Test for Thrombophilia in Cases of Late Fetal Loss.
One of those situations is unexplained fetal death in the second or third trimester, said Dr. Silver of the University of Utah, Salt Lake City, an expert in thrombophilias and pregnancy.
Other obstetric patients who probably merit testing are those with a family history of thrombosis, those with unexplained thrombosis, and those with severe preeclampsia with onset before 34 weeks' gestation.
Although heritable thrombophilias have been associated with many obstetric complications (see related story), most experts do not recommend testing in cases of recurrent spontaneous abortion, mild preeclampsia, placental abruption, or intrauterine growth restriction. The association in these cases either is not based on strong enough data or is not thought to occur with enough frequency to justify the cost, which can run into hundreds of dollars if a full array of tests is run.
Some have recommended routine screening for common heritable thrombophiias in pregnancy But "I don't think we have enough information to make that useful," Dr. Silver said.
When testing is called for, he recommended testing for factor V Leiden mutation and the prothrombin mutation and performing immunoassays for anticardiolipin antibodies (for antiphospholipid syndrome) and lupus anticoagulant.
Testing for other thrombophilias is not recommended because the conditions are too rare, the results of the tests are too variable, or the information on what to do with the results is too unclear.
Antithrombin III deficiency, protein C deficiency; and protein S deficiency for example, are extremely rare in patients without a family history of venous thromboembolism. Hyperhomocystinemia may be fairly common in the general population, but homocysteine is difficult to measure accurately and "you just get very muddled information," he said.
Most of the studies of thrombophilias and pregnancy have been retrospective, case-control studies, and therefore may be subject to bias, said Dr. Silver. Findings from some of the more definitive studies suggest the following:
* Factor V Leiden mutation. The prevalence of the factor V Leiden mutation is about 4%-6% in the general white population. Persons with the factor V mutation appear to have a 30% lifetime prevalence of thromboembolism. The actual risk of a blood clot during pregnancy is about 0.2% in patients with the mutation--an eightfold higher risk than in patients without the mutation. When both the factor V Leiden mutation and the prothrombin mutation are present, the risk increases to 4%-5%. One study of women with pregnancy-associated thromboembolism found that 44% had a factor V mutation, compared with 8% of normal controls.
* Prothrombin gene mutation. The prevalence of the prothrombin gene mutation in the general population is 1%-3%. In the study of women with pregnancy-associated thromboembolism, case patients were 15 times likelier to have the mutation than were control patients. In actual terms, the risk of having a blood clot during pregnancy is 0.5% in women with the mutation.
* Antithrombin III deficiency. Antithrombin III deficiency is present in 0.02%-0.2% of the general population. The deficiency may confer a 30% risk of thromboembolism in pregnancy, although not all studies have found the risk to be that high.
* Protein C deficiency. The prevalence in the general population is 0.2%-0.5%. In the study of women with pregnancy-associated thromboembolism, the deficiency was found in 10%-14% of cases, compared with 3%-4% of controls.
* Hyperhomocystinemia. The prevalence of hyperhomocystinemia in the population is 10%-11%. In the study of pregnancy-associated thromboembolism, the particular hyperhomocystinemia-associated genotype that was investigated did not have a higher prevalence in cases than in controls.
There is little agreement on how and when to treat thrombophilias in the general population. In obstetric patients, however, Dr. Silver said he would recommend the following, based on currently available data:
* Patients with a thrombophilia but no prior or acute thrombosis need not be treated, except for those with antithrombin III deficiency. These patients should be completely anticoagulated throughout pregnancy.
* Patients with a thrombophilia and a prior thrombosis should receive anticoagulation therapy at prophylactic doses during pregnancy and in the postpartum period.
* Pregnant patients with acute thrombosis deserve complete anticoagulation for 36 months, followed by thromboprophylaxis in the postpartum period.
* Patients with a thrombophilia and an obstetric complication can be offered treatment, but they need to be informed that it is experimental.
Thrombophilias And Pregnancy Complications
Dr. Silver gave a rundown on What the medical literature suggests about pregnancy complications and thrombophilias:
* Recurrent spontaneous abortion. The association between thrombophilias and early pregnancy loss is controversial; most studies fail to find an association between the two. In Dr. Silver's opinion, an association may not be likely. The theoretical reason thrombophilias contribute to complications is that they lead to thrombosis and infarction in the placenta. But placental insufficiency probably does not come into play in early pregnancy loss, he said.
* Fetal death. Many case-control studies have found an association between thrombophiias and secondor tbird-trimester fetal death--with a relative risk estimated to be 2.5 times higher than in patients without a thrombophilia.
* Preeclampsia. Many positive-association studies suggest that the prevalence of thrombophilias in women with severe preeclampsia is somewhere between 8% and 50%.
* Fetal growth impairment. Thrombophilias have been reported in up to 50% of women delivering infants with fetal growth impairment; however, one prospective study failed to find any association.
* Abruption. Thrombophilias have been reported in 25%-35% of women with placental abruption.
* Abnormal placenta. Reports have found a high rate of thrombophilias in women with abnormal placentas when compared with nor mal controls. Factor V Leiden mutation may be associated with a 10-fold increase in relative risk.
Cesarean Rate Portends Rise in Placenta Accreta
BEAVER CREEK, COLO. -- The rise in the cesarean rate over the last several years may portend an increase in the incidence of placenta accreta, Dr. Richard P. Porreco warned at a perinatal conference sponsored by the University of California, Irvine.
"I think that with the cesarean rate what it is we are creating a potentially very great problem downstream," Dr. Porreco, medical director of the perinatal unit at Presbyterian-St. Luke's Medical Center, Denver, said in an interview. According to one large survey, the cesarean rate in 1999 was 21%, up from 12% in 1972.
The maternal mortality rate with placenta accreta is 7%. Placenta accreta is related to placenta previa and to previous cesarean section. A woman with two prior cesareans has a 60% risk of having a placenta accreta with a placenta previa, and a woman who has had four cesareans has a 70% risk of placenta accreta, increta, or percreta.
Even when physicians are prepared and well equipped, the condition can be extremely dangerous, Dr. Porreco said. Recently at his institution a 37-year-old woman, who had undergone three previous cesareans, was diagnosed with placenta previa and percreta at 30 weeks' gestation by ultrasonography. At 34 weeks' gestation she underwent an abdominal hysterectomy and bladder resection.
Although the physicians were ready--and even had artery balloon catheters prepositioned before beginning and a team of surgeons on hand--the patient ended up going into cardiac arrest during the procedure and had postoperative complications that kept her in the hospital for 20 days.