Skip to main content
. Author manuscript; available in PMC: 2019 Aug 30.
Published in final edited form as: Xenotransplantation. 2019 Apr 29;26(4):e12517. doi: 10.1111/xen.12517

Figure 2: Thromboinflammation.

Figure 2:

Intravascular foreign substances (includingforeign bodies, immune complexes, and debris from cells) activate the coagulation, fibrinolytic, and complement systems, which in turn activate cells (monocytes, polymorphonuclear cells, endothelial cells) and platelets, and orchestrate the inflammatory and thrombotic responses.

Complement may activate the coagulation system and, in turn, the coagulation system may regulate complement: C1-INH, an inhibitor of the CP and LP, also acts as a modulator of the coagulation contact system (factor Xia, factor XIIa, and kallikrein), and the fibrinolytic system (tissue plasminogen activator and plasmin). Thrombomodulin (CD141) may inhibit thrombin, and also favor C3b inactivation and C3a and C5a degradation. von Willebrand factor also interacts with complement components.

Platelets interact with both the complement and coagulation systems. Immune complexes may activate platelets and also bind to C1q to activate the complement system. Activated platelets may induce C3 and factor XI phosphorylation, which may enhance their activities. (i) antibodies against platelet membrane glycoproteins may activate the CP through C1q; (ii) after adhering to activated platelets, pentameric C-RP complex dissociates into monomeric C-RP and recruits more platelets, and activates the AP; (iii) The activated platelets may bind ficolin-1, −2 and −3, and activate mannose-binding lectin-associated serine proteases (MASP-1 and 2), activate the LP.

After being stimulated by histamine, endothelial cells may become enriched in local acute inflammatory molecules, including molecules involved in both the complement and coagulation cascades; rug-induced injury, e.g., by calcineurin inhibitors (CNI), including sirolimus, cyclosporine, tacrolimus, may decrease expression of vascular endothelial growth factor in a graft, resulting in endothelial injury and complement activation.

So, complement cross-reacts with coagulation factors and platelets, develops thromboinflammation.

CP = Classic pathway; LP = Lectin pathway; AP = Alternative pathway; PenC-RP = pentameric C-RP; MonC-RP = monomeric C-RP; EC = Endothelial cells; MASP = mannose-binding lectin-associated serine proteases; CNI = calcineurin inhibitors; C1-INH = C1 inhibitor; TAFI = Thrombin-activatable fibrinolysis inhibitor.