In vivo platelet activation in critically ill patients with primary 2009 influenza A(H1N1)

Abstract

Background: Changes in platelet reactivity during 2009 influenza A(H1N1) (A[H1N1]) have not been characterized.

Methods: We prospectively examined platelet activation and cytokine responses in patients with A(H1N1) (n = 20), matched patients with bacterial pneumonia (n = 15), and nonhospitalized, healthy control subjects (n = 10).

Results: Platelet-monocyte aggregation was higher in patients with A(H1N1) (21.4% ± 4.7%) compared with patients with pneumonia (10.9% ± 3.7%) and control subjects (8.1% ± 4.5%, P < .05). Similarly, PAC-1 (antibody that binds to the active conformation of integrin α(IIb)β(3)) binding to platelets is increased in patients with A(H1N1) (9.5% ± 4.7%) compared with patients with pneumonia (1.0% ± 0.7%) and healthy subjects (0.61% ± 0.15%, P < .10). PAC-1 binding was twofold higher in patients with A(H1N1) with shock vs those without shock. IL-6 levels were elevated in patients with A(H1N1), indicating systemic inflammation consistent with activation of circulating platelets.

Conclusions: These findings, derived from a small but documented cohort of patients, demonstrate that platelet activation responses during A(H1N1) are enhanced-exceeding responses in patients with bacterial pneumonia-and provide new evidence that platelets may contribute to inflammatory responses during A(H1N1).

Figure 1.

A, Platelet-monocyte aggregate (PMA) formation in baseline whole blood obtained from critically ill patients with 2009 influenza A(H1N1) (A[H1N1]), patients with bacterial pneumonia, and healthy control subjects. B, PAC-1 binding in baseline whole blood obtained from critically ill patients with A(H1N1), patients with bacterial pneumonia, and healthy control subjects. C, PMA formation in TRAP-activated whole blood obtained from critically ill patients with A(H1N1), patients with bacterial pneumonia, and healthy control subjects. D, PAC-1 binding in TRAP-activated whole blood obtained from critically ill patients with A(H1N1), patients with bacterial pneumonia, and healthy control subjects. PMA formation is shown on the y-axis of A and C as the fraction of monocytes with one or more adherent platelets. PAC-1 binding is reported on the y-axis of B and D as the fraction of platelets expressing the active conformation of integrin α_IIbβ₃ on their surface as a percentage of the total number of platelets analyzed. H1N1 influenza = 2009 influenza A(H1N1); PAC-1 = antibody that binds to the active conformation of integrin α_IIbβ₃; TRAP = thrombin-receptor activating peptide.