Hantavirus infection-induced thrombocytopenia triggers increased production but associates with impaired aggregation of platelets except for collagen

Abstract

IntroductionWe evaluated the mechanisms of thrombocytopenia encountered in hantavirus disease by studying platelet production together with platelet aggregation and deposition to collagen surface. Patients and methodsThe study group consisted of 31 prospectively recruited, consecutive, hospitalized patients having acute Puumala hantavirus infection. Blood samples were collected acutely and at the control visit and subjected to analysis in Sysmex® XE-5000 to capture mean platelet volume (MPV) and immature platelet fraction (IPF%). Platelet aggregation under low shear rate conditions was assessed with impedance aggregometry Multiplate®, whereas platelet function analyzer (PFA)-100® was applied under blood flow of high shear forces. ResultsIPF% was 3.1-fold higher acutely compared with the control (median 7.4%, range 2.0–23.8% vs. median 2.4%, range 1.4%–5.2%, p<0.001) tightly associating with the low platelet count (r=−0.76, p<0.001). Accordingly, acute MPV was high (median 11.4fl, range 9.4–13.1fl vs. median 10.5fl, range 9.0–12.0fl, p=0.003). Acute platelet aggregation in Multiplate® was decreased to all agonists compared with the later control (p<0.05 for all agonists). Aggregation capacity associated with thrombocytopenia (for all agonists r≥0.81, p<0.001), but impaired aggregation occurred also among patients with a nearly normal platelet count. Triggered by collagen, 20% of values were below reference range, while 73% of responses were low with thrombin receptor activating peptide. Significantly, under high shear platelet deposition to collagen surface was normal despite thrombocytopenia. ConclusionsDuring acute hantavirus disease, platelet aggregation is impaired especially when induced with thrombin. Platelet adhesive mechanisms on collagen are intact despite thrombocytopenia while thrombopoiesis is active.