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

Abstract

A B S T R A C T The tendency of platelets and leukocytes to lyse after their interaction with antibody and complement was studied by measuring the release of '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 '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 perThis work was presented in part at the National Meeting of The American Society for Clinical Investigation on 5 May 1968 and published in Abstract form (1).

Hemoglobin interaction with GP1b induces platelet activation and apoptosis: a novel mechanism associated with intravascular hemolysis

“…9,10 Several studies demonstrated that activation of blood cells including platelets and generation of microparticles by these cells are associated with the pathogenesis of thrombosis in PNH patients. 37,38 Our data show a unique parallel correlation between plasma Hb or platelet surface-bound Hb and platelet activation markers (such as surface expression of P-selectin and PS, and the platelet-derived microparticles) in PNH patients ( Figure 6). …”

Deletion of the Platelet-Specific Alloantigen PlA1 from Platelets in Glanzmann's Thrombasthenia

“…Platelets were isolated by differential centrifugation of whole blood anticoagulated with EDTA (21). In four instances, in which blood was obtained from individuals in another city, a second sample was drawn from a normal individual at the same time; both samples were processed, transported, and handled under identical conditions.…”

SLE Thrombocytopenia: From Peripheral Platelet Destruction to Central Hemopoietic Defect

“…Chronologically they can be classified in three groups. The first group, that measured functional deviations of normal platelets incubated with patients' sera, was abandoned due to low sensitivity and specificity [28][29][30]. The second group measured the IgG bound to platelets (Platelet associated IgG, PAIgG) [31].…”