Factor II deficiency

Prothrombin deficiency can manifest at any age, with severe forms of the disease manifesting early in life. Common clinical signs include epistaxis, menorrhagia, oral cavity bleedings, mucosal bleeding, soft tissue bleeding, hemarthrosis, easy bruising, and prolonged bleeding after tooth extraction, trauma or surgery. Severe forms may present intracranial haemorrhage. The severity of the bleeding manifestations correlates with prothrombin levels. Heterozygous carriers with plasma levels between 40 and 60% of the normal value are usually asymptomatic but can develop bleedings after tooth extractions or surgical procedures.

The estimated prevalence is 1:2,000,000 to 1:3,000,000.

Congenital factor II deficiency is caused by germline pathogenic variants in F2, which encodes prothrombin (coagulation factor II). Two biochemical subtypes are distinguished: type I (hypoprothrombinaemia), with concordant reductions in factor II activity and antigen, and type II (dysprothrombinaemia), with reduced activity but preserved antigen, reflecting a dysfunctional molecule. Reported variants are predominantly missense (~80%), with smaller fractions of insertions or deletions (~10%), nonsense (~6%), and splice-site (~4%) variants; complete absence of prothrombin has not been observed and is presumed incompatible with life.

Factor II deficiency is inherited in an autosomal recessive manner. Parents of an affected individual are obligate carriers; each pregnancy carries a 25% recurrence risk. Prenatal molecular testing is technically possible once the familial pathogenic variants have been identified.

Diagnosis is based on prolonged prothrombin and activated partial thromboplastin times (PT, aPTT) and low factor II coagulation activity, as measured by a PT-based test. Molecular confirmation is performed by F2 sequencing.

• Establishing the diagnosis provides a definitive molecular cause for the clinical and laboratory findings.
• Once the familial pathogenic variants are known, predictive testing of at-risk family members and reproductive counselling become available, allowing carrier identification within the family.

• Lancellotti S, De Cristofaro R. Congenital prothrombin deficiency. Semin Thromb Hemost. 2009;35(4):367-381. doi:10.1055/s-0029-1225759. PMID: .
• Tourbih H, Harrach A, Bencharef H, Dehbi H, Oukkache B. Molecular aspects of rare coagulation factor deficiencies. Cureus. 2025;17(7):e89102. doi:10.7759/cureus.89102. PMID: . PMCID: PMC12311556.