Phenotypical variability in congenital FVII deficiency follows the ISTH-SSC severity classification guidelines: a review with illustrative examples from the clinic

Abstract

Background: One of the most common rare inherited bleeding disorders, congenital factor VII (FVII) deficiency typically has a milder bleeding phenotype than other rare bleeding disorders. Categorizing severity in terms of factor activity associated with hemophilia (severe <1%, moderate 1%-5%, mild 6%-40%) has led to the observation that bleeding phenotype does not follow closely with FVII activity. Over the past decade, large-scale global registries have investigated bleeding phenotype more thoroughly. The International Society on Thrombosis and Haemostasis has reclassified FVII deficiency as follows: severe, FVII <10%, risk of spontaneous major bleeding; moderate, FVII 10%-20%, risk of mild spontaneous or triggered bleeding; mild, FVII 20%-50%, mostly asymptomatic disease.

Case reports: Eleven illustrative cases of congenital FVII deficiency adapted from clinical practice are described to demonstrate the variability in presentation and in relation to FVII activity levels. Severe FVII deficiency usually presents at a young age and carries the risk of intracranial hemorrhage, hemarthrosis, and other major bleeds. Moderate FVII deficiency tends to present later, often in adolescence and particularly in girls as they reach menarche. Milder disease may not be apparent until found incidentally on preoperative testing, during pregnancy/childbirth, or following unexplained bleeding when faced with hemostatic challenges.

Conclusion: It is important for health care professionals to be aware of the new definitions of severity and typical presentations of congenital FVII deficiency. Failure to appreciate the risks of major bleeding, including intracerebral hemorrhage in those with FVII activity <10%, may put particularly young children at risk.

Keywords: Severity of Illness Index; blood coagulation disorders/classification; blood coagulation factors/physiology; humans’ rare diseases/classification.