Development and validation of criteria to define clinically severe hemophilia (CSH) indicate that residual plasma levels of clotting factor (F) VIII or FIX account for around 70% of bleeding phenotype, with the remaining 30% of bleeding phenotype affected by unexplained individual patient variables, according to research published in the Journal of Thrombosis and Haemostasis.

Residual plasma levels of FVIII or FIX are considered critical predictors of spontaneous bleeding in patients with hemophilia and are used to stratify patients phenotypically into severe, moderate, and mild hemophilia groups. This system of classification, however, may not be sufficiently accurate. As many as 20% of patients with CSH according to this classification system do not experience bleeding complications in adulthood, and data evaluating the relationship between mild or moderate hemophilia and FVIII levels are lacking.

To develop a consensus criteria for hemophilia, researchers met with 17 hemophilia center directors with experience in the diagnosis and treatment of hemophilia. Additionally, 100 patients with hemophilia participated in a consensus panel.

Continue Reading

Consensus on the bleeding symptoms associated with CSH included first spontaneous bleeding before 6 months, spontaneous joint bleeding before 2 years, unprovoked intracranial hemorrhage, spontaneous subcutaneous hematomas with at least 1 palm-sized or more than 3 coin-sized, and more than 10 bleeding events per year.

Related Articles

To validate the consensus, researchers analyzed data from 19 hemophilia treatment centers across 421 patients. Patients who developed an inhibitor prior to 3 years (66 patients) had a higher severity score compared with the 355 patients who did not develop an inhibitor before 3 years (median score, 3 vs 2; P < .0001). Most patients who developed an inhibitor before 3 years (85%) had residual FVIII/FIX levels less than 1 IU dL-1.

Patients who began prophylaxis before 3 years (133 patients) had a higher severity score compared with the 273 patients who started prophylaxis after 3 years (median score, 3 vs 1; P = .001). Over 90% of patients who began prophylaxis before 3 years had residual FVIII/FIX levels less than 1 IU dl-1.

The authors caution that limitations of this study include the retrospective design and the lack of centralized laboratory measurements of residual FVIII/FIX. These results suggest a need for further prognostic improvement and refinement for CSH.


1. Mancuso ME, Bidlingmaier C, Mahlangu JN, Carcao M, Tosetto A; subcommittee on factor viii, factor ix and rare coagulation disorders. The predictive value of factor VIII/factor IX levels to define the severity of hemophilia: communication from the SSC of ISTH [published online July 11, 2018]. J Thromb Haemost. doi: 10.1111/jth.14257