About 20 percent of women report ha...

About 20 percent of women report having had united miscarriage, and 5 percent have had sum of two units or more spontaneous losses. flat after extensive investigations, 30 to 40 percent of returning fetal losses remain unexplained. Several investigators have hinted that inherited thrombophilic conditions, like as factor V Leiden, could be associated with returning fetal loss. Rey and colleagues reviewed the literature to establish the solidity of such an association for the more public inherited thrombophilic disorders.

The authors identified relevant studies from electronic databases, searched respect lists, and contacted authors of various studies for additional data. Abstracts, epistles case reports, editorials, meta-analyses, and reviews were exclud from the thought Recurrent fetal loss was defined as sum of two units or more losses during the pregnancy period studied by the agency of the investigators for the individual studies; nonrecurrent fetal los was defined as single loss during a study period. The disorders of interest included factor V Leiden, homozygous methylenetetrahydrofolate reductase mutation, activated protein C resistance, prothrombin G20210A mutation, protein s deficiency, protein C deficiency, and antithrombin deficiency. Each subject of attention was independently rated for quality by the agency of two of the authors of this study

Of the studies reviewed, 31 were of appropriate quality for the analysis. These studies varied in definitions, factor or factors studied, issues and methodologies. Factor V Leiden was the chiefly studied factor, with 18 studies of renewed fetal loss. It was significantly associated with early (before 13 weeks of gestation) and late (after 22 weeks) returning fetal loss, even when other potential underlying causes were exclud Factor V Leiden was also associated with nonrecurrent fetal los especially after 19 weeks of gestation.

Weaker evidence hinted significant associations between recurrent fetal los and activated protein C resistance, protein s deficiency, and prothrombin G20210A mutation. The other thrombophilic conditions were not significantly associated with fetal loss

The authors infer that only certain thrombophilic conditions are associated with periodical fetal loss, and that the association differs for losse occurring early and later in gestation. First-trimester losse are associated with factor V Leiden, activated protein C resistance, and prothrombin G20210A mutation. For the most numerous common factor in most U populations, factor V Leiden, the risk of late returning loss is even higher than that of early miscarriage. Factor V Leiden, prothrombin G20210A mutation, and protein s deficiency are associated with nonrecurrent los late in pregnancy. The mechanism of these associations is believed to involve excessive thrombosis of placental ducts but much remains to be studied.

ANNE D WALLING, MD

Rey E et al. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet March 15 2003;361:901-8

EDITOR'S NOTE: Thrombophilic disorders are previously "small print" conditions that are rapidly becoming highly significant clinical issues in women's health. Are they necessary further not sufficient factors for clotting disorders in contraception and hormone use as well as fetal loss? Do they ne other risk factors like as smoking to trigger their pathologic potential? Will physicians betimes screen for them routinely before any treatment or surgery that has clotting potential? Taken to the ultimate will airlines ask factor V Leiden passengers to exercise during flights to avoid thrombosis? As our awareness has increased, the surprise is for what reason common these factors are in an populations. About 10 percent of patients in a typical family practice are affected. In European populations, the prevalence of factor V Leiden may be higher. Besides pregnancy los heterozygotes for this factor have a sevenfold increased risk of thromboembolism, and homozygote have an 80-fold increased risk (See Bombeli T et al. Prevalence of hereditary thrombophilia in patients with thrombosis in different venous a whole s Am J Hematol June 2002;70:126-32 and Kenneth AB. Hypercoagulable states. In: Hoffman R ed Hematology: basic principles and practice. 3d ed New York: Churchill Livingstone, 2000) single wonders what the possible evolutionary advantage could be for the mutation to be in the same manner common in European populations. Was the risk of bleeding to death from trauma greater than the dangers of thrombosis in our more physically active ancestors?--A.D.W.

COPYRIGHT 2003 American Academy of Family Physicians

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