A 65 year-old man with primary antiphospholipid syndrome (APS) was transferred to our hospital for management of refractory thrombocytopenia and thrombosis. His disease was diagnosed by positive lupus anticoagulant, anti-cardiolipin antibody, beta-2-glycoprotein IgM and IgG, and was well controlled with warfarin for years. His worsening APS was precipitated by traumatic subdural hematomas and cholecystitis requiring cessation of warfarin. He was diagnosed with probable catastrophic APS based on the development of acute kidney failure from likely thrombotic microangiopathy, skin necrosis, and progressive deep vein thromboses within a 1-week period. Treatment for thrombocytopenia included high dose steroids, plasma exchange, IVIG, rituximab, cyclophosphamide, eculizumab, eltrombopag, and romiplostim. He required frequent platelet transfusions despite maximum immunosuppression, resulting in severe allo-immunization. He ultimately underwent splenectomy without recovery of his platelet count. Heparin was intermittently held due to episodes of hemoptysis and large soft tissue hematomas requiring transfusions. His hospital course was complicated by ischemic heart failure, pulmonary emboli, embolic and micro-hemorrhagic strokes, and end-stage renal disease requiring dialysis. Due to hypoxemic respiratory failure, ongoing strokes, and refractory thrombocytopenia, the patient was transitioned to comfort care and died on hospital day 109.
This case of catastrophic APS with refractory severe thrombocytopenia is a rare cause of a common problem faced frequently by hospitalists: the tenuous balance between the risks of anticoagulation and the risks of thrombosis. Moderate thrombocytopenia (>50×109/L) occurs in 20-40% of patients with primary APS, due to presence of autoantibodies against platelet membrane glycoproteins and platelet activation, and does not require treatment. Other causes of thrombocytopenia must be ruled out. Severe thrombocytopenia (<50x109/L) in APS is uncommon, and is treated similarly to immune thrombocytopenic purpura (ITP) with IVIG, plasma exchange, high dose steroids, rituximab, and cyclophosphamide in step-wise fashion. Thrombopoietin receptor agonists, which stimulate the development of megakaryocytes, can be used for chronic ITP. Splenectomy is curative in 70-90% of refractory cases by removing the major site of platelet destruction. The treatment for APS is anticoagulation to prevent recurrent thromboembolism. However, anticoagulation is complicated in patients with severe thrombocytopenia due to the high risk of bleeding. This delicate balance requires an individualized, multi-specialty approach coordinated by a hospitalist.
Severe refractory ITP occurs rarely with APS. When present together, management should focus on stabilizing the platelet count above 50×109/L with immunomodulating agents, and continuing anticoagulation to prevent ongoing thrombosis.