G. Lissalde-Lavigne

More on: factor V Leiden and prothrombin G20210A polymorphisms as risk factors for miscarriage during a first intended pregnancy: the matched case-control ‘NOHA First’ study

evidence of a significant interaction when measured by adenosine 5¢-diphosphate (ADP)-induced platelet aggregation or urinary11-dehydro thromboxaneB2concentrations.Webelieve our results are consistent with previous reports of enhanced platelet sensitivity to ADP and collagen in patients with least inhibition of arachidonic acid-induced platelet aggregation during aspirin therapy [2,3]. However, we also agree with Almsherqi et al. that the mechanisms of aspirin resistance remain incompletely understood and require clarification [4].

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 and prothrombin mutations and fetal loss

Summary.  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.

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

Summary.  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).

Simple coagulation tests improve survival prediction in patients with septic shock

Summary.  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.

Prophylaxis and treatment of thrombophilia in pregnancy

Purpose of reviewThis review addresses the prophylaxis and treatment of thrombophilia in pregnancy, which is associated with increased risk of venous thromboembolism and placental vascular complications. Recent findingsTopics include preventing deep vein thrombosis recurrence in pregnant women with constitutional thrombophilias, using prophylactic heparins throughout pregnancy and postpartum anticoagulants. Cases of thrombosis still occur in the postpartum period and other therapeutics should be tested. Primary prophylaxis is acceptable for high-risk thrombophilias. Early pregnancy losses (before the 10th week) are not associated with constitutional thrombophilias. The natural prognosis of embryonic losses associated with current thrombogenic polymorphisms is good, unlike fetal losses associated with the same thrombophilias: in this case, a prophylactic low-molecular-weight heparin given from the beginning of the 8th week is more efficient than low-dose aspirin. Data are lacking on the prevention of severe preeclampsia, placental abruption, or intrauterine growth restriction in women with constitutional thrombophilias; preliminary results indicate that low-molecular-weight heparin may have some preventive effect. Specific studies are needed. SummaryRecent studies have shown the limits of available procedures for women with constitutional thrombophilia and have helped define the clinical situations in thrombophilia-related placental insufficiency in which prophylactic low-molecular-weight heparin may be indicated.

Analysis of the venous thromboembolic risk associated with severe postpartum haemorrhage in the NOHA First cohort

Severe postpartum haemorrhages (PPH) are responsible for maternal morbidity/mortality. Their complex management sometimes requires haemostatic supplementation, and therapeutic trials on fibrinogen or activated factor VII, which may add to the thrombotic risk, are currently being considered. Furthermore, there is a risk of venous thromboembolism (VTE) during the postpartum period, hence we studied the relationship between severe PPH and VTE in women during their first pregnancy. Among the 32,463 women enrolled between January 1, 1999 and February 1, 2004 in the NOHA First cohort, 317 developed severe PPH, 11 postpartum VTE and 60 had postpartum superficial vein thrombosis (SVT). In the women with severe PPH, whilst there were no episodes of VTE, there were three episodes of SVT, which occurred 6 weeks postpartum. All of the women with severe PPH received packed red blood cell (RBC) units, 29 (9.1%) platelets units, 51 (16.1%) fresh frozen plasma and 29 (9.1%) fibrinogen concentrates. Three patients with both severe PPH and SVT received only packed RBC. Severe PPH or packed RBC unit transfusion were associated with postpartum SVT (adjusted relative risk: 5.3 (1.6-17) and 4.7 (1.5-15) respectively), independent of caesarean section delivery and low-molecular-weight heparin (LMWH) use in the postpartum, but were not independent indicators of one another. This the VTE and SVT risks associated with severe PPH are low (<1% and <2%, respectively). Severe PPH increases the risk of postpartum SVT, but transfusion with platelet units and plasma supplementation using fresh frozen plasma or fibrinogen concentrates do not markedly modulate the risk of venous thrombosis.

ISTH overt disseminated intravascular coagulation score in patients with septic shock: automated immunoturbidimetric soluble fibrin assay vs. D-dimer assay

J . -C . G R I S ,* J . L . FA I LL I E , § É . C OCHERY -NOUVELLON,* G. L I SSALDE-LAV IGNE * and J . -Y . LE FRAN T – *Haematology Laboratory, University Hospital, Nı̂mes, France The Haematology Laboratory, Faculty of Pharmacy and Biological Sciences; Research Unit 2992, University Montpellier 1; §Department of Medical Information, University Hospital, Nı̂mes; and –Central Intensive Care Unit, University Hospital, Nı̂mes, France

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

Summary.  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.

Fibrin-related markers in patients with septic shock: Individual comparison of D-dimers and fibrin monomers impacts on prognosis

Fibrin-related markers in patients with septic shock: Individual comparison of D-dimers and fibrin monomers impacts on prognosis -

The A6936G polymorphism of the endothelial protein C receptor gene is associated with the risk of unexplained foetal loss in Mediterranean European couples

The endothelial protein C receptor (EPCR) is expressed by trophoblast cells. Mid-gestation pregnancy loss is described in animals with a haemochorial placenta lacking EPCR. The A6936G allele of the EPCR gene (PROCR) may be associated with lower EPCR densities on trophoblasts, but data are lacking for its effect on the risk of pregnancy loss in humans. A 1:2 case-control study on unexplained pregnancy loss was nested in the NOHA First cohort: 3,218 case couples and 6,436 control couples were studied for PROCR A6936G, coagulation factor V gene (F5) G1691A and coagulation factor II gene (F2) G20210A polymorphisms. Ethnicity and time of pregnancy loss defined through biometry-based gestational ages (embryonic loss < 10(th) week > or = foetal loss) were analysed. The PROCR A6936G allele, in mothers and fathers, was associated only with foetal loss in both Europeans and non-Europeans. Increasing probability levels of carrying a homozygous child were increasingly associated with the risk of foetal demise. The F5 G1691A and F2 G20210A alleles, only in mothers, were only and independently associated with foetal loss in Europeans. In our population, the PROCR A6936G allele describes women, but also men and thus couples, at risk for first unexplained foetal loss. This risk is independent of the foetal loss risk conferred to our local Mediterranean European women by the F5 G1691A and F2 G20210A alleles. Data confirm that the relationship between thrombophilias and pregnancy loss varies according to ethnicity and loss type.