Chapter 131: The Antiphospholipid Syndrome

SUMMARY

The antiphospholipid (aPL) syndrome (APS) is an acquired thrombophilic disorder in which patients have vascular thrombosis and/or pregnancy complications attributable to placental insufficiency, accompanied by laboratory evidence for the presence of antiphospholipid antibodies in blood. The disorder is referred to as primary APS when it occurs in the absence of systemic lupus erythematosus (SLE), and secondary APS in its presence. Any portion of the circulatory tree can be affected, although the most frequently affected vessels are the deep veins of the lower extremities. Abnormalities that have been reported in association with the syndrome include virtually all other autoimmune disorders, immune thrombocytopenia, acquired platelet function abnormalities, hypoprothrombinemia, acquired inhibitors of coagulation factors, livedo reticularis, heart valve abnormalities, atherosclerosis, pulmonary hypertension, and migraine. Rare patients have a catastrophic form of APS (CAPS) in which there is disseminated thrombosis in large- and small-vessel thrombi, often after a triggering event such as infection or surgery, and often with multiorgan ischemia and infarction.

APS is a misnomer, the main antigenic targets for thrombogenic aPL antibodies are epitopes on phospholipid-binding proteins, the most important of which appears to be β₂-glycoprotein I (β₂GPI). The syndrome is identified by persistent abnormalities of laboratory tests for antibodies against these phospholipid–protein cofactor complexes, detected by immunoassays and by coagulation assays (also known as “lupus anticoagulant assays”) that, paradoxically, report the inhibition of phospholipid-dependent coagulation reactions. Long-term warfarin anticoagulant therapy is the usual treatment for thrombosis in patients with APS, although there is some controversy about whether treatment of patients with APS stroke might be better treated with aspirin. Patients with recurrent spontaneous pregnancy losses and APS generally are treated with aspirin and heparin for prophylaxis against deep vein thrombosis during their pregnancies and the postpartum period. CAPS patients have a high mortality and, in addition to anticoagulants, often require plasmapheresis and immunosuppressive agents. Patients without clinical manifestations of APS or a history of SLE should generally 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.

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; CMV, cytomegalovirus; dRVVT, dilute Russell viper venom time; ELISA, enzyme-linked immunosorbent assay; HCQ, hydroxychloroquine; Ig, immunoglobulin; IL, interleukin; LA, lupus anticoagulant; LDL, low-density lipoprotein; LMWH, low-molecular-weight heparin; MAPK, mitogen-activated protein kinase; NOACs, new oral anticoagulants; RVV, Russell viper venom; SCR, short consensus repeat; SLE, systemic lupus erythematosus; TLR, toll-like receptor; TM, thrombomodulin; t-PA, tissue-type plasminogen activator; UFH, unfractionated heparin; VWF, von Willebrand factor.