Megan MacK, MD

The Things We Do for No Reason (TWDFNR) series reviews practices which have become common parts of hospital care but which may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent black and white conclusions or clinical practice standards, but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion. https://www.choosingwisely.org/

Inherited thrombophilia refers to a genetic condition that predisposes to an increased risk of venous thromboembolism (VTE). This disorder is prevalent in approximately 7% of the population and includes mutations such as factor V Leiden, prothrombin 20210, protein C deficiency, protein S deficiency, antithrombin deficiency, and methylene tetrahydrofolate reductase. The relative risk of VTE is 3‐ to 20‐fold greater in patients with inherited thrombophilia compared with the general population. Is testing for inherited thrombophilia recommended? The available evidence suggests that testing for inherited thrombophilia is not recommended in most clinical settings. In patients without a personal history of VTE, thrombophilia results do not change management, as there is no evidence to support thromboprophylaxis in this setting. In patients with a personal history of provoked or unprovoked VTE, inpatient testing is not indicated, as results do not influence management, testing is not cost‐effective, and a positive test result may lead to unnecessary patient anxiety or may result in unnecessary involvement of consultants. Testing in hospitalized patients has even more limitations because many thrombophilia tests are inaccurate in the setting of acute VTE and/or anticoagulation.

CASE PRESENTATION

A 23‐year‐old man presents to the emergency room with pleuritic chest pain and new oxygen requirement of 2 L nasal cannula. He has a history of unprovoked lower extremity deep venous thrombosis (DVT) diagnosed at age 20 and completed 3 months of systemic anticoagulation without complications. He reports no family history of clotting disorders or venous thromboembolism (VTE) and no reversible risk factors for VTE such as prolonged immobility, recent surgery, or high‐risk medications. A computed tomogram pulmonary embolism protocol shows multiple right lower lobe, segmental pulmonary emboli. Anticoagulation is initiated, and the patient is admitted to the hospital. Will inpatient inherited thrombophilia testing impact management for this case?

WHY MAY INHERITED THROMBOPHILIA TESTING PROVE HELPFUL?

The annual incidence rate of a first VTE event is estimated as 117 per 100,000 individuals per year.[1] The most common presentations are symptomatic DVT of the leg (annual incidence approximately 48 per 100,000 people), or a pulmonary embolism (annual incidence approximately 69 per 100,000 people).[1] Pulmonary embolism results in death in up to 30% of untreated patients and 2.5% of patients who receive systemic anticoagulation.[2] Principal in the pathogenesis of VTE are factors described by Virchow's triad: venous stasis, endothelial injury, and systemic hypercoagulability. By identifying a mutation in 1 or more of the factors in the clotting pathway, an evaluation for inherited thrombophilia theoretically may unearth factors that drive systemic hypercoagulability and inform decision making so as to prevent future events.

Inherited thrombophilia refers to a genetic condition that predisposes to an increased risk of VTE.[3] Approximately 7% of the general population has inherited thrombophilia, which includes factor V Leiden (FVL) mutation, prothrombin 20210 mutation (PT20210), protein C deficiency, protein S deficiency, antithrombin III (ATIII) deficiency, and methylene tetrahydrofolate reductase mutation (MTHFR).[4] Of note, the definition does not include acquired etiologies, such as antiphospholipid antibody syndrome. Depending on the underlying condition and expression of the genetic abnormality, the relative risk of VTE in patients with inherited thrombophilia is 3‐ to 20‐fold greater than that of the general population.[5] Therefore, it is logical to consider that testing for inherited thrombophilia might be clinically useful. However, the evidence for doing so is very limited.

DOES INHERITED THROMBOPHILIA TESTING CHANGE MANAGEMENT?

An inherited thrombophilia evaluation is unlikely to affect management in most clinical settings. There is no current evidence to support primary prophylaxis[6] nor is there evidence that management of patients with recurrent VTE should be altered in the setting of inherited thrombophilia.

To date, no prospective trials have evaluated the efficacy of anticoagulant use for primary prevention of VTE in patients with inherited thrombophilia.[6] Given the limited evidence for thromboprophylaxis and risks of anticoagulation, primary prevention for patients with inherited thrombophilia that remain asymptomatic is not recommended by the current American College of Chest Physicians guidelines.[7, 8]

Similarly, in patients with a first VTE or recurrent VTE, diagnosis of inherited thrombophilia is often not associated with recurrent events, which suggests that other nongenetic factors may be just as important, if not more important, in determining the risk of recurrence.[9] Although no randomized controlled or controlled clinical trials have evaluated the effects of testing for inherited thrombophilia on recurrent VTE,[10, 11] several prospective studies have assessed risk factors for recurrence. Data from these studies suggest that recurrence rates after unprovoked VTE are only weakly correlated with inherited thrombophilia status.[12, 13] Rather, it is postulated that patients with recurrent VTE may exhibit a prothrombotic tendency regardless of underlying genetic predisposition. In this case, decisions regarding anticoagulation do not vary by thrombophilia status. Instead, thrombophilia testing may divert attention away from the management of more prevalent, potentially modifiable risk factors such as immobility, oral contraceptive use, or malignancy, all of which are associated with recurrent VTE.[14] These provoking factors are the most important determinants of the chance of VTE recurrence as well as the most significant factors to take into account when deciding duration of anticoagulation.

Christiansen et al. performed a prospective study evaluating the association between recurrent VTE and thrombophilia status. After following 474 patients with confirmed first episode VTE for a mean of 7.3 years, no statistically significant risk of VTE was found for patients with FVL (hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 0.7‐1.9), PT20210 (HR: 0.7, 95% CI: 0.3‐2.0), or an anticoagulant (protein C, protein S or ATIII) deficiency (HR: 1.8, 95% CI: 0.9‐3.7).[15] Although unexplained VTE was statistically associated with VTE recurrence, heritable thrombophilia status was not.

In a systematic review and meta‐analysis investigating the association of FVL and PT20210 with recurrent VTE, Ho and colleagues found a statistically significant risk of recurrent VTE in patients with inherited thrombophilia due to FVL (odds ratio [OR]: 1.41, 95% CI: 1.14‐1.75) and PT20210 (OR: 1.72, 95% CI: 1.27‐2.31), and reported that at most, only up to 1 in 6 recurrent VTEs may be attributable to these mutations.[16] Based on this relatively modest effect, the authors question the utility of testing for inherited thrombophilia, as thrombophilia status is unlikely to warrant a change in type or duration of treatment.

Regardless of whether an underlying inherited thrombophilia is identified, patients with history of recurrent VTE are often candidates for long‐term anticoagulation. Testing for inherited thrombophilia in patients with prior VTE events will therefore not influence decisions regarding clinical management. Additionally, such testing may be confounded by ongoing disease or treatment (Table 1). For example, protein C, protein S antigen, and ATIII levels are low in the setting of acute VTE.[17, 18] Likewise, protein C and S (vitamin Kdependent proteins) will be low in the setting of anticoagulation with warfarin.[19] Moreover, ATIII activity and antigen levels are low in the setting of heparin use.[20] Lack of provider awareness regarding these interactions may have important negative consequences, including a spurious diagnosis of thrombophilia,[21, 22] unnecessary hematology consultation, and psychological distress to patients in the form of ongoing unwarranted testing or apprehension regarding recurrence.[23]

Additionally, this expensive evaluation has estimated direct costs of $1100 to $2400 per thrombophilia panel based on estimation of charges billed by a large commercial laboratory.[24, 25] In 2014, over 280,000 claims were submitted under Medicare Part B across all care settings for a thrombophilia analysis including FVL, PT20210, and MTHFR gene mutations,[24] which would equate to between $300 million to $672 million.[26] Unfortunately, there have been no large‐scale trials to assess cost‐effectiveness. However, the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group stated that cost‐effectiveness modeling studies in this area require updating with current VTE risk estimates but are suggestive that routine FVL/PT20210 testing is not cost‐effective.[27]

ARE THERE CIRCUMSTANCES IN WHICH INPATIENT INHERITED THROMBOPHILIA TESTING PROVES BENEFICIAL?

The evidence for when to test for inherited thrombophilia is very limited and is often based on individualized risk. The current EGAPP guidelines acknowledge this limitation, specifically noting that there is a paucity of data evaluating management or prophylaxis of patients with homozygous or compound heterozygous FVL or P20210 mutation, and a lack of data surrounding whether or not knowledge of thrombophilia mutation should affect anticoagulation treatment.[27] This is why an individualized approach is deemed necessary. For example, the decision to prescribe hormone replacement therapy in women with a family history of inherited thrombophilia may be better informed by testing prior to treatment. Similarly, pregnant women with a family history or personal history of VTE may also benefit from inherited thrombophilia testing, as this may influence antepartum or postpartum management.[28, 29] The National Institute for Health and Clinical Excellence (NICE) guidelines recommend consideration of testing for hereditary thrombophilia in patients with unprovoked VTE and a first‐degree relative with VTE, if stopping anticoagulation treatment is planned; however, these recommendations are based solely on Guideline Development Group's experience and opinion.[30] Regardless, testing for inherited thrombophilia has significant potential consequences. Patients at risk should meet with an outpatient hematologist and/or a genetic counselor, if available, to determine the risks and benefits of testing.

WHAT DO GUIDELINES SAY ABOUT INHERITED THROMBOPHILIA TESTING?

The most recent NICE guidelines recommend against offering inherited thrombophilia testing to patients presenting with a provoked VTE in any clinical setting.[30] In patients diagnosed with unprovoked VTE, testing should not be considered unless a first degree relative with a history of VTE exists.[30] The NICE guidelines also recommend against routinely offering thrombophilia testing to asymptomatic first‐degree relatives of patients with a history of VTE or known inherited thrombophilia. This recommendation is reflected in the American Society of Hematology's Choosing Wisely recommendations since 2013.[31] Further, The American College of Medical Genetics and Genomics' Choosing Wisely recommendations from 2015 state that MTHFR mutations should never be included in any thrombophilia workup, as recent meta‐analyses have disproven an association between the presence of these variants and venous thromboembolism.[32]

The EGAPP Working Group recommends against routine testing for FVL or PT20210 in patients who present with an idiopathic VTE, as longer‐term anticoagulation offers similar benefits to patients with or without these mutations.[27] EGAPP also recommends against testing asymptomatic adult family members of patients with VTE and/or an FVL or PT20210 mutation for the purpose of considering primary prophylactic anticoagulation. In these circumstances, it is felt that the potential risks of thrombophilia testing outweigh any potential benefits.

HOW SHOULD HOSPITALISTS APPROACH TESTING OF INHERITED THROMBOPHILIA?

The providers in our case presentation are challenged with determining whether inpatient thrombophilia evaluation will add value to the evaluation of patients with unprovoked VTE. The available evidence suggests that clinicians should avoid ordering thrombophilia testing for hospitalized patients with unprovoked VTE because (1) many thrombophilia tests are inaccurate in the setting of acute VTE and/or anticoagulation, (2) results of testing often do not influence management, (3) testing is not cost‐effective, (4) a positive test result may lead to unnecessary patient anxiety, and (5) testing may result in inappropriately prolonged anticoagulation courses or unnecessary involvement of inpatient consultants. For these reasons, the patient in our case presentation should not be tested for inherited thrombophilia. In patients with personal or family histories of recurrent thromboembolism, modifiable clinical risk factors should be addressed, as these are more likely to influence treatment decisions compared to genetic testing. Finally, patients may be referred to an outpatient hematologist or geneticist for individualized discussions of risks and benefits of testing for inherited thrombophilia.

CONCLUSION

Inpatient evaluation for inherited thrombophilia for VTE is not clinically useful, cost‐effective, or reliable in the setting of VTE. The result of such testing does not affect management of acute primary or recurrent VTE. Testing should only be considered using an individualized approach in the outpatient setting with appropriate genetic counseling.

Disclosure: Christopher M. Petrilli, MD, and Lauren Heidemann, MD, contributed equally to this work. The authors report no conflicts of interest.

Do you think this is a low‐value practice? Is this truly a Thing We Do for No Reason? Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other Things We Do for No Reason topics by emailing TWDFNR@hospitalmedicine.org.

The Things We Do for No Reason (TWDFNR) series reviews practices which have become common parts of hospital care but which may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent black and white conclusions or clinical practice standards, but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion. https://www.choosingwisely.org/

Inherited thrombophilia refers to a genetic condition that predisposes to an increased risk of venous thromboembolism (VTE). This disorder is prevalent in approximately 7% of the population and includes mutations such as factor V Leiden, prothrombin 20210, protein C deficiency, protein S deficiency, antithrombin deficiency, and methylene tetrahydrofolate reductase. The relative risk of VTE is 3‐ to 20‐fold greater in patients with inherited thrombophilia compared with the general population. Is testing for inherited thrombophilia recommended? The available evidence suggests that testing for inherited thrombophilia is not recommended in most clinical settings. In patients without a personal history of VTE, thrombophilia results do not change management, as there is no evidence to support thromboprophylaxis in this setting. In patients with a personal history of provoked or unprovoked VTE, inpatient testing is not indicated, as results do not influence management, testing is not cost‐effective, and a positive test result may lead to unnecessary patient anxiety or may result in unnecessary involvement of consultants. Testing in hospitalized patients has even more limitations because many thrombophilia tests are inaccurate in the setting of acute VTE and/or anticoagulation.

CASE PRESENTATION

A 23‐year‐old man presents to the emergency room with pleuritic chest pain and new oxygen requirement of 2 L nasal cannula. He has a history of unprovoked lower extremity deep venous thrombosis (DVT) diagnosed at age 20 and completed 3 months of systemic anticoagulation without complications. He reports no family history of clotting disorders or venous thromboembolism (VTE) and no reversible risk factors for VTE such as prolonged immobility, recent surgery, or high‐risk medications. A computed tomogram pulmonary embolism protocol shows multiple right lower lobe, segmental pulmonary emboli. Anticoagulation is initiated, and the patient is admitted to the hospital. Will inpatient inherited thrombophilia testing impact management for this case?

WHY MAY INHERITED THROMBOPHILIA TESTING PROVE HELPFUL?

The annual incidence rate of a first VTE event is estimated as 117 per 100,000 individuals per year.[1] The most common presentations are symptomatic DVT of the leg (annual incidence approximately 48 per 100,000 people), or a pulmonary embolism (annual incidence approximately 69 per 100,000 people).[1] Pulmonary embolism results in death in up to 30% of untreated patients and 2.5% of patients who receive systemic anticoagulation.[2] Principal in the pathogenesis of VTE are factors described by Virchow's triad: venous stasis, endothelial injury, and systemic hypercoagulability. By identifying a mutation in 1 or more of the factors in the clotting pathway, an evaluation for inherited thrombophilia theoretically may unearth factors that drive systemic hypercoagulability and inform decision making so as to prevent future events.

Inherited thrombophilia refers to a genetic condition that predisposes to an increased risk of VTE.[3] Approximately 7% of the general population has inherited thrombophilia, which includes factor V Leiden (FVL) mutation, prothrombin 20210 mutation (PT20210), protein C deficiency, protein S deficiency, antithrombin III (ATIII) deficiency, and methylene tetrahydrofolate reductase mutation (MTHFR).[4] Of note, the definition does not include acquired etiologies, such as antiphospholipid antibody syndrome. Depending on the underlying condition and expression of the genetic abnormality, the relative risk of VTE in patients with inherited thrombophilia is 3‐ to 20‐fold greater than that of the general population.[5] Therefore, it is logical to consider that testing for inherited thrombophilia might be clinically useful. However, the evidence for doing so is very limited.

DOES INHERITED THROMBOPHILIA TESTING CHANGE MANAGEMENT?

An inherited thrombophilia evaluation is unlikely to affect management in most clinical settings. There is no current evidence to support primary prophylaxis[6] nor is there evidence that management of patients with recurrent VTE should be altered in the setting of inherited thrombophilia.

To date, no prospective trials have evaluated the efficacy of anticoagulant use for primary prevention of VTE in patients with inherited thrombophilia.[6] Given the limited evidence for thromboprophylaxis and risks of anticoagulation, primary prevention for patients with inherited thrombophilia that remain asymptomatic is not recommended by the current American College of Chest Physicians guidelines.[7, 8]

Similarly, in patients with a first VTE or recurrent VTE, diagnosis of inherited thrombophilia is often not associated with recurrent events, which suggests that other nongenetic factors may be just as important, if not more important, in determining the risk of recurrence.[9] Although no randomized controlled or controlled clinical trials have evaluated the effects of testing for inherited thrombophilia on recurrent VTE,[10, 11] several prospective studies have assessed risk factors for recurrence. Data from these studies suggest that recurrence rates after unprovoked VTE are only weakly correlated with inherited thrombophilia status.[12, 13] Rather, it is postulated that patients with recurrent VTE may exhibit a prothrombotic tendency regardless of underlying genetic predisposition. In this case, decisions regarding anticoagulation do not vary by thrombophilia status. Instead, thrombophilia testing may divert attention away from the management of more prevalent, potentially modifiable risk factors such as immobility, oral contraceptive use, or malignancy, all of which are associated with recurrent VTE.[14] These provoking factors are the most important determinants of the chance of VTE recurrence as well as the most significant factors to take into account when deciding duration of anticoagulation.

Christiansen et al. performed a prospective study evaluating the association between recurrent VTE and thrombophilia status. After following 474 patients with confirmed first episode VTE for a mean of 7.3 years, no statistically significant risk of VTE was found for patients with FVL (hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 0.7‐1.9), PT20210 (HR: 0.7, 95% CI: 0.3‐2.0), or an anticoagulant (protein C, protein S or ATIII) deficiency (HR: 1.8, 95% CI: 0.9‐3.7).[15] Although unexplained VTE was statistically associated with VTE recurrence, heritable thrombophilia status was not.

In a systematic review and meta‐analysis investigating the association of FVL and PT20210 with recurrent VTE, Ho and colleagues found a statistically significant risk of recurrent VTE in patients with inherited thrombophilia due to FVL (odds ratio [OR]: 1.41, 95% CI: 1.14‐1.75) and PT20210 (OR: 1.72, 95% CI: 1.27‐2.31), and reported that at most, only up to 1 in 6 recurrent VTEs may be attributable to these mutations.[16] Based on this relatively modest effect, the authors question the utility of testing for inherited thrombophilia, as thrombophilia status is unlikely to warrant a change in type or duration of treatment.

Regardless of whether an underlying inherited thrombophilia is identified, patients with history of recurrent VTE are often candidates for long‐term anticoagulation. Testing for inherited thrombophilia in patients with prior VTE events will therefore not influence decisions regarding clinical management. Additionally, such testing may be confounded by ongoing disease or treatment (Table 1). For example, protein C, protein S antigen, and ATIII levels are low in the setting of acute VTE.[17, 18] Likewise, protein C and S (vitamin Kdependent proteins) will be low in the setting of anticoagulation with warfarin.[19] Moreover, ATIII activity and antigen levels are low in the setting of heparin use.[20] Lack of provider awareness regarding these interactions may have important negative consequences, including a spurious diagnosis of thrombophilia,[21, 22] unnecessary hematology consultation, and psychological distress to patients in the form of ongoing unwarranted testing or apprehension regarding recurrence.[23]

Additionally, this expensive evaluation has estimated direct costs of $1100 to $2400 per thrombophilia panel based on estimation of charges billed by a large commercial laboratory.[24, 25] In 2014, over 280,000 claims were submitted under Medicare Part B across all care settings for a thrombophilia analysis including FVL, PT20210, and MTHFR gene mutations,[24] which would equate to between $300 million to $672 million.[26] Unfortunately, there have been no large‐scale trials to assess cost‐effectiveness. However, the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group stated that cost‐effectiveness modeling studies in this area require updating with current VTE risk estimates but are suggestive that routine FVL/PT20210 testing is not cost‐effective.[27]

ARE THERE CIRCUMSTANCES IN WHICH INPATIENT INHERITED THROMBOPHILIA TESTING PROVES BENEFICIAL?

The evidence for when to test for inherited thrombophilia is very limited and is often based on individualized risk. The current EGAPP guidelines acknowledge this limitation, specifically noting that there is a paucity of data evaluating management or prophylaxis of patients with homozygous or compound heterozygous FVL or P20210 mutation, and a lack of data surrounding whether or not knowledge of thrombophilia mutation should affect anticoagulation treatment.[27] This is why an individualized approach is deemed necessary. For example, the decision to prescribe hormone replacement therapy in women with a family history of inherited thrombophilia may be better informed by testing prior to treatment. Similarly, pregnant women with a family history or personal history of VTE may also benefit from inherited thrombophilia testing, as this may influence antepartum or postpartum management.[28, 29] The National Institute for Health and Clinical Excellence (NICE) guidelines recommend consideration of testing for hereditary thrombophilia in patients with unprovoked VTE and a first‐degree relative with VTE, if stopping anticoagulation treatment is planned; however, these recommendations are based solely on Guideline Development Group's experience and opinion.[30] Regardless, testing for inherited thrombophilia has significant potential consequences. Patients at risk should meet with an outpatient hematologist and/or a genetic counselor, if available, to determine the risks and benefits of testing.

WHAT DO GUIDELINES SAY ABOUT INHERITED THROMBOPHILIA TESTING?

The most recent NICE guidelines recommend against offering inherited thrombophilia testing to patients presenting with a provoked VTE in any clinical setting.[30] In patients diagnosed with unprovoked VTE, testing should not be considered unless a first degree relative with a history of VTE exists.[30] The NICE guidelines also recommend against routinely offering thrombophilia testing to asymptomatic first‐degree relatives of patients with a history of VTE or known inherited thrombophilia. This recommendation is reflected in the American Society of Hematology's Choosing Wisely recommendations since 2013.[31] Further, The American College of Medical Genetics and Genomics' Choosing Wisely recommendations from 2015 state that MTHFR mutations should never be included in any thrombophilia workup, as recent meta‐analyses have disproven an association between the presence of these variants and venous thromboembolism.[32]

The EGAPP Working Group recommends against routine testing for FVL or PT20210 in patients who present with an idiopathic VTE, as longer‐term anticoagulation offers similar benefits to patients with or without these mutations.[27] EGAPP also recommends against testing asymptomatic adult family members of patients with VTE and/or an FVL or PT20210 mutation for the purpose of considering primary prophylactic anticoagulation. In these circumstances, it is felt that the potential risks of thrombophilia testing outweigh any potential benefits.

HOW SHOULD HOSPITALISTS APPROACH TESTING OF INHERITED THROMBOPHILIA?

The providers in our case presentation are challenged with determining whether inpatient thrombophilia evaluation will add value to the evaluation of patients with unprovoked VTE. The available evidence suggests that clinicians should avoid ordering thrombophilia testing for hospitalized patients with unprovoked VTE because (1) many thrombophilia tests are inaccurate in the setting of acute VTE and/or anticoagulation, (2) results of testing often do not influence management, (3) testing is not cost‐effective, (4) a positive test result may lead to unnecessary patient anxiety, and (5) testing may result in inappropriately prolonged anticoagulation courses or unnecessary involvement of inpatient consultants. For these reasons, the patient in our case presentation should not be tested for inherited thrombophilia. In patients with personal or family histories of recurrent thromboembolism, modifiable clinical risk factors should be addressed, as these are more likely to influence treatment decisions compared to genetic testing. Finally, patients may be referred to an outpatient hematologist or geneticist for individualized discussions of risks and benefits of testing for inherited thrombophilia.

CONCLUSION

Inpatient evaluation for inherited thrombophilia for VTE is not clinically useful, cost‐effective, or reliable in the setting of VTE. The result of such testing does not affect management of acute primary or recurrent VTE. Testing should only be considered using an individualized approach in the outpatient setting with appropriate genetic counseling.

Disclosure: Christopher M. Petrilli, MD, and Lauren Heidemann, MD, contributed equally to this work. The authors report no conflicts of interest.

Do you think this is a low‐value practice? Is this truly a Thing We Do for No Reason? Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other Things We Do for No Reason topics by emailing TWDFNR@hospitalmedicine.org.

The Things We Do for No Reason (TWDFNR) series reviews practices which have become common parts of hospital care but which may provide little value to our patients. Practices reviewed in the TWDFNR series do not represent black and white conclusions or clinical practice standards, but are meant as a starting place for research and active discussions among hospitalists and patients. We invite you to be part of that discussion. https://www.choosingwisely.org/

Inherited thrombophilia refers to a genetic condition that predisposes to an increased risk of venous thromboembolism (VTE). This disorder is prevalent in approximately 7% of the population and includes mutations such as factor V Leiden, prothrombin 20210, protein C deficiency, protein S deficiency, antithrombin deficiency, and methylene tetrahydrofolate reductase. The relative risk of VTE is 3‐ to 20‐fold greater in patients with inherited thrombophilia compared with the general population. Is testing for inherited thrombophilia recommended? The available evidence suggests that testing for inherited thrombophilia is not recommended in most clinical settings. In patients without a personal history of VTE, thrombophilia results do not change management, as there is no evidence to support thromboprophylaxis in this setting. In patients with a personal history of provoked or unprovoked VTE, inpatient testing is not indicated, as results do not influence management, testing is not cost‐effective, and a positive test result may lead to unnecessary patient anxiety or may result in unnecessary involvement of consultants. Testing in hospitalized patients has even more limitations because many thrombophilia tests are inaccurate in the setting of acute VTE and/or anticoagulation.

CASE PRESENTATION

A 23‐year‐old man presents to the emergency room with pleuritic chest pain and new oxygen requirement of 2 L nasal cannula. He has a history of unprovoked lower extremity deep venous thrombosis (DVT) diagnosed at age 20 and completed 3 months of systemic anticoagulation without complications. He reports no family history of clotting disorders or venous thromboembolism (VTE) and no reversible risk factors for VTE such as prolonged immobility, recent surgery, or high‐risk medications. A computed tomogram pulmonary embolism protocol shows multiple right lower lobe, segmental pulmonary emboli. Anticoagulation is initiated, and the patient is admitted to the hospital. Will inpatient inherited thrombophilia testing impact management for this case?

WHY MAY INHERITED THROMBOPHILIA TESTING PROVE HELPFUL?

The annual incidence rate of a first VTE event is estimated as 117 per 100,000 individuals per year.[1] The most common presentations are symptomatic DVT of the leg (annual incidence approximately 48 per 100,000 people), or a pulmonary embolism (annual incidence approximately 69 per 100,000 people).[1] Pulmonary embolism results in death in up to 30% of untreated patients and 2.5% of patients who receive systemic anticoagulation.[2] Principal in the pathogenesis of VTE are factors described by Virchow's triad: venous stasis, endothelial injury, and systemic hypercoagulability. By identifying a mutation in 1 or more of the factors in the clotting pathway, an evaluation for inherited thrombophilia theoretically may unearth factors that drive systemic hypercoagulability and inform decision making so as to prevent future events.

Inherited thrombophilia refers to a genetic condition that predisposes to an increased risk of VTE.[3] Approximately 7% of the general population has inherited thrombophilia, which includes factor V Leiden (FVL) mutation, prothrombin 20210 mutation (PT20210), protein C deficiency, protein S deficiency, antithrombin III (ATIII) deficiency, and methylene tetrahydrofolate reductase mutation (MTHFR).[4] Of note, the definition does not include acquired etiologies, such as antiphospholipid antibody syndrome. Depending on the underlying condition and expression of the genetic abnormality, the relative risk of VTE in patients with inherited thrombophilia is 3‐ to 20‐fold greater than that of the general population.[5] Therefore, it is logical to consider that testing for inherited thrombophilia might be clinically useful. However, the evidence for doing so is very limited.

DOES INHERITED THROMBOPHILIA TESTING CHANGE MANAGEMENT?

An inherited thrombophilia evaluation is unlikely to affect management in most clinical settings. There is no current evidence to support primary prophylaxis[6] nor is there evidence that management of patients with recurrent VTE should be altered in the setting of inherited thrombophilia.

To date, no prospective trials have evaluated the efficacy of anticoagulant use for primary prevention of VTE in patients with inherited thrombophilia.[6] Given the limited evidence for thromboprophylaxis and risks of anticoagulation, primary prevention for patients with inherited thrombophilia that remain asymptomatic is not recommended by the current American College of Chest Physicians guidelines.[7, 8]

Similarly, in patients with a first VTE or recurrent VTE, diagnosis of inherited thrombophilia is often not associated with recurrent events, which suggests that other nongenetic factors may be just as important, if not more important, in determining the risk of recurrence.[9] Although no randomized controlled or controlled clinical trials have evaluated the effects of testing for inherited thrombophilia on recurrent VTE,[10, 11] several prospective studies have assessed risk factors for recurrence. Data from these studies suggest that recurrence rates after unprovoked VTE are only weakly correlated with inherited thrombophilia status.[12, 13] Rather, it is postulated that patients with recurrent VTE may exhibit a prothrombotic tendency regardless of underlying genetic predisposition. In this case, decisions regarding anticoagulation do not vary by thrombophilia status. Instead, thrombophilia testing may divert attention away from the management of more prevalent, potentially modifiable risk factors such as immobility, oral contraceptive use, or malignancy, all of which are associated with recurrent VTE.[14] These provoking factors are the most important determinants of the chance of VTE recurrence as well as the most significant factors to take into account when deciding duration of anticoagulation.

Christiansen et al. performed a prospective study evaluating the association between recurrent VTE and thrombophilia status. After following 474 patients with confirmed first episode VTE for a mean of 7.3 years, no statistically significant risk of VTE was found for patients with FVL (hazard ratio [HR]: 1.2, 95% confidence interval [CI]: 0.7‐1.9), PT20210 (HR: 0.7, 95% CI: 0.3‐2.0), or an anticoagulant (protein C, protein S or ATIII) deficiency (HR: 1.8, 95% CI: 0.9‐3.7).[15] Although unexplained VTE was statistically associated with VTE recurrence, heritable thrombophilia status was not.

In a systematic review and meta‐analysis investigating the association of FVL and PT20210 with recurrent VTE, Ho and colleagues found a statistically significant risk of recurrent VTE in patients with inherited thrombophilia due to FVL (odds ratio [OR]: 1.41, 95% CI: 1.14‐1.75) and PT20210 (OR: 1.72, 95% CI: 1.27‐2.31), and reported that at most, only up to 1 in 6 recurrent VTEs may be attributable to these mutations.[16] Based on this relatively modest effect, the authors question the utility of testing for inherited thrombophilia, as thrombophilia status is unlikely to warrant a change in type or duration of treatment.

Regardless of whether an underlying inherited thrombophilia is identified, patients with history of recurrent VTE are often candidates for long‐term anticoagulation. Testing for inherited thrombophilia in patients with prior VTE events will therefore not influence decisions regarding clinical management. Additionally, such testing may be confounded by ongoing disease or treatment (Table 1). For example, protein C, protein S antigen, and ATIII levels are low in the setting of acute VTE.[17, 18] Likewise, protein C and S (vitamin Kdependent proteins) will be low in the setting of anticoagulation with warfarin.[19] Moreover, ATIII activity and antigen levels are low in the setting of heparin use.[20] Lack of provider awareness regarding these interactions may have important negative consequences, including a spurious diagnosis of thrombophilia,[21, 22] unnecessary hematology consultation, and psychological distress to patients in the form of ongoing unwarranted testing or apprehension regarding recurrence.[23]

Additionally, this expensive evaluation has estimated direct costs of $1100 to $2400 per thrombophilia panel based on estimation of charges billed by a large commercial laboratory.[24, 25] In 2014, over 280,000 claims were submitted under Medicare Part B across all care settings for a thrombophilia analysis including FVL, PT20210, and MTHFR gene mutations,[24] which would equate to between $300 million to $672 million.[26] Unfortunately, there have been no large‐scale trials to assess cost‐effectiveness. However, the Evaluation of Genomic Applications in Practice and Prevention (EGAPP) Working Group stated that cost‐effectiveness modeling studies in this area require updating with current VTE risk estimates but are suggestive that routine FVL/PT20210 testing is not cost‐effective.[27]

ARE THERE CIRCUMSTANCES IN WHICH INPATIENT INHERITED THROMBOPHILIA TESTING PROVES BENEFICIAL?

The evidence for when to test for inherited thrombophilia is very limited and is often based on individualized risk. The current EGAPP guidelines acknowledge this limitation, specifically noting that there is a paucity of data evaluating management or prophylaxis of patients with homozygous or compound heterozygous FVL or P20210 mutation, and a lack of data surrounding whether or not knowledge of thrombophilia mutation should affect anticoagulation treatment.[27] This is why an individualized approach is deemed necessary. For example, the decision to prescribe hormone replacement therapy in women with a family history of inherited thrombophilia may be better informed by testing prior to treatment. Similarly, pregnant women with a family history or personal history of VTE may also benefit from inherited thrombophilia testing, as this may influence antepartum or postpartum management.[28, 29] The National Institute for Health and Clinical Excellence (NICE) guidelines recommend consideration of testing for hereditary thrombophilia in patients with unprovoked VTE and a first‐degree relative with VTE, if stopping anticoagulation treatment is planned; however, these recommendations are based solely on Guideline Development Group's experience and opinion.[30] Regardless, testing for inherited thrombophilia has significant potential consequences. Patients at risk should meet with an outpatient hematologist and/or a genetic counselor, if available, to determine the risks and benefits of testing.

WHAT DO GUIDELINES SAY ABOUT INHERITED THROMBOPHILIA TESTING?

The most recent NICE guidelines recommend against offering inherited thrombophilia testing to patients presenting with a provoked VTE in any clinical setting.[30] In patients diagnosed with unprovoked VTE, testing should not be considered unless a first degree relative with a history of VTE exists.[30] The NICE guidelines also recommend against routinely offering thrombophilia testing to asymptomatic first‐degree relatives of patients with a history of VTE or known inherited thrombophilia. This recommendation is reflected in the American Society of Hematology's Choosing Wisely recommendations since 2013.[31] Further, The American College of Medical Genetics and Genomics' Choosing Wisely recommendations from 2015 state that MTHFR mutations should never be included in any thrombophilia workup, as recent meta‐analyses have disproven an association between the presence of these variants and venous thromboembolism.[32]

The EGAPP Working Group recommends against routine testing for FVL or PT20210 in patients who present with an idiopathic VTE, as longer‐term anticoagulation offers similar benefits to patients with or without these mutations.[27] EGAPP also recommends against testing asymptomatic adult family members of patients with VTE and/or an FVL or PT20210 mutation for the purpose of considering primary prophylactic anticoagulation. In these circumstances, it is felt that the potential risks of thrombophilia testing outweigh any potential benefits.

HOW SHOULD HOSPITALISTS APPROACH TESTING OF INHERITED THROMBOPHILIA?

The providers in our case presentation are challenged with determining whether inpatient thrombophilia evaluation will add value to the evaluation of patients with unprovoked VTE. The available evidence suggests that clinicians should avoid ordering thrombophilia testing for hospitalized patients with unprovoked VTE because (1) many thrombophilia tests are inaccurate in the setting of acute VTE and/or anticoagulation, (2) results of testing often do not influence management, (3) testing is not cost‐effective, (4) a positive test result may lead to unnecessary patient anxiety, and (5) testing may result in inappropriately prolonged anticoagulation courses or unnecessary involvement of inpatient consultants. For these reasons, the patient in our case presentation should not be tested for inherited thrombophilia. In patients with personal or family histories of recurrent thromboembolism, modifiable clinical risk factors should be addressed, as these are more likely to influence treatment decisions compared to genetic testing. Finally, patients may be referred to an outpatient hematologist or geneticist for individualized discussions of risks and benefits of testing for inherited thrombophilia.

CONCLUSION

Inpatient evaluation for inherited thrombophilia for VTE is not clinically useful, cost‐effective, or reliable in the setting of VTE. The result of such testing does not affect management of acute primary or recurrent VTE. Testing should only be considered using an individualized approach in the outpatient setting with appropriate genetic counseling.

Disclosure: Christopher M. Petrilli, MD, and Lauren Heidemann, MD, contributed equally to this work. The authors report no conflicts of interest.

Do you think this is a low‐value practice? Is this truly a Thing We Do for No Reason? Share what you do in your practice and join in the conversation online by retweeting it on Twitter (#TWDFNR) and liking it on Facebook. We invite you to propose ideas for other Things We Do for No Reason topics by emailing TWDFNR@hospitalmedicine.org.

STAT is an abbreviation of the Latin word statim, meaning immediately,[1] and has been a part of healthcare's lexicon for almost as long as there have been hospitals. STAT conveys a sense of urgency, compelling those who hear STAT to act quickly. Unfortunately, given the lack of a consistent understanding of STAT, the term in reality often has an alternate use: to hurry up or to complete sooner than routine, and is sometimes used to circumvent a system that is perceived to be too slow to accomplish a routine task in a timely manner.

As part of a larger systems redesign effort to improve patient safety and quality of care, an institutional review board (IRB)‐approved qualitative study was conducted on 2 medical‐surgical units in a US Department of Veterans Affairs (VA) hospital to explore communication patterns between physicians and nurses.[2] The study revealed wide variation in understanding between physicians and nurses on the ordering and administration of STAT medication. Physicians were unaware that when they placed a STAT order into the computerized patient record system (CPRS), nurses were not automatically alerted about the order. At this facility, nurses did not carry pagers. Although each unit had a supply of wireless telephones, they were often unreliable and therefore not used consistently. Nurses were required by policy to check the CPRS for new orders every 2 hours. This was an inefficient and possibly dangerous process,[3] because if a nurse was not expecting a STAT order, 2 hours could elapse before she or he saw the order in the CPRS and began to look for the medication. A follow‐up survey completed by physicians, nurses, pharmacists, and pharmacy technicians demonstrated stark differences on the definition of STAT and overlap with similar terms such as NOW and ASAP. Interviews with ordering providers indicated that 36% of the time a STAT was ordered it was not clinically urgent, but instead ordered STAT to speed up the process.

The STAT medication process was clearly in need of improvement, but previous quality improvement projects in our organization had varying degrees of success. For example, we used Lean methodology in an attempt to improve our discharge process. We conducted a modified rapid process discharge improvement workshop[4] structured in phases over 4 weeks. During the workshops, a strong emphasis remained on the solutions to the problem, and we were unable to help the team move from a mindset of fix it to create it. This limited the buy‐in of team members, the creativity of their ideas for improvement, and ultimately the momentum to improve the process.

In this article we describe our adaptation of A3 Thinking,[5, 6] a structure for guiding quality improvement based in Lean methodology, to improve the STAT medication process. We chose A3 Thinking for several reasons. A3 Thinking focuses on process improvement and thus aligned well with our interest in improving the STAT medication process. A3 Thinking also reveals otherwise hidden nonvalue‐added activities that should be eliminated.[7] Finally A3 Thinking reinforces a deeper understanding of the way the work is currently being done, providing critical information needed before making a change. This provides a tremendous opportunity to look at work differently and see opportunities for improvement.[8] Given these strengths as well as the lack of congruence between what the STAT process should consist of and how the STAT process was actually being used in our organization, A3 Thinking offered the best fit between an improvement process and the problem to be solved.

METHODS

A search of healthcare literature yielded very few studies on the STAT process.[9, 10] Only 1 intervention to improve the process was found, and this focused on a specific procedure.[10] An informal survey of local VA and non‐VA hospitals regarding their experiences with the STAT medication process revealed insufficient information to aid our efforts. We next searched the business and manufacturing literature and found examples of how the Lean methodology was successfully applied to other problems in healthcare, including improving pediatric surgery workflow and decreasing ventilator‐associated pneumonia.[11, 12]

Therefore, the STAT project was structured to adapt a problem‐solving process commonly used in Lean organizationsA3 Thinkingwhich challenges team members to work through a discovery phase to develop a shared understanding of the process, an envisioning phase to conceptualize an ideal process experience, and finally an experimentation phase to identify and trial possible solutions through prioritization, iterative testing, structured reflection, and adjustment on resulting changes. Our application of the term experimentation in this context is distinct from that of controlled experimentation in clinical research; the term is intended to convey iterative learning as changes are tested, evaluated, and modified during this quality improvement project. Figure 1 displays a conceptual model of our adaptation of A3 Thinking. As this was a quality‐improvement project, it was exempt from IRB review.

Figure 1

DISCOVERY

To begin the discovery phase, a workgroup consisting of representatives of all groups that had a role in the STAT process (ie, physician, pharmacist, nurse, pharmacy technician, clerk) gathered to identify the opportunity we are looking to address and learn from each other's individual experiences with the STAT medication process. The group was facilitated by an industrial engineer familiar with the A3 Thinking process. The team completed a mapping exercise to lay out, step‐by‐step, the current STAT medication process. This activity allowed the team to build shared empathy with others' experiences and to appreciate the challenges experienced by others through their individual responsibilities in the process. The current process was found to consist of 4 overarching components: a provider entered the STAT order into the CPRS; the order was verified by a pharmacist; a pharmacy technician delivered the medication to the unit (or a nurse retrieved the medication from the Omnicell (Omnicell Inc., Mountain View, CA), a proprietary automated medication dispensing system); and finally the nurse administered the medication to a patient.

A large, color‐coded flow map of the STAT medication process was constructed over several meetings to capture all perspectives and allow team members to gather feedback from their peers. To further our understanding of the current process, the team participated in a modified Go to the Gemba (ie, go to where the work is done)[13] on a real‐time STAT order. Once all workgroup members were satisfied that the flow map represented the current state of the STAT medication process, we came to a consensus on the goals needed to meet our main objective.

We agreed that our main objective was that STAT medication orders should be recognized, verified, and administered to patients in a timely and appropriate manner to ensure quality care. We identified 3 goals to meet this objective: (1) STAT should be consistently defined and understood by everyone; (2) an easy, intuitive STAT process should be available for all stakeholders; and (3) the STAT process should be transparent and ideally visual so that everyone involved can understand at which point in the process a specific STAT order is currently situated. We also identified additional information we would need to reach the goals.

Shortly after the process‐mapping sessions, 2 workgroup members conducted real‐time STAT order time studies to track medications from order to administration. Three time periods in the STAT process were identified for observation and measurement: the time from physician order entry in the CPRS to the time a pharmacist verified the medication, the time from verification to when the medication arrived on the nursing unit, and the time from arrival on the nursing unit to when that medication was administered. Using a data‐collection template, each time period was recorded, and 28 time studies were collected over 1 month. To monitor the progress of our initiatives, the time study was repeated 3 months into the project.

ENVISIONING

Following the discovery phase, the team was better equipped to identify the specific changes needed to achieve an improved process. The envisioning phase allowed the team freedom to imagine an ideal process barring any preconceived notion of constraints within the current process.

In 2 meetings we brainstormed as many improvement ideas as possible. To prioritize and focus our ideas, we developed a matrix (see Supporting Information, Appendix A, in the online version of this article), placing our ideas in 1 of 4 quadrants based on the anticipated effort to implement the change (x‐axis) and impact of making the change (y‐axis). The matrix helped us see that some ideas would be relatively simple to implement (eg, color‐coded bags for STAT medication delivery), whereas others would require more sophisticated efforts and involvement of other people (eg, monthly education sessions to resident physicians).

EXPERIMENTING

Experiments were conducted to meet each of the 3 goals identified above. The team used the outcomes of the prioritization exercise to identify initial experiments to test. To build momentum by showing progress and improvement with a few quick wins, the team began with low‐effort/high‐impact opportunities. Each experiment followed a standard Plan‐Do‐Study‐Act (PDSA) cycle to encourage reflection, learning, adaptation, and adjustment as a result of the experiential learning process.[5]

RESULTS

At the start of our project, the average time from STAT order to medication administration was 1 hour and 7 minutes (range, 6 minutes 2 hours and 22 minutes). As a result of the 2 sets of countermeasures outlined in Tables 1 and 2, the average total time from STAT order entry to administration decreased by 21% to an average of 53 minutes. The total time from medication delivery to administration decreased by 26% from 34 minutes to 25 minutes postimplementation. On average, 391 STAT medications were ordered per month during the project period, which represents a decrease of 9.5% from the 432 orders per month for the same time period the previous year. After implementing the countermeasures in Table 2, we followed another 26 STAT medications through the process to evaluate our efforts. Of 15 STAT medications requiring delivery, only 1 nurse (7%) was not notified of the delivery of a STAT medication, and 1 pharmacy technician (7%) was not informed the medication was STAT. The 151% increase in notification of nurses to delivery of a STAT medication suggests that use of the STAT bags, STAT magnets on patient doors, and whenever possible direct delivery of STAT medications to the nurse has improved communication between the technicians and nurses. Similarly, the 27% increase in technician awareness of a STAT designation suggests STAT is being better communicated to them. The improvement in awareness and notification of a STAT medication is summarized in Figure 2.

Figure 2

Due to time and financial constraints, the following limitations may have affected our findings. First, resident physicians were not directly represented in our discussions. Attending medicine hospitalists provided the physician perspective, which provides a biased view given their intimate knowledge of the CPRS and additional years of experience. Similarly, nurse perspectives were limited to staff and clinical nurse leaders. Last, our low‐cost approach was mandated by limited resources; a more resource‐rich environment may have devised alternative approaches.

CONCLUSIONS

Adapting A3 Thinking for process improvement was a low‐cost/low‐tech option for a VA facility. Having buy‐in from all levels was crucial to the success of the project. The size and diversity of the group was also very important, as different opinions and aspects of the process were represented. Cross‐discipline relationships and respect were formed, which will be valuable for collaboration in future projects. Although we focused on the STAT medication process, other quality‐improvement projects could also benefit from A3 Thinking. Moreover, there were enough people to serve as ambassadors, taking the project back to their work areas to share with their peers, gather consensus, and elicit additional feedback. The collaboration led to comprehensive understanding of the process, the nature of the problems within the process, and the complexity of solving the problem. For example, although the number of STAT orders did not decrease dramatically, we have learned from these experiments that we may need to change how we approach structuring additional experiments. Future work will focus on increasing communication between physicians and nurses when placing STAT medication orders, enhancing resident education to ensure appropriate use of the STAT designation, and continuing our efforts to improve the delivery process of STAT medications.

Other quality‐improvement methodologies we could have used include: total quality management (TQM), continuous quality improvement (CQI), business process redesign, Lean, Six Sigma, and others.[14] Differences between these can be broadly classified as putting an emphasis on people (eg, inclusion of front line staff in CQI or leadership in TQM) or on process (eg, understanding process function to reduce waste in Lean or statistical process control in Six Sigma).[14] Using A3 Thinking methodology was more useful than these others for the STAT medication process for some very important reasons. The A3 process not only led to a better understanding of the meaning of STAT across disciplines, increasing the intuitive nature, transparency and visual aspects of the whole process, but also promoted a collaborative, multidisciplinary, integrative culture, in which other hospital‐wide problems may be addressed in the future.

STAT is an abbreviation of the Latin word statim, meaning immediately,[1] and has been a part of healthcare's lexicon for almost as long as there have been hospitals. STAT conveys a sense of urgency, compelling those who hear STAT to act quickly. Unfortunately, given the lack of a consistent understanding of STAT, the term in reality often has an alternate use: to hurry up or to complete sooner than routine, and is sometimes used to circumvent a system that is perceived to be too slow to accomplish a routine task in a timely manner.

As part of a larger systems redesign effort to improve patient safety and quality of care, an institutional review board (IRB)‐approved qualitative study was conducted on 2 medical‐surgical units in a US Department of Veterans Affairs (VA) hospital to explore communication patterns between physicians and nurses.[2] The study revealed wide variation in understanding between physicians and nurses on the ordering and administration of STAT medication. Physicians were unaware that when they placed a STAT order into the computerized patient record system (CPRS), nurses were not automatically alerted about the order. At this facility, nurses did not carry pagers. Although each unit had a supply of wireless telephones, they were often unreliable and therefore not used consistently. Nurses were required by policy to check the CPRS for new orders every 2 hours. This was an inefficient and possibly dangerous process,[3] because if a nurse was not expecting a STAT order, 2 hours could elapse before she or he saw the order in the CPRS and began to look for the medication. A follow‐up survey completed by physicians, nurses, pharmacists, and pharmacy technicians demonstrated stark differences on the definition of STAT and overlap with similar terms such as NOW and ASAP. Interviews with ordering providers indicated that 36% of the time a STAT was ordered it was not clinically urgent, but instead ordered STAT to speed up the process.

The STAT medication process was clearly in need of improvement, but previous quality improvement projects in our organization had varying degrees of success. For example, we used Lean methodology in an attempt to improve our discharge process. We conducted a modified rapid process discharge improvement workshop[4] structured in phases over 4 weeks. During the workshops, a strong emphasis remained on the solutions to the problem, and we were unable to help the team move from a mindset of fix it to create it. This limited the buy‐in of team members, the creativity of their ideas for improvement, and ultimately the momentum to improve the process.

In this article we describe our adaptation of A3 Thinking,[5, 6] a structure for guiding quality improvement based in Lean methodology, to improve the STAT medication process. We chose A3 Thinking for several reasons. A3 Thinking focuses on process improvement and thus aligned well with our interest in improving the STAT medication process. A3 Thinking also reveals otherwise hidden nonvalue‐added activities that should be eliminated.[7] Finally A3 Thinking reinforces a deeper understanding of the way the work is currently being done, providing critical information needed before making a change. This provides a tremendous opportunity to look at work differently and see opportunities for improvement.[8] Given these strengths as well as the lack of congruence between what the STAT process should consist of and how the STAT process was actually being used in our organization, A3 Thinking offered the best fit between an improvement process and the problem to be solved.

METHODS

A search of healthcare literature yielded very few studies on the STAT process.[9, 10] Only 1 intervention to improve the process was found, and this focused on a specific procedure.[10] An informal survey of local VA and non‐VA hospitals regarding their experiences with the STAT medication process revealed insufficient information to aid our efforts. We next searched the business and manufacturing literature and found examples of how the Lean methodology was successfully applied to other problems in healthcare, including improving pediatric surgery workflow and decreasing ventilator‐associated pneumonia.[11, 12]

Therefore, the STAT project was structured to adapt a problem‐solving process commonly used in Lean organizationsA3 Thinkingwhich challenges team members to work through a discovery phase to develop a shared understanding of the process, an envisioning phase to conceptualize an ideal process experience, and finally an experimentation phase to identify and trial possible solutions through prioritization, iterative testing, structured reflection, and adjustment on resulting changes. Our application of the term experimentation in this context is distinct from that of controlled experimentation in clinical research; the term is intended to convey iterative learning as changes are tested, evaluated, and modified during this quality improvement project. Figure 1 displays a conceptual model of our adaptation of A3 Thinking. As this was a quality‐improvement project, it was exempt from IRB review.

Figure 1

DISCOVERY

To begin the discovery phase, a workgroup consisting of representatives of all groups that had a role in the STAT process (ie, physician, pharmacist, nurse, pharmacy technician, clerk) gathered to identify the opportunity we are looking to address and learn from each other's individual experiences with the STAT medication process. The group was facilitated by an industrial engineer familiar with the A3 Thinking process. The team completed a mapping exercise to lay out, step‐by‐step, the current STAT medication process. This activity allowed the team to build shared empathy with others' experiences and to appreciate the challenges experienced by others through their individual responsibilities in the process. The current process was found to consist of 4 overarching components: a provider entered the STAT order into the CPRS; the order was verified by a pharmacist; a pharmacy technician delivered the medication to the unit (or a nurse retrieved the medication from the Omnicell (Omnicell Inc., Mountain View, CA), a proprietary automated medication dispensing system); and finally the nurse administered the medication to a patient.

A large, color‐coded flow map of the STAT medication process was constructed over several meetings to capture all perspectives and allow team members to gather feedback from their peers. To further our understanding of the current process, the team participated in a modified Go to the Gemba (ie, go to where the work is done)[13] on a real‐time STAT order. Once all workgroup members were satisfied that the flow map represented the current state of the STAT medication process, we came to a consensus on the goals needed to meet our main objective.

We agreed that our main objective was that STAT medication orders should be recognized, verified, and administered to patients in a timely and appropriate manner to ensure quality care. We identified 3 goals to meet this objective: (1) STAT should be consistently defined and understood by everyone; (2) an easy, intuitive STAT process should be available for all stakeholders; and (3) the STAT process should be transparent and ideally visual so that everyone involved can understand at which point in the process a specific STAT order is currently situated. We also identified additional information we would need to reach the goals.

Shortly after the process‐mapping sessions, 2 workgroup members conducted real‐time STAT order time studies to track medications from order to administration. Three time periods in the STAT process were identified for observation and measurement: the time from physician order entry in the CPRS to the time a pharmacist verified the medication, the time from verification to when the medication arrived on the nursing unit, and the time from arrival on the nursing unit to when that medication was administered. Using a data‐collection template, each time period was recorded, and 28 time studies were collected over 1 month. To monitor the progress of our initiatives, the time study was repeated 3 months into the project.

ENVISIONING

Following the discovery phase, the team was better equipped to identify the specific changes needed to achieve an improved process. The envisioning phase allowed the team freedom to imagine an ideal process barring any preconceived notion of constraints within the current process.

In 2 meetings we brainstormed as many improvement ideas as possible. To prioritize and focus our ideas, we developed a matrix (see Supporting Information, Appendix A, in the online version of this article), placing our ideas in 1 of 4 quadrants based on the anticipated effort to implement the change (x‐axis) and impact of making the change (y‐axis). The matrix helped us see that some ideas would be relatively simple to implement (eg, color‐coded bags for STAT medication delivery), whereas others would require more sophisticated efforts and involvement of other people (eg, monthly education sessions to resident physicians).

EXPERIMENTING

Experiments were conducted to meet each of the 3 goals identified above. The team used the outcomes of the prioritization exercise to identify initial experiments to test. To build momentum by showing progress and improvement with a few quick wins, the team began with low‐effort/high‐impact opportunities. Each experiment followed a standard Plan‐Do‐Study‐Act (PDSA) cycle to encourage reflection, learning, adaptation, and adjustment as a result of the experiential learning process.[5]

RESULTS

At the start of our project, the average time from STAT order to medication administration was 1 hour and 7 minutes (range, 6 minutes 2 hours and 22 minutes). As a result of the 2 sets of countermeasures outlined in Tables 1 and 2, the average total time from STAT order entry to administration decreased by 21% to an average of 53 minutes. The total time from medication delivery to administration decreased by 26% from 34 minutes to 25 minutes postimplementation. On average, 391 STAT medications were ordered per month during the project period, which represents a decrease of 9.5% from the 432 orders per month for the same time period the previous year. After implementing the countermeasures in Table 2, we followed another 26 STAT medications through the process to evaluate our efforts. Of 15 STAT medications requiring delivery, only 1 nurse (7%) was not notified of the delivery of a STAT medication, and 1 pharmacy technician (7%) was not informed the medication was STAT. The 151% increase in notification of nurses to delivery of a STAT medication suggests that use of the STAT bags, STAT magnets on patient doors, and whenever possible direct delivery of STAT medications to the nurse has improved communication between the technicians and nurses. Similarly, the 27% increase in technician awareness of a STAT designation suggests STAT is being better communicated to them. The improvement in awareness and notification of a STAT medication is summarized in Figure 2.

Figure 2

Due to time and financial constraints, the following limitations may have affected our findings. First, resident physicians were not directly represented in our discussions. Attending medicine hospitalists provided the physician perspective, which provides a biased view given their intimate knowledge of the CPRS and additional years of experience. Similarly, nurse perspectives were limited to staff and clinical nurse leaders. Last, our low‐cost approach was mandated by limited resources; a more resource‐rich environment may have devised alternative approaches.

CONCLUSIONS

Adapting A3 Thinking for process improvement was a low‐cost/low‐tech option for a VA facility. Having buy‐in from all levels was crucial to the success of the project. The size and diversity of the group was also very important, as different opinions and aspects of the process were represented. Cross‐discipline relationships and respect were formed, which will be valuable for collaboration in future projects. Although we focused on the STAT medication process, other quality‐improvement projects could also benefit from A3 Thinking. Moreover, there were enough people to serve as ambassadors, taking the project back to their work areas to share with their peers, gather consensus, and elicit additional feedback. The collaboration led to comprehensive understanding of the process, the nature of the problems within the process, and the complexity of solving the problem. For example, although the number of STAT orders did not decrease dramatically, we have learned from these experiments that we may need to change how we approach structuring additional experiments. Future work will focus on increasing communication between physicians and nurses when placing STAT medication orders, enhancing resident education to ensure appropriate use of the STAT designation, and continuing our efforts to improve the delivery process of STAT medications.

Other quality‐improvement methodologies we could have used include: total quality management (TQM), continuous quality improvement (CQI), business process redesign, Lean, Six Sigma, and others.[14] Differences between these can be broadly classified as putting an emphasis on people (eg, inclusion of front line staff in CQI or leadership in TQM) or on process (eg, understanding process function to reduce waste in Lean or statistical process control in Six Sigma).[14] Using A3 Thinking methodology was more useful than these others for the STAT medication process for some very important reasons. The A3 process not only led to a better understanding of the meaning of STAT across disciplines, increasing the intuitive nature, transparency and visual aspects of the whole process, but also promoted a collaborative, multidisciplinary, integrative culture, in which other hospital‐wide problems may be addressed in the future.

STAT is an abbreviation of the Latin word statim, meaning immediately,[1] and has been a part of healthcare's lexicon for almost as long as there have been hospitals. STAT conveys a sense of urgency, compelling those who hear STAT to act quickly. Unfortunately, given the lack of a consistent understanding of STAT, the term in reality often has an alternate use: to hurry up or to complete sooner than routine, and is sometimes used to circumvent a system that is perceived to be too slow to accomplish a routine task in a timely manner.

As part of a larger systems redesign effort to improve patient safety and quality of care, an institutional review board (IRB)‐approved qualitative study was conducted on 2 medical‐surgical units in a US Department of Veterans Affairs (VA) hospital to explore communication patterns between physicians and nurses.[2] The study revealed wide variation in understanding between physicians and nurses on the ordering and administration of STAT medication. Physicians were unaware that when they placed a STAT order into the computerized patient record system (CPRS), nurses were not automatically alerted about the order. At this facility, nurses did not carry pagers. Although each unit had a supply of wireless telephones, they were often unreliable and therefore not used consistently. Nurses were required by policy to check the CPRS for new orders every 2 hours. This was an inefficient and possibly dangerous process,[3] because if a nurse was not expecting a STAT order, 2 hours could elapse before she or he saw the order in the CPRS and began to look for the medication. A follow‐up survey completed by physicians, nurses, pharmacists, and pharmacy technicians demonstrated stark differences on the definition of STAT and overlap with similar terms such as NOW and ASAP. Interviews with ordering providers indicated that 36% of the time a STAT was ordered it was not clinically urgent, but instead ordered STAT to speed up the process.

The STAT medication process was clearly in need of improvement, but previous quality improvement projects in our organization had varying degrees of success. For example, we used Lean methodology in an attempt to improve our discharge process. We conducted a modified rapid process discharge improvement workshop[4] structured in phases over 4 weeks. During the workshops, a strong emphasis remained on the solutions to the problem, and we were unable to help the team move from a mindset of fix it to create it. This limited the buy‐in of team members, the creativity of their ideas for improvement, and ultimately the momentum to improve the process.

In this article we describe our adaptation of A3 Thinking,[5, 6] a structure for guiding quality improvement based in Lean methodology, to improve the STAT medication process. We chose A3 Thinking for several reasons. A3 Thinking focuses on process improvement and thus aligned well with our interest in improving the STAT medication process. A3 Thinking also reveals otherwise hidden nonvalue‐added activities that should be eliminated.[7] Finally A3 Thinking reinforces a deeper understanding of the way the work is currently being done, providing critical information needed before making a change. This provides a tremendous opportunity to look at work differently and see opportunities for improvement.[8] Given these strengths as well as the lack of congruence between what the STAT process should consist of and how the STAT process was actually being used in our organization, A3 Thinking offered the best fit between an improvement process and the problem to be solved.

METHODS

A search of healthcare literature yielded very few studies on the STAT process.[9, 10] Only 1 intervention to improve the process was found, and this focused on a specific procedure.[10] An informal survey of local VA and non‐VA hospitals regarding their experiences with the STAT medication process revealed insufficient information to aid our efforts. We next searched the business and manufacturing literature and found examples of how the Lean methodology was successfully applied to other problems in healthcare, including improving pediatric surgery workflow and decreasing ventilator‐associated pneumonia.[11, 12]

Therefore, the STAT project was structured to adapt a problem‐solving process commonly used in Lean organizationsA3 Thinkingwhich challenges team members to work through a discovery phase to develop a shared understanding of the process, an envisioning phase to conceptualize an ideal process experience, and finally an experimentation phase to identify and trial possible solutions through prioritization, iterative testing, structured reflection, and adjustment on resulting changes. Our application of the term experimentation in this context is distinct from that of controlled experimentation in clinical research; the term is intended to convey iterative learning as changes are tested, evaluated, and modified during this quality improvement project. Figure 1 displays a conceptual model of our adaptation of A3 Thinking. As this was a quality‐improvement project, it was exempt from IRB review.

Figure 1

DISCOVERY

To begin the discovery phase, a workgroup consisting of representatives of all groups that had a role in the STAT process (ie, physician, pharmacist, nurse, pharmacy technician, clerk) gathered to identify the opportunity we are looking to address and learn from each other's individual experiences with the STAT medication process. The group was facilitated by an industrial engineer familiar with the A3 Thinking process. The team completed a mapping exercise to lay out, step‐by‐step, the current STAT medication process. This activity allowed the team to build shared empathy with others' experiences and to appreciate the challenges experienced by others through their individual responsibilities in the process. The current process was found to consist of 4 overarching components: a provider entered the STAT order into the CPRS; the order was verified by a pharmacist; a pharmacy technician delivered the medication to the unit (or a nurse retrieved the medication from the Omnicell (Omnicell Inc., Mountain View, CA), a proprietary automated medication dispensing system); and finally the nurse administered the medication to a patient.

A large, color‐coded flow map of the STAT medication process was constructed over several meetings to capture all perspectives and allow team members to gather feedback from their peers. To further our understanding of the current process, the team participated in a modified Go to the Gemba (ie, go to where the work is done)[13] on a real‐time STAT order. Once all workgroup members were satisfied that the flow map represented the current state of the STAT medication process, we came to a consensus on the goals needed to meet our main objective.

We agreed that our main objective was that STAT medication orders should be recognized, verified, and administered to patients in a timely and appropriate manner to ensure quality care. We identified 3 goals to meet this objective: (1) STAT should be consistently defined and understood by everyone; (2) an easy, intuitive STAT process should be available for all stakeholders; and (3) the STAT process should be transparent and ideally visual so that everyone involved can understand at which point in the process a specific STAT order is currently situated. We also identified additional information we would need to reach the goals.

Shortly after the process‐mapping sessions, 2 workgroup members conducted real‐time STAT order time studies to track medications from order to administration. Three time periods in the STAT process were identified for observation and measurement: the time from physician order entry in the CPRS to the time a pharmacist verified the medication, the time from verification to when the medication arrived on the nursing unit, and the time from arrival on the nursing unit to when that medication was administered. Using a data‐collection template, each time period was recorded, and 28 time studies were collected over 1 month. To monitor the progress of our initiatives, the time study was repeated 3 months into the project.

ENVISIONING

Following the discovery phase, the team was better equipped to identify the specific changes needed to achieve an improved process. The envisioning phase allowed the team freedom to imagine an ideal process barring any preconceived notion of constraints within the current process.

In 2 meetings we brainstormed as many improvement ideas as possible. To prioritize and focus our ideas, we developed a matrix (see Supporting Information, Appendix A, in the online version of this article), placing our ideas in 1 of 4 quadrants based on the anticipated effort to implement the change (x‐axis) and impact of making the change (y‐axis). The matrix helped us see that some ideas would be relatively simple to implement (eg, color‐coded bags for STAT medication delivery), whereas others would require more sophisticated efforts and involvement of other people (eg, monthly education sessions to resident physicians).

EXPERIMENTING

Experiments were conducted to meet each of the 3 goals identified above. The team used the outcomes of the prioritization exercise to identify initial experiments to test. To build momentum by showing progress and improvement with a few quick wins, the team began with low‐effort/high‐impact opportunities. Each experiment followed a standard Plan‐Do‐Study‐Act (PDSA) cycle to encourage reflection, learning, adaptation, and adjustment as a result of the experiential learning process.[5]

RESULTS

At the start of our project, the average time from STAT order to medication administration was 1 hour and 7 minutes (range, 6 minutes 2 hours and 22 minutes). As a result of the 2 sets of countermeasures outlined in Tables 1 and 2, the average total time from STAT order entry to administration decreased by 21% to an average of 53 minutes. The total time from medication delivery to administration decreased by 26% from 34 minutes to 25 minutes postimplementation. On average, 391 STAT medications were ordered per month during the project period, which represents a decrease of 9.5% from the 432 orders per month for the same time period the previous year. After implementing the countermeasures in Table 2, we followed another 26 STAT medications through the process to evaluate our efforts. Of 15 STAT medications requiring delivery, only 1 nurse (7%) was not notified of the delivery of a STAT medication, and 1 pharmacy technician (7%) was not informed the medication was STAT. The 151% increase in notification of nurses to delivery of a STAT medication suggests that use of the STAT bags, STAT magnets on patient doors, and whenever possible direct delivery of STAT medications to the nurse has improved communication between the technicians and nurses. Similarly, the 27% increase in technician awareness of a STAT designation suggests STAT is being better communicated to them. The improvement in awareness and notification of a STAT medication is summarized in Figure 2.

Figure 2

Due to time and financial constraints, the following limitations may have affected our findings. First, resident physicians were not directly represented in our discussions. Attending medicine hospitalists provided the physician perspective, which provides a biased view given their intimate knowledge of the CPRS and additional years of experience. Similarly, nurse perspectives were limited to staff and clinical nurse leaders. Last, our low‐cost approach was mandated by limited resources; a more resource‐rich environment may have devised alternative approaches.

CONCLUSIONS

Adapting A3 Thinking for process improvement was a low‐cost/low‐tech option for a VA facility. Having buy‐in from all levels was crucial to the success of the project. The size and diversity of the group was also very important, as different opinions and aspects of the process were represented. Cross‐discipline relationships and respect were formed, which will be valuable for collaboration in future projects. Although we focused on the STAT medication process, other quality‐improvement projects could also benefit from A3 Thinking. Moreover, there were enough people to serve as ambassadors, taking the project back to their work areas to share with their peers, gather consensus, and elicit additional feedback. The collaboration led to comprehensive understanding of the process, the nature of the problems within the process, and the complexity of solving the problem. For example, although the number of STAT orders did not decrease dramatically, we have learned from these experiments that we may need to change how we approach structuring additional experiments. Future work will focus on increasing communication between physicians and nurses when placing STAT medication orders, enhancing resident education to ensure appropriate use of the STAT designation, and continuing our efforts to improve the delivery process of STAT medications.

Other quality‐improvement methodologies we could have used include: total quality management (TQM), continuous quality improvement (CQI), business process redesign, Lean, Six Sigma, and others.[14] Differences between these can be broadly classified as putting an emphasis on people (eg, inclusion of front line staff in CQI or leadership in TQM) or on process (eg, understanding process function to reduce waste in Lean or statistical process control in Six Sigma).[14] Using A3 Thinking methodology was more useful than these others for the STAT medication process for some very important reasons. The A3 process not only led to a better understanding of the meaning of STAT across disciplines, increasing the intuitive nature, transparency and visual aspects of the whole process, but also promoted a collaborative, multidisciplinary, integrative culture, in which other hospital‐wide problems may be addressed in the future.