Characterization of platelet dysfunction after trauma

Abstract

Background: The increased morbidity and mortality associated with coagulopathy and thrombocytopenia after trauma are well described. However, few studies have assessed platelet function after injury.

Methods: Blood samples were prospectively collected from 101 patients with critical injury and trauma on arrival to the emergency department and serially after admission to a Level I urban trauma intensive care unit from November 2010 to October 2011 and functionally assayed for responsiveness to adenosine diphosphate, thrombin receptor-activating peptide, arachidonic acid (AA), and collagen using multiple electrode impedance aggregometry.

Results: Of the 101 enrolled patients, 46 (45.5%) had below-normal platelet response to at least one agonist ("platelet hypofunction") at admission, and 92 patients (91.1%) had platelet hypofunction some time during their intensive care unit stay. Admission platelet hypofunction was associated with low Glasgow Coma Scale score and a nearly 10-fold higher early mortality. Logistic regression identified admission Glasgow Coma Scale (odds ratio, 0.819; p = 0.008) and base deficit (odds ratio, 0.872; p = 0.033) as independent predictors of platelet hypofunction. Admission AA and collagen responsiveness were significantly lower for patients who died (p < 0.01), whereas admission platelet counts were similar (p = 0.278); Cox regression confirmed thrombin receptor-activating peptide, AA, and collagen responsiveness as independent predictors of in-hospital mortality (p < 0.05). Receiver operating characteristic analysis identified admission AA and collagen responsiveness as negative predictors of both 24-hour (AA area under the curve [AUC], 0.874; collagen AUC, 0.904) and in-hospital mortality (AA AUC, 0.769; collagen AUC, 0.717).

Conclusion: In this prognostic study, we identify clinically significant platelet dysfunction after trauma in the presence of an otherwise reassuring platelet count and standard clotting studies, with profound implications for mortality. Multiple electrode impedance aggregometry reliably identifies this dysfunction in injured patients, and admission AA and collagen responsiveness are sensitive and specific independent predictors of both early and late mortality.

Conflict of interest statement

Conflicts of interest: The Multiplate® device was loaned and reagents provided by the distributor (DiaPharma Group, Inc; West Chester, OH) for this investigator-initiated study. There are no direct financial relationships between the authors and manufacturer.

Figures

Figure 1

Scatter plots showing correlation between platelet count and adenosine diphosphate (ADP; a), thrombin receptor-activating peptide (TRAP; b), arachidonic acid (AA; c), and collagen (d) responsiveness using matched data from all time points collected. Manufacturer-provided normal ranges indicated by reference lines at the lower (5th percentile) and upper (95th percentile) boundaries. Rho values for each pairwise correlation given at bottom right of each graph, with all associated p < 0.001.

Figure 2

Platelet adenosine diphosphate (ADP; a), thrombin receptor-activating peptide (TRAP; b), arachidonic acid (AA; c), and collagen (d) responsiveness as area under the aggregation curve in units (U) over time. Platelet count measurements (e) are shown for comparison. Data points are mean values, with capped bars representing 95% confidence intervals; dotted lines represent the lower bound (5th percentile) of normal values for each measurement.

Figure 3

Kaplan-Meier 30-day survival curves showing survival differences between patients with below-normal admission platelet responsiveness to adenosine diphosphate (ADP; a), thrombin receptor-activating peptide (TRAP; b), arachidonic acid (AA; c), and collagen (d). Survival curves for patient admission platelet counts below the 25th percentile (e) are shown for comparison. *p < 0.05 by log-rank test.

Figure 4

Receiver-operator characteristic curves using admission platelet responsiveness to adenosine (ADP; a), thrombin receptor-activating peptide (TRAP; b), arachidonic acid (AA; c), and collagen (d) as predictors of in-mortality. Curve for admission platelet count (e) is shown for comparison. Area under the receiver-operator characteristic curve (AUC) values given at upper left in each graph. *AUCs for which 95% confidence intervals differ significantly from chance.