Severe congenital factor V deficiency presenting as intracranial haemorrhage in early infancy

Abstract

Congenital factor V deficiency is a rare autosomal recessive bleeding disorder with heterogeneous clinical 
manifestations. Intracranial hemorrhage is an uncommon but life-threatening presentation in infancy. We report a 
3-month-old male infant who presented with vomiting and refusal to feed and was subsequently diagnosed with a 
massive right temporal intraparenchymal hemorrhage with intraventricular extension secondary to severe congenital 
factor V deficiency. Importantly, the infant had earlier warning signs of an underlying bleeding disorder, including 
severe neonatal anemia with markedly prolonged prothrombin time (PT) and international normalized ratio and a 
hematoma at a vaccination site despite Vitamin K administration. Coagulation studies showed markedly prolonged PT 
and activated partial thromboplastin time, with factor V activity <1%; mixing studies corrected the clotting times, and 
other measured coagulation factors were not reduced. Genetic testing confirmed a homozygous pathogenic frameshift 
variant in the F5 gene (c.2862del; p.Ser955AlafsTer4). The child was managed with repeated fresh frozen plasma 
transfusions and intensive care support. This case emphasizes the importance of recognizing early bleeding clues and 
considering severe factor V deficiency in infants with intracranial hemorrhage despite Vitamin K prophylaxis.