title: Increased Thrombopoiesis and Platelet Activation in Hantavirus-Infected Patients.
abstract: BACKGROUND
  Thrombocytopenia is a common finding during viral hemorrhagic fever, which includes hemorrhagic fever with renal syndrome (HFRS). The 2 main causes for thrombocytopenia are impaired thrombopoiesis and/or increased peripheral destruction of platelets. In addition, there is an increased intravascular coagulation risk during HFRS, which could be due to platelet activation.
  
  
  METHODS
  Thrombopoiesis was determined by quantification of platelet counts, thrombopoietin, immature platelet fraction, and mean platelet volume during HFRS. The in vivo platelet activation was determined by quantification of soluble P-selectin (sP-selectin) and glycoprotein VI (sGPVI). The function of circulating platelets was determined by ex vivo stimulation followed by flow cytometry analysis of platelet surface-bound fibrinogen and P-selectin exposure. Intravascular coagulation during disease was determined by scoring for disseminated intravascular coagulation (DIC) and recording thromboembolic complications.
  
  
  RESULTS
  The levels of thrombopoietin, immature platelet fraction, and mean platelet volume all indicate increased thrombopoiesis during HFRS. Circulating platelets had reduced ex vivo function during disease compared to follow-up. Most interestingly, we observed significantly increased in vivo platelet activation in HFRS patients with intravascular coagulation (DIC and thromboembolic complications) as shown by sP-selectin and sGPVI levels.
  
  
  CONCLUSIONS
  HFRS patients have increased thrombopoiesis and platelet activation, which contributes to intravascular coagulation.
authors.affiliation: Infectious Diseases, Department of Clinical Microbiology.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Connolly-Andersen
authors.affiliation: Infectious Diseases, Department of Clinical Microbiology Clinical Chemistry, Department of Medical Biosciences, Umeå University, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Sundberg
authors.affiliation: Infectious Diseases, Department of Clinical Microbiology.
authors.forename: Clas
authors.initials: C
authors.lastname: Ahlm
authors.affiliation: Clinical Chemistry, Department of Medical Biosciences, Umeå University, Sweden.
authors.forename: Johan
authors.initials: J
authors.lastname: Hultdin
authors.affiliation: Infectious Diseases, Department of Clinical Microbiology.
authors.forename: Maria
authors.initials: M
authors.lastname: Baudin
authors.affiliation: Clinical Chemistry, Department of Medical Biosciences, Umeå University, Sweden.
authors.forename: Johanna
authors.initials: J
authors.lastname: Larsson
authors.affiliation: Clinical Research Centre, Royal College of Surgeons in Ireland, Dublin.
authors.forename: Eimear
authors.initials: E
authors.lastname: Dunne
authors.affiliation: Clinical Research Centre, Royal College of Surgeons in Ireland, Dublin.
authors.forename: Dermot
authors.initials: D
authors.lastname: Kenny
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Sweden.
authors.forename: Tomas L
authors.initials: TL
authors.lastname: Lindahl
authors.affiliation: Department of Clinical and Experimental Medicine, Linköping University, Sweden.
authors.forename: Sofia
authors.initials: S
authors.lastname: Ramström
authors.affiliation: Clinical Chemistry, Department of Medical Biosciences, Umeå University, Sweden.
authors.forename: Sofie
authors.initials: S
authors.lastname: Nilsson
mesh_terms: D000328:Adult; D001777:Blood Coagulation; D001792:Blood Platelets / Q000502:physiology; D004211:Disseminated Intravascular Coagulation / Q000097:blood* / Q000503:physiopathology; D005260:Female; D005340:Fibrinogen / Q000032:analysis; D006476:Orthohantavirus / Q000502:physiology*; D006480:Hemorrhagic Fever with Renal Syndrome / Q000097:blood* / Q000503:physiopathology; D006801:Humans; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D019007:P-Selectin / Q000097:blood; D015539:Platelet Activation; D010976:Platelet Count; D013921:Thrombocytopenia / Q000097:blood* / Q000503:physiopathology; D034061:Thrombopoiesis; D013926:Thrombopoietin / Q000097:blood
chemical_list: D019007:P-Selectin; C546937:SELP protein, human; D005340:Fibrinogen; D013926:Thrombopoietin
keywords: disseminated intravascular coagulation; hantavirus; hemorrhagic fever with renal syndrome; platelets; thrombosis; viral hemorrhagic fever