Efficacy and safety of the long-term administration of low-molecular-weight heparins in pregnancy.

Pregnancy is associated with an increased risk of venous thromboembolism, which probably varies according to the presence of single or multiple thrombophilic defects. Acquired or inherited thrombophilia is moreover associated with adverse outcomes in pregnancy. For this reason, in the past, pregnant women at risk of venous thromboembolism or pregnancyes have been treated with oral anticoagulants or unfractionated heparin. Both of them are associated with fetal or maternal side effects. Low-molecular-weight heparins (LMWHs) offer several advantages, but they have no or only partial indication for use in pregnancy in many countries. We have prospectively evaluated 114 patients and overall 130 pregnancies treated with prophylactic or therapeutic LMWHs from January 2004 to February 2007. The occurrence of allergic reactions, hemorrhagic episodes, low platelet count, pathological fractures, thromboembolic events and adverse outcomes in pregnancy were considered. There was a significant difference in pregnancy outcome following prophylaxis with LMWHs (chi2 P < 0.0001) and the absolute and the relative risks were significantly decreased in the patients with treated pregnancy compared with those with previous untreated pregnancies. Moreover, in our series of patients, the long-term use of LMWH in pregnancy was confirmed well tolerated, with the rate of adverse effects, though very low, comparable with that in literature. Our experience confirms the safety and the efficacy of LMWH but suggests the need of randomized controlled trials.

Screening of mutations of hemophilia A in 40 Italian patients: a novel G-to-A mutation in intron 10 of the F8 gene as a putative cause of mild hemophilia A in southern Italy.

Hemophilia A is an X-linked bleeding disorder caused by widespread mutations in the human coagulation factor 8 gene. We have searched for mutations in factor 8 gene DNAs from 40 unrelated Italian patients with hemophilia A. All patients came from the same region (Calabria) and were followed-up at the same hemophilia center. Of the 40 patients, 20 (50%) had severe hemophilia A, 19 (47.5%) had moderate hemophilia A, and one (2.5%) had mild hemophilia A. All patients were first screened for the common intron 22 and intron 1 inversions. Inversion-negative samples were screened for point mutations by direct sequencing of all coding regions and intron-exon boundaries of the factor 8 gene. Mutations previously reported as causative of hemophilia A were identified in 14 of the 40 patients. These included five (12.5%) intron 22 inversions, one (2.5%) small deletion, one (2.5%) small insertion and seven (17.5%) point mutations. In all patients with moderate and mild hemophilia A, a nucleotide change in the c.1538 -18G>A in intron 10, not reported in the HAMSTeRS factor 8 mutation database (http://europium.csc.mrc.ac.uk/), was found. The G-to-A change predicts the appearance of a new acceptor splice site. We have also demonstrated that all patients share a common haplotype, suggesting that the mutation probably occurred in a single ancestor. In conclusion, we suggest that the c.1538-18G>A transition can be the putative mutation, which probably occurred in a common ancestor and then spread in neighbours, in patients with moderate-mild hemophilia A investigated in the present study.

Genetic prothrombotic risk factors in women with unexplained pregnancy loss.

INTRODUCTION: Inherited thrombophilia has been associated with unexplained recurrent pregnancy loss (RPL) and stillbirth. This thrombotic tendency can manifest as thrombotic lesions in the placenta, and may lead to abortion and stillbirth. The aim of our case-control study was to investigate the prevalence of FVL and FII G20210A in women with adverse pregnancy outcome, compared to the prevalence of the same mutations in our health control group. MATERIALS AND METHODS: 102 consecutive women with unexplained pregnancy loss (55 with history of RPL, and 47 with history of stillbirth) were studied for hereditary thrombophilia. The health control group consisted of 217 healthy women from the general population. RESULTS AND CONCLUSIONS: Of the 55 women with recurrent abortions, we found the same prevalence for the FVL and the FII G20210A(9.1%, 5 pts). (p=NS compared to control group). Of the 47 women with stillbirth, 11 (23.4%) had the FVL and 9 (19.1%) had the FII G20210A(p<0.0005 for both mutations). In our experience the prevalence of FVL and the FII G20210Amutations was significantly higher in women with unexplained stillbirth, instead the prevalence of genetic thrombophilia was high but not statistically significant in women with recurrent pregnancy loss.

Thrombosis in hemophiliacs with prothrombotic molecular defect.

Thrombosis in hemophiliacs is a very unusual event mostly reported in patients treated with concentrates containing large quantities of activated coagulation factors. A patient with hemophilia A is reported who had an acute myocardial infarction and in whom investigation for hereditary thrombophilia showed a prothrombotic molecular defect, the G20210A prothrombin mutation.