Elevated thrombopoietin and platelet indices confirm active thrombopoiesis but fail to predict clinical severity of puumala hantavirus infection

Laine, Outi; Joutsi-Korhonen, Lotta; Lassila, Riitta; Huhtala, Heini; Vaheri, Antti; Mäkelä, Satu; Mustonen, Jukka

MPs and exosomes are small membrane vesicles that are released from different cell types by exocytic budding in response to cellular activation or apoptosis. They are now seen as mediators of cell-to-cell communication. [24] They express phospholipids and are classically thought to function as procoagulants supporting thrombin formation and facilitating coagulation by factor VII/TF-dependent and -independent pathways. Elevated concentrations of MPs deriving from platelets, endothelial cells, and monocytes have been reported in arterial and venous thrombotic diseases as well as in autoimmune conditions, infectious diseases, hematologic disorders, and cancer. However, the clinical significance of these findings remains controversial. [25, 26] Flow cytometry is the most widely used method to study MPs. [27] Increased TF expression , [5] enhanced thrombin formation, [6] and signs of cellular activation and apoptosis [1] are all present during acute hantavirus infection, and we presumed to detect higher level of MPs' procoagulant activity during the acute phase of the disease compared with the recovery phase. That was, Table 3 Laboratory findings of the two patients with severe Puumala hantavirus infection in the acute phase and at the recovery. however, the finding only among patients with mild kidney injury. In this study, increased thrombin formation (F1 + 2) and fibrinolysis (D-dimer) associated with the severity of AKI, and the attachment of platelet-derived MPs to fibrin clots especially in patients with more severe kidney injury could plausibly explain our observation. [13, 28] Preanalytical measures as well as analytical methods in the detection of MPs' activity are crucial [29] and even if the instructions of the ELISA-assay manufacturer were vigorously followed, the issues regarding methodology cannot be completely excluded. [12] The sample size of the study was, though not large but probably sufficient, as the difference of serum TPO level in the acute phase of the disease compared with the recovery could be verified. MPs' procoagulant activity did not associate with any of the variables depicting disease severity, and it failed to predict clinical outcome in this group of patients with acute Puumala hantavirus infection. Plasma level of TPO or MPs' activity could not predict severe hantavirus disease in the 33 patients of this study, but the 2 severely ill patients had particularly high TPO level and percentage of young platelets as well as very clearly impaired platelet functions according to PFA-100 in the acute phase of the disease ( Table 3 ). The finding regarding MPs' activity on these 2 individual patients was inconsistent and may stem from patients medical history, current treatment as well as the condition itself.