Elevated thrombopoietin and platelet indices confirm active thrombopoiesis but fail to predict clinical severity of puumala hantavirus infection

Laine, Outi; Joutsi-Korhonen, Lotta; Lassila, Riitta; Huhtala, Heini; Vaheri, Antti; Mäkelä, Satu; Mustonen, Jukka

Recent studies support the idea of platelet contribution to disease progression and binding to fibrin-covered endothelial cells as a mechanism leading to the decreased platelet count during acute hantavirus infection. [1] Upregulated tissue factor (TF) expression on the infected endothelial cells is suggested to induce increased thrombin formation noted during PUUV infection. [5, 6] Compatibly with endothelial cell activation, elevated level of tissue plasminogen activator and D-dimer have both been observed. [6, 7] Findings of enhanced platelet ligands are in concordance with those of increased platelet activation. [8, 9] Large mean platelet volume (MPV) and immature platelet fraction % (IPF%) together with elevated serum thrombopoietin (TPO) level imply active thrombopoiesis. [9, 10] Despite increased platelet production the aggregation is, however, impaired. [10] We here studied serum TPO level and the procoagulant activity of plasma microparticles (MPs) in 33 Finnish patients who were treated in hospital for acute PUUV infection. We analyzed the results in relation with clinical data, platelet function tests in whole blood (platelet function analyzer PFA-100 and Multiplate), and coagulation variables available. Our aim was to study whether active thrombopoiesis could be confirmed during the thrombocytopenia associated with acute hantavirus infection. We also sought to further characterize the procoagulant changes observed in vitro and in vivo. As the prediction of disease severity is still of utmost importance in the treatment of hantavirus infection, we particularly compared the relationship of our findings with the clinical disease severity.