Abstract: The invention provides compositions and methods for the detection of Factor XIa or Tissue Factor (TF) activity in a sample using an antibody based clotting time prolongation assay. The invention provides methods for detection of FXIa or TF activity in a sample using a fluorogenic substrate. Further provided herein is a correlation between elevated levels of FXIa and/or TF with inflammation, acute coronary syndrome (ACS), myocardial infarction, coronary artery disease (CAD), heart failure, aortic stenosis, stroke, or transient ischemic attack. The frequency of FXIa and TF activity was substantially lower in individuals with stable coronary artery disease and no history of myocardial infarction. No FXIa or TF activity was observed in healthy individuals.