Correlation between Phenotype and Coagulation Factor Activity Level in Rare Bleeding Disorders: A Systematic Review

Area of Science:

• Hematology
• Genetics
• Internal Medicine

Background:

• Rare bleeding disorders (RBDs) constitute 3-5% of inherited bleeding conditions, often autosomal recessive.
• Bleeding severity in RBDs is assessed using tools like the ISTH-BAT, but correlation with factor levels is inconsistent.
• Prevalence of RBDs is higher in consanguineous populations.

Purpose of the Study:

• To systematically review and analyze the correlation between coagulation factor activity levels and bleeding severity in patients with rare bleeding disorders.
• To enhance understanding of the genotype-phenotype relationship in RBDs.
• To inform improved management strategies for RBD patients.

Main Methods:

• Systematic review following PRISMA guidelines, registered with PROSPERO (CRD42024504537).
• PICO framework used, focusing on RBD patients.
• Comprehensive literature search across PubMed, Scopus, and Web of Science until April 1, 2024, extracting data on bleeding severity, phenotype, and factor activity levels.

Main Results:

• Inconsistent correlations observed between factor levels and bleeding severity across different RBDs.
• Moderate to strong correlations found for fibrinogen, FX, and FXIII deficiencies (66%, 97%, 100% of relevant studies, respectively).
• Weak or no correlations identified for FV, FVII, and FXI deficiencies (76%, 65%, 93% of relevant studies, respectively).

Conclusions:

• The relationship between coagulation factor activity and bleeding severity in RBDs is complex and factor-specific.
• Moderate to strong correlations exist for fibrinogen, FX, and FXIII deficiencies.
• Further prospective studies using standardized bleeding assessment tools are necessary to optimize patient management.