Abstract Number: PB0764
Meeting: ISTH 2022 Congress
Background: Viral hemorrhagic fevers caused by RNA virus families are associated with impaired haemostasis, leading to a clinical picture of increased bleeding and decreased platelet counts (thrombocytopenia). In Europe a mild form of viral hemorrhagic fever frequently occurs, which is caused by Puumala Hantavirus (PUUV). Thrombocytopenia during PUUV infection may affect not only haemostasis but also platelet-mediated immunomodulatory functions. Therefore, platelets are thought to play a pivotal role in disease manifestations of PUUV infections, but the underlying mechanism is yet unknown.
Aims: Thus, we investigated the effects of PUUV-associated thrombocytopenia on platelets in vitro by evaluating the formation of platelet-neutrophil/monocyte aggregates, platelet-induced leukocyte activation and platelet reactivity in response to various agonists at different platelet densities by flow cytometry. Further, the underlying mechanism of PUUV-induced thrombocytopenia was investigated, which could be caused by e.g. platelet desialylation, which we investigated by flow cytometry, or endothelial adhesion. Therefore, direct and indirect effects (e.g. via infected endothelial cells) of PUUV on platelet adhesion under capillary shear stress were analyzed by immunofluorescence microscopy.
Methods: Statistics were performed using GraphPad Prism 8.0 according to general guidelines using ANOVA, parametric t-test or Wilcoxon test. p-values of 0.05 or less were considered significant.
Results: Platelet function was only mildly affected by platelet density. No direct effects of PUUV on platelet sialylation nor adhesion were observed, suggesting that platelet dysfunction and thrombocytopenia are probably multifactorial and indirectly induced by PUUV. This was further supported by the observation that platelets adhered more frequently to PUUV infected HUVECs, which could represent a potential indirect mechanism of thrombocytopenia.
Conclusion(s): Taken together, we could shed light on the mechanism of PUUV-mediated thrombocytopenia and its consequences on platelet function. A better understanding of the underlying processes could path the way for urgently needed treatment options for haemorrhagic complications these patients.
To cite this abstract in AMA style:Schmuckenschlager A, Assinger A, Wigren Byström J, Fors Connoly A, Ahlm C, Forsell M, Schrottmaier W. Impact of Puumala Hantavirus infection on primary haemostasis: potential mechanisms of thrombocytopenia [abstract]. https://abstracts.isth.org/abstract/impact-of-puumala-hantavirus-infection-on-primary-haemostasis-potential-mechanisms-of-thrombocytopenia/. Accessed February 27, 2024.
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