Compound heterozygous variants in F7 gene causing severe factor VII deficiency without bleeding: A genotypic and...

Area of Science:

• Hematology
• Genetics
• Clinical Medicine

Background:

• Coagulation factor VII (FVII) initiates the extrinsic pathway; its deficiency is the most common rare bleeding disorder.
• Hereditary FVII deficiency presents with variable bleeding phenotypes, with complex heterozygous variants being clinically significant.
• Genetic factors significantly influence the presentation and severity of hereditary coagulation factor deficiencies.

Purpose of the Study:

• To report a case of hereditary FVII deficiency in a patient with complex heterozygous variants.
• To investigate the diagnostic utility of advanced coagulation assays in assessing bleeding risk in FVII deficiency.
• To emphasize the importance of genetic analysis and family screening in managing hereditary bleeding disorders.

Main Methods:

• Case report of a patient presenting with abnormal coagulation parameters before surgery.
• Genetic sequencing to identify complex heterozygous variants in the FVII gene.
• Thrombin generation assay (TGA) and thromboelastography (TEG) to assess global coagulation function.

Main Results:

• The patient was diagnosed with hereditary FVII deficiency due to compound heterozygous variants (p.Ile303Thr and p.Cys389Gly).
• Despite significantly reduced FVII activity and prolonged PT, TGA and TEG indicated no substantial impairment in global coagulation capacity.
• The patient experienced no bleeding episodes, suggesting FVII:C alone may not fully predict bleeding risk.

Conclusions:

• Compound heterozygous FVII variants can lead to markedly reduced FVII:C without overt bleeding.
• TGA and TEG may provide a more comprehensive assessment of bleeding risk than FVII:C levels alone in specific FVII deficiency cases.
• Family screening is crucial for identifying and managing individuals at risk for hereditary FVII deficiency.