title: Factor VIII concentrate infusion in patients with haemophilia results in decreased von Willebrand factor and ADAMTS-13 activity.
abstract: The effects of coagulation factor concentrate infusion on restoring secondary haemostasis in patients with haemophilia are obvious. It is not known whether coagulation factor concentrate infusion affects primary haemostasis or induces an acute inflammatory response. In this study, the influence of a factor VIII (FVIII) concentrate bolus infusion on platelet activation and responsiveness, endothelial activation, and inflammation in adult patients with severe haemophilia A was assessed. VWF showed a mild, but significant decrease 15 min after FVIII infusion (85.02 IU dL(-1)) vs. before infusion (92.04 IU dL(-1) ; P = 0.017), while ADAMTS-13 levels also show a mild but significant decrease from 66.1 ng mL(-1) before infusion, to 53.9 ng mL(-1) (P = 0.012) 15 min after and 50.8 ng mL(-1) (P = 0.050) 60 min after infusion. Platelet P-selectin expression decreased 15 min (33.3 AU) and 60 min (38.7 AU) after infusion compared to before infusion (41.3 AU; P = 0.018 and 0.036). In conclusion, a single infusion of a high dose FVIII concentrate in haemophilia A patients may influence primary haemostasis by decreasing VWF, ADAMTS-13 and the number of circulating activated platelets. These effects possibly occur as a consequence of binding of the infused FVIII to VWF, influencing its processing. When treating severe haemophilia A patients with coagulation concentrate infusion, one should realize this does not merely correct FVIII levels but also may influence primary haemostasis.
authors.affiliation: Department of Clinical Chemistry and Hematology, University Medical Center Utrecht, Utrecht, the Netherlands; Van Creveld Laboratory, University Medical Center Utrecht, Utrecht, the Netherlands.
authors.forename: E R
authors.initials: ER
authors.lastname: van Bladel
authors.forename: A
authors.initials: A
authors.lastname: Tuinenburg
authors.forename: M
authors.initials: M
authors.lastname: Roest
authors.forename: P G
authors.initials: PG
authors.lastname: de Groot
authors.forename: R E G
authors.initials: RE
authors.lastname: Schutgens
mesh_terms: D051722:ADAM Proteins / Q000097:blood / Q000378:metabolism*; D000071120:ADAMTS13 Protein; D000328:Adult; D001792:Blood Platelets / Q000378:metabolism; D016207:Cytokines / Q000096:biosynthesis / Q000097:blood; D042783:Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D005169:Factor VIII / Q000008:administration & dosage / Q000627:therapeutic use*; D006467:Hemophilia A / Q000097:blood / Q000188:drug therapy* / Q000378:metabolism*; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D055815:Young Adult; D014841:von Willebrand Factor / Q000378:metabolism*
chemical_list: D016207:Cytokines; D018836:Inflammation Mediators; D014841:von Willebrand Factor; D005169:Factor VIII; D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; C099604:ADAMTS13 protein, human
keywords: endothelium; factor VIII concentrate infusion; haemophilia; inflammation; platelet