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Objectives: To assess the real-world efficacy and safety of recombinant factor IX albumin fusion protein (rIX-FP) in patients with hemophilia B (HB) in France., Methods: Data on dosing frequency, weekly consumption, and bleeds before-and-after switching to rIX-FP, were collected from December 2021 to February 2024. Annualized (spontaneous) bleeding rates [A(s)BRs] were calculated only in patients on prophylaxis with a follow-up ≥ 6 months., Results: This interim analysis focused on 77 patients ≥ 12 years; 62 (81%) had severe HB. After switching to rIX-FP, the infusion interval was 14 (7-14) days. Weekly consumption was 43 (35.5-53) IU/kg. ABRs and AsBRs were 0.5 (0-1.9) and 0 (0-0.7) (n = 63) at 18.2 (12.3-21.9) months of follow-up. Prophylactic efficacy of rIX-FP was considered 'Excellent'/'Good' in 65/68 (95%) patients. Among the 43 patients previously treated with rFIXFc, 21 increased the infusion interval from 7 (7-11) days with rFIXFc to 14 (7-14) days with rIX-FP; 33/43 (77%) reduced weekly factor IX (FIX) consumption from 59.95 (46.35-77.93) to 42.5 (35.88-50.25) IU/kg. Patients maintained good protection against bleeds., Conclusion: This analysis confirmed that switching to rIX-FP allows for reducing injection frequency and FIX consumption while maintaining good bleed protection., (© 2024 CSL Behring and The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)

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: Immediate postpartum haemorrhage (PPH) is a major, feared and often unpredictable issue. Besides many clinical risk factors, some biological parameters could also be predictive of PPH., Objective: To study simple and easily accessible haematological parameters as potential risk factors for PPH after vaginal delivery., Methods: All women who had a vaginal delivery between April 1, 2013 and May 29, 2015 in the maternity ward of Brest University Hospital (France) were included, after oral informed consent obtained. Clinical data were collected by obstetricians or midwives during antenatal care visits, labour and delivery, and recorded by trained research assistants. Haematological variables, including immature platelet fraction, were measured from a blood sample systematically collected at the entrance in the delivery room. PPH, measured with a graduated collector bag, was defined as blood loss of at least 500 ml., Results: 2742 women were included. PPH occurred in 141 (5%) women. Seven clinical factors were independently associated with PPH: pre-eclampsia (OR 5.85, 95%CI 2.02, 16.90), multiple pregnancy (OR 3.28, 95%CI 1.21, 8.91), assisted reproduction (OR 2.75, 95%CI 1.45, 5.20), antepartum bleeding (OR 2.15, 95%CI 1.24,3.73), post-term delivery (OR 1.93, 95%CI 1.17, 3.17), obesity (OR 2.95, 95%CI 1.76, 4.93) and episiotomy (OR 2.51, 95%CI 1.63, 3.74). Three haematological factors were additionally identified as independent risk factors for PPH: platelets < 150 Giga/L (OR 2.98, 95%CI 1.63, 5.46), fibrinogen < 4.5 g/l (OR 1.86, 95%CI 1.21, 2.87) and APTT ratio ≥ 1.1 (OR 2.16, 95%CI 1.31, 3.57). Immature platelet fraction was not associated with PPH., Conclusion: Besides classical clinical risk factors, this study identifies simple haematological parameters as risk factors for PPH., Competing Interests: Declaration of Competing Interest The authors state that they have no conflict of interest., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

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: Pre-eclampsia is characterized by maternal vascular malperfusion and chronic inflammation in placenta. Our purpose was to investigate the potential correlation of biological parameters with placental parameters and pregnancy outcomes in pre-eclamptic women., Methods: Pre-eclamptic women were identified by interrogation of the Medical Registry Department in six French maternities between April 2013 and June 2018. Histological parameters in placentas (weight, macroscopic and microscopic lesions), baseline maternal characteristics and pregnancy outcomes (course of pregnancy, newborns' characteristics) were collected. Biological parameters were blood cell ratios (Platelet-to-Lymphocyte Ratio (PLR), Neutrophil-to-Lymphocyte Ratio (NLR)) collected at delivery and Placental growth factor (PlGF) measured in women with an available first trimester serum sample. Correlations of blood cell ratios and PlGF levels with placental parameters and pregnancy outcomes were assessed by Pearson's correlation test for quantitative parameters and by logistic regression analysis for qualitative parameters., Results: 202 pregnancies were included, among which 68 had a first trimester PlGF quantification. No correlation was found between biological parameters and placental lesions. Low PLR was correlated with low placental weight (r = 0.156, p = 0.036) and with low birth weight (r = 0.179, p = 0.015). Low PlGF was correlated with long time from pre-eclampsia diagnosis to delivery (r = -0.250, p = 0.048)., Conclusions: There is no correlation between biological parameters and placental lesions in pre-eclamptic women. Yet, low PLR at delivery is correlated with low placental and birth weights. Moreover, low first trimester PlGF is correlated with long time from pre-eclampsia diagnosis to delivery., (Copyright © 2019 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.)

Bernard-Soulier syndrome (BSS) is an autosomal recessive major thrombocytopathy, the symptoms of which are mainly marked by mucocutaneous bleeding. This rare disease, initially described in the 1970s, is the result of an abnormal formation of the glycoprotein complex Ib-IX-V (GP Ib-IX-V), a platelet receptor of von Willebrand factor. A large number of mutations, sometimes involving the GP9 gene, have been described as possibly responsible for the disease. We report here the case of a BSS patient who presented with persistent thrombocytopenia (31x10 9 /L) and decreased surface expression of GPIb-IX-V on large platelets with anisocytosis. Thorough molecular analyses disclosed two previously unreported GP9 variants, respectively c.230T>A (p.Leu77Gln) and c.255C>A (p.Asn85Lys). Both are likely to modify the conformation of GP-IX interactions with other glycoproteins of the Ib-IX-V complex and thus proper expression of this complex on the membrane of platelets.