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2228 Part XII: Hemostasis and Thrombosis Chapter 130: Hereditary Thrombophilia 2229

TABLE 130–5. Estimated Number of Asymptomatic Thrombophilic Women Who Should Use Low-Molecular-Weight
Heparin Prophylaxis During Pregnancy and/or the Postpartum Period to Prevent Pregnancy-Related Venous
Thromboembolism, and Estimated Number Needed to Test
Number Using Number of
Risk of VTE Per Risk Difference Prophylaxis to Female Relatives
Thrombophilia Pregnancy*, % Per 100 Women Prevent 1 VTE † to Be Tested
Antithrombin, protein C, or protein S deficiency
Deficient relatives 4.1 ‡ 3.6 28 56
Nondeficient relatives 0.5 ‡
Factor V Leiden or prothrombin 20210A mutation,
heterozygous
Relatives with the mutation 2.0 ‡ 1.5 66 132
Relatives without the mutation 0.5 ‡
Factor V Leiden or prothrombin 20210A mutation,
homozygous
Homozygous relatives 16.0 15.5 6 24
Relatives without the mutation 0.5 §
VTE, venous thromboembolism.
*Antepartum and postpartum combined.
† These estimates apply to women with a positive family history of VTE and assume an unrealistic 100% efficacy of prophylaxis with low-molec-
ular-weight heparin.
‡ Based on family studies as outlined in Table 130–4.
§ Summary estimate of the data as outlined in Table 130–4, combined for factor V Leiden and prothrombin mutation.

to women from thrombophilic families. Only for women with antith- provoked VTE, is a matter of debate. 70,104 Furthermore, given the rarity
rombin, protein C, or protein S deficiency, or those who are homozy- of homozygous or double heterozygous thrombophilias in unselected
gous for factor V Leiden (Table 130–5), the risks of 4 and 16 percent patients with VTE, the efficiency of testing is obviously very low. 10,105
respectively during pregnancy and the postpartum period may outweigh A randomized controlled trial of testing for thrombophilia in patients
the nuisance of daily subcutaneous low-molecular-weight heparin with a first episode of VTE would provide the ultimate evidence to
(LMWH) injections with frequently occurring skin reactions, and the decide whether this is justified, but no such trials have been successfully
very small risk for severe complications of anticoagulant therapy during performed. To investigate whether testing for thrombophilia reduced
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pregnancy. 99–102 Furthermore, the numbers in Table 130–5 underesti- the risk of recurrent VTE, 197 patients who had had a recurrent event
mate the number of women that need to use prophylaxis (and be tested were compared to 324 patients who did not have a recurrence. The
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prior to this decision) in order to avoid pregnancy-related VTE, because OR for recurrence was 1.2 (95% CI 0.9 to 1.8) for tested versus non-
a 100 percent efficacy of prophylaxis is assumed in these calculations. tested patients, indicating that testing, with real life clinical decisions
Whether the absolute risks of pregnancy-related VTE justifies prophy- based on the outcome of testing, did not reduce the risk of recurrent
laxis for 8 months during pregnancy, or the shorter postpartum period VTE in patients after a first episode.
of 6 weeks is a matter of the physicians' and patients' preference. The
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risk of pregnancy-related VTE in women from these families who do THROMBOPHILIA TESTING IN PATIENTS WITH
not have the hereditary thrombophilic defect is approximately 0.5 per-
cent, compared to 0.2 percent in the general population. Hence, with- ARTERIAL CARDIOVASCULAR DISEASE
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holding prophylaxis to women from thrombophilic families who do not The association between hereditary thrombophilia and arterial cardio-
have the defect is supported by evidence from well-designed studies of vascular disease is questionable, or at least much weaker than for VTE.
individuals in the same clinical context. The association is stronger in patients with events before the age of 55
years. As a result, thrombophilia test panels are often ordered in with
THROMBOPHILIA TESTING IN PATIENTS WITH arterial cardiovascular disease. In a survey among Dutch physicians that
VENOUS THROMBOEMBOLISM ordered thrombophilia tests in 2000 consecutive patients in 2003 and
2004, arterial cardiovascular disease, mainly ischemic stroke, was the
9
Thrombophilia testing is most often considered in patients with VTE, indication for testing in 23 percent of patients. Interestingly, only 54
particularly if they are young, have recurrent episodes, have thrombosis percent of those patients were younger than 50 years of age. Testing for
at unusual sites, or have a positive family history for the disease. How- hereditary thrombophilia in patients with (premature) arterial cardio-
ever, although such a strategy may lead to an increased yield of testing, vascular disease could only be justified if the test results would mandate
the main question is whether a positive test result should alter manage- different secondary prevention. However, more vigorous secondary
ment. As previously discussed, thrombophilia is a very poor predictor prevention such as long-term dual antiplatelet therapy or oral anticoag-
of recurrent VTE, and whether the very modest risk increase warrants ulation instead of ASA monotherapy is not beneficial for most patients
prolongation of the duration of anticoagulation, particularly after with arterial cardiovascular events, mainly because of the increased

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