Enhanced thrombin formation and fibrinolysis during acute Puumala hantavirus infection

Nephropathia epidemica (NE) is a viral hemorrhagic fever with renal syndrome associated with thrombocytopenia and mild bleeding. We assessed activation of coagulation and fibrinolysis during the acute phase of NE.

19 hospital-treated patients were involved. Plasma levels of D-dimer, prothrombin fragments 1+2 (F1+2), activated partial thromboplastin time (APTT), prothrombin time (PT%), thrombin time (TT), fibrinogen, antithrombin (AT), protein S free antigen (PS), protein C (PC) and complete blood count (CBC) were measured three times during the acute phase and once at 32-54 days after the onset of fever (recovery phase). Laboratory abnormalities were evaluated by the disseminated intravascular coagulation (DIC) scoring advocated by the International Society of Thrombosis and Haemostasis (ISTH).

APTT was prolonged and D-dimer and F1+2 increased during the acute phase of NE. AT, PC and PS decreased, and TT was shortened, all implying increased thrombin generation. Acutely F1+2 was 3.4-fold and D-dimer even 24-fold higher compared with the recovery phase (median 726 vs 213 pmol/l, and median 4.8 vs 0.2mg/l, respectively, p<0.001 for both). Platelet count correlated with AT, PC, and PS (r=0.73, r=0.81, and r=0.71, respectively, p<0.001 for all) as well as with fibrinogen (r=0.72, p<0.001). Only five patients fulfilled the ISTH diagnosis of DIC.

During acute NE thrombocytopenia was associated with decreased natural anticoagulants, shortened thrombin time and enhanced fibrinolysis. Augmented thrombin formation and fibrinolysis characterize this hantavirus infection.