Impaired survival of bone marrow GPIIb/IIIa+ megakaryocytic cells as an additional pathogenetic mechanism of HIV-1-related thrombocytopenia

Glycoproteic (GP)IIb/IIIa⁺ megakaryocytic cells were purified from the bone marrow (BM) of 15 HIV-1 seropositive thrombocytopenic patients, eight HIV-1 seronegative patients affected by immune thrombocytopenic purpura (ITP) and 14 HIV-1 seronegative normal donors. The presence of apoptosis was evaluated in freshly isolated GPIIb/IIIa⁺ cells by flow cytometry after propidium iodide staining and electron microscopy. GPIIb/IIIa⁺ cells from HIV-1 seropositive thrombocytopenic patients showed a significant (P <0.001) increase of apoptosis with respect to both HIV-1 seronegative ITP patients and normal donors. Moreover, the degree Or apoptosis in bone marrow GPIIb/ IIIa⁺ cells purified from HIV-1 seropositive thrombocytopenic patients was inversely (P <0.01) related to the count of circulating platelets, whereas it did not show any significant correlation with the absolute number of circulating CD4 T cells, the CD4/CD8 ratio or the presence of proviral gag DNA sequences. Therefore neither an advanced stage of HIV-1 disease nor a direct infection with HIV-1 seems to play a primary role in the impaired survival of BM GPIIb/IIIa⁺ megakaryocytic cells. These findings strengthen the notion that, besides the immune targeting of peripheral platelets, an impairment of the bone marrow megakaryocyte compartment may also contribute to the pathogenesis of HIV-1 related thrombocytopenia.