Thrombophilia Guidelines

From Mohamed Bashir, originally posted November 17, 2012: What is the guideline for thrombophilia testing, how to test antithrombin (AT, antithrombin III, ATIII), protein C (PC), and protein S (PS).

Hello, Dr. Mohamed Bashir, and thank you for your question. You may find a complete review of thrombosis risk testing in our audio modules 14, 15, and 16, Laboratory Detection of Thrombosis Risk 1, 2, and 3. If you will pardon my self-promotion, you may also find this information in Marques MB, Fritsma GA. Quick Guide to Coagulation Testing 2nd Edition, AACC Press, 2009, or Fritsma GA. Thrombosis Risk Testing in Rodak BF, Fritsma GA, Keohane EM. Hematology; Clinical Principles and Applications 4th Edition, Elsevier, 2012.

Here is a brief summary:

• Thrombophilia profiles are developed locally to meet population needs, however most include AT, PC, and PS activity, activated protein C resistance (APCR), prothrombin G20120A mutation, and lupus anticoagulant (LA) testing. Some laboratory directors include anti-cardiolipin antibody (ACA), anti-beta-2-glycoprotein 1, fasting homocysteine, and coagulation factor VIII.
• If the patient has experienced a recent thrombotic event or is currently receiving Coumadin, the tests that remain reliable are the factor V Leiden (FVL) mutation, which substitutes for the APCR, prothrombin G20210A, ACA, anti-beta-2-glycoprotein 1, and fasting homocysteine. The AT, PC, PS, APCR, and LA are reliable only when the subject is not receiving Coumadin and has not had a recent thrombotic event.
• Owing to the false positive rates of most assays, laboratory directors avoid screening healthy individuals. Thrombophilia profiles are chosen for patients who have experienced an unprovoked thrombotic event, an event in an unusual location or before age 60, or who have first-degree relatives with presumed thrombotic risk factors. A positive APCR ratio is confirmed using the FVL mutation, and low AT, PC, or PS values are repeated after 12 weeks for confirmation. Low AT, PC, and PS activity assays are then followed up using AT, PC, and PS antigen assays to distinguish qualitative from quantitative deficiencies.

I hope this is helpful. and I encourage your response in our comments section as well as comments from others whose perspectives on thrombophilia profiles may differ from these.