A Plasma Inhibitor of Platelet Aggregation in Patients with Argentine Hemorrhagic Fever

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  • University College and Middlesex School of Medicine, Instituto de Investigaciones Medicas, Universidad de Buenos Aires, Instituto Nacional de Estudios Virosis Hemorragicas, London, England

Hemorrhage in patients with Lassa fever is associated with the presence of a circulating plasma inhibitor of platelet aggregation. This study was to determine whether patients with Argentine hemorrhagic fever (AHF) develop a similar inhibitor. Normal platelets showed significantly weaker aggregation responses to a sub-maximal dose of adenosine diphosphate (ADP) when mixed with plasma from 10 patients with AHF (mean percent of control ± 1 SE = 57.2 ± 6.7%) compared to those mixed with plasma from 9 viral control patients (79.5 ± 4.1%; P < 0.05) and 9 febrile patients with septicemia (103.8 ± 3%; P < 0.001). Plasma from 3 patients with severe AHF inhibited in a dose-dependent fashion the aggregation responses of normal platelets to collagen, sodium arachidonate, a calcium ionophore (A23187), and ristocetin; none of 4 samples from convalescent AHF patients showed this inhibitory activity. The platelet inhibition was sudden in onset and unaffected by a 30 min pre-incubation, not neutralized by convalescent plasma with high titer antibody to Junin virus, and abolished after heating plasma from an AHF patient at 56°C for 30 min. Hemorrhage in AHF is associated with the presence of a circulating inhibitor of platelet aggregation, and disturbed hemostasis in arenavirus-induced hemorrhagic fevers may have a common basis.