Neoplasm-induced bleeding in inherited, heterozygous FXIII-A deficiency

Area of Science:

• Hematology
• Oncology
• Genetics

Background:

• Inherited Factor XIII (FXIII) deficiency is often underdiagnosed due to mild or absent bleeding symptoms.
• Patients with FXIII deficiency may present with bleeding complications that can be exacerbated by other conditions.

Observation:

• A 64-year-old man with no prior bleeding history presented with neck swelling, weight loss, anemia, and tonsil bleeding.
• Histopathology revealed epithelioid angiosarcoma, and coagulation tests showed decreased FXIII activity (35%) and antigen (16-26%) with elevated D-dimer.
• Plasma mixing studies ruled out neutralizing antibodies, suggesting an inherited cause.

Findings:

• A novel heterozygous nonsense mutation (p.Glu103Ter, c.307G>T) in the F13A1 gene confirmed FXIII-A deficiency, also found in asymptomatic relatives.
• The patient experienced significant bleeding post-surgery despite FXIII concentrate transfusions and antifibrinolytic therapy.
• Despite chemotherapy and radiotherapy, the patient died two months after diagnosis.

Implications:

• This case uniquely demonstrates the coexistence of aggressive angiosarcoma and inherited FXIII deficiency.
• FXIII genotyping is valuable for diagnosing inherited FXIII deficiency, distinguishing it from acquired deficiency potentially caused by neoplasm-induced consumption.
• Understanding the interplay between FXIII deficiency and malignancy is critical for patient management and prognosis.