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

We evaluated the mechanisms of thrombocytopenia and procoagulant changes in relation with clinical variables in a cohort of patients with acute hantavirus disease. Blood samples of 33 prospectively recruited, consecutive, hospitalized patients with acute Puumala virus-induced hemorrhagic fever with renal syndrome (HFRS) were collected acutely and at the recovery visit (control). Serum thrombopoietin (TPO) and activity of plasma microparticles (MPs) from various cell sources were measured with enzyme-linked immunosorbent assay-based methods. The results were related to data on platelet indices and functions, coagulation variables, and clinical disease. Serum TPO was nearly 4-fold higher acutely compared with the control (median 207pg/mL, range 56-1258pg/mL vs. median 58 pg/mL, range 11-241pg/mL, P<0.001) and coincided with high mean platelet volume (MPV) and immature platelet fraction (IPF%). Prothrombin fragments and D-dimer were high acutely compared with the control (F1+2 median 704pmol/L, range 284-1875pmol/L vs. median 249pmol/L, range 118-556pmol/L, P<0.001; D-dimer median 2.8mg/L, range 0.6-34.0mg/L vs. median 0.4mg/L, range 0.2-1.1mg/L, P<0.001), and associated with low platelet count and severe acute kidney injury (AKI). MPs' procoagulant activity was high acutely only among patients with mild AKI (plasma creatinine below the median at the time of the measurement). Upregulated TPO together with high MPV and IPF% confirm active thrombopoiesis, but do not predict severity of HFRS. Simultaneously, elevated prothrombin fragments and D-dimer suggest increased consumption of platelets in patients with severe AKI. Activity of platelet-derived MPs in HFRS should be studied with flow cytometry in a larger cohort of patients.