Thrombin Generation as an Indication of Hemophilia Severity

By Dr. David Clark

We often divide hemophilia patients into categories of severe, moderate and mild based on their level of clotting factor. However, in about 15% of patients, their bleeding behavior doesn’t fit their category. We need a better system.

A group of researchers in The Netherlands have proposed that a thrombin generation assay (TGA), rather than a factor assay would be a better way to characterize patient’s disorders.

Thrombin (factor IIa) is the final enzyme produced by the clotting system. It converts fibrinogen (factor I) to fibrin, a protein that sticks to itself to form the clot. Everything that happens in the clotting system upstream of thrombin formation just determines how much thrombin will be made, and thus, how much of a clot will be formed.

The study looked at 446 patients with hemophilia (35 Bs), measuring their levels of thrombin generation compared to their factor levels and bleeding characteristics. They found that thrombin generation did indeed appear to be a better predictor of bleeding than did factor level.

Measuring thrombin generation is not a new idea. The problem is that TGAs are very difficult assays to run. The results vary from lab to lab and are not very reproducible. However, one of the researchers in the study is also the Chief Science Officer of Enzyre, a Dutch company that, in collaboration with Takeda, is developing a small device that could allow people with hemophilia to test their clotting status at home from a drop of blood. They have developed proprietary compounds that react with thrombin and emit light in proportion to the thrombin level. The device could help patients more precisely determine the amount of factor they need at any given time.

[Verhagen MJA, et al., Res. Pract. Thromb. Haemost., 7(2):100062 (2023)]