Registry analysis links FVII levels and genotype with bleeding severity

Researchers analyzed 422 patients with factor VII deficiency from three international registries, evaluating the relationship between FVII:C levels, genetic variants and bleeding outcomes. They also assessed the sensitivity of in silico tools for identifying pathogenic variants. Overall, 61% of patients had experienced bleeding; among those with bleeding, 73% had spontaneous episodes. Grade I, II and III bleeding was reported in 20%, 27% and 14% of the cohort, respectively.

Lower FVII:C levels were moderately associated with higher bleeding scores (r = −0.49; P<.0001). FVII:C discriminated asymptomatic status with an area under the curve (AUC) of 0.72 and grade III bleeding with an AUC of 0.84. Levels of at least 19 IU/dL identified asymptomatic individuals, while levels below 11 IU/dL identified those with grade III bleeding. Homozygous or compound heterozygous variants were associated with lower FVII:C and more severe bleeding; 71% of heterozygous individuals were asymptomatic. Among prediction tools, REVEL had the highest sensitivity (96%).

The registry findings support associations, not definitive individual prediction. The reported cutoffs and genetic associations do not establish treatment thresholds or demonstrate that using them improves clinical outcomes.