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

Ki-Young Yoo; Soo-Young Jung; Sung-Ho Hwang; Su-Min Lee; Jong-Ho Park; Hyun-Ja Nam

doi:10.5045/br.2018.53.1.41

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Original Article

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Blood Res 2018; 53(1):

Published online March 31, 2018

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 Yoo^1*, Soo-Young Jung¹, Sung-Ho Hwang², Su-Min Lee², Jong-Ho Park², and Hyun-Ja Nam²

Author Info. +

¹Korea Hemophilia Foundation, Seoul, Korea.

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. gowho@hanmail.net

Received: June 26, 2017; Revised: October 11, 2017; Accepted: October 29, 2017

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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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

Article

Original Article

Blood Res 2018; 53(1): 41-48

Published online March 31, 2018 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 Yoo^1*, Soo-Young Jung¹, Sung-Ho Hwang², Su-Min Lee², Jong-Ho Park², and Hyun-Ja Nam²

¹Korea Hemophilia Foundation, Seoul, Korea.

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. gowho@hanmail.net

Received: June 26, 2017; Revised: October 11, 2017; Accepted: October 29, 2017

Abstract

Background

Methods

Results

Conclusion

Keywords: Hemophilia A, Hemophilia B, Thrombin

Abstract

Fig 1.

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Figure 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.

Blood Research 2018; 53: 41-48https://doi.org/10.5045/br.2018.53.1.41

Fig 2.

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Figure 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).

Blood Research 2018; 53: 41-48https://doi.org/10.5045/br.2018.53.1.41

Fig 3.

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Figure 3.

Thromboelastography. Thromboelastograph after injection of clotting factor Concentrates (A). TEG index after injection of clotting factor concentrates (B).

Abbreviation: TEG, thromboelastography.

Blood Research 2018; 53: 41-48https://doi.org/10.5045/br.2018.53.1.41

Fig 4.

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Figure 4.

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

Blood Research 2018; 53: 41-48https://doi.org/10.5045/br.2018.53.1.41

Table 1 . Patient characteristics..

^a)P-value is calculated between hemophilia A and hemophilia B..

Abbreviations: NA, not applicable; rFVIII, recombinant factor VIII; pdFVIII, plasma-derived factor VIII..

Table 2 . Summary of hemostatic response..

^a)P-value is calculated between hemophilia A and hemophilia B..

Abbreviations: CWA, clot wave form analysis; ETP, endogenous thrombin potential; MCF, maximum clot firmness; NA, not applicable; TEG, thromboelastography; TGA, thrombin generation assay..