Correlation of Factor Levels with Bleeding Phenotype in Non-severe Hemophilia

Background: Hemophilia is categorised into severity groups (severe-, moderate- and mild hemophilia) based on the basal activity level of factor VIII (FVIII) or -IX (FIX). This categorisation is expected to be in accordance with the severity of the bleeding phenotype.

Aims: Our study aimed at quantifying the association between the severity of the bleeding phenotype and FVIII/IX basal activity levels in non-severe hemophilia A (HA) and -B (HB) patients.

Methods: Patients with non-severe hemophilia, defined as baseline FVIII/IX activity of >1 to 40%, were eligible. Data on the bleeding history were collected via direct patient consultations and search of hospital databases. This information was used to quantify the bleeding phenotype with the Bleeding Assessment Tool of the International Society on Thrombosis and Haemostasis (ISTH-BAT).

Results: In total 105 patients were enrolled, 83 (79%) with HA and 22 (21%) with HB, median age was 51 years, [range 20–81]. Median levels of FVIII were 12% [range: 1.5%−39%] and that of FIX were 12.5% [2%−25%]. The median ISTH-BAT score was 10 points [0–28] overall, 10 [0–28] points in HA, and 7 [0–20] in HB, and did not differ significantly between HA and HB (p = 0.12). Lower basal factor levels correlated with a higher ISTH-BAT score (Spearman’s rho=−0.33, p<0.001). In linear regression, a 1% increase in basal factor levels was associated with a 0.2 point decrease in the ISTH-BAT (β=−0.21, 95%CI: −0.34-(-0.09), p = 0.001). This association was similar in HA and HB patients (p for interaction = 0.67). Basal factor levels explained only 13% of the variation in the ISTH-BAT (R2 = 0.13 for both HA and HB patients).

Conclusion: We observed a weak but significant correlation between basal FVIII/IX levels and the bleeding severity. Our data are consistent with the concept that there are other yet-tobe-explored determinants of the bleeding phenotype beyond basal factor levels in hemophilia.