Challenges in the Diagnosis of the Antiphospholipid Syndrome

Abstract

BACKGROUND:The antiphospholipid syndrome (APS) is an important cause of acquired thromboembolic complications and pregnancy morbidity. Its diagnosis is based on clinical and laboratory criteria, defined by strict guidelines. The original clinical and laboratory criteria for the identification of APS patients were published in 1999, in the so-called Sapporo criteria. In 2006 these criteria were revised, and recently more precise guidelines for analysis of the lupus anticoagulant have been provided. However, several questions related to the diagnosis of APS remain unanswered.CONTENT: In addition to providing a historical perspective, this review covers several challenges in the diagnosis of APS with respect to clinical and laboratory features, while highlighting pathogenic pathways of the syndrome. We discuss ongoing dilemmas in the diagnosis of this complex disease. Although antiphospholipid antibodies are found in association with various clinical manifestations, the older established clinical criteria were not substantively altered in the 2006 update. Several laboratory tests recommended in the latest criteria, including phospholipid-dependent coagulation tests for the detection of the lupus anticoagulant and ELISAs for measuring anticardiolipin and ␤2-glycoprotein I antibodies, still show methodological and diagnostic shortcomings. In addition, antiphospholipid antibodies have been described against other antigens, but their clinical role remains uncertain.

Antiphospholipid syndrome: a clinical and laboratorial challenge

“…11 The risk of thromboembolic phenomena and the level of certainty of the diagnosis increases with the level of APLAs and the number of different positive tests for the same patient. In a case-control study on 208 patients under investigation for APS, each 10 U increase in ACA, igM or IgC was associated with a 5-7% increase in the risk of thromboembolism, and each additional test with a positive result was associated with a 50-70% increase in the chance of thromboembolic events.…”

“…11,22 Although the prothrombin time (PT) also uses phospholipid to trigger the coagulation cascade in vitro (calcium thromboplastin), this test includes an excess of thromboplastin which even if a part of which is neutralized by the APLAs, there would still remain sufficient thromboplastin to start the reaction, so that prolongation is not observed.…”

“…11 The screening stage consists of using two tests that are based on different principles. The dRVVT is the initial examination because the reagent contains Russell's viper venom, phospholipids, calcium, prothrombin, factor V, and a heparin inhibitor.…”

“…In contrast, the correction of the aPTT after the addition of normal plasma does not occur in APS. 11,24 impossible to compare results, which has made it necessary to develop recommendations to standardize laboratory methods and the expression of the results. 11 Although laboratory results are of fundamental importance for the diagnosis of APS, many questions still remain unanswered regarding the methodology employed and the reference values of the various kits commercially available that are not concordant.…”

Anti-prothrombin antibodies in type 1 diabetes mellitus

“…In the last decade, anti-phospholipid (aPL) antibodies have been identified in various autoimmune diseases including anti-phospholipid syndrome (APS) and systemic lupus erythematosus [1][2][3]. Anti-phospholipid antibodies may recognize a variety of antigens such as phospholipid binding proteins and protein-phospholipid complexes [4][5][6].…”