Blood Res 2018; 53(1): 41-48  https://doi.org/10.5045/br.2018.53.1.41
Global hemostatic assay of different target procoagulant activities of factor VIII and factor IX
Ki-Young Yoo1, Soo-Young Jung1, Sung-Ho Hwang2, Su-Min Lee2, Jong-Ho Park2, Hyun-Ja Nam2
1Korea Hemophilia Foundation, Seoul, 2Mogam Institute for Biomedical Research, Yongin, Korea
Correspondence to: Ki-Young Yoo, M.D., Ph.D. Korea Hemophilia Foundation, 70 Saimdang-ro, Seocho-gu, Seoul 06641, Korea E-mail: gowho@hanmail.net
Received: June 26, 2017; Revised: October 11, 2017; Accepted: October 29, 2017; Published online: March 31, 2018.
© The Korean Journal of Hematology. All rights reserved.

Abstract
Background Korean National Health Insurance reimburses factor VIII (FVIII) and factor IX (FIX) clotting factor concentrate (CFC) infusions to discrepant activity levels, allowing elevation of FVIII activity to 60 IU/dL and FIX to 40 IU/dL. We aimed to assess hemostatic response to these target levels using global hemostatic assays. Methods We enrolled 34 normal healthy men, 34 patients with hemophilia A, and 36 with hemophilia B, with residual factor activity of 3 IU/dL or less and without inhibitors. Patients with hemophilia A and B received injected CFCs according to reimbursement guidelines. Fifteen minutes after injection, we assessed hemostatic response with global hemostatic assays: thrombin generation assay (TGA), thromboelastography (TEG), and clot waveform analysis (CWA). Results Normal healthy men and patients with hemophilia A and B were 36.7, 37.2, and 35.1 years old, respectively. FVIII and recombinant FIX concentrate doses were 28.8 IU/kg and 43.6 IU/kg. Post-infusion FVIII activity rose from 0.5 IU/dL to 69.4 IU/dL, while FIX activity rose from 1.4 IU/dL to 46.8 IU/dL. Post-infusion peak thrombin concentrations in hemophilia A and B were 116.6 nM/L and 76.4 nM/L (P<0.001). Post-infusion endogenous thrombin potential (ETP) in hemophilia A and B was 1349.8 nM/min and 915.6 nM (P<0.001). TEG index of hemophilia A and B was 0.11 and ‒0.51 (P=0.006). Conclusion Current reimbursed doses for FIX concentrates are insufficient to achieve hemostatic responses comparable to those after reimbursed doses for FVIII concentrates in terms of peak thrombin concentration, ETP, and TEG index.
Keywords: Hemophilia A, Hemophilia B, Thrombin


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