Recombinant Human Prothrombin Prevents Bleeding in Hemophilia A and B Mice

Both a plasma-derived human factor II (pdhFII) and an investigational recombinant human prothrombin (MEDI8111) dose-dependently decreased blood loss and bleeding time in hemophilia A mice, according to Swedish investigators at AstraZeneca’s CVMD IMED unit. Doses of MEDI8111 and pdhFII required to achieve a 50 percent reduction in blood loss and bleeding time were 37 and 87 mg/L, and 100 and 155 mg/L, respectively. In hemophilia B mice given MEDI8111, the doses required to achieve a 50 percent reduction in blood loss and bleeding time were 56 mg/L and 67 mg/L, respectively.

Plasma concentrations of both thrombin and thrombinantithrombin complex (TAT) increased dose-dependently as well with administration of either MEDI8111 or pdhFII in hemophilia A mice. Similar results were observed in hemophilia B mice.

The investigators concluded that MEDI8111 was effective in dose-dependently decreasing bleeding in hemophilia A and B mice, which supports a current hypothesis that factor II is one of the major components responsible for the efficacy of prothrombin complex concentrate (PCC) and activated prothrombin complex concentrate (aPCC) in hemophilia patients. The authors also concluded that “data suggest that MEDI8111 may be useful for preventing bleeding in patients with hemophilia A and B.”