Antiphospholipid syndrome laboratory findings

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Feham Tariq, MD [2]

Overview

Antiphospholipid syndrome is tested for in the laboratory by both liquid phase coagulation assays (lupus anticoagulant) and solid phase ELISA assays (anti-cardiolipin antibodies)

Laboratory Findings

Anticardiolipin antibodies (aCL); IgG and IgM by enzyme-linked immunosorbent assay (ELISA)

Anti-beta2-GP I antibodies; IgG and IgM by ELISA.

Genetic thrombophilia is part of the differential diagnosis of APS and can coexist in some APS patients. Thus genetic thrombophilia screening can consist of:

• Further studies for Factor V Leiden variant and the prothrombin mutation, Factor VIII levels, MTHFR mutation.
• Levels of protein C, free and total protein S, Factor VIII, antithrombin, plasminogen, tissue plasminogen activator (TPA) and plasminogen activator inhibitor-1 (PAI-1)

The testing of antibodies to the possible individual targets of aPL such as β₂ Glycoprotein 1 and antiphosphatidyl serine is currently under debate as testing for anticardiolipin appears to be currently sensitive and specific for diagnosis of APS even though cardiolipin is not considered an in vivo target for antiphospholipid antibodies.

Lupus anticoagulant

This is tested for by using a minimum of two coagulation tests that are phospholipid sensitive this is due to the heterogeneous nature of the lupus anticoagulant antibodies. The patient on initial screening will typically have been found to have a prolonged APTT 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 APTT (plus 80:20 mix), dilute Russell's viper venom time (DRVVT), the kaolin clotting time (KCT), dilute thromboplastin time (TDT/DTT) or 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 (eg: Factor VIII). This 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 antibodies (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 iudl (35%) where as a specific factor antibody will rarely give a result higher than 10iudl (10%). Monitoring IV anticoagulant therapy by the APTR 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

These 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.