Brief Report THROMBOSIS AND HEMOSTASIS The interaction between factor H and VWF increases factor H cofactor activity and regulates VWF prothrombotic status

• Complement factor H and von Willebrand factor colocalize in the Weibel-Palade bodies of endothelial cells and interact in normal plasma. • Formation of the complex enhances FH cofactor activity and VWF-mediated platelet aggregation. Vascular endothelial cells (ECs) link hemostasis, thrombosis, and complement. ECs synthesize both the clotting initiator von Willebrand factor (VWF) and the complement regulator factor H (FH). VWF is stored in EC Weibel-Palade bodies (WPBs), but the intracellular location of FH is not well defined. We found that FH colocalizes with VWF in WPBs of human umbilical vein ECs. Moreover, FH bound to VWF with an apparent nanomolar affinity and the complexwas present in normal plasma. The binding of VWF to FH enhanced FH cofactor activity toward factor I–mediated downregulation of com-plement activation. Besides, this interaction inhibited ADAMTS13-mediated proteolysis of VWF and promoted platelet aggregation. Here, we describe a novel interaction between complement and hemostasis. The simultaneous secretion of VWF and FH by activated ECs may promote adhesion of platelets to endothelial injury sites to assure wound healing, simultaneously dampening the proinflammatory effect of complement to limit bystander tissue damage. (Blood. 2014;123(1):121-125