Modulation of an acquired coagulation factor V inhibitor with intravenous immune globulin

We report that treatment of an immune mediated postoperative Factor V (FV) deficiency with intravenous immune globulin (IVIg) resulted in serological and clinical disappearance of the inhibitor.

A 9-year-old girl was exposed to bovine thrombin during cardiovascular surgery and subsequently developed severe, refractory hemorrhage caused by acquired FV deficiency (FV activity < 5%). Despite blood product transfusions, hemorrhage continued, and the patient was given IVIg, 400 mg/kg daily, for 9 day.

Prolonged clotting times immediately trended toward normal, and the hemorrhage ceased by the fifth IVIg treatment day, concomitant with increasing plasma FV activity and disappearance of human FV inhibitor activity. The patient's plasma initially had a much higher inhibitor titer against bovine FV (122-215 Bethesda units) than against human FV (3-4 Bethesda units). Circulating antibodies (IgM and IgG) to bovine and human thrombin and FV were detected by enzyme-linked immunosorbent assay (ELISA). After completion of IVIg treatment, IgG antibodies to bovine FV and thrombin persisted, as did high-titer inhibition of bovine FV, whereas the subpopulation of IgG and IgM antibodies reactive with human FV were undetectable.

The inhibitor likely developed from a heterogenetic immune response to bovine FV contaminating the topical thrombin preparation used during surgery. To our knowledge, this is the first demonstration of immunological clearance of an acquired FV antibody associated with the use of IVIg. The data suggest an antiidiotypic mechanism of IVIg in modulating clearance of antihuman FV antibodies.