The Effect of Recombinant Human Coagulation Factor Ⅷ on Alpha-thrombin Generation Activity
Haemophilia A is the most common inherited bleeding disorder and is commonly characterised by impaired generation of active thromboplastin and prolonged clotting time.The main clinical manifestations are qualitative or quantitative abnormalities of coagulation factor Ⅷ(FⅧ).Clinical manifestations are characterised by spontaneous bleeding in joints,muscles,internal organs and deep tissues or bleeding that is difficult to stop after minor trauma,often starting in childhood.Repeated bleeding in joints can lead to gradual joint mobility disorders and disability.The incidence of haemophilia A in the male population is about 1 in 5 000,while hae-mophilia A in women is extremely rare.The prevalence of haemophilia in China is 2.73/100 000 population,of which haemophilia A accounts for 80％～85％.The aim of this study was to investigate the ability of recombinant human coagulation factor Ⅷ(rhFⅧ)to activate downstream coagulation pathways and to compare it with marketed analogues.Using coagulation factor Ⅷ deficient plasma as the experimental group sample and standard plasma as the control group,three FⅧ active working solutions were obtained by diluting each product to 1,5 and 10 IU/mL using buffer,and then the prepared FⅧ working solutions were diluted 10-fold with coagulation fac-tor Ⅷ deficient plasma(simulated haemophilia A samples)to make four different FⅧ working solutions of 0,0.1,0.5 and 1 IU/mL activity FⅧ plasma samples,and the effects of rhFⅧ,Advate and blood-derived FⅧ on the rate of α-thrombin generation and the potential of generation under different concentration conditions were detected by using a thrombin generation analyser,respectively.rhFⅧ had the same effect of promoting α-thrombin generation compared with Advate and blood source FⅧ,and the peak height ofα-thrombin generation showed an increasing trend with the increase of FⅧ concentration;the peak time showed a decreasing trend with the increase of FⅧ concentration in FⅧ;and the integral area under the α-thrombin generation curve increased with the increase of FⅧ concentration.Compared with the commercially available recombinant and blood-derived FⅧ products,rhFⅧ has the same pro-α-thrombin generating activity in vitro,has good drugability,and is expected to be approved and marketed in China in the future.
haemophilia Arecombinant human coagulation factor Ⅷα-thrombingeneration ratethrombin activitycoagulation function
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