Measurement of platelet thrombus formation in patients following severe thermal injury

Abstract

Severe thermal injury significantly impacts upon hemostasis and is associated with classical changes to the circulating platelet count with a nadir followed by a rebound thrombocytosis at days ~3 and ~15 post-injury, respectively. To date, few studies have assessed platelet function following thermal injury as platelet tests often require large quantities of blood, are not representative of normal platelet pathophysiology, and are usually dependent on a normal platelet count. The purpose of this study was to measure platelet thrombus formation in vitro using a whole blood flow chip-based system following thermal injury and to study how platelet counts may impact upon the measurement. Adult (≥16 years) patients (N = 10) with ≥ 20% total burn surface area (TBSA) burn were recruited within 24 h of injury. Healthy controls (N = 25) were also recruited. Whole blood counts were measured using a hematology analyzer (Sysmex XN-1000). Platelet function was measured using the Total Thrombus-formation Analyzer System (T-TAS) within chips coated with tissue factor and collagen at shear rates of either 600 sec-1 (AR chips) or 1200 sec-1 (HD chips), the latter test being independent of platelet count. We confirmed the classical nadir in platelet counts following severe thermal injury at days 2, 3, 4 (p < 0.0001) and day 5 (p < 0.01) post-injury compared to healthy controls. Physiological platelet thrombus formation was significantly (p < 0.01) abnormal at day 3 post-injury using the AR chips but was related to the platelet count. However, although platelet dysfunction was not significant using HD chips, some of the results were independent of platelet count. A small number of samples, however, still gave abnormal results suggesting that there can be an underlying acquired platelet functional abnormality. Furthermore, the AR chip Area Under the Curve (AUC) was significantly lower on day 1 post-injury and negatively associated with severity of injury (TBSA, p < 0.05) and higher platelet function (AUC) positively associated with survival (p < 0.05). This study suggests that measuring platelet dysfunction within a more physiological in vitro test may have potential clinical utility. Larger studies are required to fully understand the impact of platelet dysfunction following severe thermal injury.