| First Author | Kowalska MA | Year | 2007 |
| Journal | Blood | Volume | 110 |
| Issue | 6 | Pages | 1903-5 |
| PubMed ID | 17540840 | Mgi Jnum | J:146406 |
| Mgi Id | MGI:3837528 | Doi | 10.1182/blood-2007-03-081901 |
| Citation | Kowalska MA, et al. (2007) Endogenous platelet factor 4 stimulates activated protein C generation in vivo and improves survival after thrombin or lipopolysaccharide challenge. Blood 110(6):1903-5 |
| abstractText | Pharmacologic infusion of activated protein C (APC) improves survival in severe sepsis, and platelet factor 4 (PF4) accelerates APC generation in a primate thrombin-infusion model. We now tested whether endogenous platelet PF4 content affects APC generation. Mice completely deficient in PF4 (mPF4(-/-)) had impaired APC generation and survival after thrombin infusion, similar to the impairment seen in heterozygote protein C-deficient (PC(+/-)) mice. Transgenic mice overexpressing human PF4 (hPF4(+)) had increased plasma APC generation. Overexpression of platelet PF4 compensated for the defect seen in PC(+/-) mice. In both a thrombin and a lipopolysaccharide (LPS) survival model, hPF4(+) and PC(+/-)/hPF4(+) mice had improved survival. Further, infusion of hPF4(+) platelets improved survival of wild-type mice after an LPS challenge. These studies suggest that endogenous PF4 release may have biologic consequences for APC generation and survival in clinical sepsis. Infusions of PF4-rich platelets may be an effective strategy to improve outcome in this setting. |
