Case Presentation: A 22 year-old female with a history of recurrent DVTs in the left lower extremity, May-Thurner syndrome with left common iliac vein stent place 12 months ago, Heparin-Induced Thrombocytopenia, and previous thromboembolism presented with one week history of intermittent, localized substernal chest pain. A diagnosis of antiphospholipid syndrome (APS) was established based on prior investigations of prothrombotic state. Fondaparinux, apixiban, Coumadin were tried in the past with recurring episodes of thromboembolism, suggesting failure of treatment. At current presentation, she was on rivaroxaban.
CT Pulmonary Angiogram at the time of admission showed complete occlusion of left main pulmonary artery (Figure 1). As she was hemodynamically unstable (tachycardia, hypotension, significant hypoxemia) she was admitted to the ICU. She was started on bivalirudin infusion with a therapeutic APTT of 90 seconds. Catheter directed thrombolysis of left pulmonary artery was attempted with continuous tPA infusion with no significant clot lysis. She was subsequently started on warfarin, overlapping with Bivalirudin infusion, with aim to achieve an international normalized ratio (INR) of around 3.0. Through several days of bivalirudin infusion, no bleeding complication was noted. Her hemodynamic status gradually improved with a brief period of vasopressor support. She received two doses of rituximab weekly in the hospital with three additional doses planned as an outpatient. She was also started hydroxychloroquine 200 mg daily and atorvastatin 80 mg daily. In the last outpatient follow-up 2 weeks after discharge, she reported no significant symptoms.

Discussion: APS is a systemic autoimmune disease characterized by venous or arterial thrombosis and/or pregnancy loss in the setting of persistent antiphospholipid antibodies. Major treatment issues include the choice and duration of anticoagulation and the treatment of acute thromboembolic manifestations.

Primary treatment of APS is anticoagulation which typically involves heparin overlapped with warfarin.Secondary prophylaxis with long-term anticoagulation is needed due to high rates of recurrent thrombosis. Recurrent thromboembolism while being treated with anticoagulation is rare, and other therapies need to be considered on an individualized basis. Options include increasing anticoagulation with warfarin to a higher INR of 3 to 4, switching to a low-molecular-weight heparin, or adding low-dose aspirin, hydroxychloroquine, and/or statin drugs. There are no data to demonstrate the superiority of any of these approaches.

Our patient with APS with recurrent thromboses was complicated by a history of HIT and apparent failure through multiple anticoagulants. Therapeutic range of bivalirudin infusion could be achieved after several trial and error adjustments. On 2-week follow-up, the combination of hydroxychloroquine, rituximab, and warfarin with a target INR of 3.5 has been well tolerated. Long term efficacy remains to be seen.

Conclusions: Patients with a history of APS presenting with recurrent thromboses are rare and difficult to treat. Suspicion of ineffective anticoagulation should prompt the internist to consider other anticoagulation therapies. Appropriate monitoring of therapy is needed in this setting. Given the rarity of the condition, it is difficult to conduct well-designed controlled clinical trials and case reports and case series remain the mainstay of clinical evidence with newer anticoagulant agents.

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