Diminished coagulation capacity assessed by calibrated automated thrombography during acute Puumala hantavirus infection

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Abstract

Coagulation abnormalities are associated with Puumala-virus-induced hemorrhagic fever with renal syndrome (PUUV–HFRS). We evaluated the coagulation capacity of plasma during acute PUUV–HFRS by measuring thrombin generation using calibrated automated thrombography (CAT). The study cohort comprised 27 prospectively collected, consecutive, hospital-treated patients with acute PUUV infection. Blood samples were drawn in the acute phase and at the control visit approximately 5 weeks later. To evaluate thrombin generation, the lag time of initiation, endogenous thrombin potential (ETP), and peak and time to peak thrombin concentration were assessed by CAT in platelet poor plasma without corn trypsin inhibitor. Plasma levels of D-dimer, fibrinogen and prothrombin fragments (F1 + 2) were also evaluated. When the acute phase was compared with the control phase, ETP was decreased (median 1154 nmol/l/min, range 67–1785 vs. median 1385 nmol/l/min, range 670–1970; P < 0.001), while the lag time was prolonged (median 3.8 min, range 2.1–7.7 vs. median 2.9 min, range 2.0–4.1; P < 0.001). Low ETP correlated with low peak thrombin concentration (r = 0.833, P < 0.001). Prolonged time to peak associated with the lag time (r = 0.78, P < 0.001). ETP was associated with thrombocytopenia (r = 0.472, P = 0.015) and weakly with fibrinogen level (r = 0.386, P = 0.047). The measured CAT parameters did not associate with D-dimer and F1 + 2 levels. Decreased ETP together with low peak and prolonged lag time indicate decreased plasma potential for thrombin generation in vitro. Together with low platelet count and enhanced fibrinolysis, this further refers to altered blood coagulation and increased propensity toward bleeding in acute PUUV–HFRS.

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