Silver and coworkers (2010) tested nearly 4200 women for the prothrombin G20210A mutation. A total of 157-or 3.8 percent-of the women carried the mutation, and only one of these was homozygous. Carriers had similar rates of pregnancy loss, preeclampsia, fetal-growth restriction, and placental abruption compared with noncarriers. hree thromboembolic events occurred in women who tested negative for the mutation.
Homozygous patients, or those who coinherit a G20210A mutation with a factor V Leiden mutation, have a greater thromboembolism risk than heterozygous carriers (Connors, 2017). Lim and associates (2016) have provided detailed information on pregnancy outcomes in women with such rare compound thrombophilias.
he most common cause of elevated homocysteine is the C667T thermolabile mutation of the 5,1 O-methylene-tetrahydrofolate reductase (MTHFR) enzyme. Inheritance is autosomal recessive. Elevated homocysteine levels may also result from deiciency of one of several enzymes involved in methionine metabolism and from correctible nutritional deficiencies of folic acid, vitamin B6, or vitamin Bl2 (Hague, 2003). During normal pregnancy, mean homocysteine plasma concentrations decline (Lopez-Quesada, 2003). hus, to make a diagnosis during pregnancy, Lockwood (2002) recommends a fasting threshold > 12 �mol/L to deine hyperhomocysteinemia.
In an interesting metaanalysis, Den Heijer and associates (2005) found that international studies of MTHFR polymorphisms were collectively associated with slightly greater risks for thrombosis. In contrast, studies conducted in North America collectively demonstrated no such association. The authors speculated that folic acid supplementation could explain the diference. Recall that folic acid serves as a cofactor in the remethylation reaction of homocysteine to methionine. Similarly, the American College of Chest Physicians concluded that the lack of an association with thromboembolism could relect the physiological reductions in homocysteine levels associated with pregnancy and the efects of widespread prenatal folic acid supplementation (Bates, 2012). he American College of Obstetricians and Gynecologists (2017 c) has concluded that there is insuicient evidence to support assessment of MTHFR polymorphisms or measurement of fasting homocysteine levels in the evaluation for VTE.
Potentially thrombophilic polymorphisms are being discovered at an ever-increasing rate. Unfortunately, information regarding the prognostic signiicance of such newly discovered mutations is limited. For example, protein Z is a vitamin K-dependent protein that serves as a cofactor in factor Xa inactivation. Studies have found that low protein Z levels are associated with an elevated thromboembolism risk in nonpregnant patients and may be implicated in the pathogenesis of poor pregnancy outcomes (lmawi, 2013). Similarly, plasminogen activator inhibitor ype I (PAl-I) is an important regulator of ibrinolysis. Certain polymorphisms in the gene promoter have been associated with slightly greater VTE risks. Although these thrombophilias may exacerbate risk among patients when coinherited with other thrombophilias, the American College of Obstetricians and Gynecologists (2017 c) has concluded that evidence to recommend screening is insuicient.