A 35-year-old woman with no past medical history is hospitalized with severe shortness of breath. She also has swelling and tenderness of her right calf. CT angiogram of the chest shows pulmonary embolism. Compression ultrasonography is consistent with right femoral vein thrombosis. The patient is started on anticoagulation therapy. On the sixth day of hospitalization, she develops right arm pain. Physical examination shows a cold right upper extremity with no palpable peripheral pulse. Laboratory results are as follows:
Hematocrit 42% Leukocytes 8,500/µL Platelets 76,000/µL (246,000/µL at presentation) Prothrombin time 13 sec Activated partial thromboplastin time (aPTT) 63 sec
Which of the following drugs was most likely used to treat this patient's deep venous thrombosis?
This patient's markedly elevated aPTT is suggestive of unfractionated heparin use. The presentation of new-onset thrombocytopenia and arterial thrombosis in the setting of heparin use is due to heparin-induced thrombocytopenia (HIT). The 2 forms of HIT differ in onset, clinical course, and severity of disease.
Type 1 HIT occurs due to a nonimmune direct effect of heparin on platelet activation and usually presents within the first 2 days of heparin exposure. The platelet count then normalizes with continued heparin therapy and there are no clinical consequences.
Type 2 HIT is a more serious immune-mediated disorder due to antibodies to platelet factor 4 (PF4) complexed with heparin. This leads to platelet aggregation, thrombocytopenia, and thrombosis (both arterial and venous). Platelet counts usually drop >50% from baseline, with a nadir of 30,000-60,000/µL. Type 2 HIT usually presents 5-10 days after the initiation of heparin therapy and may lead to life-threatening consequences (eg, limb ischemia, stroke).
(Choice A) Enoxaparin typically does not prolong the activated partial thromboplastin time (it may in rare cases cause mild prolongation). However, the risk of HIT is lower with enoxaparin than with unfractionated heparin therapy.
(Choices B and C) The risk of developing HIT is negligible with factor X-a inhibitors such as fondaparinux and rivaroxaban.
(Choice E) Oral warfarin is typically co-administered with intravenous unfractionated heparin (or low-molecular-weight heparin) in the initial treatment of venous thromboembolism. It is not used alone due to initial hypercoagulable state from transient protein C depletion and risk of thrombosis and skin necrosis. Warfarin typically causes prothrombin time prolongation (normal in this patient) and does not affect platelet count.
Educational objective:
Heparin-induced thrombocytopenia should be suspected in patients receiving heparin anticoagulation who have thrombocytopenia, thrombosis (arterial or venous), or a >50% drop in the platelet count from baseline 5-10 days after the initiation of treatment.