Antiphospholipid Antibody Syndrome

Introduction

The antiphospholipid syndrome (APS) is defined as a constellation of clinical and laboratory features including thrombosis and/or obstetrical complications associated with the presence of the following antiphospholipid antibodies (aPL): anticardiolipin antibody (aCL), anti-β2-glycoprotein 1 antibody (a-β2-GP1) or the lupus anticoagulant (LA) . The unfortunate misnomer used for the coagulation-based tests, “Lupus Anticoagulant,” is a historical phenomenon. Phospholipid-dependent coagulation assays were found to be prolonged in some patients with systemic lupus erythematosus (SLE), and initially thought to be a risk for bleeding. Paradoxically, patients with a positive LA were found to have a higher frequency of thrombosis. This set the stage for the research that followed, leading to the recognition of APS as a clinical syndrome, studies of disease mechanism and pathogenesis, and treatment.

Unlike many hypercoagulable states, thrombosis can occur commonly in the arterial as well as the venous circulation. The most common vascular territory for arterial thrombosis is in the brain, causing stroke. Although many other clinical manifestations have been linked to aPL, there is insufficient evidence to warrant inclusion in the APS diagnostic criteria. It is important to recognize that a single aPL-positive laboratory test at low titer or present on only a single occasion (with or without clinical manifestations) is insufficient to make the diagnosis of APS. Treatment with long-term warfarin at an (international normalized ratio) INR-producing dose of 2.0–3.5 (target 2.5) is the current recommended treatment for patients with APS. Adjunctive treatments include hydroxychloroquine and statins. Search for vitamin D deficiency in patients with APS is important as vitamin D deficiency is both common in APS and has been associated with an increased frequency of thrombotic events. Newer immunomodulatory therapies and oral direct thrombin inhibitors are currently being studied as effective therapies for patients with APS .

What Are Antiphospholipid Antibodies?

Antiphospholipid antibodies are a heterogeneous group of autoantibodies, either inherited or acquired, associated with an increased risk for thrombosis and obstetrical complications. As the aPL field has evolved, the number of aPL with different specificities that have been associated with thrombosis and obstetric risk has expanded . Commonly tested aPL include aCL (IgG, IgM, or IgA) antibodies, a-β2-GP1 (IgG, IgM, or IgA) antibodies, and LA (also called lupus inhibitor). The presence of these autoantibodies can lead to an autoimmune hypercoagulable state. Pathogenic aPL bind to phospholipid-binding proteins, which in turn activate cell surface receptors leading to changes in intracellular signaling pathways creating a proinflammatory or hypercoagulable environment. It should be stressed, however, that the mere presence of one or more of these antibodies in an asymptomatic individual does not necessarily increase the risk for either thrombosis or pregnancy morbidity in such individuals. It is possible that some aPL are not pathogenic or other factors in addition to aPL presence are needed for pathogenicity. The body of research that has emerged over the last decade suggests that treatment decisions cannot be made on the basis of a positive aPL test alone, and both laboratory data and clinical manifestations must be considered.

Clinical and Laboratory Features of Antiphospholipid Antibody Syndrome

The diagnostic clinical features of APS include stroke, venous thrombosis, and obstetrical complications, but many other clinical features have been recognized as well ( Table 116.1 ). These nondiagnostic clinical features can be commonly seen; however, there is insufficient evidence to include them among the diagnostic clinical features. Nonetheless, the presence of these nondiagnostic features can be helpful in some cases to suggest the need for a full APS evaluation. Likewise, the presence of a prolonged activated partial thromboplastin time in patients not receiving heparin or a false-positive rapid plasma reagin can also be clues to check for the presence of aPL.