title: Elevated thrombopoietin and platelet indices confirm active thrombopoiesis but fail to predict clinical severity of puumala hantavirus infection.
abstract: 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 207 pg/mL, range 56-1258 pg/mL vs. median 58 pg/mL, range 11-241 pg/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 704 pmol/L, range 284-1875 pmol/L vs. median 249 pmol/L, range 118-556 pmol/L, P < 0.001; D-dimer median 2.8 mg/L, range 0.6-34.0 mg/L vs. median 0.4 mg/L, range 0.2-1.1 mg/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.
authors.affiliation: Department of Internal Medicine, Tampere University Hospital School of Medicine, University of Tampere, Tampere Coagulation Disorders Unit, Clinical Chemistry, HUSLAB Laboratory Services, Helsinki University Hospital Coagulation Disorders Unit, Department of Hematology, Comprehensive Cancer Center, Helsinki University, and Helsinki University Hospital, Helsinki School of Health Sciences, University of Tampere, Tampere Department of Virology, Faculty of Medicine, University of Helsinki, Helsinki.
authors.forename: Outi
authors.initials: O
authors.lastname: Laine
authors.forename: Lotta
authors.initials: L
authors.lastname: Joutsi-Korhonen
authors.forename: Riitta
authors.initials: R
authors.lastname: Lassila
authors.forename: Heini
authors.initials: H
authors.lastname: Huhtala
authors.forename: Antti
authors.initials: A
authors.lastname: Vaheri
authors.forename: Satu
authors.initials: S
authors.lastname: Mäkelä
authors.forename: Jukka
authors.initials: J
authors.lastname: Mustonen
mesh_terms: D000208:Acute Disease; D058186:Acute Kidney Injury / Q000097:blood / Q000821:virology; D000328:Adult; D000368:Aged; D055252:Cell-Derived Microparticles; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D006480:Hemorrhagic Fever with Renal Syndrome / Q000097:blood* / Q000150:complications*; D006801:Humans; D008297:Male; D063847:Mean Platelet Volume; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D010976:Platelet Count; D011446:Prospective Studies; D011498:Protein Precursors / Q000097:blood; D011516:Prothrombin; D029262:Puumala virus; D012720:Severity of Illness Index; D013921:Thrombocytopenia / Q000097:blood* / Q000821:virology; D034061:Thrombopoiesis; D013926:Thrombopoietin / Q000097:blood*; D055815:Young Adult
chemical_list: D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; D011498:Protein Precursors; C036309:fibrin fragment D; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D011516:Prothrombin; D013926:Thrombopoietin