PLASMA MACROPHAGE-COLONY-STIMULATING FACTOR AND P-SELECTIN LEVELS IN MALARIA-ASSOCIATED THROMBOCYTOPENIA

Thrombocytopenia is a common finding in malaria. In clinical trials, r ecombinant macrophage colony-stimulating factor (M-CSF) causes a rever sible, dose-dependent thrombocytopenia, and high M-CSF has been report ed in autoimmune thrombocytopenias. P-selectin, which is secreted into the plasma following platelet/endothelial activation or damage, is el evated in certain consumptive thrombocytopenic disorders. The relation ships between thrombocytopenia, M-CSF and P-selectin were analysed in 63 patients with severe (n = 13) or uncomplicated (n = 26) P. falcipar um (PF) or P. vivax (PV) malaria (n = 24). On admission, 69% of PF pat ients and 75% of PV patients were thrombocytopenic (platelets < 150 x 10(9)/l). M-CSF was elevated in PF (3021 +/- 1844 pg/ml) and PV (2602 +/- 1668 pg/ml) patients, compared to controls (589 +/- 200 pg/ml). Th e platelet count was inversely correlated with M-CSF in PF (r = -0.681 ), and in PV malaria (r = -0.548). Elevated P-selectin was found in se vere PF malaria, but not in PV malaria. Severe PF malaria was associat ed with marked thrombocytopenia, very high M-CSF, elevated P-selectin and compelling evidence of disseminated intravascular coagulopathy (DI G). Platelet counts, M-CSF and P-selectin returned to control values i n 7-14 days. These data suggest that elevated M-CSF in malaria, by enh ancing macrophage activity, may result in increased macrophage-mediate d platelet destruction. Further, platelet/endothelial activation or da mage, as measured by P-selectin, or DIC could intensify thrombocytopen ia in severe PF malaria, but does not appear to contribute to thromboc ytopenia in uncomplicated PF or PV malaria.