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Clot lysis phenotype and response to recombinant factor VII a in plasma of haemophilia A inhibitor patients
Author(s) -
Bakhtiari Kamran,
Kamphuisen Pieter W.,
Mancuso Maria E.,
Hamulyak Karly,
Schutgens Roger E. G.,
Santagostino Elena,
Meijers Joost C. M.
Publication year - 2013
Publication title -
british journal of haematology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.907
H-Index - 186
eISSN - 1365-2141
pISSN - 0007-1048
DOI - 10.1111/bjh.12470
Subject(s) - thrombomodulin , haemophilia a , coagulation , fibrinolysis , haemophilia , tissue factor , immunology , medicine , recombinant dna , thrombin , protein c , pharmacology , chemistry , biochemistry , surgery , platelet , gene
Summary Recombinant activated factor VII ( rFVII a) is a haemostatic agent that is used for the treatment of haemophilia A patients with inhibitors. However, clinical response to rFVII a is variable and unpredictable with currently available assays. We investigated the anti‐fibrinolytic effects of rFVII a in relation to thrombin generation ( TG ) and other haemostatic parameters in haemophilia A patients with inhibitors. After addition of rFVII a to plasma, the clot‐lysis assay, TF ‐dependent TG , TF ‐independent TG and parameters involved in coagulation, anticoagulation and fibrinolysis were assessed. The clot‐lysis test distinguished two groups of patients: a group with a normal and a group with impaired anti‐fibrinolytic response to rFVII a. Our results showed a dose‐dependent increase in TF ‐dependent TG and TF ‐independent TG in all individuals. There was a significant difference in TF ‐independent TG parameters between the normal and impaired response groups. In addition, there was a difference between the normal and impaired response group in prothrombin time, which could be explained by significantly higher levels of coagulation factors in the normal response group, and soluble thrombomodulin. In conclusion, we observed different in vitro responses following rFVII a addition in plasma of patients with haemophilia A and inhibitors, which could be partially attributed to levels of procoagulant proteins and soluble thrombomodulin.