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FⅨa-Triggered Thrombin Generation Assay for Monitoring Very Low Levels of FⅧ Activity in Hemophilia A

1Fujian Institute of Haematology, Fujian Provincial Key Laboratory on Haematology, Fujian Medical University Union Hospital, Fuzhou, China, 2McMaster University /Thrombosis and Atherosclerosis Research Institute, Hamilton, Canada, 3McMaster University / Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario，, Canada, 4McMaster University / Thrombosis and Atherosclerosis Research Institute, Hamilton, Ontario, Canada, 5Hong Kong University-Shenzhen Hospital, Health Management Department, Shenzhen, China

Abstract Number: PB0883

Meeting: ISTH 2020 Congress

Theme: Hemophilia and Rare Bleeding Disorders » Hemophilia - Clinical

Background: It has been well documented that assay discrepancies between the severity of bleeding and factor VIII (FVIII) level in severe hemophilia A, lead to inaccuracy over the actual level after factor infusion. One of the possible explanations may be that the current assays are not sensitive enough to quantify FVIII level when it is less than 1%. The potentially close to physiological approach, thrombin generation assay (TGA), may be used to monitor coagulation function in these patients, but the relationship between main parameters and the FVIII level (< 0.01 IU/mL) is not linear.

Aims: To find the optimal protocol of TGA to estimating the coagulation function in severe hemophilia A patients.

Methods: Hemophiliac Platelet-Poor-Plasma (commercialized FVIII -deficient plasma) was mixed with normal plasma. Different concentrations of TF or FIX were used as triggers to generate thrombin and the TGA parameters were recorded. The correlations between FVIII level and TGA parameters were estimated using linear regression.

Results: An optimal level of FIXa to trigger the thrombin generation instead of TF is 0.6 nM with phospholipid (4µM) when the FVIII level is lower than 0.01 IU/mL. There was a linear relationship between FVIII levels (<0.01 IU/mL) and TGA parameters. The Peak thrombin value rose sharply with a growing level of FVIII until it reached to 0.01 IU/mL; the ETP augmented dramatically before the FVIII level rose to 0.1 IU/mL. After the cutoff point, the Peak thrombin value and ETP entered a plateau period.

Conclusions: low level of FIXa-triggered TGA is more sensitive with high or low concentrations of FVIII than currently used protocols. It could be helpful for tailoring in hemophilia prophylaxis, adapting replacement in surgical situations, monitoring bypassing agents in patients with inhibitors, and measuring efficacy of gene therapy. But these in vitro results need ex-vivo studies to confirm.

To cite this abstract in AMA style:

Huang MJ, Gantioqui J, Atkinson H, Chan AAK, Chan HHW. FⅨa-Triggered Thrombin Generation Assay for Monitoring Very Low Levels of FⅧ Activity in Hemophilia A [abstract]. Res Pract Thromb Haemost. 2020; 4 (Suppl 1). https://abstracts.isth.org/abstract/f%e2%85%a8a-triggered-thrombin-generation-assay-for-monitoring-very-low-levels-of-f%e2%85%a7-activity-in-hemophilia-a/. Accessed November 29, 2023.

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