CA activation of the classical complement pathway on RBCs results in anemia in CAD patients. (1) CA-bound RBCs fix C1, the CP-activating complex, on the RBC surface, which triggers the classical complement cascade. (2) Activation of the CP results in complement opsonin deposition (C3b) on the RBC surface. (3) In general, CP activity terminates after C3 cleavage, and C3b/iC3b-opsonized RBCs then travel to the liver where they are phagocytosed by liver-resident macrophages, a process termed extravascular hemolysis. (4) Under exceptional circumstances such as immunologic stress that induces production of complement proteins, activation of the terminal complement cascade can occur, resulting in the formation of the membrane attack complex and direct cellular lysis known as intravascular hemolysis. By inhibiting classical complement pathway activation at the level of the C1 complex, an upstream CP inhibitor such as TNT003 can prevent both extra- and intravascular hemolysis.