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. 2021 Jan-Dec:27:1076029620976913.
doi: 10.1177/1076029620976913.

The Evaluation of APTT Reagents in Reference Plasma, Recombinant FVIII Products; Kovaltry® and Jivi® Using CWA, Including sTF/7FIX Assay

Hideo Wada  1   2 , Katsuya Shiraki  1   2 , Takeshi Matsumoto  3 , Kohshi Ohishi  3 , Hideto Shimpo  4 , Yumi Sakano  5 , Hiroko Nishii  5 , Motomu Shimaoka  5
Affiliations

The Evaluation of APTT Reagents in Reference Plasma, Recombinant FVIII Products; Kovaltry® and Jivi® Using CWA, Including sTF/7FIX Assay

Hideo Wada et al. Clin Appl Thromb Hemost. 2021 Jan-Dec.

Abstract

The FVIII activity in patients treated with several extended half-life FVIII (EHL-FVIII) agents different when various activated partial thromboplastin time (APTT) reagents were used. The present study examined the difference in clot waveform analysis (CWA) findings and FVIII activity when various APTT reagents and CWA were used. The CWA including FVIII activity was measured using 12 APTT reagents, and the FIX activation based on a small amount of tissue factor assay (sTF/FIX) were examined in reference plasma (RP), EHL-FVIII (Jivi®) and Kovaltry®. The 3 APTT reagents were associated with high variation in the peak time and height in the CWA when analyzing low concentrations of FVIII. The peak time and height could not be measured with one APTT reagent, and there were marked differences in the CWA findings between Jivi® and Kovaltry® among APTT reagents. Several APTT reagents showed a markedly lower FVIII activity with Jivi® than with Kovaltry®. In the FVIII assay, the peak time measured with sTF/FIX did not differ markedly between Jivi® and Kovaltry®; however, the FVIII activity in Jivi® (as measured by the peak height) tended to be higher than in Kovaltry®. The CWA findings for monitoring Jivi® varied for monitoring Jivi® depending on the APTT reagents used, and sTF/FIX assay may be able to measure the EHL-FVIII.

Keywords: APTT reagent; CWA; EHL-FVIII; FVIII; sTF/FIX assay.

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Conflict of interest statement

Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Figures

Figure 1.
Figure 1.
The FFT and 2nd DPT with various APTT reagents and various concentrations of FVIII. [APTT reagents] A, APTT-SP; B, APTT-SS; C, STA Cephascreen; D, Coagpia APTT-N; E, APTT PSL; F, C.K. Prest; G, APTT-SLA; H, TC APTT; I, APTT FS; J, APTT FSL; K, PTT ACT; L, STA PTT A. [Abbreviations] HemosIL APTT-SP; APTT-SP and HemosIL SynthASil; APTT-SS (Instrumentation Laboratory), STA Cephascreen; STA Cephascreen, D, STA PTT Automate; STA PTT A and C.K. Prest (Diagnostica Stago S.A.S), Coagpia APTT-N; APTT-N (SEKISUI MEDICAL CO., LTD.), Thrombocheck APTT-SLA; APTT-SLA and Thrombocheck APTT; TC APTT (Sysmex Corporation) and Dade® Actin® FS Activated PTT Reagent; APTT FS, Dade® Actin ® FSL Activated PTT Reagent; APTT FSL, Dade® Actin® FSL Activated Cephaloplastin Reagent; APTT ACT and Pathromtin ® SL; APTT PSL (Siemens Healthcare Diagnostics Products GmbH). FFT, fibrin formatin time; 2ndDPT, 2nd derivative peak time; FVIII, coagulation factor FVIII.
Figure 2.
Figure 2.
The 1st DPT (A), and 1st DPH (B) and FVIII concentrations with various APTT reagents. [FVIII concentrations] 1, 1.00 IU; 2, 0.50 IU; 3, 0.10 IU; 4, 0.05 IU; 5, 0.01 IU; 6, 0.005 IU and 7, 0.001 IU. [APTT reagents] A, APTT-SP; B, APTT-SS; C, STA Cephascreen; D, Coagpia APTT-N; E, APTT PSL; F, C.K. Prest; G, APTT-SLA; H, TC APTT; I, APTT FS; J, APTT FSL; K, PTT ACT; L, STA PTT A. [Abbreviations] HemosIL APTT-SP; APTT-SP and HemosIL SynthASil; APTT-SS (Instrumentation Laboratory), STA Cephascreen; STA Cephascreen, D, STA PTT Automate; STA PTT A and C.K. Prest (Diagnostica Stago S.A.S), Coagpia APTT-N; APTT-N (SEKISUI MEDICAL CO., LTD.), Thrombocheck APTT-SLA; APTT-SLA and Thrombocheck APTT; TC APTT (Sysmex Corporation) and Dade® Actin® FS Activated PTT Reagent; APTT FS, Dade® Actin ® FSL Activated PTT Reagent; APTT FSL, Dade® Actin® FSL Activated Cephaloplastin Reagent; APTT ACT and Pathromtin ® SL; APTT PSL (Siemens Healthcare Diagnostics Products GmbH). FFT, fibrin formation time; FVIII, coagulation factor FVIII.
Figure 3.
Figure 3.
The 1st DP time (A) and 1st DPH (B), and FVIII concentration in Kovaltry® and Jivi® measured with various APTT reagents. Closed circle, Kovaltry®; open circle, Jivi®; [FVIII concentrations] 1, 1.00 IU; 2, 0.50 IU; 3, 0.10 IU; 4, 0.05 IU; 5, 0.01 IU; 6, 0.005 IU. [APTT reagents] A, APTT-SP; B, APTT-SS; C, STA Cephascreen; D, Coagpia APTT-N; E, APTT PSL; F, C.K. Prest; G, APTT-SLA; H, TC APTT; I, APTT FS; J, APTT FSL; K, PTT ACT; L, STA PTT A. [Abbreviations] HemosIL APTT-SP; APTT-SP and HemosIL SynthASil; APTT-SS (Instrumentation Laboratory), STA Cephascreen; STA Cephascreen, D, STA PTT Automate; STA PTT A and C.K. Prest (Diagnostica Stago S.A.S), Coagpia APTT-N; APTT-N (SEKISUI MEDICAL CO., LTD.), Thrombocheck APTT-SLA; APTT-SLA and Thrombocheck APTT; TC APTT (Sysmex Corporation) and Dade® Actin® FS Activated PTT Reagent; APTT FS, Dade® Actin ® FSL Activated PTT Reagent; APTT FSL, Dade® Actin® FSL Activated Cephaloplastin Reagent; APTT ACT and Pathromtin ® SL; APTT PSL (Siemens Healthcare Diagnostics Products GmbH). 1stDPT, 1st derivative peak time: FVIII, coagulation factor FVIII.
Figure 4.
Figure 4.
The 1st DPT (A) and 1st DPH (B) of the sTF/FIX assay with FVIII reagents of various concentrations. Closed circle, Kovaltry®; open circle, Jivi®; 1st DPT, first derivative peak time; 1st DPH, first derivative peak height.
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