Leading Edge 2021 Issue 2

LEADING EDGE - 2021-2 14 Two Tests According to recommendations from the International Society on Thrombosis and Haemostasis, laboratory detection of LA screening should be performed using two tests, based on different principles. If one of the two screening tests comes back positive for LA, a mixing study is performed. If the result of the mixing study is prolonged, a confirmatory test showing PL dependence should be performed. Testing Pathway LA detection is based on PL-dependent coagulation tests, which complicate the methodology and hamper its interpretation because of interference, for instance by anticoagulant therapy and some acute phase response proteins. Testing for LA should focus on individuals that present with symptoms of APS and asymptomatic testing is discouraged. 1) Screening Test – Screening is completed using a dRVVT assay, such as CRYOcheck™ LA check, and an aPTT assay with a low PL concentration with silica as an activator. If both tests come back negative, no further testing will be completed on the patient. If one or both tests are positive, with positive regarded to be a clotting time that is prolonged beyond the locally established cut-off, a mixing test will be completed. This is part of the recommended first line testing from ISTH. 2) Mixing Test – The patient sample is mixed with pooled normal plasma. Pooled normal plasma for mixing studies can be prepared in-house, or a commercially available lyophilised or frozen pooled normal plasma may be used, such as CRYOcheck™ Pooled Normal Plasma. The mixed sample (1:1 ratio) is then re-tested. If the addition of pooled normal plasma corrected the aPTT, the patient is negative for LA and will be investigated for other causes of symptoms, such as factor deficiencies or inhibitors. If the mixed sample does not correct, a confirmatory test will then be completed. 3) Confirmatory Test – This is performed using Bilayer or Hexagonal (II) phase phospholipids with increased levels of PL showing a shortening of the clot time (PNP). Antiphospholipid syndrome (APS) is an autoimmune disorder characterised by the presence of antibodies directed at phospholipids and plasma proteins that bind to the phospholipid, causing a hypercoagulable state. The risk factors for APS include acquired infections such as HIV/Aids, Hepatitis C and Lyme disease. Also, a number of other autoimmune diseases and the use of various medications. Gender is also significant with APS found more commonly in women than men. There are four types of classification of antiphospholipid antibodies (APA): Anti-β2GP1, Anti-cardiolipin (aCL), Anti-prothrombin (aPT) and Lupus Anticoagulant (LA). Lupus Anticoagulant LA is thought to be present in 1-2% of the general population. It consists of antibodies that inhibit phospholipid (PL)-dependant coagulation in vitro. These antibodies are directed against a phospholipid binding protein, usually a β2-GP1. When β2-GP1 is bound by antibodies this results in enhanced PL binding, which then causes a prolongation of in vitro clotting times. The presence of LA indicates a greater association with unexplained thrombosis, recurrent foetal loss and is strongly associated with autoimmune disorders such as Systemic Lupus Erythematosus (SLE). The antibodies interfere with the prolonged phospholipid-dependent tests in vitro in coagulation such as APTT and PTT. Antiphospholipid Syndrome Lupus Anticoagulant Testing and Diagnosis

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