Denninger MH, de Prost D, for the PPH Study Group. The decrease of fibrinogen is an early predictor of the severity of postpartum hemorrhage. 2007; 5: 266-73. Summary. Background: Postpartum hemorrhage (PPH) is a major source of maternal morbidity. Objectives: This study's objective was to determine whether changes in hemostasis markers during the course of PPH are predictive of its severity. Patients and methods: We enrolled 128 women with PPH requiring uterotonic prostaglandin E2 (sulprostone) infusion. Two groups were defined (severe and non-severe PPH) according to the outcome during the first 24 hours. According to our criteria, 50 of the 128 women had severe PPH. Serial coagulation tests were performed at enrollment (H0), and 1, 2, 4 and 24 hours thereafter. Results: At H0, and through H4, women with severe PPH had significantly lower fibrinogen, factor V, antithrombin activity, protein C antigen, prolonged prothrombin time, and higher D-dimer and TAT complexes than women with non-severe PPH. In multivariate analysis, from H0 to H4, fibrinogen was the only marker associated with the occurence of severe PPH. At H0, the risk for severe PPH was 2.63-fold higher for each 1 gL )1 decrease of fibrinogen. The negative predictive value of a fibrinogen concentration >4 gL )1 was 79% and the positive predictive value of a concentration £2 gL )1 was 100%. Conclusion: These findings indicate that a simple fibrinogen measurement can anticipate the risk of severe bleeding in PPH. J Thromb Haemost

MYH9-Related Disorders are a group of rare autosomal dominant platelet disorders presenting as nonsyndromic forms characterized by macrothrombocytopenia with giant platelets and leukocyte inclusion bodies or as syndromic forms combining these hematological features with deafness and/or nephropathy and/or cataracts. They are caused by mutations in the MYH9 gene encoding the nonmuscle myosin heavy chain II-A (NMMHC-IIA). Until now, at least 49 MYH9 mutations have been reported in isolated cases or small series but only rarely in large series. We report the results of an 8-year study of a large cohort of 109 patients from 37 sporadic cases and 39 unrelated families. We have identified 43 genetic variants, 21 of which are novel to our patients. A majority, 33 (76.7%), were missense mutations and six exons were preferentially targeted, as previously published. The other alterations were three deletions of one nucleotide, one larger deletion of 21 nucleotides, and one duplication. For the first time, a substitution T>A was found in the donor splice site of intron 40 (c.5765+2T>A). Seven patients, four from the same family, had two genetic variants. The analysis of the genotype-phenotype relationships enabled us to improve the knowledge of this heterogeneous but important rare disease.

Pregnancy in women with inherited thrombocytopenias is a major matter of concern as both the mothers and the newborns are potentially at risk of bleeding. However, medical management of this condition cannot be based on evidence because of the lack of consistent information in the literature. To advance knowledge on this matter, we performed a multicentric, retrospective study evaluating 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia. Neither the degree of thrombocytopenia nor the severity of bleeding tendency worsened during pregnancy and the course of pregnancy did not differ from that of healthy subjects in terms of miscarriages, fetal bleeding and pre-term births. The degree of thrombocytopenia in the babies was similar to that in the mother. Only 7 of 156 affected newborns had delivery-related bleeding, but 2 of them died of cerebral hemorrhage. The frequency of delivery-related maternal bleeding ranged from 6.8% to 14.2% depending on the definition of abnormal blood loss, suggesting that the risk of abnormal blood loss was increased with respect to the general population. However, no mother died or had to undergo hysterectomy to arrest bleeding. The search for parameters predicting delivery-related bleeding in the mother suggested that hemorrhages requiring blood transfusion were more frequent in women with history of severe bleedings before pregnancy and with platelet count at delivery below 50 x 10 9 /L. ABSTRACT antepartum intracranial hemorrhage. On this basis, it has been concluded that bBSS is associated with a very high risk of serious bleeding in the mother and the neonate. Analysis of 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopeniaSome information on pregnancy outcome is available also for MYH9-related disease (MYH9-RD), one of the most frequent forms of IT. A recent review of the literature examined 25 case reports and one case series describing a total of 75 pregnancies in 40 women.5 Postpartum hemorrhage in the mother occurred in 4 cases, while no obvious bleeding complications were reported among the newborns. Based on these data, MYH9-RD does not seem to increase bleeding risk either in mothers or neonates.Limited data on pregnancy outcomes have been provided for patients with mild to moderate thrombocytopenia due to monoallelic BSS (mBSS), in all cases induced by the p.Ala156Val substitution in GPIb alpha (Bolzano mutation). 6 Overall, 20 women delivered 34 children with no excessive maternal or neonatal bleeding. Although the authors did not provide information on management of pregnancies and childbirths, this study suggests that women with mBSS have gestational outcomes similar to healthy subjects.A moderate risk of bleeding during delivery has been reported in a series of subjects with thrombocytopenia induced by ANKRD26 mutations (ANKRD26-related thrombocytopenia, ANKRD26-RT).7 Thirteen patients gave birth, either vaginally or by caesarean section, with bleeding complications in 3 women. No information was provided o...

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Determination of PCT is of value in excluding bacterial infection in neonates since it has a negative predictive value of 93%.