ASH: Mechanism of Activated Protein C Investigated
Animal study disproves notion that APC's anticoagulant activity controls severe sepsis
MONDAY, Dec. 11 (HealthDay News) -- The anticoagulant action of activated protein C, or APC, -- the only FDA-approved treatment for severe sepsis -- is not the key reason the treatment is effective, according to research presented this week at the 48th Annual Meeting of the American Society of Hematology in Orlando.
Hartmut Weiler, Ph.D., of the Blood Center of Wisconsin in Milwaukee, and colleagues exposed mice to a bacterial toxin. After sepsis developed, the mice were treated with standard APC or APC variants that had reduced anticoagulant activity.
Overall, the researchers found that treatment with all types of APC reduced mortality from 50 percent to less than 10 percent in normal mice. But they found that APC did not improve survival in mice genetically altered to lack endothelial protein C receptor or protease-activated receptor-1, suggesting that both receptors are necessary for APC's action. They also found that death occurred in all of the mice receiving standard APC treatment within hours of Staphylococcus aureus infection, but not in those receiving APC variants, showing that APC's anticoagulant activity may actually impair the body's natural defenses.
"These results highlight the importance of the cellular protein C pathway for APC therapy and suggest that APC variants with reduced anticoagulant action but normal potency for beneficial direct cellular effects merit further evaluation for sepsis therapy," the authors conclude.