Congenital Factor XIII (Fibrin Stabilizing Factor) Deficiency: Report of Two Unrelated Cases with Episodes of Intracranial Bleeding

Abstract

Case 1: A boy, born in 1960, was referred to us in 1969 because of a painful swelling of the left thigh due to intramuscular bleeding. The first bleeding episode was umbilical bleeding at 7 days of age. The family history was negative for bleeding tendency, although the maternal grandfather and grandmother were first cousins. Routine hemostatic tests revealed no abnormalities except moderately shortened plasma euglobulin lysis time and mildly abnormal “ma” and “k” values in thrombelastogram. The plasma clot solubility test both in 5M urea and in 1% MCA was positive and the level of plasma FSF was less than 1% of normal. These levels of the elder brother, parents and the maternal grandmother were from 25 to 50% of normal. In 1970 he was hospitalized because of subarachnoidal bleeding, when the plasma FSF level was maintained with plasma infusion in from 3 to 12% of normal for the following one month, and he was recovered without any neurological sequelae.
Case 2: A girl, born in 1966, was first seen by us in 1972 because of repeated episodes of hematoma and ecchymosis following minor traumas. Although her elder sister died at the age of 8 months from subdural hemorrhage, the other members of the family were non bleeders. The umbilical bleeding was the first episode of bleeding and she was operated for subdural hematoma at the age of 10 months. The plasma clot solved completely in a few minutes both in 5M urea and in 1% MCA and the level of plasma FSF was less than 1% of normal in the patient and from 30 to 50% in the parents.
In the solid phase immunoradiometric assay using anti-F. XIII subunit A serum, nearly normal level of FSF-like substance was measured in case 1 and 20% in case 2.
The concentrated F. XIII preparation (Factor-XIII-Konzentrat, Behringwerke, AG) was infused and evaluated in each patient. The infusion of the preparation (25 units/kg of body weight) yielded the rise of about 40% in plasma FSF activity and the half-life in vivo was estimated to be 7 days. The clinical hemostatic effect seemed to continue much longer.