Levels of platelet-leukocyte aggregates in women with both thrombophilia and recurrent pregnancy loss.

The aim of our study was to investigate the significance of platelet-leukocyte aggregates (PLA) in women with recurrent pregnancy loss (RPL) as well as to identify association between common thrombophilic factors and whole blood levels of PLA in these patients. We measured PLA by whole blood flow cytometry in 66 nonpregnant women with hereditary and/or acquired thrombophilia and RPL, classified to 3 study groups, according to the type of losses (first, second, and third trimester) and 35 age-matched healthy controls. Platelet-leukocyte aggregates levels in all study groups were significantly increased compared to the control group (median values 2.13%, 2.32%, and 2.41%, vs median value in the control group 1.39%, P < .05 for all comparisons). Women with a single thrombophilic factor and women with combination of thrombophilic factors did not differ significantly as regards the PLA levels (2.13% vs 2.27%, P = .4). This study suggests that PLA may have a role in the pathogenesis of RPL in women affected by hereditary or acquired thrombophilia.

Polymorphism A1/A2 in the cell surface integrin subunit ß3 and disturbance of implantation and placentation in women with recurrent pregnancy loss.

Polymorphism A1/A2 in the ß3 subunit of integrins αIIb/ß3 and αV/ß3 is implicated in the risk of development of embryonic and fetal recurrent pregnancy loss (RPL). In 191 women with RPL, polymorphism A1/A2 was statistically significantly associated with RPL at <10 weeks of gestation (29.3% versus 16.4% in controls), but it was much more pronounced in 67 women with RPL between 10 and 20 weeks of gestation (41.8%), illustrating its role in recurrent fetal loss.

Association of inherited thrombophilia with embryonic and postembryonic recurrent pregnancy loss.

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.

Impact of thrombophilic genetic factors on pulmonary embolism: early onset and recurrent incidences.

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.