Effects of FEIBA on platelet and leucocyte activation in severe haemophilia patients with inhibitors.
Factor eight inhibitory bypassing agent (FEIBA) is used as a therapeutic option in haemophilia patients who have developed inhibitors. The measurement of thrombin generation has been applied to monitor the efficacy of FEIBA. However, a major concern about the clinical use of FEIBA is whether or not an increase in thrombin activity causes subsequent platelet activation and risk of thrombosis. Our aim is to evaluate whether FEIBA causes platelet and leucocyte activation in haemophilia patients with inhibitors. We evaluated the effects of FEIBA on platelet and leucocyte activity in correlation with thrombin generation. Initially, an in vitro study was conducted to evaluate the effects of FEIBA on platelet and leucocyte activity (using flow cytometry) using peripheral blood from normal volunteers. We then performed an ex vivo study looking at the effect of FEIBA on the above parameters in two haemophiliacs with high-titre inhibitors. A parallel study was also carried out ex vivo to evaluate thrombin generation using a thrombinoscope. FEIBA did not cause platelet or leucocyte activation in either the in vitro or ex vivo studies but showed a predictable increase in thrombin generation. Our study is the first one to address the effect of FEIBA on platelet and leucocyte function. We found no evidence of 'systemic' platelet activation. The findings suggest that whilst FEIBA improves global haemostasis, platelet activation is likely to be contained to the site of injury and systemic platelet activation, a previously feared consequence of FEIBA infusion that that may have contributed to thrombotic risk is absent.
Institute of Haematology, Royal Prince Alfred Hospital, Camperdown, Sydney, Australia.
Lian
L
Zhao
Elaine
E
Uhr
Geoff
G
Kershaw
Scott
S
Dunkley
D001779:Blood Coagulation Factors / Q000494:pharmacology* / Q000627:therapeutic use; D001792:Blood Platelets / Q000187:drug effects*; D005434:Flow Cytometry; D006467:Hemophilia A / Q000097:blood* / Q000188:drug therapy*; D006487:Hemostasis / Q000187:drug effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects*; D018375:Neutrophil Activation / Q000187:drug effects; D015539:Platelet Activation / Q000187:drug effects*; D012720:Severity of Illness Index; D013917:Thrombin / Q000378:metabolism; D013918:Thrombin Time; D013927:Thrombosis / Q000517:prevention & control*
D001779:Blood Coagulation Factors; C065655:anti-inhibitor coagulant complex; D013917:Thrombin