Paternal endothelial protein C receptor 219Gly variant as a mild and limited risk factor for deep vein thrombosis during pregnancy.

BACKGROUND: Half of all venous thromboembolism (VTE) cases during pregnancy are associated with a maternal thrombophilia. The influence of paternal genotype on the placenta and in the genesis of VTE has not been described. OBJECTIVES: To determine if the maternal and paternal Ser219Gly dimorphism of the endothelial protein C receptor (EPCR), evaluated through detection of the PROCR 6936G allele, is a risk factor for VTE during pregnancy. METHODS: Using a case-control study nested in the NOHA first cohort of primigravidae, 66 patient couples with a first episode of gestational VTE and randomly selected non-thrombotic control couples were investigated. For each couple, factor V gene (F5) G1691A, factor II gene (F2) G20210A, factor XII gene (F12) C46T and PROCR A6936G polymorphisms were determined. RESULTS: Only maternal F5 1691A, F2 20210A and F12 46T alleles were independently associated with iliac and infra-iliac deep vein thromboses (DVT). The maternal PROCR 6936G allele was a mild risk factor for iliac DVT (OR = 5.5 [2.3-13.0]). The paternal PROCR 6936G allele was also a mild independent risk factor for iliac DVT (OR = 2.6 [1.1-6.2]) and only during pregnancy (rather than postpartum) among maternal carriers of the F5 1691A allele (OR = 77.6 [4.2 to > 999.9]). CONCLUSIONS: The paternal PROCR 6936G allele could be a risk factor for maternal iliac DVT. Its impact was milder than the F5 1691A and F2 20210A polymorphisms in mothers. We hypothesize that the prothrombotic effect of the paternal PROCR 6936G allele is localized. Therefore, DVT during pregnancy may be influenced by trophoblastic cell-surface proteins inherited from both maternal and paternal alleles.

[A new automated haematology analyser: the Excell 2280]. / Un nouvel automate de cytologie hématologique: l'Excell 2280.

Excell 2280 analyser is a new automated haematology analyser manufactured by Drew Scientific Inc, Texas, USA, and distributed in France by MAXMAT S.A., Montpellier. It can achieve 80 complete blood cell counts per hour, with leukocyte differential counts. Three sampling possibilities are included: a direct one (open tubes, 180 microL), a blood saver one (80 microL) and an automatic, through-the-cap one (180 microL). The analytic principles are: electrical impedance for cell counting (WBC, RBC, platelets, MCV) and RBC/platelet sizing; and a new multidimensional optical system using a laser light scattering flow cytometer for WBC counting and classification. We evaluated the Excell 2280 in our laboratory: we quantified intra-run and within-run variations, correlations between the automatic and the direct sampling method, stability of the results over time, linearity of the detections and finally correlation between results obtained with this analyzer and the Gen'S one from Beckman-Coulter Inc. The obtained results were within the theoretical ranges given by the manufacturer. The presence of any abnormal result, or of any flag, must systematically lead to check the blood smear. This new automated haematology analyser appears to be convenient for emergency room-related laboratories, and for routine small-to-medium laboratories.

Simple coagulation tests improve survival prediction in patients with septic shock.

BACKGROUND: Classic mortality prediction models in intensive care units (ICUs) are based on clinical scores, which do not contain any coagulation test (SAPS-II or SOFA scores). OBJECTIVES: To determine whether coagulation tests can improve mortality prediction in patients with septic shock. PATIENTS AND METHODS: One hundred fifty-eight consecutive patients with septic shock entering our institution's ICU were investigated on the first day of admission, and deaths were registered during the first month. RESULTS: Among all the coagulation tests performed, only the fibrinogen (Fg) plasma level, together with the SAPS-II score and the age, were included in our simplified mortality score [area under the receiver operating curve (AUC) 0.927, standard deviation (SD) 0.030], which was more efficient than SAPS-II and SOFA scores themselves in predicting first-week mortality, its optimized cut-off having a very high negative predictive value (NPV) [0.989; 95% confidence interval (CI) 0.967-1.000)]. A simplified score predicting first-month mortality, containing the prothrombin ratio and the antithrombin activity values in addition to the age, the hemoglobin concentration, and the SAPS-II and SOFA scores (AUC 0.889, SD 0.026), was found to be superior to the SAPS-II and SOFA scores, the optimized cut-off value having a high NPV (0.952; 95% CI 0.888-1.000). CONCLUSIONS: In patients admitted to an ICU with septic shock, some initial coagulation test values can help identify those who will survive in the first week and then in the first month.

Homozygosity for the C46T polymorphism of the F12 gene is a risk factor for venous thrombosis during the first pregnancy.

BACKGROUND: A first thromboembolic event during pregnancy and puerperium is predisposed to by polymorphisms G1691A in the factor V gene (F5) (F5G1691A) and G20210A in the prothrombin gene (F2) (F2G20210A). OBJECTIVES: To study another potentially frequent thrombogenic polymorphism, C46T in the factor XII gene (F12) (F12C46T). PATIENTS AND METHODS: The 32 463 previously asymptomatic women included in the NOHA First cohort in their first pregnancy were investigated for these three polymorphisms. No other constitutional or acquired thrombophilic risk factor was studied. RESULTS: The overall incidence--absolute risk--of venous thromboembolic events (VTE) was 127 per 100,000 woman-years and was reduced to 22 per 100,000 women-years in women negative for the three polymorphisms (P < 0.0001). Homozygosity for F12C46T was associated with a significant relative risk (RR) of VTE [RR: 5.99, 95% confidence interval (95% CI): 2.1-17.3, P = 0.001], as was heterozygosity for F5G1691A (RR: 18.7, 95% CI: 8.3-42, P < 0.0001), heterozygosity for F2G20210A (RR: 14.3, 95% CI: 6.2-33.2, P < 0.0001), maternal age (RR: 1.18, 95% CI: 1.07-1.29, P = 0.0006), maternal body mass index (RR: 1.31, 95% CI: 1.11-1.55, P = 0.002), conceptus weight (percentiles adjusted for term of delivery; RR: 0.90, 95% CI: 0.88-0.93, P < 0.0001) and pre-eclampsia (RR: 3.03, 95% CI: 1.06-8.69, P = 0.039). CONCLUSIONS: Homozygosity for the C46T polymorphism of the F12 gene is associated with venous thrombosis during the first pregnancy/puerperium in previously asymptomatic women.

Factor V Leiden and prothrombin G20210A polymorphisms as risk factors for miscarriage during a first intended pregnancy: the matched case-control 'NOHA first' study.

Factor V Leiden (FVL) and prothrombin G20210A (FIIG20210A) mutations are associated with a higher risk of miscarriage: we sought to understand whether this association differs by clinical time of unexplained miscarriage, and by ethnic origin, among women with no previous thrombotic episode, during the first intended pregnancy. We performed a case-control study nested in a cohort of 32 683 women. We analyzed 3496 pairs of women matched for classical confounding factors. The FVL and FIIG20210A mutations were associated with an increased risk of miscarriage in Caucasian women [odds ratio (OR) 3.19, 95% confidence interval (CI) 2.37-4.30, P < 0.001 and OR 2.36, 95% CI, 1.72-3.24, P < 0.001, respectively]. Among non-Caucasian women, the mutations were rare and the associations with risk of miscarriage less clear. FVL and FIIG20210A mutations were independent risk factors for miscarriages only for women with related clinical signs occurring from the 10th week of gestation on (OR 3.46, 95% CI 2.53-4.72, P < 0.001 and OR 2.60, 95% CI 1.86-3.64, P < 0.001, respectively). These results indicate that FVL and FIIG20210A mutations are associated with a significant risk of spontaneous abortion which clinical signs occur from the 10th week on of the first intended pregnancy.