<unk>  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<unk>  and can coexist in some patients with<unk> . 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)<unk>  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<unk> . 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<unk>  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<unk>  classification criteria (1998, published in 1999) were replaced by the Sydney criteria in 2006. Based on the most recent criteria, classification with<unk>  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<unk>  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<unk>  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<unk>  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.
Antiphospholipid syndrome
Protein C deficiency
Protein S deficiency
Catastrophic antiphospholipid syndrome
Acquired haemophilia
Antithrombin III deficiency
Sticky platelet syndrome
Congenital hypofibrinogenemia