Characterization of platelet glycoproteins and platelet/endothelial cell antibodies in patients with thrombotic thrombocytopenic purpura

Platelets and sera from 12 thrombotic thrombocytopenic purpura (TTP) and 12 healthy normal control subjects were examined.;ls determined by quantitati ve now cytometry: prior to plasma exchange therapy platelet surface glycopr otein (GP) Ib levels were similar in TTP patients and normal controls (mean 20188 and 20226 molecules/platelet, respectively). Platelets from patients with TTP did, however have significantly reduced levels of GPIIb/IIIa prio r to plasmapheresis (mean 36 348 v 52 505 molecules/platelet in controls: P = 0.0004) and of GPIV (mean 13 331 v 26 212 molecules/platelet in controls ; P = 0.0002), An increase in activated platelets, as determined by CD62 ex pression, was observed in 82% of patients, Increased platelet-associated im munoglobulins and/or complement was also seen in approximately 60% of the p atients. In general, with return of platelet counts to normal levels follow ing seven plasmaphereses, the above abnormalities were reversed, although o ften not to normal levers. Western blot analysis indicated the presence of antibodies reactive to platelet GPIV (88 kD) in 70% of pretreatment sera fr om patients with TTP: a similar band was observed in 80% of patient sera ag ainst microvascular endothelial cells, Immunofluorescence microscopic exami nation indicated the presence of antibody in pretreatment sera from patient s with TTP to microvascular (73%) and large vessel (36%) endothelial cells, As measured by an indirect now cytometric assay, pretreatment sera from 55 % of patients with TTP were reactive with large vessel endothelial cells an d 100% reacted with microvascular endothelial cells: reactivity was signifi cantly greater against the microvascular endothelial cells (P = 0.0048) and was reduced following plasma exchange therapy. These results indicate abno rmalities in platelet glycoprotein expression in TTP and suggest that anti- platelet and anti-endothelial cell antibodies play a role in the thrombocyt openia and vasculitis characteristic of this disorder.