Thrombophilia is a disorder of hemostasis in which there is a tendency forthe occurrence of thrombosis. This tendency can be inherited or acquired. In general, heritable thrombophilia is associated with a predisposition to venous, not arterial, thromboembolism.

Screening assays:

• AT
• Protein C
• Protein S
• Factor V Leiden (molecular biology)
• Prothrombin gene mutation

Lupus anticoagulants (LA)
     - Dilute Russel’s Viper Venom Test (screen and confirm)
     - APTT Pathway
Anticardiolipin antibodies (aCL) IgG IgM
Anti-B2 glycoprotein 1 antibodies (a-B2GP1) IgG IgM

Diagnosis of Antiphospholipid Syndrome (APS)

Antiphospholipid syndrome is defined by the presence of persistent antiphospholipid antibodies (aPL) in patients with vascular thrombosis or pregnancy morbidity.

Clinical manifestations are nonspecific for APS so diagnosis is reliant on accurate detection in the diagnostic laboratory of the three aPL markers.

• anticardiolipin antibodies (aCL) IgG IgM
• anti-B2 glycoprotein 1 antibodies (a- 2GPI) IgG IgM
• lupus anticoagulants (LA)

Should be repeated after at least 12 weeks to confirm the persistence of antibodies.

The Scientific Subcommittee on Lupus Anticoagulant/Phospholipid-dependent Antibodies of the International Society on Thrombosis and Hemostasis established the classification criteria for APS. It is comprised of two criteria: a clinical criteria and a laboratory criteria. APS is considered present when both criteria are met.

Clinical Criteria for APS (at least one event)

• Vascular Thrombosis - arterial, venous, or small vessel thrombosis in any tissue or organ.
• Pregnancy Complication - One or more unexplained deaths of normal fetuses at or beyond the 10th week of gestation, or one or more premature births before the 34th week. Three or more unexplained consecutive spontaneous miscarriage before the 10th gestational week.

Guidelines for Lupus Anticoagulant

The ISTH recommendation is to employ only dRVVT and Activated Partial Thromboplastin Time. In CLSI guideline, dRVVT & aPTT are mentioned as preferred assays but not in a particular order.

Decision tree for lupus anticoagulant testing

According to the International Society on Haemostasis and Thrombosis (ISTH) 2009, the British Committee for Standards in Haematology (BCSH) 2012 and the Clinical and Laboratory Standards Institute (CLSI) 2014 guidelines.

Express results as normalized ratios: ratio of clotting time of Patient Plasma (PP) to local Normal Pooled Plasma (NPP)

The diagnostic indication that the test is positive for the presence of Lupus Anticoagulants was calculated as the mean DVVtest/DVVconfirm ratio + 2 SD (Standard Deviation), and as the Normalized Ratio + 2 SD.

Each laboratory must establish its own normal values

99th percentile of a normal population statistically larger number of normal samples, minimum 120 (CLSI EP28).

Use Local cutoff values
CLSI: transfer reference values of the manufacturer
Check by 20 (or 2x20) normal (CLSI EP28)

Bibliography

Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4:295-306.

Devreese KMJ, Ortel TL, Pengo V, de Laat B, Subcommittee on Lupus anticoagulant/ Antiphospholipid antibodies.
Laboratory criteria for antiphospholipid syndrome: communication from the SSC of the ISTH. J Thromb Haemost. 2018;16:809-813.

Guidance from the Scientific and Standardization Committee for lupus anticoagulant/ antiphospholipid antibodies of the International Society on Thrombosis and Haemostasis.

Update of the guidelines for lupus anticoagulant detection and interpretation.
October, 29 2020. doi.org/10.1111/jth.15047.