The dirty side of the intrinsic pathway of coagulation

Abstract

Whereas the extrinsic pathway of coagulation seals off bleeding at the cut tissue edges, it is proposed that the intrinsic pathway exploits the dirt from the skin surface to generate an outer coagulum of the oozing blood. Activated Factor XII (FXIIa) in this outer cap generates Factor XIa, which triggers clotting, and kallikrein that feeds back to form more FXIIa to promote the process. This dirty-wound hypothesis of coagulation function by the intrinsic pathway is supported by the use of dirt-based compounds in activated partial thromboplastin time assays as well as the evolutionary record where marine life that do not have skin-adherent dirt lack Factor XII, including marine mammals that have returned to sea life.