Congenital factor XIII (FXIII) deficiency is an extremely rare autosomal recessive blood clotting disorder with an incidence of approximately one in two million, which is caused mainly by mutations in the F13A1 gene. Recently, we identified a Chinese family with FXIII deficiency carrying a likely pathogenic variant and explored its pathogenic mechanism. The aim of this study was to investigate the pathogenic mechanism associated with the Ser414 mutation in the F13A1 gene. We performed clinical diagnosis, phenotypic assessment, and genetic analysis of the proband and her family members. The FXIII antigen level of the proband was 1.3%, which was significantly lower than the normal reference range. A mutation was identified through targeted next-generation sequencing (NGS). The effects of these variations on protein function were assessed using bioinformatics tools. Homology analysis revealed that Ser414 was also highly conserved in homologous species. Protein model analysis revealed that the Ser414Leu variation could induce alterations in the spatial structure of F13A1, potentially increasing its instability. This is the first time that F13A1 gene variants have been analyzed in a patient with FXIII deficiency, contributing to the expansion of the pathogenic variant database for congenital FXIII deficiency. These findings provide valuable data accumulation that can contribute to the prevention of congenital FXIII deficiency, the exploration of potential pathogenic mechanisms, and the enrichment of genetic mutation databases.

This case report describes a male infant with congenital Factor XIII deficiency who presented with severe intracranial hemorrhage. The late preterm infant (36+4 weeks) exhibited early signs of bleeding, including a hematoma at an injection site and umbilical stump bleeding. At two months of age, he experienced a spontaneous, grade IV intracranial hemorrhage complicated by hydrocephalus. Notably, routine coagulation studies were within normal limits. The diagnosis was confirmed by genetic testing, which identified compound heterozygous mutations in the F13A1 gene. Management involved external ventricular drainage and regular fresh frozen plasma transfusions as replacement therapy, resulting in a favorable outcome. This case underscores that congenital FXIII deficiency should be considered in the differential diagnosis for infants presenting with unexplained perinatal bleeding or intracranial hemorrhage, especially when standard coagulation screens are normal. Early genetic testing and institution of structured replacement therapy are crucial for preventing life-threatening bleeding and improving long-term prognosis.

Severe congenital factor XIII deficiency is a rare blood coagulation disorder that poses a risk of life-threatening bleeding complications. Conversely, patients with mild or moderate factor XIII deficiency frequently exhibit delayed or provoked bleeding patterns. This case report presents a patient who received a delayed diagnosis of moderate factor XIII deficiency following significant bleeding episodes in the postoperative period. We will examine the symptoms indicative of mild and moderate factor XIII deficiency, as well as the current therapeutic options. This discussion emphasizes the vital importance of early diagnosis for achieving optimal management and improved patient outcomes.

Spontaneous splenic rupture is a rare, life-threatening event, infrequently associated with congenital factor XIII deficiency, a rare coagulation disorder. We present a case of an 18-year-old female with known factor XIII deficiency who presented with acute abdominal pain and was diagnosed with spontaneous splenic rupture. The patient underwent splenectomy due to hemodynamic instability and massive hemorrhage. Postoperative management included factor XIII replacement and standard postsplenectomy prophylaxis. Spontaneous splenic rupture in the setting of factor XIII deficiency is exceedingly rare, with only a limited number of cases reported in the literature. This case highlights the importance of considering coagulation disorders in the differential diagnosis of atraumatic splenic rupture. Prompt diagnosis and multidisciplinary management, including surgical intervention when necessary, are critical for optimizing patient outcomes. This case underscores that factor XIII deficiency can lead to spontaneous life-threatening hemorrhage. Clinicians should maintain a high index of suspicion for this pathology in patients with known coagulopathies, and timely intervention is essential to improve patient outcomes. The importance of this approach is to quickly treat it when needed because is very deadly.