This regulates the activation of alpha-2-macroglobulin (as an acute-phase reactant) and promotes intravascular coagulation, vascular permeability, and the generation of oxygen-free radicals in the microvasculature of the pancreas, mechanisms proposed to drive pancreatic inflammation [16].  A retrospective study of patients with massive hemolysis of various causes found acute pancreatitis occurred in over 20%, suggesting it may be an underrecognized complication [17]. This evidence concerns the gene A2M and inflammatory response.