The importance of genetic thrombophilic factors in the development of venous thromboembolism has been increasingly recognized. Factor V Leiden (FVL), prothrombin gene mutation G20210A (FII G20210), genetic variant C677T of the methylentetrahydrofolate reductase (MTHFR), as well as the polymorphism A2 (PlA2) in platelet glycoprotein IIb/IIIa were recently discussed. We analyzed the contribution of genetic thrombophilic factors to the pathogenesis of pulmonary embolism (PE) and their association with the early onset and recurrence of PE using DNA analysis methods. In this case control trial we found thrombophilic genetic variants in 58.8% of 51 patients with PE. FVL was found in 23.5% of the patients versus 7.1% of the 98 controls (p=0.01), PlA2 IIb/IIIa was found in 35.3% vs. 14.3% (p=0.03), and FII G20210A was found in 5.9% vs. 2.0% (NS). Patients with recurrent PE had a very high prevalence of genetic factors, 70.4%. High prevalence of FVL was found in patients under 45 years of age: 39.3% (OR=14.23, 95% CI=1.58-330.03, p=0.01) as well as in patients with recurrent incidence (37%, OR=7.647, 95% CI=2.27-26.44, p=0.001). FVL was also significantly higher in the subgroup of patients with PE combined with deep venous thrombosis (OR=6.500, 95% CI=1.81-23.76, p=0.002) in comparison with patients with isolated PE (OR=2.261, 95% CI=0.50-9.69). The carriers of FVL are at higher risk for early and recurrent PE events. High prevalence of PlA2 in PE patients evidently shows the impact of this polymorphism in PE development. A different treatment should be considered in carriers of thrombophilic defects.

To investigate the impact of maternal-inherited thrombophilia: effects of factor V Leiden (FVL) and prothrombin gene mutation (FII 20210G>A) on the development of recurrent pregnancy loss in embryonic and postembryonic periods. A total of 153 patients were analysed for FVL and FII 20210G>A according to placenta gestation: 94 women with embryonic loss prior 10 weeks of gestation and 59 women with postembryonic (early fetal) loss occurring between 10 and 14 weeks of gestation. The control group consisted of 100 healthy women, with at least one uncomplicated full-term pregnancy. FVL prevalence was not significantly associated with pregnancy loss prior to 10 weeks of gestation (9.6%) compared with controls (7%) [odds ratio (OR) 1.41; 95% confidence interval (CI) 0.454-4.416, P > 0.05], but it was much more pronounced in women with postembryonic loss (10-14 weeks of gestation) - 18.6% (OR 3.05; 95% CI 1.010-9.387, P = 0.047). FII 20210G>A was significantly higher in both groups with embryonic (17%) and early fetal losses (16.9%) as compared to controls (3%) (OR 6.63; 95% CI 1.731-29.752, P = 0.003; OR 6.60; 95% CI 1.572-31.856, P = 0.006). FII 20210G>A is significantly associated with an increased risk of early recurrent pregnancy loss throughout the entire first trimester. FVL was significantly higher only in early fetal period after starting of the placentation process, but not associated with embryonic recurrent pregnancy loss. These results suggested that the first trimester should be viewed rather as a heterogeneous interval, with different relation to FVL in the embryonic and postembryonic fetal period. Genetic testing should be applied according to the diverse contribution of thrombophilic markers to embryonic and postembryonic period.

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Trends and Causes of Congenital Anomalies in the Pleven Region, BulgariaWe describe the secular trend, pattern and causes of congenital anomalies (CAs) in the Pleven region, Bulgaria. The source of the data was the regional population-based registry of CAs using criteria according to EUROCAT recommendations. During the period 1988-2006, 47,622 births were surveyed. A total of 1,225 cases of CAs were ascertained, giving a total prevalence of 25.72 [95% confidence interval (95% CI) 24.3 to 27.15 per 1,000 births. There was a significant increase in total prevalence from 17.76 per 1,000 births in 1988 to 29.40 in 2006 (χ2 test for trend = 5.03;p= 0.025). Congenital heart disease (4.3 per 1,000 registered births), nervous system anomalies (3.3 per 1,000 births), limb defects (2.5 per 1,000 births) and neural tube defects (2.0 per 1,000 births) demonstrated the highest prevalence. There was a significant upward trend in the prevalence of some specific anomalies: digestive system, tumors, gastroschisis and non syndromal dysmorphologic conditions. Genetic causes were identified in approximately 62% of all cases with CAs (chromosomal 8%, single gene defects 14%, multifactorial 40%). The secular trend and particular pattern of CAs in the Pleven region require some potential underlying contributing factors to be considered: case ascertainment and diagnostic methods, and some environmental factors. These data draw attention to the need of further regional epidemiological studies. The high proportion of genetic causes emphasize the role of genetic services as an integral part of preventive medical care.