Pathological effects of plasma from patients with thrombotic thrombocytopenic purpura on platelets and cultured vascular endothelial cells

E. R. Burns, D. Zucker-Franklin

Research output: Contribution to journalArticlepeer-review

118 Scopus citations


The pathological 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 three consecutive patients with TTP were subjected to determine whether they induced endothelial injury and/or platelet activation, two 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% versus 8.6% for control sera. Cytotoxicity induced by an IgG fraction of TTP sera averaged 70% versus 16.8% for control IgG. Removal of IgG by immune precipitation diminished cytotoxicity by 70%. Using indirect immunofluorescence IgG was detected in EC incubated with TTP serum but not on EC treated with control serum. Ultrastructural changes became apparent within 30m 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 three patients with TTP caused spontaneous aggregation of normal washed platelets as monitored by aggregometry. No spontaneous aggregation occurred in response to control plasmas. These results indicate that the sera of the three TTP patients studied were able to mediate time-dependent immune destruction of human cultured endothelial cells and that their plasmas were capable of causing spontaneous aggregation of normal human platelets in vitro. It would seem likely that these mechanisms are also operative in vivo to produce the endothelial destruction as well as the thrombotic vascular occlusions seen in this disorder.

Original languageEnglish (US)
Pages (from-to)1030-1037
Number of pages8
Issue number4
StatePublished - Jan 1 1982
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology


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