Whole blood impedance aggregometry as a biomarker for the diagnosis and prognosis of severe sepsis

Abstract

Introduction: Sepsis leads to an activation of the immune system and hemostatis. However, studies on platelet aggregation in severe sepsis using impedance aggregometry have not been performed and the diagnostic and prognostic capabilities are unknown. In the present study we hypothesized that impedance aggregometry findings might serve as a biomarker for the diagnosis and prognosis of severe sepsis.

Methods: Eighty patients with severe sepsis and 50 postoperative patients were included in the prospective observational study. Platelet function was determined at the first day of severe sepsis and surgery, respectively, using impedance aggregometry (Multiplate®). Moreover, platelet count, procalcitonin, interleukin 6, C-reactive protein and 30-day mortality were determined.

Results: Compared to postoperative patients, platelet aggregation was significantly reduced in patients with severe sepsis (collagen-test: 70.8 (44.4, 83.2) arbitrary units (A.U.) vs. 26.8 (12.7, 45.8) A.U.; P <0.001; median and quartiles). Furthermore, marked differences in platelet function were observed in survivors and non-survivors of severe sepsis (collagen-test: 33.4 (10.9, 48.8) A.U. vs. 12.4 (6.5, 25.0) A.U.; P = 0.001). Kaplan-Meier analysis demonstrated that higher platelet function was associated with a mortality of 10%, while mortality was 40% when platelet function was low (collagen-test; P = 0.002). The odds ratio was 6.0. In both univariate and multivariate analyses (including procalcitonin, IL6, C-reactive protein and platelet count) impedance aggregometry using collagen as the activator proved to be the best and an independent predictor for the diagnosis and prognosis of severe sepsis in critical illness.

Conclusions: In severe sepsis, impedance aggregometry allows better prediction of diagnosis and survival than conventional biomarkers and platelet count.

Figure 1

Platelet aggregation, as determined by impedance aggregometry, in postoperative and septic patients. Shown are the aggregometry findings (area under curve (AUC) in arbitrary units (A.U.)) with the activators adenosine diphosphate (ADP), collagen (COL), arachidonic acid (AA) and thrombin receptor activating peptide 6 (TRAP). Results are given as boxplots (with median, quartiles, minimum and maximum). For the statistical evaluation the Mann-Whitney test was used.

Figure 2

Conventional sepsis marker in postoperative patients and patients with severe sepsis. Values for procalcitonin, interleukin 6 (IL-6), and C-reactive protein are given as boxplots (with median, quartiles, minimum and maximum). The Mann-Whitney test was used for statistical evaluation.

Figure 3

Impedance aggregometry findings (A) and conventional sepsis markers (B) in postoperative patients and patients with severe sepsis. Shown are the receiver operating characteristic curves. The activators used for impedance aggregometry were adenosine diphosphate (ADP), collagen (COL), arachidonic acid (AA) and thrombin receptor activating peptide (TRAP). The conventional biomarkers were procalcitonin (PCT), interleukin 6 (IL-6), and C-reactive protein (CRP).

Figure 4

Kaplan-Meier-analysis demonstrating 30-day survival of severe sepsis in patients in dependence on impedance aggregometry findings. As the activators adenosine diphosphate (ADP), arachidonic acid (AA), collagen (COL) and thrombin receptor activating peptide (TRAP) were used. Moreover, the significance levels and the odds ratios (OR) are given.

Figure 5

Relation between platelet aggregation and estimated survival of patients with severe sepsis. Values were calculated from the results of the logistic regression analysis obtained from collagen activated impedance aggregometry.