title: Prospective assessment of thrombin generation test for dose monitoring of bypassing therapy in hemophilia patients with inhibitors undergoing elective surgery.
abstract: Clinical response to bypassing agents (BPAs) may vary between patients. Surgery is a particular situation, requiring effective hemostasis during the procedure and for several days postoperatively to obtain satisfactory wound healing. However, the optimal dose of BPA in different surgical situations has not been clearly established. We report here a prospective assessment of thrombin generation test (TGT) in monitoring the effectiveness of BPA during 10 elective invasive procedures performed in 6 patients with severe hemophilia and high-titer inhibitors. A standardized 3-step protocol was used in all cases to individually tailor BPA. Thrombin-generating capacity of patients increased after in vitro and ex vivo addition of BPA in a dose-dependent manner. Our results also showed a correlation between in vivo clinical response to BPA and thrombin-generating capacity. These data suggest that TGT may represent a surrogate marker for monitoring bypassing therapies in surgical situations.
authors.affiliation: Unité d'Hémostase Clinique, Hôpital Edouard Herriot, Lyon, France.ydargaud@univ-lyon1.fr
authors.forename: Yesim
authors.initials: Y
authors.lastname: Dargaud
authors.forename: Anne
authors.initials: A
authors.lastname: Lienhart
authors.forename: Claude
authors.initials: C
authors.lastname: Negrier
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers; D001777:Blood Coagulation / Q000187:drug effects; D019774:Blood Coagulation Factor Inhibitors / Q000627:therapeutic use*; D016903:Drug Monitoring; D017558:Elective Surgical Procedures; D006467:Hemophilia A / Q000188:drug therapy* / Q000378:metabolism* / Q000601:surgery; D006801:Humans; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D013917:Thrombin / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D019774:Blood Coagulation Factor Inhibitors; D013917:Thrombin