Venous Thromboembolism Prophylaxis in Hospitalized Patients

The American College of Physicians recently published guidelines on venous thromboembolism prophylaxis in hospitalized medical patients (Ann. Intern. Med. 2011;155:625-32).

Venous thromboembolism (VTE) – including pulmonary embolism (PE) and deep vein thrombosis (DVT) – is a cause of serious morbidity and mortality in hospitalized patients. Between 5% and 10% of all in-hospital deaths are a direct result of PE, and PE accounts for 200,000-300,000 hospitalizations per year.

Two main approaches to VTE prophylaxis exist. The first is heparin or related agents, including low-dose unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), or fondaparinux, all given subcutaneously. The second option is mechanical leg compression, which primarily includes graduated compression stockings and intermittent pneumatic compression.

Studies from 1950 and 2011 were analyzed that compared heparin or related agents vs. no heparin; LMWH vs. UFH; and mechanical prophylaxis vs. no prophylaxis. The primary outcome for the extracted data was total mortality up to 120 days from randomization, whereas secondary outcomes included symptomatic DVT, all PE, fatal PE, all bleedings events, major bleeding events, and – for mechanical prophylaxis – skin damage.

Prophylaxis vs. No Prophylaxis

In nonstroke medical patients (10 trials, n = 20,717), heparin or related agent (UFH, LMWH, or fondaparinux) prophylaxis did not significantly reduce total mortality, compared with no prophylaxis. There was a statistically significant reduced risk of PE and an increased risk of bleeding events with heparin or related agents. There was an increase in major bleeding and a reduction in symptomatic DVT with heparin that was not statistically significant.

Heparin prophylaxis in acute stroke patients (eight trials, n = 15,405) did not show a significant reduction in mortality, PE, or symptomatic DVT, although there was a nonsignificant increased risk for major bleeding events. Most of the evidence for this group came from one large study that also showed a significant increase in 14-day hemorrhagic stroke or serious extracranial hemorrhage, as well as a significant decrease in 14-day recurrent ischemic stroke with heparin prophylaxis.

Analyzing combined data from acute stroke and nonstroke medical patients, heparin prophylaxis decreased mortality to a borderline but not to a statistically significant degree (relative risk, 93%). There was a significant reduction in risk of PE (RR, 0.70) but no significant decrease in symptomatic DVT with heparin prophylaxis. With heparin, there was a significantly increased risk of all bleeding events (RR, 1.28) and major bleeding events (RR, 1.61).

LMWH vs. UFH

In a comparison of LMWH vs. UFH, nonstroke medical patients (nine trials, n = 11,650) and acute stroke patients showed no significant difference in mortality, PE, symptomatic DVT, or major bleeding. Combined data from acute stroke and nonstroke medical patients also showed no significant difference for any outcome.

Mechanical vs. No Prophylaxis

Most data come from one large study of acute stroke patients that compared graduated compression stockings vs. no prophylaxis. There was not a significant difference in mortality, symptomatic DVT, or PE. There was, however, a significant increase in skin damage with compression stockings. There are insufficient data to evaluate benefit and risk of intermittent pneumatic compression in medical patients. Based on data from surgical patients, intermittent pneumatic compression may be used for VTE prophylaxis in medical patients when bleeding risk makes heparin contraindicated for prophylaxis.

Recommendations

• Assess all medical inpatients for the risk for thromboembolism and bleeding prior to initiation of prophylaxis. A thoughtful assessment of benefit to risk should be done for each patient, and then a decision should be made about initiating prophylaxis.

• Pharmacologic prophylaxis with heparin or a related drug for VTE in medical (including stroke) patients is usually beneficial, unless the assessed risk for bleeding outweighs the likely benefits. In medical inpatients, prophylaxis leads to a statistically significant reduction in PE (four events per 1,000 people treated) and an increase in all bleeding events (nine per 1,000 people) and a nonstatistically significant increase in major bleeding events (one per 1,000 people). There is no effect on mortality or DVT. The increased risk for major bleeding is greater in patients with stroke (six per 1,000). For most people, the reduction in PE outweighs the harm of increased bleeding. The evidence in patients with stroke is weaker than for medical inpatients in general.

• Recommend against the use of mechanical prophylaxis with graduated compression stockings for prevention of VTE.

Notably, the guidelines do not support the application in hospitals of quality performance measures that encourage universal VTE prophylaxis, because such measures would encourage increased use of prophylaxis without regard to risk stratification and assessment. The evidence simply does not support routine prophylaxis of all medical inpatients.

Risk factors for thromboembolism include inherited conditions (such as protein C and protein S deficiencies and the factor V Leiden mutation), and acquired-risk factors (such as cancer, immobilization, presence of central venous catheters, heart failure, smoking, chronic kidney disease, and history of thromboembolism). Risk factors for bleeding with anticoagulant therapy include hypertension, cancer, prior stroke, diabetes, a bleeding disorder, and use of NSAIDs, aspirin, or antiplatelet agents. Unfortunately, these conditions exist together in many hospitalized patients, and there are no validated tools to formally assess risk and benefit of VTE prophylaxis.

Bottom Line

Assess risk for venous thromboembolism as well as bleeding risk in all hospitalized medical patients. Heparin or related agent prophylaxis does not decrease total mortality, but it does decrease the risk of PE while increasing risk of bleeding. For most people, the reduction in PE outweighs the harm of increased bleeding. When benefit outweighs risk, use subcutaneous low-dose UFH, LMWH, or fondaparinux for VTE prophylaxis. Graduated compression stockings are not recommended for VTE prophylaxis.

Dr. Olsen is a chief resident in the family medicine residency program at Abington (Pa.) Memorial Hospital. Dr. Skolnik is an associate director of the family medicine residency program at Abington Memorial Hospital.

The American College of Physicians recently published guidelines on venous thromboembolism prophylaxis in hospitalized medical patients (Ann. Intern. Med. 2011;155:625-32).

Venous thromboembolism (VTE) – including pulmonary embolism (PE) and deep vein thrombosis (DVT) – is a cause of serious morbidity and mortality in hospitalized patients. Between 5% and 10% of all in-hospital deaths are a direct result of PE, and PE accounts for 200,000-300,000 hospitalizations per year.

Two main approaches to VTE prophylaxis exist. The first is heparin or related agents, including low-dose unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), or fondaparinux, all given subcutaneously. The second option is mechanical leg compression, which primarily includes graduated compression stockings and intermittent pneumatic compression.

Studies from 1950 and 2011 were analyzed that compared heparin or related agents vs. no heparin; LMWH vs. UFH; and mechanical prophylaxis vs. no prophylaxis. The primary outcome for the extracted data was total mortality up to 120 days from randomization, whereas secondary outcomes included symptomatic DVT, all PE, fatal PE, all bleedings events, major bleeding events, and – for mechanical prophylaxis – skin damage.

Prophylaxis vs. No Prophylaxis

In nonstroke medical patients (10 trials, n = 20,717), heparin or related agent (UFH, LMWH, or fondaparinux) prophylaxis did not significantly reduce total mortality, compared with no prophylaxis. There was a statistically significant reduced risk of PE and an increased risk of bleeding events with heparin or related agents. There was an increase in major bleeding and a reduction in symptomatic DVT with heparin that was not statistically significant.

Heparin prophylaxis in acute stroke patients (eight trials, n = 15,405) did not show a significant reduction in mortality, PE, or symptomatic DVT, although there was a nonsignificant increased risk for major bleeding events. Most of the evidence for this group came from one large study that also showed a significant increase in 14-day hemorrhagic stroke or serious extracranial hemorrhage, as well as a significant decrease in 14-day recurrent ischemic stroke with heparin prophylaxis.

Analyzing combined data from acute stroke and nonstroke medical patients, heparin prophylaxis decreased mortality to a borderline but not to a statistically significant degree (relative risk, 93%). There was a significant reduction in risk of PE (RR, 0.70) but no significant decrease in symptomatic DVT with heparin prophylaxis. With heparin, there was a significantly increased risk of all bleeding events (RR, 1.28) and major bleeding events (RR, 1.61).

LMWH vs. UFH

In a comparison of LMWH vs. UFH, nonstroke medical patients (nine trials, n = 11,650) and acute stroke patients showed no significant difference in mortality, PE, symptomatic DVT, or major bleeding. Combined data from acute stroke and nonstroke medical patients also showed no significant difference for any outcome.

Mechanical vs. No Prophylaxis

Most data come from one large study of acute stroke patients that compared graduated compression stockings vs. no prophylaxis. There was not a significant difference in mortality, symptomatic DVT, or PE. There was, however, a significant increase in skin damage with compression stockings. There are insufficient data to evaluate benefit and risk of intermittent pneumatic compression in medical patients. Based on data from surgical patients, intermittent pneumatic compression may be used for VTE prophylaxis in medical patients when bleeding risk makes heparin contraindicated for prophylaxis.

Recommendations

• Assess all medical inpatients for the risk for thromboembolism and bleeding prior to initiation of prophylaxis. A thoughtful assessment of benefit to risk should be done for each patient, and then a decision should be made about initiating prophylaxis.

• Pharmacologic prophylaxis with heparin or a related drug for VTE in medical (including stroke) patients is usually beneficial, unless the assessed risk for bleeding outweighs the likely benefits. In medical inpatients, prophylaxis leads to a statistically significant reduction in PE (four events per 1,000 people treated) and an increase in all bleeding events (nine per 1,000 people) and a nonstatistically significant increase in major bleeding events (one per 1,000 people). There is no effect on mortality or DVT. The increased risk for major bleeding is greater in patients with stroke (six per 1,000). For most people, the reduction in PE outweighs the harm of increased bleeding. The evidence in patients with stroke is weaker than for medical inpatients in general.

• Recommend against the use of mechanical prophylaxis with graduated compression stockings for prevention of VTE.

Notably, the guidelines do not support the application in hospitals of quality performance measures that encourage universal VTE prophylaxis, because such measures would encourage increased use of prophylaxis without regard to risk stratification and assessment. The evidence simply does not support routine prophylaxis of all medical inpatients.

Risk factors for thromboembolism include inherited conditions (such as protein C and protein S deficiencies and the factor V Leiden mutation), and acquired-risk factors (such as cancer, immobilization, presence of central venous catheters, heart failure, smoking, chronic kidney disease, and history of thromboembolism). Risk factors for bleeding with anticoagulant therapy include hypertension, cancer, prior stroke, diabetes, a bleeding disorder, and use of NSAIDs, aspirin, or antiplatelet agents. Unfortunately, these conditions exist together in many hospitalized patients, and there are no validated tools to formally assess risk and benefit of VTE prophylaxis.

Bottom Line

Assess risk for venous thromboembolism as well as bleeding risk in all hospitalized medical patients. Heparin or related agent prophylaxis does not decrease total mortality, but it does decrease the risk of PE while increasing risk of bleeding. For most people, the reduction in PE outweighs the harm of increased bleeding. When benefit outweighs risk, use subcutaneous low-dose UFH, LMWH, or fondaparinux for VTE prophylaxis. Graduated compression stockings are not recommended for VTE prophylaxis.

Dr. Olsen is a chief resident in the family medicine residency program at Abington (Pa.) Memorial Hospital. Dr. Skolnik is an associate director of the family medicine residency program at Abington Memorial Hospital.

The American College of Physicians recently published guidelines on venous thromboembolism prophylaxis in hospitalized medical patients (Ann. Intern. Med. 2011;155:625-32).

Venous thromboembolism (VTE) – including pulmonary embolism (PE) and deep vein thrombosis (DVT) – is a cause of serious morbidity and mortality in hospitalized patients. Between 5% and 10% of all in-hospital deaths are a direct result of PE, and PE accounts for 200,000-300,000 hospitalizations per year.

Two main approaches to VTE prophylaxis exist. The first is heparin or related agents, including low-dose unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), or fondaparinux, all given subcutaneously. The second option is mechanical leg compression, which primarily includes graduated compression stockings and intermittent pneumatic compression.

Studies from 1950 and 2011 were analyzed that compared heparin or related agents vs. no heparin; LMWH vs. UFH; and mechanical prophylaxis vs. no prophylaxis. The primary outcome for the extracted data was total mortality up to 120 days from randomization, whereas secondary outcomes included symptomatic DVT, all PE, fatal PE, all bleedings events, major bleeding events, and – for mechanical prophylaxis – skin damage.

Prophylaxis vs. No Prophylaxis

In nonstroke medical patients (10 trials, n = 20,717), heparin or related agent (UFH, LMWH, or fondaparinux) prophylaxis did not significantly reduce total mortality, compared with no prophylaxis. There was a statistically significant reduced risk of PE and an increased risk of bleeding events with heparin or related agents. There was an increase in major bleeding and a reduction in symptomatic DVT with heparin that was not statistically significant.

Heparin prophylaxis in acute stroke patients (eight trials, n = 15,405) did not show a significant reduction in mortality, PE, or symptomatic DVT, although there was a nonsignificant increased risk for major bleeding events. Most of the evidence for this group came from one large study that also showed a significant increase in 14-day hemorrhagic stroke or serious extracranial hemorrhage, as well as a significant decrease in 14-day recurrent ischemic stroke with heparin prophylaxis.

Analyzing combined data from acute stroke and nonstroke medical patients, heparin prophylaxis decreased mortality to a borderline but not to a statistically significant degree (relative risk, 93%). There was a significant reduction in risk of PE (RR, 0.70) but no significant decrease in symptomatic DVT with heparin prophylaxis. With heparin, there was a significantly increased risk of all bleeding events (RR, 1.28) and major bleeding events (RR, 1.61).

LMWH vs. UFH

In a comparison of LMWH vs. UFH, nonstroke medical patients (nine trials, n = 11,650) and acute stroke patients showed no significant difference in mortality, PE, symptomatic DVT, or major bleeding. Combined data from acute stroke and nonstroke medical patients also showed no significant difference for any outcome.

Mechanical vs. No Prophylaxis

Most data come from one large study of acute stroke patients that compared graduated compression stockings vs. no prophylaxis. There was not a significant difference in mortality, symptomatic DVT, or PE. There was, however, a significant increase in skin damage with compression stockings. There are insufficient data to evaluate benefit and risk of intermittent pneumatic compression in medical patients. Based on data from surgical patients, intermittent pneumatic compression may be used for VTE prophylaxis in medical patients when bleeding risk makes heparin contraindicated for prophylaxis.

Recommendations

• Assess all medical inpatients for the risk for thromboembolism and bleeding prior to initiation of prophylaxis. A thoughtful assessment of benefit to risk should be done for each patient, and then a decision should be made about initiating prophylaxis.

• Pharmacologic prophylaxis with heparin or a related drug for VTE in medical (including stroke) patients is usually beneficial, unless the assessed risk for bleeding outweighs the likely benefits. In medical inpatients, prophylaxis leads to a statistically significant reduction in PE (four events per 1,000 people treated) and an increase in all bleeding events (nine per 1,000 people) and a nonstatistically significant increase in major bleeding events (one per 1,000 people). There is no effect on mortality or DVT. The increased risk for major bleeding is greater in patients with stroke (six per 1,000). For most people, the reduction in PE outweighs the harm of increased bleeding. The evidence in patients with stroke is weaker than for medical inpatients in general.

• Recommend against the use of mechanical prophylaxis with graduated compression stockings for prevention of VTE.

Notably, the guidelines do not support the application in hospitals of quality performance measures that encourage universal VTE prophylaxis, because such measures would encourage increased use of prophylaxis without regard to risk stratification and assessment. The evidence simply does not support routine prophylaxis of all medical inpatients.

Risk factors for thromboembolism include inherited conditions (such as protein C and protein S deficiencies and the factor V Leiden mutation), and acquired-risk factors (such as cancer, immobilization, presence of central venous catheters, heart failure, smoking, chronic kidney disease, and history of thromboembolism). Risk factors for bleeding with anticoagulant therapy include hypertension, cancer, prior stroke, diabetes, a bleeding disorder, and use of NSAIDs, aspirin, or antiplatelet agents. Unfortunately, these conditions exist together in many hospitalized patients, and there are no validated tools to formally assess risk and benefit of VTE prophylaxis.

Bottom Line

Assess risk for venous thromboembolism as well as bleeding risk in all hospitalized medical patients. Heparin or related agent prophylaxis does not decrease total mortality, but it does decrease the risk of PE while increasing risk of bleeding. For most people, the reduction in PE outweighs the harm of increased bleeding. When benefit outweighs risk, use subcutaneous low-dose UFH, LMWH, or fondaparinux for VTE prophylaxis. Graduated compression stockings are not recommended for VTE prophylaxis.

Dr. Olsen is a chief resident in the family medicine residency program at Abington (Pa.) Memorial Hospital. Dr. Skolnik is an associate director of the family medicine residency program at Abington Memorial Hospital.