The correct answer is: E. All of the above

Acute medical illness is a prothrombotic state. Patients hospitalized for medical illness are at risk for venous thromboembolism (VTE), and this risk persists after discharge. Antithrombotic agents, historically parenteral anticoagulants such as heparin (unfractionated or low molecular weight) have been used during hospitalization to prevent VTE in patients at increased risk, but the extended use of thromboprophlyaxis beyond hospital discharge is not routine. The risk of post-discharge VTE appears highest for patients with certain conditions and greatest within the first 15-30 days post-discharge.¹ Admitting diagnoses of heart failure, acute stroke, chronic obstructive pulmonary disease, respiratory infection, rheumatologic disorders, inflammatory bowel diseases, and cancer confer the highest risk for VTE.² The most recent American College of Chest Physicians (ACCP) guidelines recommend anticoagulant thromboprophylaxis for acutely ill hospitalized medical patients at increased risk of thrombosis for 6 to 21 days, until full mobility is restored, or until discharge from hospital, whichever comes first.³

VTE is associated with a host of modifiable and non-modifiable risk factors.⁴ In the Nurses' Health Study cohort of 112,822 women, obesity, cigarette smoking, and hypertension were independent risk factors for pulmonary embolism (PE). Among women with a BMI ≥29 kg/m² the relative risk for PE was 2.9. The relative risk of PE was 1.9 for women currently smoking 25−34 cigarettes/day and 3.3 for women smoking >35 cigarettes daily. compared to those who never smoked. Hypertension was associated with a relative risk of 1.9 for PE.⁵ Thus, the correct answer here is "All of the above."

The use of antithrombotic agents in high-risk medically ill patients after discharge is associated with decreased all-cause mortality at 90 days post-discharge.² However, current guidelines do not include extended duration prophylaxis for medical patients, and no anticoagulants are currently approved for this indication. The use of prophylaxis during hospitalization reduces the incidence of VTE, and is a Core Measure of quality care. Standard prophylaxis regimens utilized in clinical trials were typically 6 to 14 days in duration, related to the standard duration of hospitalization. However, contemporary medical patients are frequently discharged after shorter inpatient stays. Certain patients who would previously have been hospitalized for extended periods may have prolonged VTE risk after discharge, such as those with reduced mobility and ongoing disease. In this situation, inpatient prophylaxis alone may be insufficient.⁶

Three recent studies of extended anticoagulation treatment failed to demonstrate a positive benefit-risk profile, primarily due to increased bleeding with the anticoagulants.^7,8,9 However, extending antithrombotic therapy beyond the index hospitalization may be useful when the benefit to bleeding-risk ratio is favorable. Patients with renal impairment, cancer, bleeding during hospitalization, or dual antiplatelet therapy have an unacceptably high risk of bleeding with anticoagulant therapy. The use of extended prophylaxis after discharge appears most favorable for women, the elderly (>75 years), and patients with immobility or prolonged bed rest.⁷ Optimal strategies are under investigation.

The phase 3 Study of Rivaroxaban on the Venous Thromboembolic Risk in Post-Hospital Discharge Patients (MARINER) study is currently underway to determine if the use of the factor Xa inhibitor, rivaroxaban, can prevent symptomatic VTE and VTE-related death post-hospital discharge in high-risk, medically ill patients. Patients with active malignancy or those using dual antiplatelet therapy are excluded, and patients with decreased creatinine clearance receive a lower dose of rivaroxaban to optimize the benefit to bleeding risk ratio.¹⁰

References

1. Mahan CE, Fields LE, Mills RM, et al. All-cause mortality and use of antithrombotics within 90 days of discharge in acutely ill medical patients. Thromb Haemost. 2015;114,4.
2. Spyropoulos AC, Anderson FA Jr, Fitzgerald G, et al. Predictive and associative models to identify hospitalized medical patients at risk for VTE. Chest. 2011;140:706-14.
3. Kahn SR, Lim W, Dunn AS, et al. American College of Chest Physicians. Prevention of VTE in nonsurgical patients: Antithrombotic Therapy and Prevention of Thrombosis. 9th ed. American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141 :e195S-e226S.
4. Goldhaber SZ. Risk factors for venous thromboembolism. J Am Coll Cardiol. 2010;56:1-7.
5. Goldhaber SZ, Grodstein F, Stampfer MJ, et al. A prospective study of risk factors for pulmonary embolism in women. JAMA. 1997;277:642-45.
6. Stark JE, Smith WJ. Standard or extended-duration prophylaxis in medical patients? A review of the evidence. J Thromb Thrombolysis. 2011;32:318-327.
7. Cohen AT, Spiro TE, Büller HR, et al. Rivaroxaban for thromboprophylaxis in acutely ill medical patients. N Engl J Med. 2013;368:513-23.
8. Goldhaber SZ, Leizorovicz A, Kakkar AK, et al. Apixaban versus enoxaparin for thromboprophylaxis in medically ill patients. New Engl J Med. 2011;365:2167-77.
9. Hull RD, Schellong SM, Tapson VF, et al. Extended-duration venous thromboembolism prophylaxis in acutely ill medical patients with recently reduced mobility: a randomized trial. Ann Intern Med. 2010;153:8-18.