Antiphospholipid Antibody Syndrome

The cardinal features of APS include thrombotic manifestations, recurrent fetal loss, and thrombocytopenia. Cardiac valvular abnormalities, livedo reticularis, and hemolytic anemia are additional common findings. Patients are typically 35 to 45 years old when they develop their first thrombotic event. Men and women are equally affected. Almost two thirds of patients have thrombi limited to the venous system, 20% to 30% are arterial, and in 10% to 15% of individuals both circulations are affected. Most patients present with deep vein thrombosis of the lower extremities, up to half of whom subsequently develop pulmonary emboli. Thrombosis can also affect the superficial and deep cerebral venous system, and typically does so at a young age with relatively more extensive involvement.

Ischemic stroke and transient ischemic attacks are the most common presentation of APS arterial disease. This occurs in approximately one fifth of patients, followed by myocardial infarction at about half this frequency. Most of these events are clinically indistinguishable from atherosclerotic or small vessel strokes, therefore requiring a high level of suspicion. The syndrome should be suspected in young patients with ischemic stroke whenever other atypical vascular beds are involved, particularly the subclavian, renal, or retinal arteries, or when a patient experiences recurrent thromboembolic events with no defined etiology. Of note, not all arterial episodes are thrombotic in origin. Emboli, especially from mitral valve or aortic valve vegetations, can lead to cerebral events. Paradoxic embolization through a patent foramen ovale may occur. The association of livedo reticularis with cerebral thrombosis characterizes the Sneddon syndrome. The most severe and fortunately infrequent form of APS is a catastrophic one wherein patients develop multiorgan failure subsequent to widespread thrombotic disease. The mortality rate is greater than 50%.

The mechanisms by which antiphospholipid antibodies induce thrombosis are not entirely appreciated. It is postulated that these antibodies interfere with endogenous anticoagulant pathways, bind and activate platelets, and lead to activation of the complement cascade. Thrombosis in APS may occur spontaneously or in the setting of predisposing factors, including smoking, oral contraceptive use, vascular stasis, surgery, or trauma. Women are at particularly high risk for venous thromboembolism during pregnancy and their postpartum period. Some patients, generally those with venous rather than arterial thrombosis, also have concurrent genetic thrombophilic conditions. There is no definitive association between specific clinical manifestations and particular subgroups of antiphospholipid antibodies. However, the risk for recurrence after a first episode of venous thromboembolism in the presence of aCL is particularly high (approximately 30%); this correlates with the antibody titer.

The diagnosis of APS is made by combining clinical features with laboratory evidence of medium- or hightiter circulating antiphospholipid antibodies that are identified to be present on two or more occasions at least 12 weeks apart. The antibodies can be of either IgG or IgM subtypes and are measured by a standard enzyme-linked immunosorbent (ELISA). The term lupus anticoagulant is a misnomer that resulted from the early observation that its presence can prolong the partial thromboplastin time (PTT). An abnormal PTT should not be used as a screening test for APS. However, patients with APS need to be screened for possible concomitant systemic lupus erythematosus (SLE).

Given the high risk of recurrent thromboembolism that characterizes this condition, the mainstay of treatment in patients with APS is antithrombotic therapy. Warfarin is the usual drug of choice, with the international normalized ratio (INR) often kept in the upper range for anticoagulation (i.e., INR 3.0-4.0). The addition of aspirin may also need to be considered. Because thrombocytopenia is a frequent finding in patients with APS, therapy must be carefully balanced against the bleeding risks associated with a low platelet count.

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