The antiphospholipid (aPL) syndrome (APS) is an acquired thrombophilic disorder that is identified by the concurrence of vascular thrombosis and/or pregnancy complications with laboratory evidence for the presence of autoantibodies against phospholipid-associated proteins in blood. The main antigenic targets for thrombogenic aPL antibodies are epitopes on phospholipid-binding proteins, the most important of which is β2-glycoprotein I (β2GPI). The pathophysiologic basis of the disorder has not yet been established; the currently proposed mechanisms are reviewed in this chapter. The syndrome is identified by immunoassays for antibodies against phospholipid–protein cofactor complexes and by coagulation assays (“lupus anticoagulant assays”) that report the inhibition of phospholipid-dependent coagulation reactions in vitro. Testing should be limited to individuals with clinical manifestations of the disorder or with a history for systemic lupus erythematosus (in which a high proportion of patients have aPL antibodies). With rare exceptions, other patients should not undergo diagnostic screening for aPL antibodies and, if tested and found to be positive, should not be committed to antithrombotic therapy solely on the basis of laboratory abnormalities.
Although any portion of the circulatory tree can be affected, the deep veins of the lower extremities are the most frequently targeted. Patients with APS may present with several other abnormalities, referred to as “noncriteria manifestations,” such as additional autoimmune disorders, immune thrombocytopenia, acquired platelet function abnormalities, hypoprothrombinemia, acquired inhibitors of coagulation factors, livedo reticularis, cardiac valve abnormalities, atherosclerosis, pulmonary hypertension, and migraine. Rare patients present with a catastrophic form of APS (CAPS) in which there is disseminated thrombosis in large- and small-vessel thrombi, often occurring after an infection or surgery. Long-term warfarin anticoagulant therapy is the usual treatment for thrombosis in patients with APS; treatment with direct oral anticoagulants is currently discouraged because they have been associated with an increased risk of arterial thrombotic events. Patients with recurrent spontaneous pregnancy losses attributed to APS are generally treated with aspirin and heparin during their pregnancies through the postpartum period. Patients with CAPS have a high mortality rate and, in addition to anticoagulants, often require plasmapheresis and immunosuppressive agents; patients refractory to these treatments have been reported to respond to complement C5 inhibitors.
Acronyms and Abbreviations
aCL, anticardiolipin; APC, activated protein C; aPL, antiphospholipid; APS, antiphospholipid syndrome; aPTT, activated partial thromboplastin time; ARDS, acute respiratory distress syndrome; ASIA, autoimmune/autoinflammatory syndrome induced by adjuvants; AVWS, acquired von Willebrand syndrome; BFP syphilis test, biologic false-positive serologic test for syphilis; β2GPI, β2-glycoprotein I; CAPS, catastrophic APS; CFX, Chromogenic factor X; CMV, cytomegalovirus; DOACs, direct-acting oral anticoagulants; dRVVT, dilute Russell viper venom time; ELISA, enzyme-linked immunosorbent assay; HCQ, hydroxychloroquine; Ig, immunoglobulin; IL, interleukin; INR, international normalized ratio; LA, lupus anticoagulant; LDL, low-density lipoprotein; LMWH, low-molecular-weight heparin; MAPK, mitogen-activated protein kinase; RVV, Russell viper venom; SCR, short consensus repeat; SLE, systemic lupus erythematosus; TIA, transient ischemic attack; TLR, toll-like receptor; TM, thrombomodulin; t-PA, tissue-type plasminogen activator; UFH, unfractionated heparin; VWF, von Willebrand factor.