Paroxysmal nocturnal hemoglobinuria: the role of properdin in the diagnostic thrombin test.

By WILLIArsI H. CROSBY AND NAOMI R. BENJAMIN I HE RED BLOOD CELLS of patients with paroxysmal nocturnal hemoglobinuria ( PNH ) possess an apparently unique susceptibility to the hemolytic activity of certain naturally occurring plasma factors. Hemolysis occurs readily in vitro and the reaction is intensified when the incubating mixture has been made slightly acid. This phenomenon is the basis of a standard diagnostic test for the disease, the Ham acid-hemolysis test.’ Several years ago it was noted that increased hemolysis in patients with PNH was sometimes associated with increased activity of the blood coagulation mechanism.2 A relationship between PNH hemolysis and the coagulation system was also demonstrated in vitro: hemolysis was increased by adding to the Ham test small amounts of thrombin or thromboplastin. This phenomenon has proved diagnostically useful in the “thrombin test” for PNH.3 It has been suggested that thrombin causes this increased hemolysis by destroying or blocking an inhibitor of the PNH hemolytic system.4 More recently it has been announced that the PNH hemolytic system depends upon the bactericidal globulin, properdin.5 This protein has been prepared in a relatively pure form, and it has been demonstrated that properdmn plus Mg+ + , together with other plasma factors as yet unidentified, can hemolyze PNH cells in acidified serum. It was also found that commercially available preparations of thrombin, of the sort used for the “thrombin test,” are contaminated with properdin. On the basis of these data, it was suggested that the effect of thrombin on the PNH hemolytic system is due to the presence of the contaminating properdin.6 In the present report are described some further observations bearing upon this point.