Without a personal or family history, therefore, women with these lower-risk thrombophilia do not require anticoagulation during pregnancy unless they have other risk factors for thrombosis, such as significant obesity or orders for bed rest.
Patients with known inherited thrombophilia and a positive history, on the other hand, should receive antepartum thromboprophylaxis followed by postpartum anticoagulation. (Women who have a cesarean delivery should receive postpartum anticoagulation whether they have a personal or family history or not.)
Anticoagulation during pregnancy is also warranted—regardless of personal or family history—in the rare cases in which a patient is known to have homozygosity for FVL or homozygosity for PGM, or if a patient is known to have “double heterozygosity” for both FVL and PGM. Antithrombin deficiency, the most thrombogenic of all the inherited thrombophilias, also warrants antepartum anticoagulation as well as antithrombin infusions during labor and delivery.
To date, two studies have attempted to determine the value of screening for inherited thrombophilia based on a family history of prior VTE, and neither has shown that widespread screening would be particularly useful or cost effective in this setting. One certainly can argue, on the other hand, in favor of screening for thrombophilia in women who have a strong family history of VTE coupled with other risk factors.
Individualized risk assessment is always valuable. A woman with multiple risk factors—one who is obese, smokes, and is being put on bed rest, for instance—is a candidate for low-molecular-weight heparin (LMWH) therapy, for instance, even without a history of thrombosis and regardless of her thrombophilia status. If such a patient also has hypertension or preeclampsia, however, I'd be reluctant to give her either heparin or LMWH, for fear of abruption or even intracranial hemorrhage.
In what other circumstances is screening for thrombophilia warranted?
It can be justified when there is a personal history of VTE associated with a risk factor that is not recurrent. In this case, the absence of a thrombophilia reduces the risk of occurrence/recurrence of VTE during pregnancy to a very low level, while the presence of a thrombophilia would mandate antepartum anticoagulation. In any case, she should receive postpartum prophylaxis since 75%-80% of fatal pulmonary emboli in pregnancy occur after cesarean delivery.
For instance, screening is valuable in a woman who had a VTE earlier in her life when she was on oral contraception and was put in a cast after a skiing accident. If she does not have a documented thrombophilia, you will not need to give her anticoagulation during the pregnancy—only post partum.
The Work-Up
When screening for inherited thrombophilia is warranted, I recommend limiting it to FVL, PGM, protein C deficiency, antithrombin deficiency, and protein S deficiency. (See table, p. 20.)
Screening for FVL, even during pregnancy, can be done with a second-generation screening test for active protein C resistance, or by polymerase chain reaction (PCR).
Screening for the PGM should be done by PCR, and I recommend getting an antithrombin activity level and a protein C activity level to screen for antithrombin deficiency and protein C deficiency, respectively.
Screening for protein S deficiency is trickier, since circulating protein S activity levels can vary dramatically in pregnancy (i.e., various conditions from infections to surgery to hormonal status can affect activity levels of protein S).
I recommend first assessing the protein S free antigen level. In nonpregnant patients, a free antigen level less than 55% indicates risk for deficiency. Free antigen levels drop significantly in pregnancy, however, making a level at or below 29% in the first and second trimesters, and a level at or below 24% in the third trimester, indicative of risk. Such levels can be accepted as indicating protein S deficiency, or deficiency can be confirmed by then measuring the protein S activity level.
I do not recommend screening for MTHFR mutations or hyperhomocysteinemia. There does not appear to be any association between MTHFR mutations and adverse pregnancy outcomes, and the probable association between hyperhomocysteinemia and maternal venous thrombotic events that exists in general is of far less concern in the United States since grains are fortified with folate. If there is any concern, extra folic acid supplementation should be protective.
Source Elsevier Global Medical News
Key Points
▸ Most positive associations between inherited thrombophilia and adverse pregnancy outcomes were derived from small case-control studies. Many studies are contradictory.
▸ Large prospective cohort studies have failed to demonstrate any consistent association between inherited thrombophilia and adverse pregnancy outcomes.
▸ There appears to be a modest association between thrombophilia and fetal loss after 10 weeks in retrospective, but not most prospective, studies.