Prothrombin (Factor II) Deficiency
Due to the limited number of cases described in the literature, an evaluation of the correlation between prothrombin activity level and bleeding phenotype is difficult. However, homozygous or compound heterozygous individuals with prothrombin activity levels <10% tend to manifest with severe bleeding symptoms.27 A smaller subset of patients have prothrombin levels of <5%. Heterozygotes typically have plasma FII levels between 30-60%.
Patients with hypoprothrombinemia may present with prolonged bleeding (particularly after injury or surgery), mucosal bleeding, or subcutaneous or muscle hematomas. Interestingly, gastrointestinal bleeding is less common in prothrombin deficiency.27 Severe intracranial hemorrhage has been reported in 12% of cases (n = 39), while hemarthrosis has been reported in 42% of patients.27 Other bleeding symptoms include bleeding after tooth extraction, umbilical cord bleeding, and easy bruising. However, no bleeding symptoms are specific for FII deficiency.
Patients with heterozygote prothrombin deficiency typically have FII activity levels between 30-60% and tend to be asymptomatic. However, menorrhagia is a common symptom in females with heterozygous and homozygous prothrombin mutations.28 Additionally, heterozygotes may occasionally manifest with excessive bleeding after moderate-intensity trauma, tooth extraction, or following a surgical procedure.6
The bleeding phenotype in dysprothrombinemia can vary. Bleeding symptoms that do occur in patients with dysprothrombinemia tend to be less severe than in patients with hypoprothrombinemia. In some variants of dysprothrombinemia, the bleeding tendency does not correlate with the measured FII level. For instance, Prothrombin Salakta and Prothrombin Himi may have significantly low procoagulant FII levels but minimal bleeding symptoms.29-31 Other rare forms of dysprothrombinemia (such as Prothrombin Yukuhashi) can cause a paradoxical thrombotic phenotype in patients due to antithrombin resistance.20 In general, patients with dysprothrombinemia tend to be asymptomatic.