PURPOSE: Influenza A virus subtype H1N1 is a common cause of human influenza infections. Platelet activation during H1N1 sepsis may contribute to the inflammatory and thrombotic milieu in these patients but remains poorly characterized.
METHODS: We prospectively studied 20 critically-ill patients with confirmed H1N1 sepsis and 10 age- and gender-matched, healthy control patients. Following informed consent, whole blood was drawn upon admission to the Intensive Care Unit (H1N1 patients) or following an overnight fast (control subjects). Whole blood flow cytometry was performed to measure baseline and thrombin-receptor activating peptide (TRAP)-stimulated levels of the PAC-1 binding (for integrin αIIb activation), platelet surface P-selectin expression (P-SEL), and platelet-monocyte aggregates (PMA).
RESULTS: The average(SD) age and gender of H1N1 patients and healthy controls was similar [40.5(12.6) and 40.5(13.6) years, p=NS] and 50% were female in both groups. The average(SD) APACHE II score of H1N1 patients was 20(8) and 90% had the more severe sepsis or septic shock. In-hospital all-cause mortality was 38.5%. Mean(SEM) levels of PAC-1 binding and PMA were significantly higher in H1N1 patients vs. healthy subjects [6.4(3.7) vs. 0.6(0.9), p<0.10; 18.6(21.0) vs. 8.8(14.3), p<0.05]. In contrast, P-SEL expression didn’t differ between H1N1 patients and healthy subjects, perhaps due to the rapid shedding of P-SEL upon platelet activation. Upon whole blood stimulation with TRAP, H1N1 patients exhibited a blunted response in PMA formation vs. healthy controls [5.5(1.4) vs. 19.7(6.3) fold-change, p<0.05]. Platelet-poor plasma (PPP) from H1N1 patients incubated with unstimulated, freshly-isolated platelets from healthy subjects did not cause increased PAC-1 binding or P-SEL expression. When freshly-isolated platelets from healthy subjects were incubated with PPP from H1N1 patients or control subjects and stimulated with TRAP, levels of PAC-1 binding were significantly reduced compared to controls [12.8(3.7) vs. 47.0(30), p<0.05].
CONCLUSIONS: These data provide novel evidence of platelet activation during H1N1 sepsis and suggest the presence of plasma factors in H1N1 sepsis that reduce normal platelet activation responses.
CLINICAL IMPLICATIONS: Understanding the role of platelets in H1N1 infections may lead to novel therapeutic strategies.
DISCLOSURE: The following authors have nothing to disclose: Matthew Rondina, BreAnna Brewster, Diana Kastendieck, Saritha Kalva, Shaohua Men, Estelle Harris, Colin Grissom
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