Factor V Leiden and factor II G20210A in preeclampsia and HELLP syndrome

BACKGROUND: The association of factor V and factor II mutations with preeclampsia and hemolysis, elevated liver enzymes, and low platelets (HELLP) syndrome, and a possible role of the two thrombophilic mutations in the pathogenesis of the diseases have been previously investigated. The results, however, are still inconclusive and contradictory. METHODS: A case-control study was performed over an interval of 24 months, on 111 subjects with preeclampsia and 111 normal pregnant women matched for age and parity, without previous thromboembolic disorders. The subjects were tested for the mutation A1691G in the factor V gene (R506Q or Leiden mutation) and the mutation A20210G in the factor II (prothrombin) gene. The Student's t-test and the chi2-test were applied when appropriate, and odds ratios and 95% confidence intervals were calculated. RESULTS: Fourteen patients with preeclampsia (12.6%) had at least one of the two mutations, as compared with six controls (5.4%). Factor V Leiden was found in eight patients with preeclampsia (7.2%) and in five controls (4.5%). Factor II G20210A was detected in eight preeclamptic women (7.2%) and in one normal pregnant woman (0.9%)(p = 0.041). In the subgroup of 32 preeclamptic subjects with HELLP syndrome, factor V Leiden was found in three patients (9.3%) and factor II G20210A in two (6.2%). CONCLUSIONS: The prevalence of factor V and factor II mutations is increased in patients with preeclampsia; the thrombophilic mutations may interact with other pathogenic factors to determine the clinical features of the disease and of its complications.     

Hemorragia intraventricular fetal por factor V Leiden

We present a case of fetal intraventricular hemorrhage diagnosed at week 28 of gestation. The cause was resistance to activated protein C due to factor V Leiden. We describe the maternal and fetal risk factors associated with intraventricular hemorrhage, as well as sonographic findings.     

HELLP syndrome

HELLP syndrome is a serious, life-threatening form of pre-eclampsia with a typical laboratory triad. The incidence of the disease is reported as being 0.17-0.85% of all live births. There has been, to date, neither reliable early recognition nor effective prevention of HELLP syndrome. As a result of endothelial dysfunction, activation of intravascular coagulation occurs with fibrin deposition in the capillaries and consecutive microcirculation disorders. The disease manifests itself on average between 32-34 weeks' gestation. HELLP syndrome will occur postpartum in up to 30% of the cases. The clinical cardinal symptom of the disease is right upper quadrant pain or epigastric pain accompanied with nausea, vomiting and malaise. In 20% of the cases with HELLP syndrome there is no hypertension and 5-15% of the pregnant patients present a low level of proteinuria or none at all. The early recognition of hemolysis is most sensitively managed by the determination of the serum haptoglobin. The increase of the aspartate transaminase (AST) and the alanine transaminase (ALT) often precedes a decrease in platelets. The course of HELLP syndrome is incalculable. It is universally agreed that a pregnancy from 32-34 weeks should be immediately delivered. Before 32-34 weeks, expectant management is generally possible in a perinatal center. The frequency for a repeated hypertensive disease in pregnancy ranges from 27% to 48%.     

Pregnancy outcome in women with factor V Leiden and recurrent miscarriage

We compared the outcome of 25 untreated pregnancies among women with recurrent miscarriage (RM) at <12 weeks' gestation who were heterozygous for factor V Leiden with women with unexplained RM. The livebirth rate was lower among pregnancies in carriers of factor V Leiden (12/25; 48%) compared with pregnancies in women with unexplained RM (175/307; 57%), but the difference did not reach statistical significance. The best possible treatment regimen to improve livebirth rate in this group of women needs to be assessed in the form of a randomised controlled trial.     

HELLP syndrome]

The Hellp syndrome is a rare complication of hypertension in pregnancy, characterized by haemolysis, elevated liver enzymes and thrombocytopenia. Since the disease progresses very rapidly, it is important for successful treatment, to make an early diagnosis, evaluating the typical laboratory data changes, which are evident prior to clinical manifestations. Means of diagnosis and therapeutic approach are described, on the basis of personal experience.     

Factor V Leiden and contraception

Factor V Leiden is the most common genetic cause of primary and recurrent venous thromboembolism in women. It is an inherited thrombophilia that results from a genetic mutation. A college-aged woman who presented for care and had a positive family history of venous thrombosis tested positive for Factor V Leiden. Laboratory tests and plans for continuing care are discussed.     

Obstetric implications of activated protein C resistance and factor V Leiden mutation

An increasing number of reports have focused on activated protein C resistance (APCR) as it has been shown not only to be the most common genetic factor predisposing patients to thromboembolic disease but the most common identifiable cause overall. More than 90 percent of the cases of APCR are caused by the factor V Leiden mutation, in which a guanine to adenine substitution in the factor V gene at nucleotide position 1691 results in a glutamine to arginine switch at position 506. Recent studies have also pointed to evidence of an association between APCR/factor V Leiden mutation and hypertensive disorders of pregnancy, first and second trimester miscarriage, placental infarction, and placental abruption.     

Factor V Leiden as a risk factor for miscarriage and reduced fertility

The Leiden mutation is a recent discovery. It is the main cause of inherited thrombophilia and has been found in 20-60% of deep vein thrombosis cases. More recently it has been found in a significant number of cases of obstetric complications attributable to placental thrombosis. Current patient management practice for dealing with the Leiden mutation is based mainly on information about deep vein thrombosis because there is little information on pregnancy complications. There are no prospective studies examining the risk of developing pregnancy complications for Leiden mutation carriers. The aim of this study is to do that by comparing the frequency of unfavourable pregnancy outcomes among carriers with those among controls. The number of women developing miscarriages, intrauterine deaths, or infertility problems among 128 Leiden mutation carriers was compared with the number among 461 controls. The risk of having at least one miscarriage or infertility problems was 1.5 times greater for Leiden mutation carriers than controls. This result was statistically significant (95% CI 1.2, 2.7). The risk of having at least two miscarriages or infertility problems was 2.5 times greater for Leiden mutation carriers than controls. This was also statistically significant (95% CI 1.2, 5.13).