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Background: Hypercoagulability seems to contribute to SARS-CoV-2 pneumonia pathogenesis. However, age and metabolic syndrome are potential confounders when assessing the value of coagulation biomarkers' prediction of COVID-19 outcomes. We assessed whether coagulation biomarkers, including factor VIII (FVIII) and von Willebrand factor (VWF) levels, measured at time of admission, were predictive of COVID-19 adverse outcomes irrespective of age and major comorbidities associated with metabolic syndrome., Methods: Blood was sampled at admission in 243 adult COVID-19 patients for analysis of coagulation biomarkers including FVIII and VWF on platelet-poor plasma. The association between baseline C-reactive protein (CRP), activated partial thromboplastin time ratio, prothrombin time ratio, D-dimers, fibrinogen, FVIII, VWF antigen (VWF:Ag), and FVIII/VWF:Ag ratio levels and adverse outcomes (increased oxygen requirements, thrombosis, and death at day 30) was assessed by regression analysis after adjustment on age, sex, body mass index (BMI), diabetes, and hypertension., Results: In univariable regression analysis increased CRP (subdistribution hazard ratio [SHR], 1.68; 95% confidence interval [CI], 1.26-2.23), increased fibrinogen (SHR, 1.32; 95% CI, 1.04-1.68), and decreased FVIII/VWF:Ag ratio (SHR, 0.70; 95% CI, 0.52-0.96) levels at admission were significantly associated with the risk of increased oxygen requirement during follow-up. Leucocytes (SHR, 1.36; 95% CI, 1.04-1.76), platelets (SHR,1.71; 95% CI, 1.11-2.62), D-dimers (SHR, 2.48; 95% CI, 1.66-3.78), and FVIII (SHR, 1.78; 95% CI, 1.17-2.68) were associated with early onset of thrombosis after admission. After adjustment for age, sex, BMI, hypertension, and diabetes, these associations were not modified., Conclusion: Coagulation biomarkers are early and independent predictors of increased oxygen requirement in COVID-19 patients., (© 2020 International Society on Thrombosis and Haemostasis.)

Replacement therapy with plasma-derived or recombinant FVIII and FIX (pdFVIII/pdFIX or rFVIII/rFIX) concentrates is the standard of treatment in patients with haemophilia A and B, respectively. Measurement of factor VIII (FVIII:C) or factor IX (FIX:C) levels can be done by one-stage clotting assay (OSA) or chromogenic substrate assay (CSA). The French study group on the Biology of Hemorrhagic Diseases (a collaborative group of the GFHT and MHEMO network) presents a literature review and proposals for the monitoring of FVIII:C and FIX:C levels in treated haemophilia A and B patients, respectively. The use of CSA is recommended for the monitoring of patients treated with pdFVIII or rFVIII including extended half-life (EHL) rFVIII. Except for rFVIII-Fc, great caution is required when measuring FVIII:C levels by OSA in patients substituted by EHL-rFVIII. The OSA is recommended for the monitoring of patients treated with pdFIX or rFIX. Large discordances in the FIX:C levels measured for extended half-life rFIX (EHL-rFIX), depending on the method and reagents used, must lead to great attention when OSA is used for measuring FIX:C levels in patients substituted by EHL-rFIX. Data of most of recent studies, obtained with spiked plasmas, deserve to be confirmed in plasma samples of treated patients., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Replacement therapy with plasma-derived or recombinant FVIII (pdFVIII or rFVIII) concentrates is the standard of treatment in patients with hemophilia A. The reference method used for measuring factor VIII (FVIII:C) levels in patients treated by FVIII concentrates is the chromogenic substrate assay (CSA). However, the one-stage clotting assay (OSA) is predominantly used in current clinical practice, but this method depends on the activated partial thromboplastin time (APTT) reagent and the coagulation analyzer used, and wide variations in the measurements of FVIII recovery have been reported with some factor concentrates. The French study group on the biology of hemorrhagic diseases (a collaborative group of the GFHT and MHEMO network) presents a review of the literature and proposals for the monitoring of FVIII:C levels in treated hemophilia A patients. The use of CSA calibrated with a plasma reference tested against the current FVIII WHO (World Health Organization) International Standard is recommended for the monitoring of patients treated with pdFVIII or rFVIII including extended half-life (EHL) rFVIII. OSA are adequate for the monitoring of patients treated with pdFVIII or with most of rFVIII concentrates. However, preliminary comparison with CSA is mandatory before measuring FVIII:C by OSA in patients treated by Refacto AF ® . For rFVIII-EHL, OSA are only acceptable for Elocta®. Great caution is therefore required when measuring FVIII:C levels by OSA in patients substituted by other EHL-rFVIII. Indeed, most of recent studies reported data obtained with spiked plasmas, which deserve to be confirmed on plasma samples collected in treated patients.

Systemic sclerosis (SSc) is an autoimmune disease associated with endothelial activation and fibrosis. Non-O blood group patients carry an increased risk of thrombosis, fibrosis and autoimmune diseases. The aim of our work was to evaluate the distribution of ABO groups in SSc patients and their association with the disease's characteristics. ABO groups were determined in 504 SSc patients (with 131 completed by a genotypic analysis). The distribution of ABO groups and their diplotypes in SSc patients was comparable to that of the general population, except for haplotypes O1 and B (65.6% vs. 61.6% and 8.8% vs. 5.8% in SSc patients vs. the general population, respectively, p = 0.01). The frequency of interstitial lung disease, pulmonary hypertension, calcinosis, digital ulcers, digestive diseases and venous thrombosis, and the Medsger score, were higher in non-O than in O-SSc patients, although they did not display statistical significance. Patients in the non-O group had higher levels of inflammation and endothelial activation biomarkers. In conclusion, the ABO blood group distribution of SSc patients did not differ significantly from that of the general population, but non-O blood groups were associated with inflammation and endothelial activation, and with a non-significant higher frequency of pulmonary and vascular complications in SSc. [ABSTRACT FROM AUTHOR]

Résumé: Une surveillance biologique des hémophiles substitués est nécessaire pour ajuster la dose de facteurs administrés qu'ils soient d'origine plasmatique ou recombinante. La méthode de référence pour le dosage de l'activité du facteur VIII (FVIII:C) chez les patients hémophiles A substitués est la méthode chromogénique, mais elle est peu répandue dans les laboratoires qui utilisent le plus souvent la méthode chronométrique basée sur la mesure du temps de céphaline avec activateur (TCA). Le nombre important de réactifs de TCA et les différents couples automates/réactifs expliquent les difficultés de standardisation de ces dosages. Le groupe français d'études de la biologie des maladies hémorragiques (groupe collaborateur du GFHT et de la filière MHEMO), présente une revue de la littérature et des propositions pour le suivi biologique des patients hémophiles A substitués. Une méthode chromogénique, calibrée avec un standard raccordé à l'étalon international de l'Organisation mondiale de la santé (OMS), est recommandée pour le suivi des patients traités par FVIII plasmatique (pdFVIII) ou recombinant (rFVIII) y compris pour les nouveaux rFVIII à demi-vie allongée (extended half life : EHL). Une méthode chronométrique est acceptable pour le pdFVIII et la plupart des rFVIII. Pour la surveillance d'un traitement par Refacto AF®, une comparaison préalable avec la méthode chromogénique est requise. Concernant les rFVIII-EHL, la méthode chronométrique n'est acceptable aujourd'hui que pour l'Elocta®. Une grande vigilance doit être apportée lors de l'utilisation d'une méthode chronométrique pour les autres rFVIII-EHL. La majorité des études présente des résultats obtenus avec des plasmas surchargés qui doivent être confirmés avec des plasmas de patients traités. Replacement therapy with plasma-derived or recombinant FVIII (pdFVIII or rFVIII) concentrates is the standard of treatment in patients with hemophilia A. The reference method used for measuring factor VIII (FVIII:C) levels in patients treated by FVIII concentrates is the chromogenic substrate assay (CSA). However, the one-stage clotting assay (OSA) is predominantly used in current clinical practice, but this method depends on the activated partial thromboplastin time (APTT) reagent and the coagulation analyzer used, and wide variations in the measurements of FVIII recovery have been reported with some factor concentrates. The French study group on the biology of hemorrhagic diseases (a collaborative group of the GFHT and MHEMO network) presents a review of the literature and proposals for the monitoring of FVIII:C levels in treated hemophilia A patients. The use of CSA calibrated with a plasma reference tested against the current FVIII WHO (World Health Organization) International Standard is recommended for the monitoring of patients treated with pdFVIII or rFVIII including extended half-life (EHL) rFVIII. OSA are adequate for the monitoring of patients treated with pdFVIII or with most of rFVIII concentrates. However, preliminary comparison with CSA is mandatory before measuring FVIII:C by OSA in patients treated by Refacto AF®. For rFVIII-EHL, OSA are only acceptable for Elocta®. Great caution is therefore required when measuring FVIII:C levels by OSA in patients substituted by other EHL-rFVIII. Indeed, most of recent studies reported data obtained with spiked plasmas, which deserve to be confirmed on plasma samples collected in treated patients. [ABSTRACT FROM AUTHOR]