Blood Res.  2018 Mar;53(1):41-48. 10.5045/br.2018.53.1.41.

Global hemostatic assay of different target procoagulant activities of factor VIII and factor IX

• Yoo KY
• Jung SY
• Hwang SH
• Lee SM
• Park JH
• Nam HJ

• KMID: 2414363
• DOI: http://doi.org/10.5045/br.2018.53.1.41

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.

Keyword

Hemophilia A; Hemophilia B; Thrombin

MeSH Terms

Factor IX*
Factor VIII*
Hemophilia A
Hemophilia B
Humans
Male
National Health Programs
Thrombelastography
Thrombin
Factor IX
Factor VIII
Thrombin

Figure

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  Fig. 1 One-stage clotting factor assay. Factor activity in healthy males, pre- and post-infusion of factor concentrates in hemophilia A and B patients (A). In-vivo recovery of hemophilia A and B patients (B). Abbreviations: FL-FVIII, full-length factor VIII; IVR, in-vivo recovery; pdFVIII, plasma-derived factor VIII; rFVIII, recombinant factor VIII.

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  Fig. 2 Thrombin generation assay. Thrombogram (A). Peak thrombin concentration after injection of clotting factor concentrates (B). Endogenous thrombin potential after injection of clotting factor concentrates (C).

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  Fig. 3 Thromboelastography. Thromboelastograph after injection of clotting factor Concentrates (A). TEG index after injection of clotting factor concentrates (B). Abbreviation: TEG, thromboelastography.

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  Fig. 4 Clot waveform analysis. Second derivatives of aPTT after injection of clotting factor concentrates (A). MIN2 values after injection of clotting factor concentrates (B).

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