Getting to the Heart of the Matter: A Case of Seronegative Antiphospholipid Syndrome

Case Presentation: A 52-year-old gentleman with past medical history of lupus nephritis, non-ST-elevation myocardial infarction, venous thromboembolism (on anticoagulation), and peripheral vascular disease requiring arterial bypass grafting presented to the hospital with two days of left toe pain, fever and chills. Physical exam demonstrated gangrenous changes of the left second toe as well as nontender, nonblanching erythematous macules along the plantar surface of the foot. Laboratory evaluation revealed prolonged partial thromboplastin time and elevated inflammatory markers without leukocytosis. Infectious serologies and final blood cultures were negative. Hypercoagulability studies, including antiphospholipid antibody titers and lupus anticoagulant, were normal. On imaging, he was found to have a patent bypass graft but was noted to have a 2.5-cm vegetation on the tricuspid valve. He had no atrial septal defect. Intravenous antibiotics were initiated for 4 weeks without resolution, and the patient underwent surgical tricuspid valve replacement and toe amputation. Intraoperative pathology was notable for sterile vegetation and toes with arterial thrombus but no vasculitis nor organisms on Gram stain or final culture. Discussion: Antiphospholipid syndrome (APS) is a hypercoagulable state which often occurs secondary to systemic lupus erythematosus (SLE). The diagnostic criteria for APS require the presence of at least one clinical and one laboratory criterion. Clinical criteria include vascular thrombosis or pregnancy morbidity and laboratory criteria include the presence of lupus anticoagulant, anti-cardiolipin, or anti-β2-glycoprotein. APS also predisposes to the development of sterile thrombotic Libman-Sacks endocarditis, which most commonly affects the mitral valve. Seronegative APS (SN-APS) is diagnosed when clinical criteria are met but serologic testing is negative. Testing must be performed outside the contexts of acute thrombosis and treatment with anticoagulation, as these conditions can cause a transient loss or consumption of antiphospholipid antibodies. This patient\u27s case was unusual for several reasons. His Libman-Sacks endocarditis was located on the tricuspid valve, a rare presentation. Moreover, his toe ischemia was the result of an arterial thrombus rather than embolism or ischemia from graft stenosis. Given his extensive history of hypercoagulability in the setting of known SLE, thrombosis secondary to SN-APS was the unifying diagnosis. Conclusions: APS is a hypercoagulable state associated with SLE. It confers increased risk of developing Libman-Sacks endocarditis as well as peripheral thrombotic events which may mimic other clinical entities such as limb ischemia or embolism. It is a clinically important diagnosis to consider in patients with clinical manifestations of the syndrome but persistently negative serology