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12/8/2000

VTE Unlikely to Repeat During Pregnancy

Kate Traynor

Women who have had one episode of venous thromboembolism (VTE) are unlikely to have another when pregnant and can avoid the expense and inconvenience of heparin injections, say Canadian researchers.

In a study described in the Nov. 16 New England Journal of Medicine, 125 pregnant women with a single previous VTE episode forwent anticoagulation therapy but started heparin and warfarin regimens within 24 hours after giving birth. Three of the women had an episode of VTE during pregnancy, and three others had a recurrence within three months after giving birth.

The women whose prior VTE occurred without a reasonable medical explanation were 4.4 times as likely to have a recurrent embolism during or after pregnancy as were women whose previous VTE could be explained by their having a temporary risk factor. Women who were heterozygous for a mutation in the gene encoding coagulation factor V were 10 times as likely as women with normal blood test results to have a recurrent VTE.

The multicenter study was conducted between July 1994 and September 1998. All pregnant women up to 20 weeks' gestation were eligible for the study if they had had a single pulmonary embolism or a deep venous thromboembolism of the leg. Women who required anticoagulant therapy or had clotting disorders were excluded from the study, as were women whose VTE had occurred less than three months before the pregnancy.

Of 127 eligible participants, two opted not to enroll in the study. About a third of the study participants’ qualifying VTE episodes were idiopathic, while two-thirds were attributed to temporary risk factors such as pregnancy, oral contraceptive use, or surgery. At baseline, the women who participated in the study were, on average, 30 years old and in the 15th week of gestation.

Blood samples were obtained from 95 of the women at the start of the study and analyzed for clotting abnormalities after the monitoring period ended. All of the women who had a recurrent VTE during the monitoring period had provided a blood sample.

During pregnancy, women were monitored for symptoms of VTE but treated with an anticoagulant only if a thromboembolism was diagnosed by ultrasound or ventilation-perfusion lung scanning. Women diagnosed with antepartum venous thromboembolism were treated with a low-molecular-weight heparin through the end of their pregnancies.

Within 24 hours after delivery, all women were given warfarin and 5,000 or 7,500 units of unfractionated heparin subcutaneously, twice a day. At discharge, heparin therapy was stopped regardless of the patient’s International Normalized Ratio (INR). The women continued to take warfarin for four to six weeks—33 days on average—with dosages adjusted to attain INR values of 2.0 to 3.0.

The women returned to the clinic when they stopped taking warfarin. Follow-up information was obtained by telephone three months after the women gave birth.

A pulmonary embolism—the patient’s second episode—was diagnosed in one woman during the ninth week of pregnancy. The other five confirmed VTE episodes, including one that followed a missed abortion, were deep-vein clots in the patients’ legs.

None of the three women who had a VTE after delivery was actually taking warfarin when her thromboembolism recurred. Warfarin therapy was withheld from one woman who had uterine bleeding and refused by a second woman who instead received 12,500 units of unfractionated heparin twice daily, without laboratory monitoring. The third woman had a thromboembolism two weeks after she stopped taking warfarin.

None of the study participants had a recurrent VTE or an episode of bleeding during anticoagulation therapy. According to lead author Patrick Brill-Edwards, M.D., none of the 125 pregnant women died during the study, though eight fetal deaths occurred. All but the two women noted above received postpartum warfarin.

Brill-Edwards and his colleagues had initially planned to enroll 250 women, under the assumption that 6 percent would have a second VTE during the study. However, study enrollment ceased after a planned interim analysis showed that the incidence of antepartum VTE—4 percent per patient-year of follow-up—was lower than expected and lower than average for people at risk for recurrent VTE.

On the basis of their study findings, Brill-Edwards and colleagues advised against the routine use of anticoagulants during pregnancy in women with a single past episode of VTE. The research team also recommended that genetic assays for the factor V Leiden mutation be used to identify women who might be at increased risk for having a recurrent VTE.