Direct evidence for systemic fibrinogenolysis in patients with acquired alpha 2-plasmin inhibitor deficiency

To examine whether or not acquired alpha 2-plasmin inhibitor deficiency is associated with systemic fibrinogenolysis, we analyzed the fibrin and fibrinogen degradation products in eight patients with this condition in various disease states. The underlying disease was gastric cancer in three patients, metastatic prostatic cancer in two, acute promyelocytic leukemia in two, and abdominal aortic aneurysm in one patient. In all eight patients, the alpha 2-plasmin inhibitor level was reduced to less than 50% of normal, and plasmin-alpha 2-plasmin inhibitor complex levels were increased. Immunoblotting of serum using an antifibrinogen antibody detected a 250 kDa protein (corresponding to fragments X or DY) in all eight patients. Fragment Y and D monomer were detected in seven of the eight patients, indicating the occurrence of systemic fibrinogenolysis. However, they were not detected in one patient with metastatic prostatic cancer. To determine whether or not fibrinogen degradation was also occurring in the patient without fragment Y, we characterized the 250 kDa protein in all eight patients. The protein was found to be fragment X in the metastatic prostatic cancer patient without fragment Y, while it was fragment DY in the other seven patients. Thus, systemic fibrinogenolysis was present in all eight patients. In the two patients with metastatic prostatic cancer, the level of alpha 2-plasmin inhibitor gradually increased with the reduction of tumor size by treatment. Fragment X, fragment Y, and D monomer were not detected when the alpha 2-plasmin inhibitor level exceeded 60% of normal in both patients. In the other six patients fragment Y and D monomer also disappeared when the alpha 2-plasmin inhibitor level exceeded 60% of normal. These findings suggest that systemic fibrinogenolysis only occurs when the plasma levels of alpha 2-plasmin inhibitor falls below 60% of normal due to activation of the fibrinolytic system by various pathological conditions.