Researchers measured very low levels of factor IX activity in patients with severe hemophilia B by using a technique called clot waveform analysis and published their findings in the International Journal of Hematology.

It is essential to be able to measure factor IX levels, even if they are very low since this can help determine the severity of the disease and influence treatment decisions like the dosage of factor IX products. It can also help determine the risk of inhibitor development. However, there are currently no reliable methods that are sensitive enough to measure very low levels of the protein.

Here, a team of researchers led by Keiji Nogami, MD, PhD, from the Department of Pediatrics at Nara Medical University in Japan showed their clot waveform analysis technique.


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They first investigated the levels of factor IX activity in the plasma of patients with severe hemophilia B. They did this by assessing the coagulation potentials in commercially available plasma from patients with severe hemophilia B preincubated with an antifactor IX monoclonal antibody and evaluating the clot waveform analysis parameters before and after the addition of the antibody.

They also compared these parameters to those in the plasma of patients with severe hemophilia B with inhibitors. They found that the addition of the antibody led to an increase in clotting times. “These results indicated that the plasma from patients with severe [hemophilia B] contained very low levels of [factor IX activity],” they wrote. 

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To estimate very low levels of factor IX activity in the plasma of patients with severe hemophilia B, the researchers added serially diluted recombinant factor IX preparations to commercially available plasma samples and then analyzed the clot waveform parameters. They found that the mean clotting time shortened with the addition of at least 0.1 IU/dL of recombinant factor IX.

Finally, the team assessed factor IX activity in 4 patients with severe hemophilia B who visited their hospital using the reference curves generated by clot waveform analysis. They found that 2 patients had factor IX levels between 0.6 and 0.7 IU/dL and 2 had levels that were too low to detect. Following recombinant factor IX administration, factor IX levels could be detected in these patients.

The researchers concluded that clot waveform analysis using the right factor IX-deficient plasma can enable the measurement of very low levels of factor IX.

Reference

Nishiyama A, Ogiwara K, Mizumachi K, Hashimoto N, Takeyama M, Nogami K. Activated partial thromboplastin time-based clot waveform analysis enables measurement of very low levels of factor IX activity in patients with severe hemophilia B. Int J Hematol. Published online July 21, 2022. doi:10.1007/s12185-022-03419-4