Abstract
Congenital prothrombin (factor II) deficiency is a rare autosomal recessive coagulation disorder, here we report a pediatric adolescent female case with a homozygous F2 gene mutation, presenting with early bleeding symptoms followed by deep vein thrombosis and cerebral venous sinus thrombosis, despite persistently low prothrombin activity.
Our patient was first evaluated for recurrent ecchymoses when she was one year old, and it has been demonstrated that she has prothrombin activity <10%, consistent with congenital factor II deficiency. Till she was 14 years old, she didn't have any bleeding; her menstruation was on time without any abnormal uterine bleeding, and before invasive procedures, she was treated with fresh frozen plasma (FFP). At the age of 14, she developed deep vein thrombosis (DVT) involving the right popliteal and femoral veins. She was treated with enoxaparin for three months, supported by FFP by two times a week while she was on enoxaparin. During that time, thrombophilia work-up revealed MTHFR and PAI-1 heterozygosity, mild hyperhomocysteinemia (20 µmol/L), and normal protein C, S, antithrombin III, and lipoprotein(a) levels.
In March 2025, she presented with a headache, altered consciousness, and seizures. Cranial MRI and MR venography revealed thrombosis of bilateral internal cerebral veins, inferior sagittal sinus, straight sinus, and left transverse/sigmoid sinuses, along with left putaminal hemorrhagic venous infarction. The patient underwent an emergent decompressive craniectomy. After that, endovascular thrombectomy was performed by the interventional surgery team. In the meantime, she had another thrombosis in her femoral vein according to the catheters.
Over the following month, serial imaging showed progressive resolution of cerebral venous thromboses. The patient is still being followed with ongoing enoxaparin prophylaxis and twice-weekly FFP infusions after the acute cranial event.
The patient was found to carry a homozygous F2 c.1273C>T (p.Arg425Cys) variant, which results in the substitution of a conserved arginine residue with cysteine in the serine protease domain of prothrombin. There is limited data available on these mutations; however, there are variants that have been associated with markedly reduced fibrinogen clotting activity and with dysprothrombinemia phenotype. These mutationsmay lead to bothhypoprothrombinemia and dysfunctional thrombin activity, explaining the paradoxical presentation of bleeding diathesis and recurrent thrombosis as in our patient.
This case presents a rare phenotype of homozygous dysprothrombinemia, featuring lifelong bleeding tendency and multiple thrombotic events. In rare cases, patients with congenital prothrombin deficiency may exhibit both bleeding and thrombosis. Genetic diagnosis is essential to clarify the phenotype, and it may guide treatment. This case emphasizes the need for individualized management and multidisciplinary care in patients with complex coagulation disorders.
