BACKGROUND: Myocardial injury and platelet activation play important roles in the pathogenesis of unstable coronary syndromes. We sought to determine whether the combined measurement of platelet and necrosis markers would improve risk stratification, and yield higher diagnostic utility in patients presenting to the emergency department with chest pain. METHODS AND RESULTS: Platelet and soluble P-selectin together with myoglobin, creatine kinase, CK-MB fraction, and troponin I were measured from the autologous samples in 122 consecutive patients. Statistical analysis revealed strong Spearman correlation coefficients (0.141--0.412; p<0.001) between platelet expression of P-selectin and plasma levels of necrosis markers. Platelet P-selectin and necrosis markers were independent predictors (c-index>0.7) for acute myocardial infarction, while plasma P-selectin exhibited random distribution. Elevated soluble P-selectin and myoglobin were the most valuable in identifying patients with congestive heart failure. None of the markers were useful for triaging chest pain patients with unstable angina. Analysis of incremental gains (Chi-squares) reveals that with respect to platelet P-selectin, myoglobin adds 50 % to AMI diagnostic value, and creatine kinase yields an additional 20 % in triaging these patients. The diagnostic value of soluble P-selectin is substantially (72 %) increased by myoglobin measurements, and enhanced even further (44 %) by adding cardiac troponin I for identifying heart failure patients among the chest pain population. CONCLUSION: Simultaneous determination of platelet and necrosis markers improve the early diagnosis of acute myocardial infarction and congestive heart failure among patients with chest pain presenting into the Emergency Department. Well controlled clinical trials are needed to prove the advantage of combining platelet and necrosis data over presently used techniques in emergency medicine.