Clinical Pearls & Morning Reports
Published January 25, 2023
The diagnostic criteria for antiphospholipid syndrome (APS) that have been proposed by the International Society on Thrombosis and Haemostasis require laboratory identification of a lupus anticoagulant, anticardiolipin antibody, or anti–β2-glycoprotein I antibody in two blood specimens, with testing performed 12 or more weeks apart and within 5 years after an imaging-confirmed thrombotic event or pregnancy complication. Read the NEJM Case Records of the Massachusetts General Hospital here.
Q: What causes CAPS?
A: CAPS is thought to result from the binding of antiphospholipid antibodies to cell surfaces, which activates endothelial cells, monocytes, and platelets and leads to inflammation, complement activation, and thrombosis. The formation of thrombi in patients with antiphospholipid antibodies is thought to be a multihit process. The presence of antiphospholipid antibodies in the blood is the first event, but the antibodies typically do not cause disease until another event occurs. In a registry of children with CAPS, the most common second event was infection (61%). Cancer (17%), surgery (7%), and lupus flares (4%) were other common triggers for CAPS in children.
Q: What are some of the differences between children and adults diagnosed with APS or CAPS?
A: Children are more likely than adults to have primary APS (68% vs. 60%), rather than APS that is secondary to a connective tissue disease. Children are also more likely than adults to have CAPS as the first manifestation of APS (87% vs. 45%) and to have infection as a trigger for the catastrophic event (61% vs. 27%).
A: For patients with antiphospholipid antibodies and a history of unprovoked thrombosis (e.g., patients with APS), long-term thromboprophylaxis is recommended. The standard of care for these patients is warfarin, which is administered to maintain an international normalized ratio of 2.0 to 3.0. Direct oral anticoagulants do not appear to provide any benefits and incur excess risk. Low-dose aspirin may be added in patients with arterial thrombosis.
A: Although data from randomized trials to guide treatment for CAPS in children are lacking, treatment is generally composed of triple therapy, which includes glucocorticoids, anticoagulation, and plasma exchange or intravenous immune globulin. In a registry of patients with CAPS, all the children who were treated with triple therapy survived the catastrophic event, whereas 26% of the patients in the overall pediatric cohort died. More recently, rituximab (an anti-CD20 monoclonal antibody) and eculizumab (which inhibits complement activation) have been used in children with CAPS, with reports of good efficacy.