Procoagulant effects of key DAMPs
| DAMP . | Procoagulant mechanisms . | Reference . |
|---|---|---|
| CFHs | Upregulates TF expression and decryption on endothelial and monocytic surfaces | 83,84 |
| Autoactivates FVII-activating protease, which activates FVII and degrades TFPI | 85 | |
| Autoactivates prothrombin | 86 | |
| Binds to prothrombin and facilitates thrombin generation through the alternative prothrombinase complex | 87 | |
| Activates platelets, resulting in platelet degranulation and aggregation | 56 | |
| Induces endothelial Weibel-Palade body degranulation and ultralarge VWF release | 88 | |
| Induces coagulant-active phosphatidylserine expression on platelet, endothelial, and erythrocyte surfaces | 89,90 | |
| Increases clot robustness and fibrinolytic resistance by covalent and noncovalent incorporation | 52,91 | |
| Competitive inhibition of plasmin | 91 | |
| Induces NET formation | 92 | |
| Downregulates TM expression on endothelial surfaces | 83 | |
| Inhibits TM function by binding to extracellular domain, inhibiting PC activation | 93 | |
| Competitive inhibition of APC as an APC substrate | 47 | |
| Competitive inhibition of AT potentiation by binding to glycosaminoglycans including heparan sulfate | 94 | |
| NETs | A source of procoagulant DAMPs including CFHs, HMGB1, calprotectin, and cfDNA | 95 |
| Allows for the accumulation and juxtaposing of procoagulant cells and material | 35,41 | |
| Confers fibrinolytic resistance through clot incorporation | 35 | |
| Extruded neutrophil proteases degrade innate anticoagulants, including TFPI and AT | 41 | |
| cfDNA | Contact activation of FXI and FXII | 50 |
| Enhances TFPI degradation by neutrophil elastase | 41 | |
| Confers fibrinolytic resistance when incorporated into clots | 52 | |
| Inhibition of plasmin by competitive binding or by the formation of a plasmin-fibrin-cfDNA ternary complex | 53,96 | |
| Induces thrombin autoproteolysis, generating thrombin C-terminal fragments which protect cfDNA against degradation | 54 | |
| cfRNA | Contact activation of FXI and FXII | 50 |
| HMGB1 | Stimulates monocyte TF expression | 40,62 |
| Activates platelets, resulting in platelet degranulation and aggregation | 40,61,62 | |
| Induces NET formation | 40 | |
| Inhibits TM function by binding to extracellular domain, inhibiting PC activation | 62 | |
| Calprotectin | Augments platelet activation and aggregation | 63,64 |
| Polyphosphates | Contact activation of FXI and FXII | 50,55,56 |
| Inhibits TFPI activity and enhances its inactivation by FXIa | 50 | |
| Enhances HMGB1-mediated endothelial VWF release | 57 | |
| Augments VWF-GP1b interactions | 57 |
| DAMP . | Procoagulant mechanisms . | Reference . |
|---|---|---|
| CFHs | Upregulates TF expression and decryption on endothelial and monocytic surfaces | 83,84 |
| Autoactivates FVII-activating protease, which activates FVII and degrades TFPI | 85 | |
| Autoactivates prothrombin | 86 | |
| Binds to prothrombin and facilitates thrombin generation through the alternative prothrombinase complex | 87 | |
| Activates platelets, resulting in platelet degranulation and aggregation | 56 | |
| Induces endothelial Weibel-Palade body degranulation and ultralarge VWF release | 88 | |
| Induces coagulant-active phosphatidylserine expression on platelet, endothelial, and erythrocyte surfaces | 89,90 | |
| Increases clot robustness and fibrinolytic resistance by covalent and noncovalent incorporation | 52,91 | |
| Competitive inhibition of plasmin | 91 | |
| Induces NET formation | 92 | |
| Downregulates TM expression on endothelial surfaces | 83 | |
| Inhibits TM function by binding to extracellular domain, inhibiting PC activation | 93 | |
| Competitive inhibition of APC as an APC substrate | 47 | |
| Competitive inhibition of AT potentiation by binding to glycosaminoglycans including heparan sulfate | 94 | |
| NETs | A source of procoagulant DAMPs including CFHs, HMGB1, calprotectin, and cfDNA | 95 |
| Allows for the accumulation and juxtaposing of procoagulant cells and material | 35,41 | |
| Confers fibrinolytic resistance through clot incorporation | 35 | |
| Extruded neutrophil proteases degrade innate anticoagulants, including TFPI and AT | 41 | |
| cfDNA | Contact activation of FXI and FXII | 50 |
| Enhances TFPI degradation by neutrophil elastase | 41 | |
| Confers fibrinolytic resistance when incorporated into clots | 52 | |
| Inhibition of plasmin by competitive binding or by the formation of a plasmin-fibrin-cfDNA ternary complex | 53,96 | |
| Induces thrombin autoproteolysis, generating thrombin C-terminal fragments which protect cfDNA against degradation | 54 | |
| cfRNA | Contact activation of FXI and FXII | 50 |
| HMGB1 | Stimulates monocyte TF expression | 40,62 |
| Activates platelets, resulting in platelet degranulation and aggregation | 40,61,62 | |
| Induces NET formation | 40 | |
| Inhibits TM function by binding to extracellular domain, inhibiting PC activation | 62 | |
| Calprotectin | Augments platelet activation and aggregation | 63,64 |
| Polyphosphates | Contact activation of FXI and FXII | 50,55,56 |
| Inhibits TFPI activity and enhances its inactivation by FXIa | 50 | |
| Enhances HMGB1-mediated endothelial VWF release | 57 | |
| Augments VWF-GP1b interactions | 57 |
GP1b, glycoprotein 1b; PC, protein C.