A 24-year-old woman, gravida 1 para 0, at 14 weeks gestation, comes to the emergency department due to left leg swelling and pain for the past 2 days. She has had no chest pain or shortness of breath. The patient has no prior medical conditions and her only medication is a prenatal vitamin. She is a lifetime nonsmoker. Physical examination shows 1+ edema of the left lower extremity to the knee, associated with mild erythema. The left calf diameter measures 3 cm greater than the right. Doppler ultrasonography shows left popliteal and femoral vein thrombosis. Serum creatinine level is 0.7 mg/dL. Which of the following is the most appropriate pharmacotherapy for this patient?
Pregnancy increases the risk of venous thromboembolism (VTE) due to anatomic changes (eg, uterine compression of the inferior vena cava and iliac veins) and physiologic hypercoagulability (eg, increased production of clotting factors, decreased protein S levels, protein C resistance). Heparins are ideal anticoagulants for most pregnant women as they do not cross the placenta and the risk of fetal bleeding and teratogenicity is low:
Low-molecular-weight heparin (LMWH) (eg, enoxaparin, dalteparin) is preferred as it has a relatively long half-life (4.5 hours) and does not require routine laboratory monitoring. However, it is renally cleared and cannot be used in patients with severe renal insufficiency (creatinine clearance <30 mL/min).
Unfractionated heparin has a short half-life (1-2 hours) and requires frequent lab draws (ie, PTT) due to its more varied anticoagulant effect. However, it may be used in patients with renal insufficiency. It is also used in place of LMWH at term (37 weeks gestation) as it can be discontinued at the onset of labor to minimize hemorrhagic risk.
(Choices A and C) Direct thrombin inhibitors (eg, dabigatran) and factor Xa inhibitors (eg, apixaban) are not recommended in pregnant women. Both have been associated with fetal toxicity in animal studies.
(Choices B and E) Clopidogrel and aspirin have no role in acute VTE treatment. Clopidogrel, which blocks the platelet adenosine diphosphate receptor and limits platelet aggregation, is used in treatment of coronary artery disease, acute coronary syndrome, and prevention of recurrent ischemic stroke. Low-dose aspirin is prescribed to certain pregnant patients at risk of preeclampsia.
(Choice F) Recombinant tissue plasminogen activator is used for clot lysis. It has a high risk of major bleeding and is typically reserved for those with massive deep vein thrombosis at risk of limb ischemia or life-threatening pulmonary embolism with hypotension. Anticoagulation alone is preferred for VTE in hemodynamically stable patients.
(Choice G) Warfarin crosses the placenta, increasing risks of teratogenicity and fetal hemorrhage, and is typically avoided in pregnancy.
Educational objective:
Heparins are ideal anticoagulants for most patients with thromboembolic disease in pregnancy as they do not cross the placenta and therefore the risk of fetal bleeding or teratogenicity is low. Low molecular weight heparin (eg, enoxaparin) is the preferred therapy, with patients transitioned to unfractionated heparin at term.