PATHOLOGIC EFFECTS OF PLASMA FROM PATIENTS WITH THROMBOTIC THROMBOCYTOPENIC PURPURA ON PLATELETS AND CULTURED VASCULAR ENDOTHELIAL-CELLS

  • 1 January 1982
    • journal article
    • research article
    • Vol. 60  (4) , 1030-1037
Abstract
The pathologic hallmarks of thrombotic thrombocytopenic purpura (TTP) include endothelial cell proliferation and subendothelial hyalin deposits in the microvasculature leading to symptomatic thrombotic occlusions. Plasma or sera from 3 consecutive patients with TTP were subjected to multiple analyses to determine whether they induce endothelial injury and/or platelet activation, 2 pathogenic mechanisms that may account for this disorder. Sera were utilized in a microcytotoxicity assay against cultured human umbilical vein endothelial cells (EC). These cells were assessed ultrastructurally and with immunofluorescence techniques to ascertain the nature of inflicted cell damage. Control plasmas were obtained from healthy volunteers as well as patients with immune complex disease and the adult hemolytic uremic syndrome. In the presence of TTP serum, cell kill of 3H-proline-labeled EC averaged 42 vs. 8.6% for control sera. Cytotoxicity induced by an IgG fraction of TTP sera averaged 70 vs. 16.8% for control IgG. Removal of IgG by immune precipitation diminished cytotoxicity by 70%. Using indirect immunofluorescence, IgG was detected on EC incubated with TTP serum, but not on EC treated with control serum. Ultrastructural changes became apparent within 30 min after exposure of cultured EC to TTP serum. Virtually every cell developed numerous cytoplasmic inclusions rarely seen in EC in the presence of normal serum. Prolonged incubation with the TTP serum led to progressive cytolysis, terminating with complete cytoplasmic and nuclear degeneration. Plasma from all 3 patients with TTP caused spontaneous aggregation of normal washed platelets as monitored by aggregometry. No spontaneous aggregation occurred in response to control plasmas. The sera of the 3 TTP patients studied apparently were able to mediate time-dependent immune destruction of human cultured endothelial cells; their plasmas were capable of causing spontaneous aggregation of normal human platelets in vitro. These mechanisms apparently are also operative in vivo to produce the endothelial destruction and the thrombotic vascular occlusions seen in this disorder.

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