title: Hantavirus infection-induced thrombocytopenia triggers increased production but associates with impaired aggregation of platelets except for collagen.
abstract: BACKGROUND
  We evaluated the mechanisms of thrombocytopenia encountered in hantavirus disease by studying platelet production together with platelet aggregation and deposition to collagen surface.
  
  
  METHODS
  The study group consisted of 31 prospectively recruited, consecutive, hospitalized patients having acute Puumala hantavirus infection. Blood samples were collected acutely and at the control visit and subjected to analysis in Sysmex® XE-5000 to capture mean platelet volume (MPV) and immature platelet fraction (IPF%). Platelet aggregation under low shear rate conditions was assessed with impedance aggregometry Multiplate®, whereas platelet function analyzer (PFA)-100® was applied under blood flow of high shear forces.
  
  
  RESULTS
  IPF% was 3.1-fold higher acutely compared with the control (median 7.4%, range 2.0-23.8% vs. median 2.4%, range 1.4%-5.2%, p<0.001) tightly associating with the low platelet count (r=-0.76, p<0.001). Accordingly, acute MPV was high (median 11.4f l, range 9.4-13.1 fl vs. median 10.5 fl, range 9.0-12.0 fl, p=0.003). Acute platelet aggregation in Multiplate® was decreased to all agonists compared with the later control (p<0.05 for all agonists). Aggregation capacity associated with thrombocytopenia (for all agonists r ≥ 0.81, p<0.001), but impaired aggregation occurred also among patients with a nearly normal platelet count. Triggered by collagen, 20% of values were below reference range, while 73% of responses were low with thrombin receptor activating peptide. Significantly, under high shear platelet deposition to collagen surface was normal despite thrombocytopenia.
  
  
  CONCLUSIONS
  During acute hantavirus disease, platelet aggregation is impaired especially when induced with thrombin. Platelet adhesive mechanisms on collagen are intact despite thrombocytopenia while thrombopoiesis is active.
authors.affiliation: Department of Internal Medicine, Tampere University Hospital, PO Box 2000, 33521 Tampere, Finland; School of Medicine, University of Tampere, 33014 Tampere, Finland. Electronic address: outi.laine@staff.uta.fi.
authors.forename: Outi
authors.initials: O
authors.lastname: Laine
authors.affiliation: Coagulation Disorders Unit, Clinical Chemistry, HUSLAB Laboratory Services, Helsinki University Hospital, PO Box 372, 00029 Helsinki, Finland. Electronic address: lotta.joutsi-korhonen@hus.fi.
authors.forename: Lotta
authors.initials: L
authors.lastname: Joutsi-Korhonen
authors.affiliation: Coagulation Disorders Unit, Department of Hematology, Comprehensive Cancer Center, Helsinki University, and Helsinki University Hospital, PO Box 372, 00029 Helsinki, Finland. Electronic address: riitta.lassila@hus.fi.
authors.forename: Riitta
authors.initials: R
authors.lastname: Lassila
authors.affiliation: Fimlab Medical Laboratories, Tampere University Hospital, PO Box 66, 33101 Tampere, Finland. Electronic address: tomi.koski@fimlab.fi.
authors.forename: Tomi
authors.initials: T
authors.lastname: Koski
authors.affiliation: School of Health Sciences, University of Tampere, 33014 Tampere, Finland. Electronic address: heini.huhtala@uta.fi.
authors.forename: Heini
authors.initials: H
authors.lastname: Huhtala
authors.affiliation: Department of Virology, Faculty of Medicine, University of Helsinki, PO Box 21, 00014 Helsinki, Finland. Electronic address: antti.vaheri@helsinki.fi.
authors.forename: Antti
authors.initials: A
authors.lastname: Vaheri
authors.affiliation: Department of Internal Medicine, Tampere University Hospital, PO Box 2000, 33521 Tampere, Finland. Electronic address: satu.marjo.makela@uta.fi.
authors.forename: Satu
authors.initials: S
authors.lastname: Mäkelä
authors.affiliation: Department of Internal Medicine, Tampere University Hospital, PO Box 2000, 33521 Tampere, Finland; School of Medicine, University of Tampere, 33014 Tampere, Finland. Electronic address: jukka.mustonen@uta.fi.
authors.forename: Jukka
authors.initials: J
authors.lastname: Mustonen
mesh_terms: D000328:Adult; D000368:Aged; D001792:Blood Platelets / Q000502:physiology*; D003094:Collagen / Q000494:pharmacology*; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D018778:Hantavirus Infections / Q000150:complications*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010974:Platelet Aggregation / Q000187:drug effects*; D010976:Platelet Count; D013921:Thrombocytopenia / Q000097:blood*
chemical_list: D005340:Fibrinogen; D003094:Collagen
keywords: Aggregation; Function; Hantavirus; Platelet; Thrombocytopenia; Thrombopoiesis