[Diagnosis and treatment of acquired factor XIII/13 deficiencies: for all doctors treating the MHLW's designated intractable diseases].

Coagulation factor XIII (FXIII/13) comprises a hetero-tetramer formed by two catalytic A subunits and two carrier B subunits. Inherited/congenital FXIII/13 deficiency is a rare hemorrhagic disease, leading to severe bleeding and recurrent miscarriages. By contrast, acquired FXIII/13 deficiency is common, and is characterized by a secondary decrease in FXIII/13 resulting from its hypo-synthesis and/or hyper-consumption due to primary diseases. Autoimmune hemorrhaphilia--a severe bleeding disorder that occurs mainly in the elderly--results from the generation of anti-FXIII/13 antibodies (AH13). Although this disease is still rare, the number of patients diagnosed with AH13 has recently increased. To improve understanding of this disease, we conducted a nation-wide survey on AH13. We found approximately 50% of cases to be idiopathic. In the remaining half, autoimmune diseases and malignancies were the most common underlying disorders. Intramuscular and subcutaneous bleeding were the most frequently reported symptoms. AH13 patients with intracranial, intra-peritoneal, or retroperitoneal bleeding (s) were prone to hemorrhagic death. Therefore, physicians/hematologists must raise awareness of AH13 as a life-threatening disease. Most patients were treated with FXIII/13 concentrates to arrest bleeding and with prednisolone and cyclophosphamide to eradicate anti-FXIII/13 autoantibodies. AH13 became a 'designated intractable disease of Japan,' and 'Board Certified Hematologists' can now be qualified as designated doctors.