Antiphospholipid thrombosis syndromes

Abstract

Antiphospholipid antibodies are strongly associated with thrombosis and are the most common of the acquired blood protein defects causing thrombosis. Although the precise mechanism(s) whereby antiphospholipid antibodies alter hemostasis to induce a hypercoagutable state remain unclear, numerous theories, as previously discussed, have been advanced. The most common thrombotic events associated with anticardiolipin antibodies are deep vein thrombosis and pulmonary embolus (type I syndrome), coronary or peripheral artery thrombosis (type II syndrome), or cerebrovascular/retinal vessel thrombosis (type II syndrome); occasionally, patients present with mixtures of these types (type IV syndrome). Type V patients are those with antiphospholipid antibodies and RMS. It is as yet unclear how many seemingly normal individuals who may never develop manifestations of antiphospholipid syndrome (type VI) harbor asymptomatic antiphospholipid antibodies. The relative frequency of anticardiolipin antibodies in association with arterial and venous thrombosis strongly suggests that these should be looked for in any individual with unexplained thrombosis; all three idiotypes (IgG, IgA, and IgM) should be assessed. Also, the type of syndrome (I through VI) should be defined if possible, as this may dictate both type and duration of both immediate and long-term anticoagulant therapy. Unlike those with anticardiolipin antibodies, patients with primary lupus anticoagulant thrombosis syndrome usually experience venous thrombosis. Because the aPTT is unreliable inpatients with lupus anticoagulant (prolonged in only about 40 to 50% of patients) and is not usually prolonged in patients with anticardiolipin antibodies, definitive tests, including ELISA for anticardiolipin antibodies, the dRVVT for lupus anticoagulant, hexagonal phospholipid neutralization procedure, and beta-2-GP-I (IgG, IgA, and IgM) should be immediately ordered when suspecting antiphospholipid syndrome or in individuals with otherwise unexplained thrombotic or thromboembolic events. If results of these tests are negative, in the appropriate clinical setting, subgroups should also be assessed. Finally, most patients with antiphospholipid thrombosis syndrome will fail warfarin therapy and, except for retinal vascular thrombosis, may fail some types of antiplatelet therapy; thus it is of major importance to make this diagnosis so that patients can be treated with the most effective therapy for secondary prevention--LMWH or UH in most instances, and clopidogrel in some instances.