly recognized. In our medical center, hospitalized patients diagnosed with UEDVT were more likely to have CVCs, malignancy, renal disease, and severe infection. Many of these patients were transferred critically ill, had prolonged LOS, and had high in‐hospital mortality. Most developed UEDVT despite prophylaxis, and the majority of UEDVTs were treated even in the absence of concurrent LEDVT or PE. As we move toward an era of increasing accountability, with a focus on preventing hospital‐acquired conditions including VTE, additional research is needed to identify modifiable risks, explore opportunities for effective prevention, and optimize outcomes such as prevention of complications or readmissions, particularly in critically ill patients with UEDVT.

Venous thromboembolism (VTE) is a major cause of morbidity and mortality in hospitalized patients.13 Major efforts are underway to increase appropriate VTE prophylaxis (VTEP)4 and adherence to VTEP guidelines are increasingly used as a quality of care measure. National 2008 VTEP guidelines suggest that all medical patients ill enough to require hospitalization, particularly those requiring admission to the Intensive Care Unit (ICU), have at least a moderate risk of developing VTE and prophylaxis is recommended.4 Hospitalized patients with end‐stage liver disease (ESLD), despite their coagulopathy, are known to be at risk for VTE48 and may be VTEP candidates.

Based on available literature, it is unknown whether pharmacologic VTEP should be utilized in acutely ill, hospitalized patients with ESLD, particularly in those admitted with variceal bleeding. These patients are at high risk for rebleeding, with the highest risk in the first 5 days.9 Early rebleeding, defined as recurrent bleeding within 6 weeks of initial bleed, declined from 47% in the 1980s to 13% by 2000 because of increased early endoscopic intervention and use of medications to prevent rebleeding.911 In multicenter cohort studies, D'Amico and De Franchis12 reported that 13% of patients with variceal bleeding had uncontrolled bleeding, rebleeding, or death within 5 days of admission while Bahmba et al.13 reported a 16% rate of rebleeding within 5 days. We are unaware of prior reports regarding the safety of VTEP in this high‐risk group of patients.

Objective

We sought to describe rebleeding in a series of 22 patients with ESLD admitted with variceal bleeding who received pharmacologic VTEP.

Methods

We identified all patients 18 years and older with upper gastrointestinal bleeding admitted to Harborview Medical Center, a 400‐bed urban county teaching hospital in Seattle, Washington, between January 1, 2003 and December 31, 2005 (Figure 1), just prior to medical center‐wide implementation of a VTEP guideline. Potential cases were identified using administrative data based on 8 discharge diagnoses (Supporting Information Appendix 1) and 10 procedure codes (Supporting Information Appendix 2).14 Inpatient pharmacy data indicating continuous octreotide infusion were used to refine the sample. At our institution, it is a standard of care to initiate octreotide in patients admitted with variceal bleeding. We excluded patients who did not have ESLD (defined as evidence of cirrhosis and associated complications including but not limited to ascites, encephalopathy, variceal bleeding, portal hypertension) documented in their problem list or past medical history and those with no variceal bleeding based on medical record review. We identified cases receiving pharmacologic VTEP, either subcutaneous unfractionated heparin (UFH) or low molecular weight heparin (LMWH), during hospitalization from pharmacy records.

Figure 1

We obtained demographic and clinical data from administrative billing systems, electronic and paper medical records, and inpatient pharmacy databases and verified transfusion data from the Puget Sound Blood Center. We abstracted esophagogastroduodenoscopy (EGD) findings indicating high risk of rebleeding including variceal grade and stigmata of recent bleeding such as red spots or wales.15, 16 Data were abstracted by the first 3 authors (AS, MS, KJ) and reviewed again by 2 authors (AS, KJ) blinded to the others' abstractions.

We calculated Model for ESLD (MELD) scores on admission. These scores correlate with 3 month mortality in ESLD.17 We tabulated 5 factors shown in some studies to predict bleeding including high International Normalized Ratio (INR) (>1.5), low hematocrit (<25%), low platelet count (<100,000 per microliter), active bleeding at EGD, and transfusion of four or more units of red cells within 24 hours of admission.1013

We defined rebleeding as a decrease in hematocrit of greater than 5 percentage points compared with postresuscitation hematocrit, transfusion of additional red cells more than 48 hours after initial resuscitation, repeat unscheduled EGD, or return to the ICU for therapies related to rebleeding.18 The University of Washington Human Subjects Board approved this study.

Results

Of 224 patients initially identified, 36 received pharmacologic VTEP. We excluded 14 who did not have ESLD (n = 1) or did not have a variceal bleed (n = 13). The remaining 22 patients form the sample described in Figure 1.

The median age of patients was 52 years (range 42‐85) and 77% were men (Table 1). Twenty‐one of 22 patients (95%) were initially admitted to the ICU; median length of stay was 8 days (range 4‐30). Median MELD score on admission was 15 (range 825). On EGD, the number of variceal columns ranged from 1 to 4; 17 patients (77%) had at least 3. A total of 15 patients (68%) had stigmata of recent bleeding and 16 (72%) underwent banding (range 16 bands). All patients had at least 1 bleeding risk factor (Table 1) of which the most common factors observed were initial transfusion of 4 or more units of red cells (50%, n = 11), INR > 1.5 (45%, n = 10), and hematocrit < 25% (45%, n = 10).

A total of 12 patients (55%) received 5000 units of UFH every 8 hours, 8 (36%) received 5000 units UFH every 12 hours, and 2 (9%) received LMWH. VTEP was initiated as early as day of admission and as late as day 19. Median VTEP start date was hospital day 4. Median duration of of VTEP was 5 days.

Only 1 patient (4.5%) rebled after VTEP initiation. The patient received UFH every 8 hours starting on hospital day 6, and rebleeding occurred on day 9. Repeat EGD showed ulcers at banding sites. The patient was restarted on VTEP on hospital day 13 without recurrence of rebleeding. This patient had a MELD score of 24, initial INR >2, hematocrit <25%, had grade 3 varices and stigmata of recent bleeding on EGD, and received 4 units of packed red cells. These values are similar to those of the cohort as a whole (Table 1). This patient also was diagnosed with DVT while receiving VTEP on hospital day 15. This patient's coagulopathy was in the setting of terminal illness; the patient expired on hospital day 25.

One additional patient rebled prior to VTEP initiation on day 3 with repeat EGD showing a bleeding varix. This patient was nevertheless started on VTEP 4 days after rebleeding. Despite use of VTEP, this patient was diagnosed with DVT on hospital day 9 (and may well have had the DVT at the time of VTEP initiation). The patient was transitioned to therapeutic dose heparin which was tolerated without recurrence of rebleeding.

There were no other confirmed cases of DVT in this series. One additional patient underwent angiogram that showed no pulmonary embolism; 2 other patients underwent lower extremity ultrasounds that were negative for DVT.

Discussion

At our medical center, only a few inpatients with ESLD admitted with variceal bleed received VTEP. These patients were seemingly at high risk for bleeding and rebleeding given high MELD scores, variceal bleeding, and presence of at least one clinical factor suggesting bleeding risk, and in several cases 3 or more such factors.13, 18 Despite this, only 1 patient rebled while receiving VTEP. We captured rebleeding rates only during the index hospitalization. We therefore may underestimate early rebleeding rates.1013 Nevertheless, our inpatient data included complete coverage of the earliest period after the index bleeds and the period during which patients were exposed to VTEP, which should be the time of highest rebleeding risk related to VTEP exposure. Interestingly the patient who rebled while on VTEP was also diagnosed with VTE while on VTEP. Two patients (9%) in our sample were diagnosed with VTE.

This case series is limited by its small sample size, retrospective nature, single center observation, and perhaps especially by possible selection bias. We were unable to specifically quantify rebleeding risk. Several authors have identified individual factors associated with rebleeding,1013 these were tabulated for patients in this case series (Table 1) and all patients had at least 1 of these factors. Concurrent infection and hepatic vein pressure gradient have been shown to predict rebleeding;9, 19 we were unable to identify these factors in our data.

There was considerable variability in this case series in timing of VTEP initiation relative to initial bleed. We were unable to characterize provider or patient characteristics that may have influenced the decision to initiate VTEP and timing. The sample size was also too small to comment upon factors associated with choice of UFH versus LMWH and any potential differences in rebleeding risk between the 2. We also did not look at outcomes postindex hospitalization so we can not comment on the extended risk of rebleeding with VTEP after discharge. However, the risk of rebleeding is highest within the first 96 hours13 and all patients in this series were hospitalized at least 4 days. Nonetheless, we captured all patients with ESLD and variceal bleeding exposed to VTEP at a large center over a three‐year period and found rebleeding rates less than what might be expected.

Conclusions

Our observations suggest that some inpatients with ESLD and variceal bleeding may tolerate pharmacologic VTEP. In this small group of patients, VTEP was associated with an unexpectedly low incidence of rebleeding. While this case series does not support broad use of VTEP in this population, the lower‐than‐expected rates of rebleeding suggest that further study of the safety and effectiveness of pharmacologic VTEP in inpatient populations with ESLD may be warranted, particularly given the recommendations of recent national VTE prophylaxis guidelines.4

Venous thromboembolism (VTE) is a major cause of morbidity and mortality in hospitalized patients.13 Major efforts are underway to increase appropriate VTE prophylaxis (VTEP)4 and adherence to VTEP guidelines are increasingly used as a quality of care measure. National 2008 VTEP guidelines suggest that all medical patients ill enough to require hospitalization, particularly those requiring admission to the Intensive Care Unit (ICU), have at least a moderate risk of developing VTE and prophylaxis is recommended.4 Hospitalized patients with end‐stage liver disease (ESLD), despite their coagulopathy, are known to be at risk for VTE48 and may be VTEP candidates.

Based on available literature, it is unknown whether pharmacologic VTEP should be utilized in acutely ill, hospitalized patients with ESLD, particularly in those admitted with variceal bleeding. These patients are at high risk for rebleeding, with the highest risk in the first 5 days.9 Early rebleeding, defined as recurrent bleeding within 6 weeks of initial bleed, declined from 47% in the 1980s to 13% by 2000 because of increased early endoscopic intervention and use of medications to prevent rebleeding.911 In multicenter cohort studies, D'Amico and De Franchis12 reported that 13% of patients with variceal bleeding had uncontrolled bleeding, rebleeding, or death within 5 days of admission while Bahmba et al.13 reported a 16% rate of rebleeding within 5 days. We are unaware of prior reports regarding the safety of VTEP in this high‐risk group of patients.

Objective

We sought to describe rebleeding in a series of 22 patients with ESLD admitted with variceal bleeding who received pharmacologic VTEP.

Methods

We identified all patients 18 years and older with upper gastrointestinal bleeding admitted to Harborview Medical Center, a 400‐bed urban county teaching hospital in Seattle, Washington, between January 1, 2003 and December 31, 2005 (Figure 1), just prior to medical center‐wide implementation of a VTEP guideline. Potential cases were identified using administrative data based on 8 discharge diagnoses (Supporting Information Appendix 1) and 10 procedure codes (Supporting Information Appendix 2).14 Inpatient pharmacy data indicating continuous octreotide infusion were used to refine the sample. At our institution, it is a standard of care to initiate octreotide in patients admitted with variceal bleeding. We excluded patients who did not have ESLD (defined as evidence of cirrhosis and associated complications including but not limited to ascites, encephalopathy, variceal bleeding, portal hypertension) documented in their problem list or past medical history and those with no variceal bleeding based on medical record review. We identified cases receiving pharmacologic VTEP, either subcutaneous unfractionated heparin (UFH) or low molecular weight heparin (LMWH), during hospitalization from pharmacy records.

Figure 1

We obtained demographic and clinical data from administrative billing systems, electronic and paper medical records, and inpatient pharmacy databases and verified transfusion data from the Puget Sound Blood Center. We abstracted esophagogastroduodenoscopy (EGD) findings indicating high risk of rebleeding including variceal grade and stigmata of recent bleeding such as red spots or wales.15, 16 Data were abstracted by the first 3 authors (AS, MS, KJ) and reviewed again by 2 authors (AS, KJ) blinded to the others' abstractions.

We calculated Model for ESLD (MELD) scores on admission. These scores correlate with 3 month mortality in ESLD.17 We tabulated 5 factors shown in some studies to predict bleeding including high International Normalized Ratio (INR) (>1.5), low hematocrit (<25%), low platelet count (<100,000 per microliter), active bleeding at EGD, and transfusion of four or more units of red cells within 24 hours of admission.1013

We defined rebleeding as a decrease in hematocrit of greater than 5 percentage points compared with postresuscitation hematocrit, transfusion of additional red cells more than 48 hours after initial resuscitation, repeat unscheduled EGD, or return to the ICU for therapies related to rebleeding.18 The University of Washington Human Subjects Board approved this study.

Results

Of 224 patients initially identified, 36 received pharmacologic VTEP. We excluded 14 who did not have ESLD (n = 1) or did not have a variceal bleed (n = 13). The remaining 22 patients form the sample described in Figure 1.

The median age of patients was 52 years (range 42‐85) and 77% were men (Table 1). Twenty‐one of 22 patients (95%) were initially admitted to the ICU; median length of stay was 8 days (range 4‐30). Median MELD score on admission was 15 (range 825). On EGD, the number of variceal columns ranged from 1 to 4; 17 patients (77%) had at least 3. A total of 15 patients (68%) had stigmata of recent bleeding and 16 (72%) underwent banding (range 16 bands). All patients had at least 1 bleeding risk factor (Table 1) of which the most common factors observed were initial transfusion of 4 or more units of red cells (50%, n = 11), INR > 1.5 (45%, n = 10), and hematocrit < 25% (45%, n = 10).

A total of 12 patients (55%) received 5000 units of UFH every 8 hours, 8 (36%) received 5000 units UFH every 12 hours, and 2 (9%) received LMWH. VTEP was initiated as early as day of admission and as late as day 19. Median VTEP start date was hospital day 4. Median duration of of VTEP was 5 days.

Only 1 patient (4.5%) rebled after VTEP initiation. The patient received UFH every 8 hours starting on hospital day 6, and rebleeding occurred on day 9. Repeat EGD showed ulcers at banding sites. The patient was restarted on VTEP on hospital day 13 without recurrence of rebleeding. This patient had a MELD score of 24, initial INR >2, hematocrit <25%, had grade 3 varices and stigmata of recent bleeding on EGD, and received 4 units of packed red cells. These values are similar to those of the cohort as a whole (Table 1). This patient also was diagnosed with DVT while receiving VTEP on hospital day 15. This patient's coagulopathy was in the setting of terminal illness; the patient expired on hospital day 25.

One additional patient rebled prior to VTEP initiation on day 3 with repeat EGD showing a bleeding varix. This patient was nevertheless started on VTEP 4 days after rebleeding. Despite use of VTEP, this patient was diagnosed with DVT on hospital day 9 (and may well have had the DVT at the time of VTEP initiation). The patient was transitioned to therapeutic dose heparin which was tolerated without recurrence of rebleeding.

There were no other confirmed cases of DVT in this series. One additional patient underwent angiogram that showed no pulmonary embolism; 2 other patients underwent lower extremity ultrasounds that were negative for DVT.

Discussion

At our medical center, only a few inpatients with ESLD admitted with variceal bleed received VTEP. These patients were seemingly at high risk for bleeding and rebleeding given high MELD scores, variceal bleeding, and presence of at least one clinical factor suggesting bleeding risk, and in several cases 3 or more such factors.13, 18 Despite this, only 1 patient rebled while receiving VTEP. We captured rebleeding rates only during the index hospitalization. We therefore may underestimate early rebleeding rates.1013 Nevertheless, our inpatient data included complete coverage of the earliest period after the index bleeds and the period during which patients were exposed to VTEP, which should be the time of highest rebleeding risk related to VTEP exposure. Interestingly the patient who rebled while on VTEP was also diagnosed with VTE while on VTEP. Two patients (9%) in our sample were diagnosed with VTE.

This case series is limited by its small sample size, retrospective nature, single center observation, and perhaps especially by possible selection bias. We were unable to specifically quantify rebleeding risk. Several authors have identified individual factors associated with rebleeding,1013 these were tabulated for patients in this case series (Table 1) and all patients had at least 1 of these factors. Concurrent infection and hepatic vein pressure gradient have been shown to predict rebleeding;9, 19 we were unable to identify these factors in our data.

There was considerable variability in this case series in timing of VTEP initiation relative to initial bleed. We were unable to characterize provider or patient characteristics that may have influenced the decision to initiate VTEP and timing. The sample size was also too small to comment upon factors associated with choice of UFH versus LMWH and any potential differences in rebleeding risk between the 2. We also did not look at outcomes postindex hospitalization so we can not comment on the extended risk of rebleeding with VTEP after discharge. However, the risk of rebleeding is highest within the first 96 hours13 and all patients in this series were hospitalized at least 4 days. Nonetheless, we captured all patients with ESLD and variceal bleeding exposed to VTEP at a large center over a three‐year period and found rebleeding rates less than what might be expected.

Conclusions

Our observations suggest that some inpatients with ESLD and variceal bleeding may tolerate pharmacologic VTEP. In this small group of patients, VTEP was associated with an unexpectedly low incidence of rebleeding. While this case series does not support broad use of VTEP in this population, the lower‐than‐expected rates of rebleeding suggest that further study of the safety and effectiveness of pharmacologic VTEP in inpatient populations with ESLD may be warranted, particularly given the recommendations of recent national VTE prophylaxis guidelines.4

Venous thromboembolism (VTE) is a major cause of morbidity and mortality in hospitalized patients.13 Major efforts are underway to increase appropriate VTE prophylaxis (VTEP)4 and adherence to VTEP guidelines are increasingly used as a quality of care measure. National 2008 VTEP guidelines suggest that all medical patients ill enough to require hospitalization, particularly those requiring admission to the Intensive Care Unit (ICU), have at least a moderate risk of developing VTE and prophylaxis is recommended.4 Hospitalized patients with end‐stage liver disease (ESLD), despite their coagulopathy, are known to be at risk for VTE48 and may be VTEP candidates.

Based on available literature, it is unknown whether pharmacologic VTEP should be utilized in acutely ill, hospitalized patients with ESLD, particularly in those admitted with variceal bleeding. These patients are at high risk for rebleeding, with the highest risk in the first 5 days.9 Early rebleeding, defined as recurrent bleeding within 6 weeks of initial bleed, declined from 47% in the 1980s to 13% by 2000 because of increased early endoscopic intervention and use of medications to prevent rebleeding.911 In multicenter cohort studies, D'Amico and De Franchis12 reported that 13% of patients with variceal bleeding had uncontrolled bleeding, rebleeding, or death within 5 days of admission while Bahmba et al.13 reported a 16% rate of rebleeding within 5 days. We are unaware of prior reports regarding the safety of VTEP in this high‐risk group of patients.

Objective

We sought to describe rebleeding in a series of 22 patients with ESLD admitted with variceal bleeding who received pharmacologic VTEP.

Methods

We identified all patients 18 years and older with upper gastrointestinal bleeding admitted to Harborview Medical Center, a 400‐bed urban county teaching hospital in Seattle, Washington, between January 1, 2003 and December 31, 2005 (Figure 1), just prior to medical center‐wide implementation of a VTEP guideline. Potential cases were identified using administrative data based on 8 discharge diagnoses (Supporting Information Appendix 1) and 10 procedure codes (Supporting Information Appendix 2).14 Inpatient pharmacy data indicating continuous octreotide infusion were used to refine the sample. At our institution, it is a standard of care to initiate octreotide in patients admitted with variceal bleeding. We excluded patients who did not have ESLD (defined as evidence of cirrhosis and associated complications including but not limited to ascites, encephalopathy, variceal bleeding, portal hypertension) documented in their problem list or past medical history and those with no variceal bleeding based on medical record review. We identified cases receiving pharmacologic VTEP, either subcutaneous unfractionated heparin (UFH) or low molecular weight heparin (LMWH), during hospitalization from pharmacy records.

Figure 1

We obtained demographic and clinical data from administrative billing systems, electronic and paper medical records, and inpatient pharmacy databases and verified transfusion data from the Puget Sound Blood Center. We abstracted esophagogastroduodenoscopy (EGD) findings indicating high risk of rebleeding including variceal grade and stigmata of recent bleeding such as red spots or wales.15, 16 Data were abstracted by the first 3 authors (AS, MS, KJ) and reviewed again by 2 authors (AS, KJ) blinded to the others' abstractions.

We calculated Model for ESLD (MELD) scores on admission. These scores correlate with 3 month mortality in ESLD.17 We tabulated 5 factors shown in some studies to predict bleeding including high International Normalized Ratio (INR) (>1.5), low hematocrit (<25%), low platelet count (<100,000 per microliter), active bleeding at EGD, and transfusion of four or more units of red cells within 24 hours of admission.1013

We defined rebleeding as a decrease in hematocrit of greater than 5 percentage points compared with postresuscitation hematocrit, transfusion of additional red cells more than 48 hours after initial resuscitation, repeat unscheduled EGD, or return to the ICU for therapies related to rebleeding.18 The University of Washington Human Subjects Board approved this study.

Results

Of 224 patients initially identified, 36 received pharmacologic VTEP. We excluded 14 who did not have ESLD (n = 1) or did not have a variceal bleed (n = 13). The remaining 22 patients form the sample described in Figure 1.

The median age of patients was 52 years (range 42‐85) and 77% were men (Table 1). Twenty‐one of 22 patients (95%) were initially admitted to the ICU; median length of stay was 8 days (range 4‐30). Median MELD score on admission was 15 (range 825). On EGD, the number of variceal columns ranged from 1 to 4; 17 patients (77%) had at least 3. A total of 15 patients (68%) had stigmata of recent bleeding and 16 (72%) underwent banding (range 16 bands). All patients had at least 1 bleeding risk factor (Table 1) of which the most common factors observed were initial transfusion of 4 or more units of red cells (50%, n = 11), INR > 1.5 (45%, n = 10), and hematocrit < 25% (45%, n = 10).

A total of 12 patients (55%) received 5000 units of UFH every 8 hours, 8 (36%) received 5000 units UFH every 12 hours, and 2 (9%) received LMWH. VTEP was initiated as early as day of admission and as late as day 19. Median VTEP start date was hospital day 4. Median duration of of VTEP was 5 days.

Only 1 patient (4.5%) rebled after VTEP initiation. The patient received UFH every 8 hours starting on hospital day 6, and rebleeding occurred on day 9. Repeat EGD showed ulcers at banding sites. The patient was restarted on VTEP on hospital day 13 without recurrence of rebleeding. This patient had a MELD score of 24, initial INR >2, hematocrit <25%, had grade 3 varices and stigmata of recent bleeding on EGD, and received 4 units of packed red cells. These values are similar to those of the cohort as a whole (Table 1). This patient also was diagnosed with DVT while receiving VTEP on hospital day 15. This patient's coagulopathy was in the setting of terminal illness; the patient expired on hospital day 25.

One additional patient rebled prior to VTEP initiation on day 3 with repeat EGD showing a bleeding varix. This patient was nevertheless started on VTEP 4 days after rebleeding. Despite use of VTEP, this patient was diagnosed with DVT on hospital day 9 (and may well have had the DVT at the time of VTEP initiation). The patient was transitioned to therapeutic dose heparin which was tolerated without recurrence of rebleeding.

There were no other confirmed cases of DVT in this series. One additional patient underwent angiogram that showed no pulmonary embolism; 2 other patients underwent lower extremity ultrasounds that were negative for DVT.

Discussion

At our medical center, only a few inpatients with ESLD admitted with variceal bleed received VTEP. These patients were seemingly at high risk for bleeding and rebleeding given high MELD scores, variceal bleeding, and presence of at least one clinical factor suggesting bleeding risk, and in several cases 3 or more such factors.13, 18 Despite this, only 1 patient rebled while receiving VTEP. We captured rebleeding rates only during the index hospitalization. We therefore may underestimate early rebleeding rates.1013 Nevertheless, our inpatient data included complete coverage of the earliest period after the index bleeds and the period during which patients were exposed to VTEP, which should be the time of highest rebleeding risk related to VTEP exposure. Interestingly the patient who rebled while on VTEP was also diagnosed with VTE while on VTEP. Two patients (9%) in our sample were diagnosed with VTE.

This case series is limited by its small sample size, retrospective nature, single center observation, and perhaps especially by possible selection bias. We were unable to specifically quantify rebleeding risk. Several authors have identified individual factors associated with rebleeding,1013 these were tabulated for patients in this case series (Table 1) and all patients had at least 1 of these factors. Concurrent infection and hepatic vein pressure gradient have been shown to predict rebleeding;9, 19 we were unable to identify these factors in our data.

There was considerable variability in this case series in timing of VTEP initiation relative to initial bleed. We were unable to characterize provider or patient characteristics that may have influenced the decision to initiate VTEP and timing. The sample size was also too small to comment upon factors associated with choice of UFH versus LMWH and any potential differences in rebleeding risk between the 2. We also did not look at outcomes postindex hospitalization so we can not comment on the extended risk of rebleeding with VTEP after discharge. However, the risk of rebleeding is highest within the first 96 hours13 and all patients in this series were hospitalized at least 4 days. Nonetheless, we captured all patients with ESLD and variceal bleeding exposed to VTEP at a large center over a three‐year period and found rebleeding rates less than what might be expected.

Conclusions

Our observations suggest that some inpatients with ESLD and variceal bleeding may tolerate pharmacologic VTEP. In this small group of patients, VTEP was associated with an unexpectedly low incidence of rebleeding. While this case series does not support broad use of VTEP in this population, the lower‐than‐expected rates of rebleeding suggest that further study of the safety and effectiveness of pharmacologic VTEP in inpatient populations with ESLD may be warranted, particularly given the recommendations of recent national VTE prophylaxis guidelines.4