Antiphospholipid syndrome is diagnosed using either liquid-phase coagulation assays to detect lupus anticoagulant or solid phase ELISA (enzyme-linked immunosorbent assay) to detect anti-cardiolipin antibodies or anti-apolipoprotein antibodies. Genetic thrombophilia is part of the differential diagnosis of APS and can coexist in some patients with APS. Presence of genetic thrombophilia may determine the need for anticoagulation therapy. Thus genetic thrombophilia screening can consist of: * Screening for factor V Leiden variant and the prothrombin G20210A and MTHFR mutations. * Measuring serum levels of protein C, free and total protein S, factor VIII, antithrombin, plasminogen, tissue plasminogen activator (TPA) and plasminogen activator inhibitor-1 (PAI-1) Antiphospholipid antibodies do not recognize isolated cardiolipin, but bind to a cardiolipin-β2GPI (apolipoprotein H) complex. The use of testing for antibodies specific for individual targets of aPL such as β2 glycoprotein 1 and phosphatidylserine is currently under debate. Lupus anticoagulant This is tested for by using a minimum of two coagulation tests that are phospholipid-sensitive, due to the heterogeneous nature of the lupus anticoagulant antibodies. The patient on initial screening will typically have been found to have a prolonged partial thromboplastin time (PTT) that does not correct in an 80:20 mixture with normal human plasma (50:50 mixes with normal plasma are insensitive to all but the highest antibody levels). The PTT (plus 80:20 mix), dilute Russell's viper venom time (DRVVT), kaolin clotting time (KCT), dilute thromboplastin time (TDT/DTT), silica clotting time (SCT) and prothrombin time (using a lupus-sensitive thromboplastin) are the principal tests used for the detection of lupus anticoagulant. These tests must be carried out on a minimum of two occasions at least 6 weeks apart and be positive on each occasion, demonstrating persistent positivity, to allow a diagnosis of antiphospholipid syndrome. This is to prevent patients with transient positive tests (due to infection etc.) being diagnosed as positive. Distinguishing a lupus antibody from a specific coagulation factor inhibitor (e.g.: factor VIII) is normally achieved by differentiating the effects of a lupus anticoagulant on factor assays from the effects of a specific coagulation factor antibody. The lupus anticoagulant will inhibit all the contact activation pathway factors (factor VIII, factor IX, factor XI and factor XII). Lupus anticoagulant will also rarely cause a factor assay to give a result lower than 35 iu/dl (35%) whereas a specific factor antibody will rarely give a result higher than 10 iu/dl (10%). Monitoring IV anticoagulant therapy by the PTT ratio is compromised due to the effects of the lupus anticoagulant and in these situations is generally best performed using a chromogenic assay based on the inhibition of factor Xa by antithrombin in the presence of heparin. Anticardiolipin antibodies Anti-cardiolipin antibodies can be detected using an enzyme-linked immunosorbent assay (ELISA) immunological test, which screens for the presence of β2glycoprotein 1 dependent anticardiolipin antibodies (ACA). A low platelet count and positivity for antibodies against β2-glycoprotein 1 or phosphatidylserine may also be observed in a positive diagnosis. Criteria Classification with APS requires evidence of both one or more specific, documented clinical events (either a vascular thrombosis and/or adverse obstetric event) and the confirmed presence of a repeated aPL. The Sapporo APS classification criteria (1998, published in 1999) were replaced by the Sydney criteria in 2006. Based on the most recent criteria, classification with APS requires one clinical and one laboratory manifestation: * Clinical: * A documented episode of arterial, venous, or small vessel thrombosis — other than superficial venous thrombosis — in any tissue or organ by objective validated criteria with no significant evidence of inflammation in the vessel wall * 1 or more unexplained deaths of a morphologically normal fetus (documented by ultrasound or direct examination of the fetus) at or beyond the 10th week of gestation and/or 3 or more unexplained consecutive spontaneous abortions before the 10th week of gestation, with maternal anatomic or hormonal abnormalities and paternal and maternal chromosomal causes excluded or at least 1 premature birth of a morphologically normal neonate before the 34th week of gestation due to eclampsia or severe pre-eclampsia according to standard definitions, or recognized features of placental insufficiency * Laboratory: * Anti-cardiolipin IgG and/or IgM measured by standardized, non-cofactor dependent ELISA on 2 or more occasions, not less than 12 weeks apart; medium or high titre (i.e., > 40 GPL or MPL, or > the 99th percentile) * Anti-β2 glycoprotein I IgG and/or IgM measured by standardized ELISA on 2 or more occasions, not less than 12 weeks apart; medium or high titre (> the 99th percentile) * Lupus anticoagulant detected on 2 occasions not less than 12 weeks apart according to the guidelines of the International Society of Thrombosis and Hemostasis. There are 3 distinct APS disease entities: primary (the absence of any comorbidity), secondary (when there is a pre-existing autoimmune condition, most frequently systemic lupus erythematosus, SLE), and catastrophic (when there is simultaneous multi-organ failure with small vessel occlusion). According to a 2006 consensus statement, it is advisable to classify APS into one of the following categories for research purposes: * I: more than one laboratory criterion present in any combination; * IIa: lupus anticoagulant present alone * IIb: anti-cardiolipin IgG and/or IgM present alone in medium or high titers * IIc: anti-β2 glycoprotein I IgG and/or IgM present alone in a titer greater than 99th percentile The International Consensus Statement is commonly used for Catastrophic APS diagnosis. Based on this statement, Definite CAPS diagnosis requires: * a) Vascular thrombosis in three or more organs or tissues and * b) Development of manifestations simultaneously or in less than a week and * c) Evidence of small vessel thrombosis in at least one organ or tissue and * d) Laboratory confirmation of the presence of aPL. VDRL, which detects antibodies against syphilis, may have a false positive result in aPL-positive patients (aPL bind to the lipids in the test and make it come out positive), although the more specific test for syphilis, FTA-Abs, that use recombinant antigens will not have a false-positive result.
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