A platelet and granulocyte membrane defect in paroxysmal nocturnal hemoglobinuria: usefulness for the detection of platelet antibodies

Abstract

The tendency of platelets and leukocytes to lyse after their interaction with antibody and complement was studied by measuring the release of (51)Cr from cells labeled with this isotope. Platelets from six patients with paroxysmal nocturnal hemoglobinuria (PNH) were 15-230 times more sensitive to antibodies and 10-32 times more sensitive to complement than normal platelets or platelets from patients with other types of thrombocytopenic or hemolytic disorders. Mixed white blood cell (WBC) preparations from patients with PNH were 3-20 times more sensitive to anti-WBC antibodies and 5-10 times more sensitive to C' than were WBC preparations from normal subjects, but PNH lymphocytes showed normal immunologic reactivity. PNH platelets, like PNH erythrocytes, lysed more readily than normal platelets in acidified serum and in media of reduced ionic strength, but these characteristics were not demonstrable with PNH WBC's under the conditions of study. In PNH, platelets appear to comprise a single population with respect to their sensitivity to immune lysis, yet their survival time as measured with (51)Cr falls within normal limits. PNH granulocytes likewise appear to consist of a single, uniformly sensitive population. It is concluded that, in PNH, platelets and granulocytes share the membrane defect characteristic of erythrocytes in this disorder. These observations support the concept that PNH arises as the result of a somatic mutation in a primitive cell capable of differentiating into erythroblast, myeloblast, and megakaryoblast lines. PNH platelets or enzymatically treated normal platelets permit the detection of some types of platelet antibodies in dilutions up to 2000-fold greater than is possible with currently available methods, a finding suggesting that the immune lysis technique will prove useful for the study of platelet immunology.