Abstract and Introduction
Antiphospholipid antibody syndrome (APS) is a common acquired thrombophilia. The diagnosis of APS is based on both clinical and laboratory criteria. The clinical criteria include vascular thrombosis or pregnancy morbidity. The laboratory criteria include a positive test for lupus anticoagulant, anticardiolipin antibodies, or anti–β2-glycoprotein I (anti-β2GPI) antibodies on two or more occasions at least 12 weeks apart. Antiphospholipid antibodies with lupus anticoagulant activity may prolong phospholipid-dependent coagulation tests such as the activated partial thromboplastin time (aPTT) and the activated clotting time (ACT). This prolongation adds a level of complexity to monitoring heparin therapy in patients with APS who have thrombosis. A literature search of the PubMed database was conducted for relevant articles published from 1995–April 2011. The usual management approach in nonsurgical patients with APS is to switch to low-molecular-weight heparin. In patients in whom heparin remains the agent of choice, management options include monitoring heparin antifactor Xa levels, determining an individualized therapeutic aPTT range, targeting an aPTT goal of 2 times the baseline aPTT, or using an aPTT reagent insensitive to lupus anticoagulant. An algorithm for anticoagulation management in nonsurgical patients with APS who require heparin is provided. The strategies to monitor intraoperative heparin in patients undergoing cardiac surgery include measuring heparin concentrations by an automated protamine titration device, targeting twice the baseline ACT, using preoperative in vitro heparin-ACT titration curves, and measuring heparin antifactor Xa levels. The available published case reports on the use of these strategies are reviewed. Each institution should determine an approach to managing heparin in patients with APS that best meets its needs and resources.
The antiphospholipid antibody syndrome (APS) is an autoimmune disorder characterized by the clinical presence of thromboembolic disease or pregnancy complications associated with the demonstration of persistent antiphospholipid antibodies.[1,2] This syndrome is now generally recognized as one of the most common causes of acquired thrombophilia. The factors that determine who is at risk for the development of APS are not well delineated, although there is a clear association with autoimmune disorders, especially systemic lupus erythematosus (SLE). However, many patients with APS do not have SLE or another underlying autoimmune disease; these patients are considered to have primary APS.
Preliminary classification criteria for a definite diagnosis of APS were established in 1998 at an international workshop in Sapporo, Japan, and updated criteria were published in 2006 after an international conference in Sydney, Australia. The updated Sapporo criteria are summarized in Figure 1.[2,5]
Summary of updated 2006 Sapporo classification criteria for a definite diagnosis of antiphospholipid antibody syndrome. GPL = immunoglobulin G phospholipid units; MPL = immunoglobulin M phospholipid units; ELISA = enzymelinked immunosorbent assay. (Adapted from reference 2.)
The diagnosis of APS requires not only the appropriate clinical presentation, but also laboratory confirmation of the presence of antiphospholipid antibodies. Antiphospholipid antibodies are a heterogeneous group of antibodies directed against phospholipid-binding proteins complexed to negatively charged (anionic) phospholipids. Although antiphospholipid antibodies can be directed to phospholipid complexes with a number of phospholipid-binding proteins, including annexin V or II, protein C, platelet factor 4, and several clotting factors, such as prothrombin, the most prevalent and clinically significant protein component is the weak natural anticoagulant β2-glycoprotein I (β2GPI).
Pharmacotherapy. 2011;31(12):1221-1231. © 2011 Pharmacotherapy Publications