Summary
Thrombotic thrombocytopenic purpura (TTP) and the related hemolytic uremic syndrome
(HUS) are disorders characterized by thrombocytopenia, microangiopathic hemolytic
anemia, a variable degree of impairment of renal function and fluctuating neurological
symptoms, which are thought to be due to platelet activation and subsequent formation
of thrombi in the microcirculation. Since platelet activation is accompanied by the
generation of microvesicles (PMPs), we determined their presence in patients with
TTP and HUS by flow cytometry. The analysis was performed in whole blood, using FITC-conjugated
monoclonal antibodies (CD 42b and/or CD 61a). PMPs were discriminated from platelets
on the basis of size and fluorescence profiles. Their levels in 21 normal controls
ranged between 2.4% and 9.4% (mean ± SD: 5.2 ± 1.99%). No correlations were found
with platelet number. PMPs were then evaluted in 13 patients with TTP and 2 cases
of HUS. In all patients they were found higher than in controls, ranging from 11.0
to 91.1% (45.0 ± 26.0%; p = 0.0001 vs controls). PMPs were serially measured in patients
with TTP: at diagnosis a correlation between PMPs and platelet number was found (R^2
= 0.669) and the time-course showed that the improvement of both microangiopathy and
clinical manifestations of cerebral and renal involvement was accompanied by a progressive
normalization of PMP levels and platelet count.
PMP levels were measured also in patients suffering from other forms of thrombocytopenia:
they were 17 patients with idiopathic thrombocytopenic purpura and 10 patients with
acute leukemias and severe thrombocytopenia during the aplastic phase following chemotherapy.
PMP ranges were: 2.0−79.6% (21.6 ± 20.8%; p = 0.001 vs controls) and 4.6−12.5% (8.8
± 2.4%; p = 0.0001 vs controls), respectively. No correlations were found between
platelet number and the absolute number of PMPs in these 2 groups of patients.
These findings show that increased levels of PMPs may be found in peripheral thrombocytopenias
and suggest that their presence may be clinically relevant, particularly in the microangiopathic
forms.
