Thrombocytopenia, Coagulation and Disease Severity in Puumala Hantavirus Infection

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Arvo building, auditorium F114, address: Arvo Ylpön katu 34.

Sirpa Koskela

Doctoral defence of Lic.Med. Sirpa Koskela

Thrombocytopenia, Coagulation and Disease Severity in Puumala Hantavirus Infection

The field of science of the dissertation is Internal Medicine.

The opponent is docent Taru Kuittinen (University of Eastern Finland). Professor emeritus Jukka Mustonen  acts as the custos.

The language of the dissertation defence is Finnish.

Thrombocytopenia, coagulation system and disease severity in Puumala hantavirus disease

Puumala virus causes a hemorrhagic fever of renal syndrome, also called nephropathia epidemica in Europe. Thrombocytopenia is encountered in 90% of the hospital treated patients. Mild bleedings are common, but also fatal bleedings in various organs are reported. Increased capillary permeability, coagulation activation and endothelial dysfunction are essential in the pathogenesis of viral hemorrhagic fever.

In this study an enlarged spleen was commonly detected in 20 studied patients by magnetic resonance imaging during acute infection. Low platelet count did not associate with enlarged spleen or acute kidney injury. This finding does not support platelet seqvestration by enlarged spleen behind thrombocytopenia.

In nineteen patients disease predictive markers, 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. Study findings underline the crosstalk of inflammation and coagulation systems during acute PUUV infection.

Thrombin generation in vitro was assessed by Calibrated automated thrombography (CAT) assay. The finding of lowered ETP together with  low peak and prolonged lag time indicate decreased plasma potential for thrombin generation. Together with low platelet count and enhanced fibrinolysis this further refers to altered blood coagulation and increased propensity toward hypocoagulability during acute Puumala hantavirus infection.

Polymorphisms of nitric oxide synthaseses which may affect both endothelial and vascular function, were studied in 172 patients with acute PUUV infection. Patients with the rare TT-genotype of eNOS G894T gene variant had more severe AKI, longer hospital stay, higher haematocrit value and higher maximum leukocyte count measured during acute PUUV infection.


The dissertation is published in the publication series of Acta Universitatis Tamperensis; 2400, Tampere University Press, Tampere 2018. The dissertation is also published in the e-series Acta Electronica Universitatis Tamperensis; 1909, Tampere University Press 2018.

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