Thrombophilia Screening

Introduction

Tests are of limited clinical value.

The hereditary thrombophilic factors are weak risk factors in arterial disease and should not be used as part of routine investigations of strokes, infarcts or peripheral vascular disease. 

Venous thrombosis has a multifactorial aetiology. In up to 50% of patients with recurrent thrombosis or a strong family history one of the laboratory "thrombophilic" risk factors can be identified. However: "There is no evidence that the detection of heritable thrombophilic defect is useful in guiding clinical decision making in relation to the choice of anticoagulant or to the intensity or duration of anticoagulant therapy to treat a thrombotic event. Seeking laboratory evidence of heritable thrombophilia in most cases of venous thrombosis is unlikely to lead to information of value in the clinical management of an individual case." (BCSH 2001). Guidelines updated in 2022

Timing of Tests

Generally the patient should not be tested while there is active disease or they are receiving anticoagulation therapy. Therefore, tests should be deferred until 1 month after anticoagulants have been stopped. 

Where this is impractical, e.g. with recurrent thrombosis where lifelong anticoagulation is indicated, the following should be noted:

• Protein C and Protein S are lowered by Warfarin, but they may be measured if the patient is on Heparin 
• Antithrombin (formerly Antithrombin III) is lowered during the active phase of thrombosis and by Heparin. It may be measured once the patient is stabilised on Warfarin and off Heparin
• Tests for lupus anticoagulant are extremely difficult while the patient is on Heparin or Warfarin, but anti-cardiolipin assays are not affected

Action if Abnormal Results are Found

• Check there were no confounding variables at time of sampling (especially acute disease, anticoagulants) and if possible repeat the abnormal assay to confirm.
• Consider the need for lifelong anticoagulation.
• Consider the need to investigate other family members.

Given the uncertainty of this area, the Consultant Haematologist would welcome discussion of any patient in whom thrombophilia is considered and if required, can see the patient in clinic.

The Laboratory Tests

Tests include:

• Dilute Russell's Viper Venom Time (DRVVT)
• Anti-Cardiolipin Antibodies
• Protein S
• Protein C
• Factor V Leiden
• Antithrombin III (ATIII)
• Prothrombin Gene Mutation 

Prothrombin (G20210A) Gene Mutation analysis is performed alongside Factor V Leiden testing.

Tests are carried out at GRH.

Sample requirements

For a full Thrombophilia screen:

• 4 x 3ml or 3.5ml Trisodium Citrate samples (for Protein S, Protein C, ATIII, DRVVT)
• 1 x 5ml Gold-top SST tube or 3.5ml Rust-top gel tube (for Cardiolipin antibodies)
• 1 x 4ml EDTA sample (for Factor V Leiden and Prothrombin gene mutation)

x4

x1

x1

For Lupus anticoagulant screening only, please see the DRVVT test page

Sample Storage and Retention

Pre analysis storage: do not store, send to laboratory within 2 hours.

Sample retention by lab: The EDTA sample and plasma aliquots from the citrate samples will be frozen until analysis (or up to two months) at between -15 and -40°C. After analysis, these samples will be retained for a further 24 hours at 15-30°C. The primary Cardiolipin antibodies sample is retained for a minimum of 2 weeks at 2°C-8°C. Post analysis, and if there is sufficient sample, an aliquot will be frozen and stored for 4-6 weeks between -15°C and -20°C.

Due to the number and variety of samples required for a full Thrombophilia screen, it is unlikely that the department will have sufficient samples to allow performance of these tests as additional requests to samples already received.

Turnaround Times

Full thrombophilia screen: up to 6 weeks

Reference Ranges