title: Plasma pentraxin-3 and coagulation and fibrinolysis variables during acute Puumala hantavirus infection and associated thrombocytopenia.
abstract: Thrombocytopenia and altered coagulation characterize all hantavirus infections. To further assess the newly discovered predictive biomarkers of disease severity during acute Puumala virus (PUUV) infection, we studied the associations between them and the variables reflecting coagulation, fibrinolysis and endothelial activation. Nineteen hospital-treated patients with serologically confirmed acute PUUV infection were included. Acutely, plasma levels of pentraxin-3 (PTX3), cell-free DNA (cf-DNA), complement components SC5b-9 and C3 and interleukin-6 (IL-6) were recorded as well as platelet ligands and markers of coagulation and fibrinolysis. High values of plasma PTX3 associated with thrombin formation (prothrombin fragments F1+2; r = 0.46, P = 0.05), consumption of platelet ligand fibrinogen (r = -0.70, P < 0.001) and natural anticoagulants antithrombin (AT) (r = -0.74, P < 0.001), protein C (r = -0.77, P < 0.001) and protein S free antigen (r = -0.81, P < 0.001) and a decreased endothelial marker ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 domain 13) (r = -0.48, P = 0.04). Plasma level of AT associated with C3 (r = 0.76, P < 0.001), IL-6 (r = -0.56, P = 0.01) and cf-DNA (r = -0.47, P = 0.04). High cf-DNA coincided with increased prothrombin fragments F1+2 (r = 0.47, P = 0.04). Low C3 levels reflecting the activation of complement system through the alternative route predicted loss of all natural anticoagulants (for protein C r = 0.53, P = 0.03 and for protein S free antigen r = 0.64, P = 0.004). Variables depicting altered coagulation follow the new predictive biomarkers of disease severity, especially PTX3, in acute PUUV infection. The findings are consistent with the previous observations of these biomarkers also being predictive for low platelet count and underline the cross-talk of inflammation and coagulation systems in acute PUUV infection.
authors.affiliation: aDepartment of Internal Medicine, Tampere University Hospital bSchool of Medicine, University of Tampere cCoagulation Disorders, Department of Clinical Chemistry (HUSLAB Laboratory Services), Helsinki University Central Hospital dSchool of Health Sciences, University of Tampere eDepartment of Virology, Haartman Institute, University of Helsinki fLaboratory Centre, Tampere University Hospital, Tampere, Finland.
authors.forename: Outi K
authors.initials: OK
authors.lastname: Laine
authors.forename: Sirpa M
authors.initials: SM
authors.lastname: Koskela
authors.forename: Tuula K
authors.initials: TK
authors.lastname: Outinen
authors.forename: Lotta
authors.initials: L
authors.lastname: Joutsi-Korhonen
authors.forename: Heini
authors.initials: H
authors.lastname: Huhtala
authors.forename: Antti
authors.initials: A
authors.lastname: Vaheri
authors.forename: Mikko A
authors.initials: MA
authors.lastname: Hurme
authors.forename: Juulia
authors.initials: J
authors.lastname: Jylhävä
authors.forename: Satu M
authors.initials: SM
authors.lastname: Mäkelä
authors.forename: Jukka T
authors.initials: JT
authors.lastname: Mustonen
mesh_terms: D051722:ADAM Proteins / Q000097:blood; D000071120:ADAMTS13 Protein; D000208:Acute Disease; D000328:Adult; D000990:Antithrombin III / Q000378:metabolism; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D002097:C-Reactive Protein / Q000378:metabolism*; D003176:Complement C3 / Q000378:metabolism; D015938:Complement Membrane Attack Complex / Q000378:metabolism; D004247:DNA / Q000097:blood; D005260:Female; D005340:Fibrinogen / Q000378:metabolism; D006480:Hemorrhagic Fever with Renal Syndrome / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000821:virology; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011486:Protein C / Q000378:metabolism; D017293:Protein S / Q000378:metabolism; D029262:Puumala virus / Q000502:physiology; D000683:Serum Amyloid P-Component / Q000378:metabolism*; D012720:Severity of Illness Index; D013917:Thrombin / Q000378:metabolism; D013921:Thrombocytopenia / Q000097:blood* / Q000150:complications / Q000175:diagnosis / Q000821:virology; D000099153:Pentraxins
chemical_list: D051722:ADAM Proteins; D000071120:ADAMTS13 Protein; D000990:Antithrombin III; D015415:Biomarkers; D002097:C-Reactive Protein; D003176:Complement C3; D015938:Complement Membrane Attack Complex; D004247:DNA; D005340:Fibrinogen; D015850:Interleukin-6; D011486:Protein C; D017293:Protein S; D000683:Serum Amyloid P-Component; D013917:Thrombin; D000099153:Pentraxins; C508600:IL6 protein, human; C047610:SC5b-9 protein complex; C099604:ADAMTS13 protein, human