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Abstract: Introduction: The correct diagnosis and classification of VWD (von Willebrand disease) is crucial and must be optimized by including the collagen binding assay (VWF:CB). VWF:CB remains an under‐recognized tool, not fully automated. The objective of this study was to evaluate and to compare the previously evaluated automated chemiluminescent assay (HemosIL AcuStar VWF:CB) to the ELISA ASSERACHROM® assay used routinely in our laboratory in patients with molecular diagnosis of VWD. Methods: A plasma sample from 49 patients previously diagnosed with VWD (type 1; type 2A, type 2M, type 2B) through phenotype and VWF (von Willebrand factor) analysis and 15 healthy controls was analysed. The VWF ristocetin cofactor activity (VWF:Rco) and VWF antigen (VWF:Ag) were performed simultaneously on the VWD plasma samples, and VWF:CB/VWF:Ag ratios were calculated. Results: The AcuStar VWF:CB assay was quickly performed with Pearson's correlation coefficient (r²) of .9571 between assays and a bias of +5.1U/dL (AcuStar > ELISA). Discrepancies of VWF:CB/VWF:Ag ratio were observed in type 2M‐2A‐like VWD (ratio <0.6 with AcuStar assay in 4/5 samples). Conclusion: The AcuStar VWF:CB assay has demonstrated good performance to detect VWF mutational changes with capacity to discriminate quickly principal types of VWD. [ABSTRACT FROM AUTHOR]

Introduction Haemostatic assessments of patients with von Willebrand disease ( VWD) who undergo total knee arthroplasty ( TKA) and total hip arthroplasty ( THA) have mainly relied on subjective parameters. Aims To compare objective haemostatic outcomes of TKA/ THA in VWD patients and controls without bleeding disorders. Methods We retrospectively analysed haemostatic outcomes in VWD patients undergoing TKA/ THA from 1993 to 2011 and compared them with two matched controls per operation. Using one-way analysis of variance, we tested the effect of VWD on bleeding risk after TKA and THA. Results Twelve VWD patients (6 type 1, 3 type 2M, 1 each of types 2A/2B/3) undergoing 19 operations (12 TKA, 7 THA) were matched to 38 controls. One (5%) of 19 operations in VWD patients and none of the control operations met clinical criteria for major bleeding. Baseline and postoperative day 1 haemoglobin levels, postoperative blood loss, transfused red blood cells ( RBCs) and mean hospitalization days were not significantly different. More VWD patients than controls received RBC transfusions [12 (63%) vs. 12 (32%)]. Only 9 (47%) VWD patients vs. 38 (100%) controls received pharmacologic VTE prophylaxis. No postoperative symptomatic VTE occurred in either group. Conclusion In this largest, single-institutional study, von Willebrand factor replacement based on daily levels resulted in low frequency of major bleeding in VWD patients after TKA/ THA. RBC transfusion was more frequent compared with matched controls, but other objective measures of haemostasis were similar. Lack of sufficient details in published reports precluded comparison of haemostatic outcomes. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the usefulness of score based management of pregnancies with high risk of venous thromboembolism (VTE).Method: 116 consecutive pregnancies in 109 women with confirmed thrombophilia and/or history of VTE were studied. Patients were managed in accordance with international recommendations. Recently, a VTE risk prediction score was established. An independent group assessed retrospectively and in a blinded way the usefulness of this score.Results: Of the 116 pregnancies, an antithrombotic prophylaxis by low molecular weight heparin was prescribed in 61 cases (52.6%). All patients with a positive score (n=57, 49.1%) have been treated with an antenatal thromboprophylaxis. In the population where the score was negative (n=55 cases), none of the patients received antenatal prophylaxis. But, despite a negative score, four patients were treated by their general practitioner. During the study period, there was only one episode of VTE.Conclusion: Implementing this scoring system has resulted in favorable outcomes and a low risk of recurrent thrombosis in this limited series of women with increased risk of VTE. [ABSTRACT FROM AUTHOR]

We report a patient with a previously known primary antiphospholipid syndrome who had life threatening multiple arterial thromboses. The patient experienced a myocardial infarction with intraventricular thrombi under bromocriptine therapy in the puerperium, despite prophylactic low molecular weight heparin therapy. In this patient, no microvascular involvement was identified, thus eliminating the diagnosis of catastrophic antiphospholipid syndrome. Arterial thromboses may be explained by peripheral emboli originating from the intraventricular thrombi. This case emphasizes the necessity of a careful evaluation of the risk – benefit balance of bromocriptine therapy in patients with arterial risk factors. It also emphasizes the need for a correct diagnosis of catastrophic antiphospholipid syndrome allowing to limit the prescription of aggressive therapies. [ABSTRACT FROM AUTHOR]

Comments on an article about the relation between neonatal thrombocytopenia and maternal platelet count. Differential diagnosis for neonatal thrombocytopenia; Treatment approach to neonatal thrombocytopenia.

Abstract: Acquired anti-factor V (FV) antibodies are uncommon and the majority of reported cases are idiopathic or associated with pregnancy, malignancy, autoimmune diseases or the use of bovine thrombin preparations. Clinical presentation is highly variable, ranging from asymptomatic to life-threatening bleeding and the optimal treatment is not clearly established. We here report two patients with different clinical presentations. The first patient presented with an acute severe rectal bleeding related to acquired FV deficiency and recurrent colon cancer while the second patient was asymptomatic with a FV inhibitor detected during a routine blood testing. We discuss treatment modalities that are not consensual. [Copyright &y& Elsevier]

Introduction La prévention du risque de maladie thromboembolique veineuse (MTEV) pendant la grossesse chez les patientes à risque (antécédents personnels de MTEV ou thrombophilie biologique) fait l’objet de recommandations peu précises. Le score de Lyon propose une stratification du risque en trois groupes avec une attitude thérapeutique adaptée à chaque groupe. Notre travail évalue les résultats de l’application de ce score sur une période prospective de 10 ans. Patients et méthodes Le score de Lyon s’applique aux patientes enceintes ayant un ou plusieurs antécédents de MTEV et/ou porteuses de thrombophilie biologique. Le score ne s’applique pas aux patientes sous anticoagulant au long cours, à celles atteintes de déficit en antithrombine ou de syndrome des antiphospholipides, et aux pathologies vasculoplacentaires. Il prend en compte le type d’accident thrombotique, les circonstances de survenue, les facteurs de risque identifié. En fonction du résultat du score, la prévention par HBPM n’est indiquée qu’en post-partum, au troisième trimestre et post-partum ou tout au long de la grossesse et post-partum. Une contention élastique toute la grossesse et post-partum est prescrite quel que soit le résultat du score. Le score et l’attitude thérapeutique sont calculés en début de grossesse et réévalués à chaque trimestre. Les patientes sont revues systématiquement en post-partum. Résultats Quatre cent quarante-cinq patientes ont été prises en charge prospectivement entre 2004 et 2014 au cours de 542 grossesses selon un schéma thérapeutique préventif adapté au risque de MTEV calculée par le score de Lyon. L’âge moyen est de 33 ans avec 29 % de plus de 35 ans. L’IMC moyen est de 24,3 avec 8 patientes en obésité morbide. Cent quatre-vingt-dix patientes sont primipares et 255 multipares. On comptait 12 grossesses gémellaires. L’accident thrombotique était une TVP distale dans 41 % des cas, une TVP proximale dans 28 % et une EP dans 20 %, une thrombose veineuse cérébrale dans 3,6 % et une pathologie récidivante (mais sans indication de traitement au long cours) dans 9 % des cas ; 14,7 % avaient des séquelles de thromboses. Deux cent quatre-vingt-dix-neuf patientes (67,2 %) ont une thrombophilie soit 26 un déficit en protéine C, 18 un déficit en protéine S, 152 une mutation hétérozygote en facteur V leiden, 65 une mutation hétérozygote en facteur II, 9 une mutation homozygote en facteur V et 4 une mutation homozygote en facteur II. Vingt-cinq avaient des anomalies conjuguées. La stratification du risque selon le score de Lyon était de 158 patientes en risque modéré, traitées uniquement en post-partum, 153 avec un risque élevé traitées au 3 e trimestre + post-partum et 134 un risque très élevé traitées préventivement toute la grossesse et en post-partum. Pendant les 10 ans de l’étude sont survenus 6 épisodes thrombotiques (1,35 %) : 2 en ante partum et 4 en post-partum. Les 2 événement en ante partum étaient : 1 TVP proximale chez une patiente porteuse d’une mutation hétérozygote facteur V asymptomatique au 8 e mois de grossesse lors d’un alitement prolongé n’ayant pas conduit à modification de l’attitude thérapeutique et une TVP distale à 28 semaines d’aménorrhée chez une patiente à risque très élevée ne portant pas la contention élastique. Les 4 événements du post-partum sont une thrombose ovarienne à j3, 2 TVP survenue dans la semaine suivant l’arrêt de l’HBPM préventive et [ABSTRACT FROM AUTHOR]

Background:  For the treatment of von Willebrand disease (VWD), von Willebrand factor (VWF) concentrates can be used in on-demand, long-term prophylaxis, and surgical prophylaxis regimens., Methods:  This systematic literature review was conducted to evaluate the efficacy, consumption, and safety of plasma-derived human coagulation FVIII/human VWF (pdVWF/FVIII; Voncento/Biostate) for the treatment of patients with any inherited VWD type. An electronic search was conducted in MEDLINE and Cochrane Library databases on VWD therapies. All retrieved publications were assessed against predefined inclusion/exclusion criteria following the Cochrane group recommendations. Associated pharmacovigilance data were collected across the same time period., Results:  Eleven publications from eight study cohorts were identified for data retrieval. All were from multicenter studies and included both pediatric and adult patients. Eight publications included evaluations of the efficacy of pdVWF/FVIII for on-demand treatment, eight included long-term prophylactic treatment, and eight included surgical prophylaxis. Treatment protocols and VWF administration methods differed between studies, as did safety evaluations. The clinical response was rated as excellent/good for on-demand treatment in 66 to 100% of nonsurgical bleeds, 89 to 100% in the treatment of breakthrough bleeds during long-term prophylaxis treatment, and hemostatic efficacy in surgical procedures was 75 to 100%. Pharmacovigilance data confirmed a low incidence of adverse events in treated patients., Conclusion:  This review provides a comprehensive summary of studies that evaluated the use of pdVWF/FVIII in VWD demonstrating the long-term effectiveness and safety of this pdVWF/FVIII across all ages, types of VWD, and treatment settings., Competing Interests: L.R. has been a consultant for CSL Behring and Octapharma and received honoraria from LFB for speeches at congresses. G.A. received honoraria from CSL Behring for speeches at congresses and travel expenses. W.T. has received speakers' fees from Takeda, Bayer, Sobi, Pfizer, NovoNordisk, CSL Behring, Alexion, Portola, and Sanofi, and participated in advisory boards for Pfizer, Takeda, Ablynx, Sanofi, Daiichi Sankyo, LFB, Grifols, and Novo Nordisk. K.S. and L.H. are employees of CSL Behring., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Despite the wide use of bleeding scores and the reliability of clotting factor level measurement, bleeding risk stratification before surgery remains challenging in patients with rare inherited bleeding disorders., Objectives: This multicenter observational prospective study assessed in patients with rare coagulation factor deficiency, the perioperative hemostatic management choices by hemostasis experts and the bleeding outcomes after surgery., Methods: One hundred seventy-eight patients with low coagulation activity level (factor [F] II, FV, combined FV-FVIII, FVII, FX, or FXI <50%) underwent 207 surgical procedures. The bleeding outcome, Tosetto's bleeding score, and perioperative hemostatic protocols were collected., Results: Among the 81 procedures performed in patients with severe factor deficiency (level ≤10%), 27 were done without factor replacement (including 6 in patients at high bleeding risk), without any bleeding event. Factor replacement therapy was used mainly for orthopedic procedures. In patients with mild deficiency, 100/126 surgical procedures were carried out without perioperative hemostatic treatment. In patients with FVII or FXI deficiency, factor replacement therapy was in function of the procedure, bleeding risk, and to a lesser extent previous bleeding history. Tranexamic acid was used in almost half of the procedures, particularly in case of surgery in tissues with high fibrinolytic activity (76.8%)., Conclusions: The current perioperative hemostatic management of patients with rare bleeding disorders appears to be adapted. Among the 207 procedures, only 6 were associated with excessive bleeding. Our findings suggest that rather than the bleeding score, factor level and surgery type are the most relevant criteria for perioperative factor replacement therapy., (© 2023 The Authors.)

Introduction: The rare coagulation disorders may present significant difficulties in diagnosis and management. In addition, considerable inter-individual variation in bleeding phenotype is observed amongst affected individuals, making the bleeding risk difficult to assess in affected individuals. The last international recommendations on rare inherited bleeding disorders (RIBDs) were published by the United Kingdom Haemophilia Centre Doctors' Organisation in 2014. Since then, new drugs have been marketed, news studies on surgery management in patients with RIBD have been published, and new orphan diseases have been described., Aim: Therefore, the two main objectives of this review, based on the recent recommendations published by the French Reference Centre on Haemophilia and Rare Bleeding Disorders, are: (i) to briefly describe RIBD (clinical presentation and diagnostic work-up) to help physicians in patient screening for the early detection of such disorders; and (ii) to focus on the current management of acute haemorrhages and long term prophylaxis, surgical interventions, and pregnancy/delivery in patients with RIBD., (© 2023 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Background: Availability of multichannel cytometers and specific commercial antibodies makes flow cytometry a new option to simultaneously assess multiple intracellular platelet signaling pathways for clinical purposes, in small volume of blood or low platelet count., Objectives: To describe a multicolor flow cytometry with fluorescent barcoding technique for screening signaling pathways downstream membrane receptors of major platelet agonists (adenosine diphosphate, thrombin, thromboxane, and collagen)., Methods: By comparison with immunoblotting, we first selected the target phosphoproteins, AKT, P38MAPK, LIMK, and SPL76; the times of stimulation; and phosphoflow barcoding conditions. We then performed a clinical study on whole blood of patients without evidence of blood platelet disorder on standard biological screening, consulting for trivial or occasionally provoked bleeds without familial antecedent (bleeding of unknown origin, n  = 23) or type-1 von Willebrand disease ( n  = 9). In addition, we included a small group of patients with definite platelet disorders (Glanzmann thrombasthenia, δ-storage pool deficiency, and immune glycoprotein VI-related disease with granule secretion defect)., Results: The range, kinetics, and distribution of fluorescence intensity were established for each agonist-target protein combination. Principal component analysis indicates a correlation in response to a target phosphoprotein (AKT and P38MAPK) to different agonists but no correlation in the response of different target phosphoproteins to the same agonist. The heterogeneity of individual responses in the whole population displayed was analyzed using clustering algorithm. Patients with platelet storage pool deficiency were positioned as lowest responders on the heatmap., Conclusion: In complement of functional tests, this study introduces a new approach for rapid platelet signaling profiling in clinical practice., (© 2023 The Authors.)

Background:  A plasma-derived factor VIII product (pdFVIII; Factane 100 or 200 IU/mL) and a plasma-derived von Willebrand factor product (pdVWF; Wilfactin 100 IU/mL) are approved for replacement therapy by intravenous bolus injections in hemophilia A (HA) and von Willebrand disease (VWD), respectively. However, in situations requiring intensive treatment, continuous infusion (CI) may be desirable to better control target plasma factor levels., Aim:  To evaluate the perioperative hemostatic efficacy and safety of these concentrates administered by CI., Methods:  Three phase III trials were conducted. Adults with HA (FVIII:C < 1%) (studies 1 and 2) or VWD (VWF:RCo < 20%) (Study 3) received a preoperative bolus followed by CI of undiluted concentrate for at least 6 days. Bolus doses and CI rates were based on individual recovery and clearance, respectively. The initial infusion rate had to be higher for 48 hours for HA and 24 hours for VWD patients to anticipate potential fluctuations of factor concentrations during major surgery. Target levels of FVIII:C in HA and VWF:RCo in VWD were 80 and 70 IU/dL, respectively. Efficacy was assessed using a global hemostatic efficacy score., Results:  Studies 1, 2, and 3 included 12, 4, and 6 patients, respectively. Efficacy outcomes were excellent/good in all 22 major surgeries including 18 orthopedic procedures. Most daily measured FVIII and VWF levels (92%) were on target. No safety concerns, thrombotic events, or inhibitors were identified., Conclusion:  pdFVIII and pdVWF administered by CI represent an effective and safe alternative to bolus injections in patients with severe HA or VWD undergoing surgery., Competing Interests: J.W. received grant support from Alnylam Pharmaceuticals, Baxalta, LFB, Novo Nordisk, Octapharma, Rigel Pharmaceuticals, Roche, Shire/Takeda, and Sobi; also sponsored lectures from Alexion, Baxalta, CSL Behring, Ferring Pharmaceuticals, Novo Nordisk, Octapharma, Roche, Sanofi/Genzyme, Shire/Takeda, Siemens, Sobi, and Werfen. B.G. has received grant support from CSL Behring, Octapharma and Sobi; also sponsored lectures from CSL Behring, Novo Nordisk, Roche, and Shire/Takeda. L.R. has no conflicts of interest to declare. E.S.-W. has no conflicts of interest to declare. V.C. has received honoraria or consultation fees from Roche, Novo Nordisk, and Sobi, also support for attending scientific meetings from LFB and Sobi. S.P. is an employee of LFB; C.H. is an employee of LFB. F.B. is a former employee of LFB. C.N. received research grant or honoraria or participated in clinical trials from Alnylam/Sanofi, Bayer, Biomarin, Bioverativ/Sobi, Bayer, CSL Behring, Novo Nordisk, Octapharma, Pfizer, Roche/Spark, and Shire/Takeda., (The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/).)

Background: Patients with symptomatic von Willebrand disease (VWD) should be offered long-term prophylaxis (LTP) to prevent recurrent bleedings. Our objective was to evaluate the effectiveness and safety of Voncento®, a plasma-derived FVIII/VWF concentrate (ratio 1:2.4), administrated in LTP., Methods: We included patients from the OPALE study (May 2016 to April 2021), a French multicenter observational study following patients with inherited VWD, who received a Voncento® LTP during the study period., Results: Among the 130 OPALE-study patients, 23 patients (12 women) received a LTP and were therefore included. The median (range) age was 16 (1-85) years; 16 patients were type 3, 1 was type 2A, 6 were type 2B. Before inclusion, 19 (83%) were under LTP and 4 (17%) received on-demand (OD) treatment. The indications for initiating prophylaxis in the overall population were joint bleeding (43%), ear, nose, and throat (ENT) bleeding including epistaxis or oral bleeding (39%), and recurrent muscle hematoma (22%). The medians (ranges) dose of Voncento® per infusion, frequency, and weekly dose were 45 (33-109) IU/kg, 2 infusions per week, and 96 (44-222) IU/kg/week, respectively. The median (range) annualized bleeding rate (ABR) was 0.8, 0.7 (0-3.5), and 0 (0-2.3) for type 2A, 2B, 3 patients, respectively. There was no difference regarding to the dose, frequency of infusion, or in terms of ABR in 9/19 patients who replaced previous concentrates with Voncento®. During the study period, no adverse event was reported., Conclusion: These results suggest that Voncento® is effective to prevent recurrent bleedings in patients symptomatic VWD., (© 2022 The Authors. European Journal of Haematology published by John Wiley & Sons Ltd.)

Background: In patients with FXI deficiency, the risk of surgery-related bleeding is poorly correlated with plasma FXI activity (FXI:C); the latter can therefore not be used as a reliable predictor of bleeding in surgeries., Objectives: The aim of this retrospective study was to determine whether thrombin generation assay (TGA) could be used to evaluate the risk of surgery-related bleeding in FXI-deficient patients. TGA parameters were compared to FXI:C values, haemostatic treatments and surgical outcomes., Patients: All patients followed at the haemophilia treatment care centre (Lyon, France) with a FXI:C < 50IU/dL, and for whom a baseline TGA was performed between January 2014 and December 2019, were included., Results: Among the 175 surgeries reported herein in 49 patients, FXI concentrates were used for 11 (6%) surgeries and fresh frozen plasma was used for five (3%) surgeries; these surgeries were performed in patients with two or three impaired TGA parameters. No haemostatic treatment was prescribed for 119 (68%) surgeries. A surgery-related bleeding occurred in 12 patients during 21 (12%) surgeries. Thrombin generation was significantly reduced or delayed in patients who reported surgery related-bleeding. Among the 34 (68%) surgeries performed without haemostatic treatment in patients with three impaired TGA parameters, a surgery-related bleeding was reported in 44% of cases (15 surgeries out of 34)., Conclusion: The present study confirmed that TGA is an interesting laboratory test in FXI deficiency, for determining the bleeding risk and guiding the haemostatic management of surgeries, while taking into account the surgical bleeding risk and the history of bleeding., (© 2022 John Wiley & Sons Ltd.)

Acquired factor V inhibitor (AFVI) is an extremely rare disorder that may cause severe bleeding. To identify factors associated with bleeding risk in AFVI patients, a national, multicentre, retrospective study was made including all AFVI patients followed in 21 centres in France between 1988 and 2015. All patients had an isolated factor V (FV) deficiency <50% associated with inhibitor activity. Patients with constitutional FV deficiency and other causes of acquired coagulation FV deficiencies were excluded. The primary outcome was incident bleeding and factors associated with the primary outcome were identified. Thirty-eight (74 [36-100] years, 42·1% females) patients with AFVI were analysed. Bleeding was reported in 18 (47·4%) patients at diagnosis and in three (7·9%) during follow-up (7 [0·2-48.7] months). At diagnosis, FV was <10% in 31 (81·6%) patients. Bleeding at diagnosis was associated with a prolonged prothrombin time that strongly correlated with the AFVI level measured in plasma {r = 0·63, 95% confidence interval (CI) [0·36-0·80], P < 0·05}. Bleeding onset during follow-up was associated with a slow AFVI clearance (P < 0·001). The corresponding receiver operating characteristics curve showed that AFVI clearance was predictive of bleeding onset with an AFVI clearance of seven months with a sensitivity of 100% (95% CI: 29-100) and a specificity of 86% (95% CI: 57-98, P = 0·02). Kaplan-Meier analysis showed that AFVI clearance >7 months increased the risk of bleeding by 8 (95% CI: [0·67-97], P = 0·075). Prothrombin time at diagnosis and time for clearance of FV inhibitor during follow-up are both associated with bleeding in patients with AFVI., (© 2021 British Society for Haematology and John Wiley & Sons Ltd.)

Background: In patients with moderate to severe qualitative and quantitative von Willebrand disease (VWD), even minor surgical procedures can be associated with a risk of life-threatening bleeding. Treatment strategies vary according to the levels of von Willebrand factor (VWF) and Factor VIII (FVIII). The aim of this study was to evaluate the effectiveness and the safety of Voncento ® (CSL Behring, Marburg, Germany), a plasma-derived FVIII/VWF concentrate (ratio 1:2.4), during surgeries performed in patients with inherited VWD., Materials and Methods: The OPALE study, a French multicentre observational study, was carried out from May 2016 to May 2019. It evaluated and analysed patients with inherited VWD (any type) requiring treatment with Voncento ® who underwent surgery., Results: In total, 92 patients were enrolled, and 66 patients underwent 100 surgical procedures: 69 minor and 31 major surgeries conducted in 30 patients with type 1, 50 patients with type 2, and 20 patients with type 3 VWD. During minor surgeries, the median number of infusions was one (range: 1-9), the pre-operative loading dose was 41 IU VWF:RCo kg -1 (range: 18-147), and the total dose was 63 (range: 18-594). During major surgeries, the number of infusions was 4 (range: 1-23), the pre-operative loading dose was 43 (range: 25-66) IU VWF: RCo kg -1 , and the total dose was 155 (range: 40-575). The median FVIII:C levels ranged from 78 to 165 IU dL -1 during 5 days after minor surgeries and from 86 and 167 IU dL -1 during 11 days after major surgeries. VW:RCo levels ranged between 35 and 65 IU dL -1 and between 34 and 76 IU dL -1 after minor and major surgeries, respectively. The overall clinical effectiveness was qualified as "excellent" or "good" in 99% of patients. No thrombotic events related to Voncento ® were recorded., Discussion: The present study suggests that Voncento ® is an effective and well-tolerated therapy for the peri-operative management of patients with all VWD types.

Introduction: Congenital factor XIII deficiency is a very rare bleeding disorder affecting 33 patients in France. Besides its role in fibrin clot stabilization, factor XIII is involved in placental attachment. Fetal miscarriages represent a frequent and concerning issue for these patients. The aim of the present study was to describe clinical characteristics of women presenting severe congenital FXIII deficiency in France, to focus on gynecological and obstetrical events, and to report the management of these rare situations., Methods: We conducted a retrospective study in the French Hemophilia Comprehensive Care and Clinical Hemostasis Centers. Women between 15 and 65 years with factor XIII activity <10 IU dL -1 were included. Biological, clinical and therapeutic events that occurred to these patients during their gynecological and obstetrical period were recorded., Results: Among 31 centers, eleven patients were included. The median age at diagnosis was 1.5 years (range: 0-35), and at inclusion it was 30 years (range: 15-63). Fetal miscarriage was the primary manifestations in 2 (18%) patients, the remaining were diagnosed during hemorrhage. Menorrhagias were reported by 2 women (27%), 13 pregnancies were reported by 9 women including one abortion. Every pregnancy was conducted under factor XIII substitution, no hemorrhagic episode was reported. Four patients (36%) experienced at least one fetal miscarriage with a total amount of 30 miscarriages with 6 occurring during substitution., Conclusion: Altogether, our data confirmed the high incidence of miscarriage in women with factor XIII deficiency. Good outcome of pregnancies required prophylaxis in accordance with international guidelines., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background:  Heparin-induced thrombocytopenia (HIT) is a rare complication of heparin treatments, and only a few large patient cohorts have been reported. In this study, biological and clinical data from 144 French patients with HIT were analyzed in comparison with the literature., Methods:  The diagnosis of HIT was confirmed in all patients by an immunoassay combined with serotonin release assay. In the literature, only cohorts of at least 20 HIT patients published from 1992 were selected for a comparative analysis., Results:  Two-thirds of patients were hospitalized in surgery and most were treated with unfractionated heparin (83.2% vs. 16.8% with low molecular weight heparin only). Thrombotic events in 54 patients (39.7%) were mainly venous (41/54). However, arterial thrombosis was more frequent after cardiac surgery (13.2% vs. 2.4% in other surgeries, p  = 0.042) with a shorter recovery time (median = 3 vs. 5 days, p  < 0.001). The mortality rate was lower in our series than in the 22 selected published studies (median = 6.3% vs. 15.9%). Three genetic polymorphisms were also studied and homozygous subjects FcγRIIA RR were more frequent in patients with thrombosis (37.8 vs. 18.2% in those without thrombosis, p  = 0.03)., Conclusion:  This study shows that the mortality rate due to HIT has recently decreased in France, possibly due to earlier diagnosis and improved medical care. It also confirms the strong association between polymorphism FcγRIIA H131R and thrombosis in HIT., Competing Interests: Y.G.: Consulting and/or travel fees from Octapharma, Shire, CSL Behring, Novo Nordisk, Bayer, LFB, and Léo Pharma. J.R.: Travel fees from Octapharma, Shire, and CSL Behring. C.V.: Travel fees from Sobi, Roche, Shire, and CSL Behring. D.F.: Consulting and/or travel fees from Aspen, Boehringer, Werfen, Stago, and Léo Pharma. A.B.: Travel fees from Aspen, Boehringer, Werfen, Pfizer, and LFB. A.L.: Consulting and/or travel fees from Bayer, LFB, Pfizer, Sobi, and Octapharma. E.D.M.: Travel fees from Sobi, Bayer, Novo Nordisk, and Pfizer. B.T.P.: Consulting and/or travel fees from Sobi, Bayer, Shire, CSL Behring, and Pfizer. I.E.: Consulting and/or travel fees from BMS, Aspen, Léo Pharma, Daiichi Sankyo, Pfizer, Sanofi-Aventis, and Shire. C.L.B.: Travel fees from Sobi, Octapharma, CSL Berhing, and Novo Nordisk. C.M.: Consulting and/or travel fees from BMS, Aspen, Pfizer, and Bayer. C.B.: Consulting and/or travel fees from CSL, Sobi, Bayer, and Novo Nordisk. C.T.: Consulting and travel fees from Sobi, Roche, Octapharma. F.N.G.: Travel fees from Sobi, Bayer, BMS, and Boehringer. J.D.: Travel fees from CSL and Novo Nordisk. T.B.A.: Travel fees from Servier and MSD. E.D.R.: Consulting and/or travel fees from Shire, Alexion, Sobi, Bayer, and Novo Nordisk. I.G.T.: Consulting and/or travel fees from Bayer, MSD, Pfizer, Sanofi-Aventis, and BMS. L.R.: Consulting and/or travel fees from CSL, LFB, Novo Nordisk, Sobi, and Bayer. B.T.: Consulting and/or travel fees from Sobi, Bayer, Novo Nordisk Aspen, CSL Behring, and Pfizer. C.P.: Consulting and/or travel fees from Sobi, Roche, Novo Nordisk, and CSL Behring. P.W., M.A.G., S.V., V.G.G., J.P., and B.G. have no conflict to disclose. All the authors did not receive any personal honorarium or funds related to the study reported in this manuscript. Y.G. reports grants from Ministère de la Santé (Government), during the conduct of the study; personal fees and nonfinancial support from CSL Behring, personal fees and nonfinancial support from Octapharma, nonfinancial support from Shire, personal fees from Léo Pharma, personal fees and nonfinancial support from LFB, nonfinancial support from Bayer, nonfinancial support from Novo Nordisk, outside the submitted work., (Georg Thieme Verlag KG Stuttgart · New York.)