Background and Consensus Guidelines
No general consensus exists as to which patients with blood clots and which family members should be tested for thrombophilias. At least five guidelines or consensus statements exist (ref 1-5). They vary markedly in their recommendations as to who should be tested and who not, suggesting very limited testing (ref 1), widespread testing (ref 2), or some intermediate level (ref 3-5). Some are quite outdated (ref 3,4).
Reasons to Test or Not Test:
Table 1 (Table 1 – Reasons for testing) summarizes possible reasons for and against testing. There are only 2 hard-core good reasons to test, and these are if finding a thrombophilia would lead to
- different treatment (i.e. longer therapy with “blood thinners”) of the patient with a DVT (deep vein thrombosis) or PE (pulmonary embolism). However, noteworthy is, that the respected American College of Chest Physician (ACCP) guidelines do not use presence of hereditary thrombophilia to guide duration of therapy with “blood thinners”.
- different treatment (avoidance of estrogen contraceptive; therapy with “blood thinners” during pregnancy; etc) of a family member who has never had a blood clot, but who is also found to have thrombophilia.
Two things to be aware of: (a) It is important to realize that negative thrombophilia testing in an individual who has a family history with DVT or PE and thrombophilia is not completely reassuring: that person is still at increased risk for DVT and PE simply because his/her positive family history of DVT or PE (ref 7,8). (b) In the United States, health insurance and employment discrimination based on a person’s genetic testing results is illegal, as signed into law in May 2008 (GINA – Genetic Information Nondiscrimination Act). However, life insurance consequences – denial of insurance or higher premiums to be paid – based on genetic results is not included into GINA and, therefore, may occur.
My Approach to Thrombophilia Testing
The main reason why I test patients with blood clots is to detect a stronger thrombophilia. There are 7 stronger thrombophilias:
- antiphospholipid antibody syndrome
- antithrombin deficiency
- homozygous factor V Leiden
- heterozygous factor V Leiden PLUS prothrombin 20210 mutation (i.e. both at the same time)
- protein C deficiency
- protein S deficiency
- possibly homozygous prothrombin 20210 mutation
Finding a weaker thrombophilia (i.e. heterozygous factor V Leiden alone or heterozygous prothrombin 20210 mutation alone) typically has no impact on the management of a patient who has had a blood clot. It does not influence the decision how long to treat the person with “blood thinners” (anticoagulants). However, finding of a stronger thrombophilia has a number of consequences in my practice:
a) Consequences for the patient:
- It decreases my threshold to recommend long-term “blood thinners” (anticoagulants) in a patient who has had an episode of unprovoked (= idiopathic) DVT or PE;
- It leads to discussion with the patient with an unexplained arterial, non-arteriosclerotic clot (heart attack, stroke, arm or leg arterial clot, etc) (create link to blog #4), whether “blood thinners” (anticoagulant drugs) or antiplatelet drugs might be the preferred treatment for prevention of another clot;
b) Consequences for family members (Table 2 – Which family member to test):
- It prompts me to recommend testing of the identified thrombophilia(s) in asymptomatic female family members and advice (a) against the use of estrogen birth control methods and (b) for anticoagulation prophylaxis during 6 weeks after delivery), and possibly during the 9 months of pregnancy.
- It prompts me to consider testing in some male and female family members and consideration for anticoagulation prophylaxis during (a) future long-distance airline travel, (b) casts and limb immobilizers/casts after fracture and trauma, and (c) non-major surgery, such as knee arthroscopy.
The thrombophilia tests that I do when I embark on a thrombophilia work-up are listed in table 3 (Table 3 – What to test). I do not test for
- factor VIII levels
- levels of fibrinogen, factor IX, XI or other clotting factors
- parameters of fibrinolysis (PAI-1 level or mutations, tPA levels or mutations)
- the MTHFR polymorphisms (mutations)
- I limit homocysteine testing to the individual less than 30 years of age with thrombosis, to assess for the presence of homocysteinuria (very high homocysteine levels > 100 mg/dL).
Table 4 ( Table 4 – Which patient to test) lists the type of patients in whom I consider thrombophilia testing. However, individual decisions, typically in discussion with the patient, need to be made when deciding on whom to test and how extensively to test.
Interpreting test results
When interpreting thrombophilia laboratory test results, it is important to be aware of the circumstances that lead to abnormal test results without a true thrombophilia being present. Several results are temporarily abnormal in the patient with acute thrombosis and therapy with heparin and warfarin. When a thrombophilia is identified, educating the patient and the patient’s family members is important. Finally, to avoid inappropriate testing, thrombophilia testing should only be ordered by health care providers who know how to (a) interpret the test results and (b) counsel the patient and his/her family members as to what the results mean for him/her/them.
- Baglin T, et al. Br J Haematol. 2010;149:209-220
- Nicolaides AN et al. Int Angiol. 2005;24:1-26
- Van Cott EM, et al. Arch Pathol Lab Med. 2002;126:1281-1295
- Grody WW, et al. Genet Med. 2001;3:139-148
- Kearon C et al. Chest. 2008;133:454S-545S
- Noboa S et al. Thromb Res. 2008;122:624-629
- Bezemer ID et al. Arch Intern Med. 2009;169:610-615
Disclosure: I have no financial conflict of interest relevant to this blog entry.
Last updated Nov 20th, 2010
Tags: antithrombin, Clotting disorder - thrombophilia, factor II mutation, factor V Leiden, Family member, Genetic testing, protein C, protein S, prothrombin 20210 mutation, Thrombophilia, Whom to test