Consequences of intravascular hemolysis in the mechanisms of thrombosis in PNH
1. Release of free hemoglobin resulting in: |
a. Platelet activation |
b. Thrombophlebitis |
c. NO depletion with consequences of: |
i. Vasoconstriction |
ii. Platelet activation and aggregation |
iii. Increased expression of cellular adhesion molecules |
iv. Secretion of procoagulant proteins |
v. Ischemia-reperfusion injury |
vi. Endothelial proliferation |
vii. Increased inflammatory markers |
viii. Factor XIII activation |
ix. Increased levels of thrombin-antithrombin complexes and fibrin split products |
d. Inhibition of ADAMTS13 |
e. Direct endothelial dysfunction |
f. Activation of endothelial cells and release of microparticles |
g. Increased levels of tissue factor |
h. Increased levels of reactive oxygen species |
2. Release of arginase resulting in NO depletion |
3. Release of procoagulant red cell microparticles |
1. Release of free hemoglobin resulting in: |
a. Platelet activation |
b. Thrombophlebitis |
c. NO depletion with consequences of: |
i. Vasoconstriction |
ii. Platelet activation and aggregation |
iii. Increased expression of cellular adhesion molecules |
iv. Secretion of procoagulant proteins |
v. Ischemia-reperfusion injury |
vi. Endothelial proliferation |
vii. Increased inflammatory markers |
viii. Factor XIII activation |
ix. Increased levels of thrombin-antithrombin complexes and fibrin split products |
d. Inhibition of ADAMTS13 |
e. Direct endothelial dysfunction |
f. Activation of endothelial cells and release of microparticles |
g. Increased levels of tissue factor |
h. Increased levels of reactive oxygen species |
2. Release of arginase resulting in NO depletion |
3. Release of procoagulant red cell microparticles |