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.

Mice deficient in the anti-haemophilic coagulation factor VIII show increased von Willebrand factor plasma levels

“…In line with a previous report, describing the reduction of VWF plasma levels by FVIII infusion in haemophilia A patients [20], we repeatedly found a 2.5-fold increase in VWF plasma levels in F8 -/y mice relative to F8 +/y littermate controls (Fig 5A). This increase was also recognized in the intensity of the plasmatic VWF multimers (Fig 5B).…”

“…Our finding that F8 deficiency leads to increased plasmatic VWF levels in mice is in line with the published report that haemophilia A patients that were injected with FVIII concentrate showed reduced VWF plasma levels [20]. Also, the involvement of FVIII in the control of VWF plasma levels could be clearly demonstrated as substituting F8 -/y mice with recombinant human FVIII led to lowering of VWF plasma levels.…”

Comparing thrombin generation in patients with hemophilia A and patients on vitamin K antagonists

“…Hemophilia samples were obtained from patients with severe (FVIII activity < 1%), moderate (FVIII activity 1–5%) and mild (FVIII activity 6–50%) hemophilia A. Plasma samples from patients with hemophilia A were collected previously in other studies between July 2009 and January 2012 . The participating hemophilia patients gave permission to store their plasma for use in future research on cardiovascular disease.…”

Adult males with haemophilia have a different macrovascular and microvascular endothelial function profile compared with healthy controls

“…Nor is there proof that historical exposure would cause ongoing vascular response. Furthermore, a recent study showed that infusion of recombinant factor VIII concentrates did not elicit an acute inflammatory response or endothelial cell activation in patients with severe haemophilia A …”