title: Early markers of blood coagulation and fibrinolysis activation in Argentine hemorrhagic fever.
abstract: Junin virus, an arenaviridae, is the etiological agent of Argentine hemorrhagic fever. In addition to thrombocytopenia, patients present several alterations in both the blood coagulation and the fibrinolytic system, but diffuse intravascular coagulation could not be demonstrated. To investigate further the activation status of the two systems, levels of thrombin-antithrombin complexes (TAT), prothrombin fragment 1 + 2, protein C, total and free protein S, C4bBP, antithrombin III, t-PA, PAI-1 and D-dimer were measured. Fourteen patients with a confirmed diagnosis of Argentine hemorrhagic fever were included in the study, 2 were severe, 3 moderate and 9 mild clinical cases, but hemorrhages were slight throughout. Blood samples were collected for 6 consecutive days on admission and on remission. At admission TAT and F1 + 2 levels were increased in 13/14 patients, reaching 0.33 nM (0.06-0.87) and 2.16 nM (0.96-6.5), respectively. PC was low in 4 cases, fPS in 6 and tPS in 2, whereas C4bBP and ATIII values were within normal range. t-PA and D-dimer levels were high in 11/14 patients, reaching 20 ng/ml (2.7-106) and 1660 ng/ml (877-3780) respectively, while PAI-1 was considerably increased in the 2 severe cases and normal in the remainder. These results suggest low level though persistent process of blood coagulation and fibrinolysis activation in this viral hemorrhagic disease. We believe these abnormalities may lead to the well described bleeding manifestations in these patients.
authors.affiliation: Instituto de Investigaciones Médicas Alfredo Lanari, Facultad de Medicina, Universidad de Buenos Aires, Argentina.
authors.forename: M V
authors.initials: MV
authors.lastname: Heller
authors.forename: R F
authors.initials: RF
authors.lastname: Marta
authors.forename: A
authors.initials: A
authors.lastname: Sturk
authors.forename: J I
authors.initials: JI
authors.lastname: Maiztegui
authors.forename: C E
authors.initials: CE
authors.lastname: Hack
authors.forename: J W
authors.initials: JW
authors.lastname: Cate
authors.forename: F C
authors.initials: FC
authors.lastname: Molinas
mesh_terms: D000990:Antithrombin III / Q000032:analysis; D015415:Biomarkers / Q000097:blood*; D001777:Blood Coagulation; D001798:Blood Proteins / Q000032:analysis*; D015935:Complement C4b / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005342:Fibrinolysis; D006478:Hemorrhagic Fever, American / Q000097:blood*; D006801:Humans; D010446:Peptide Fragments / Q000032:analysis; D010447:Peptide Hydrolases / Q000032:analysis; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D011486:Protein C / Q000032:analysis; D017293:Protein S / Q000032:analysis; D011516:Prothrombin / Q000032:analysis; D010959:Tissue Plasminogen Activator / Q000097:blood
chemical_list: D015415:Biomarkers; D001798:Blood Proteins; D005338:Fibrin Fibrinogen Degradation Products; D010446:Peptide Fragments; D017395:Plasminogen Activator Inhibitor 1; D011486:Protein C; D017293:Protein S; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; C045879:prothrombin fragment 1.2; D015935:Complement C4b; D000990:Antithrombin III; D011516:Prothrombin; D010447:Peptide Hydrolases; D010959:Tissue Plasminogen Activator