• It is thought that microangiopathic hemolytic anemia is mediated by endothelial injury, platelet activation, microthrombi formation, intra-vascular hemolysis and thrombocytopenia.
• In diseases such as hemolytic uremic syndrome, disseminated intravascular coagulation, thrombotic thrombocytopenic purpura, as well as malignant hypertension, the endothelial layer of small vessels are damaged with resulting fibrin deposition and platelet aggregation.
• The mechanism of endothelial injury varies depending on the underlying cause. It results in platelets aggregation and activation the coagulation cascade. There is the formation of a fibrin mesh due to increased activity of coagulation cascade.
• This results in the formation of microthrombi in the [[blood vessel] and reduction of the caliber of the blood vessels.
• The red blood cells are fragmented due to mechanical sheering by the microthrombi.

The red blood cells are physically cut by these protein networks, and the fragments are identical to the schistocytes seen on light microscopy.