Paroxysmal Nocturnal Hemoglobinuria

Abstract

The C3 activator system, a newly discovered pathway for the activation of late acting complement components, was tested for its capacity to initiate hemolysis of erythrocytes from patients with paroxysmal nocturnal hemoglobinuria. Erythrocytes from such patients were lysed at pH 8.0 by whole human serum in presence of inulin, a potent activating substance of the C3 activator system. Serum depleted of C3 proactivator (C3PA) failed to support lysis of the erythrocytes, but regained this capacity after addition of highly purified C3PA. A requirement of C3PA was also demonstrated for the acidified serum test (Ham test). The mechanisms of this pH-dependent hemolytic reaction was explained in part by the observation that activation of C3PA and C3 occurs in the absence of erythrocytes when serum alone is incubated at pH 6.5. It seems likely that the C3 activator system may participate in the causation of intravascular hemolysis and thrombotic episodes in patients with paroxysmal nocturnal hemoglobinuria.