Complement and coagulation crosstalk – Factor H in the spotlight

The immune complement and the coagulation systems are blood-based proteolytic cascades that are activated by pathway-specific triggers, based on protein–protein interactions and enzymatic cleavage reactions. Activation of these systems is finely balanced and controlled through specific regulatory mechanisms. The complement and coagulation systems are generally viewed as distinct, but have common evolutionary origins, and several interactions between these homologous systems have been reported. This complement and coagulation crosstalk can affect activation, amplification and regulatory functions in both systems. In this review, we summarize the literature on coagulation factors contributing to complement alternative pathway activation and regulation and highlight molecular interactions of the complement alternative pathway regulator factor H with several coagulation factors. We propose a mechanism where factor H interactions with coagulation factors may contribute to both complement and coagulation activation and regulation within the haemostatic system and fibrin clot microenvironment and introduce the emerging role of factor H as a modulator of coagulation. Finally, we discuss the potential impact of these protein interactions in diseases associated with factor H dysregulation or deficiency as well as evidence of coagulation dysfunction.