Conference Coverage

Thrombin generation looks promising as a hemophilia biomarker



– Thrombin generation may edge out baseline factor activity as a biomarker for predicting bleeding severity among patients with mild and moderate hemophilia, according to a study of 81 patients with nonsevere hemophilia.

Both baseline factor activity and thrombin generation had a similar correlation with bleeding severity, but thrombin generation had a higher sensitivity when differentiating between bleeding severities, Fadi Nossair, MD, of Children’s Hospital of King’s Daughters in Norfolk, Va., reported in a poster at the annual meeting of the American Society of Hematology.

Nonsevere cases of hemophilia A and B account for about half of all hemophilia cases in which factor level does not consistently correlate with bleeding phenotype. That makes it difficult to determine prophylaxis or surgery and highlights the need for a predictive biomarker, the investigators noted.

In the study, 81 patients had their bleeding assessed using standardized, self-administered and investigator-administered questionnaires. Bleeding phenotypes were also collected from EMRs.

One-time venous blood samples were collected after a washout period, when applicable. Additionally, platelet poor plasma was obtained to measure thrombin generation, phospholipid-dependent factor Xa initiated clotting time, factor VIII and IX activities, and von Willebrand factor.

Nearly three-quarters of patients in the study had a low bleeding score.

Both baseline factor level and thrombin generation values obtained with a regular reagent (5 pM of tissue factor) demonstrated a significant correlation with bleeding score (P less than .05). Values obtained with other reagents and biomarkers did not show a significant correlation, according to the researchers.

However, a sensitivity and specificity analysis that helped the researchers narrow down the optimal cutoff values for differentiating between bleeding severities also found that thrombin generation had superior sensitivity, compared with baseline factor level. All thrombin generation values had a higher sensitivity to predict bleeding severity, compared with baseline factor level (57%-62% versus 29%).

“Long-term prospective studies should evaluate the utility of this approach in predicting bleeding severity in this population,” the researchers said.

The study was supported by grants from Novo Nordisk. Dr. Nossair reported financial disclosures related to Novo Nordisk.

SOURCE: Nossair F et al. ASH 2018, Poster 3788.

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