Search

Unlabelled Boxce:textbox-body/

Case reports on recombinant human factor VIIa (rhuFVIIa) use in women with severe postpartum hemorrhage (PPH) showed encouraging results, but no randomized controlled trial (RCT) is available.

Le caractère non optimal de la prise en charge anesthésique au cours de l’HPP est un facteur de risque de morbidité et de mortalité maternelle. La phase initiale étant abordée ailleurs, le présent chapitre est consacré à la prise en charge de l’HPP sévère.

Background: A clinical subtype of purely obstetrical antiphospholipid antibody (aPL‐Ab) syndrome (APS) requires three or more unexplained consecutive embryonic losses before the 10th week of gestation associated with persistently positive lupus anticoagulant (LAC), and/or anticardiolipin IgG or IgM, and/or anti‐β2‐glycoprotein I (aβ2GpI) IgG or IgM. Although this diagnostic classification of APS appeared to be the most sensitive, the APS‐associated serological criteria are still debated. Patients/methods: We prospectively observed the second pregnancy of 284 women with a previous embryonic loss, both with and without aPL‐Ab. Results: aPL‐Ab‐positive women were more prone to pregnancy loss, embryonic loss, pre‐eclampsia, placental abruption and intrauterine fetal growth restriction. Type IIa aPL‐Ab positivity (LAC present alone) was associated with the highest risk of recurrent embryonic loss and intrauterine growth restriction. Type I aPL‐Ab positivity (combinations of aPL‐Ab type positivity) was associated with the strongest risks of late complications, pre‐eclampsia and placental abruption. Finally, aβ2GpI‐M positivities were not clinically relevant in these women. Conclusion: Patients with a first unexplained pregnancy loss before the 10th week of gestation who are also positive for aPL‐Abs have a higher risk of various complications in their second pregnancy. In this study, measurement of aβ2GpI‐M had a questionable prognostic value.

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.

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).

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.

We describe six families in which associated high levels of coagulation factors (F) XI, FIX and FVIII (each with a plasma concentration higher than the 95th percentile found in a control group of 500 asymptomatic individuals: respectively, 135, 145 and 155 IU dL−1) were inherited as a dominant autosomic genetic traits. In these six families, this syndrome is associated with venous thromboembolic events (Odds ratio 41 [4.9–353], P = 0.0006). It seems to predispose to idiopathic events and, as age increases, is often associated with recurrence. First thrombotic episodes occur in young patients (50% of the carriers are symptomatic at the age of 32 years) and in women, can be unmasked by hormonal treatments, mainly oral contraceptives. The association of high levels of coagulation FXI, FIX and FVIII is thus a new rare high-risk inherited thrombophilia syndrome.

Using a newly-developed technique, a severe acquired plasma resistance to activated protein C has been described in women using third-generation (rather than second-generation) oral contraceptives. The following items are discussed: (i) the technical parameters used to appreciate the effect of activated protein C induce a bias of interpretation, the mean intrinsic effect of activated protein C, in plasmas from women on second or third-generation oral contraceptives being strictly identical; (ii) there are no data available to show that this assay can indicate a thromboembolic risk in asymptomatic women on oral contraceptives; and (iii) this assay is a global and non-specific test, basically sensitive to the plasma concentrations of many coagulation factors which are increased or decreased by oestrogens and progestogens. For instance protein S, in which oral contraceptive-induced modifications account for the differential effect of oral contraceptives on Rosing's assay, but which modifications are not related to the thromboembolic risk of oral contraceptives. The androgenic potential of the progestogen may counteract the effect of oestrogens in the test. More generally, in such a complex situation in which there is a 'modification of the modification', there is no haemostasis-related test which provides a risk indicator for thrombosis. Based on testing of the plasma response to activated protein C, it is impossible to state that third-generation oral contraceptives induce a more important thromboembolic risk than oral contraceptives containing a more androgenic progestogen.

Summary Over the past few years, the methodologies used for the identification of hemoglobin A variants have been greatly improved. Both the protein- and DNA-based strategies have their own advantages and limitations. In this report we illustrate the use of both assays for the characterization of a hemoglobin Cocody variant in a woman of Spanish descent. After evaluating the mobility value matrix of the abnormal hemoglobin, the amino acid transition was determined by HPLC and microsequencing of the protein. Theß21 Asp was shown to be substituted by an Asn. At the DNA level, the only nucleotide replacement responsible for this amino acid substitution is GAT- ? AAT at codon 21. The analysis of theß-globin gene by denaturing gradient gel electrophoresis (DGGE) method showed that the mutation was situated in a fragment including exon 1. The hemoglobin variant was then identified to be hemoglobin Cocody by DNA sequencing of this fragment.

In vitro experiments were designed to investigate the effect of low oxygen tensions on tissue-type plasminogen activator (t-PA) production by vascular endothelium. Cultured human umbilical vein endothelial cells were submitted for 1-8 h to hypoxia (30 mm Hg). t-PA antigen, measured by specific enzyme-linked immunosorbent assay (ELISA), was found significantly decreased either in culture supernatants or in cell lysates/extracellular matrix. By contrast, the secretion of plasminogen activator inhibitor-1 (PAI-1), also measured by specific ELISA, was not affected. Addition of superoxide dismutase (a superoxide anion scavenger) or oxypurinol (a xanthine oxidase inhibitor) to monolayers before hypoxia prevented t-PA modification. The flavonoid rutin (a hydroxyl radical scavenger) also presented a protective effect whereas catalase (a hydrogen peroxide scavenger) was inefficient. These results suggest that hypoxia stimulates endothelial cells to produce oxygen radicals and in particular xanthine oxidase-derived superoxide anions which mediate the inhibition of t-PA production.

The Sapporo criteria-related definition commonly used for diagnosis of the antiphospholipid syndrome (APS) associates the occurrence of thrombotic and/or obstetrical events with persistently positive antiphospholipid antibodies (aPL-Ab), including lupus anticoagulant (LAC), anticardiolipin IgG (aCL-G) or IgM, and/or anti-b2-glycoprotein I IgG or IgM antibodies. Criteria used to define the purely obstetrical clinical subtype of the APS syndrome include the aPLs listed above plus a fetal loss later than 10-weeks gestation, 3 or more unexplained consecutive embryonic losses before the 10th week gestation, or eclampsia or features of placental insufficiency requiring the preterm birth before 34 weeks of a morphologically normal child. Some investigators have questioned the serological criteria associated with this form of APS and have suggested that the aCL-G, anticardiolipin IgM, and anti-b2-glycoprotein I IgM measurements should be excluded.

See alsoDrewlo S, Levytska K, Sobel M, Baczyk D, Lye SJ, Kingdom JCP. Heparin promotes soluble VEGF receptor expression in human placental villi to impair endothelial VEGF signalling. J Thromb Haemost2011; 2486–97.

A 32-year-old pregnant woman developed meningococcemia associated purpura fulminans and quickly improved with therapy. After this disease C4b-Binding Protein (C4bBP) plasma levels remained very low while protein S activity was in the normal range. Familial investigation proved a hereditary C4bBP deficiency. This observation points out the role of the protein C-protein S system during acquired purpura fulminans.