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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.)

Von Willebrand disease-type 2A (VWD-2A) and acquired von Willebrand syndrome (AVWS) due to aortic stenosis (AS) or left ventricular assist device (LVAD) are associated with an increased proteolysis of von Willebrand factor (VWF). Analysis of VWF multimeric profile is the most sensitive way to assess such increased VWF-proteolysis. However, several technical aspects hamper a large diffusion among routine diagnosis laboratories. This makes early diagnosis and early appropriate care of increased proteolysis challenging. In this context of unmet medical need, we developed a new ELISA aiming a quick, easy and reliable assessment of VWF-proteolysis. This ELISA was assessed successively in a LVAD-model, healthy subjects (n=39), acquired TTP-patients (n=4), VWD-patients (including VWD-2A(IIA), n=22; VWD-2B, n=26; VWD-2A(IIE), n=21; and VWD-1C, n=8) and in AVWS-patients (AS, n=9; LVAD, n=9; and MGUS, n=8). A standard of VWF-proteolysis was specifically developed. Extent of VWF-proteolysis was expressed as relative percentage and as VWF proteolysis/VWF:Ag ratio. A speed-dependent increase in VWF-proteolysis was assessed in the LVAD model whereas no proteolysis was observed in TTP-patients. In VWD-patients, VWF-proteolysis was significantly increased in VWD-2A(IIA) and VWD-2B and significantly decreased in VWD-2A(IIE) versus controls (p< 0.0001). In AVWS-patients, VWF-proteolysis was significantly increased in AS- and LVAD-patients compared to controls (p< 0.0001) and not detectable in MGUS-patients. A significant increase in VWF-proteolysis was detected as soon as three hours after LVAD implantation (p< 0.01). In conclusion, we describe a new ELISA allowing a rapid and accurate diagnosis of VWF-proteolysis validated in three different clinical situations. This assay represents a helpful alternative to electrophoresis-based assay in the diagnosis and management of AVWS with increased VWF-proteolysis.

The ristocetin cofactor activity assay (VWF:RCo) is the reference method for assessing von Willebrand factor (VWF) activity but remains difficult to perform, and the coefficient of variation of the method is high (about 20-30%). This study evaluated and compared the performance for measuring the VWF activity of two newly commercialised assays [VWF:Ac Innovance (VWF:Ac) and VWF:RCo Acustar (VWF:RCo Acu)] with the reference VWF:RCo aggregation in 123 pathological plasma samples. The correlation and concordance between both new tests (VWF:RCo-Acu and VWF:Ac) and the reference VWF:RCo were good. The results of the VWF activity to VWF antigen ratio were also comparable whatever the method for the classification of VWF deficiency in all patients. Our results showed that both new tests could replace the "gold standard" VWF:RCo in aggregometry with several benefits: they are fully automated, easier and faster to perform, better adapted to emergency situations if necessary.