Understanding the dynamics of thrombin in cardiovascular disease: Pathobiology and biochemistry for the clinician

Intravascular coagulation occurring within the arterial, venous, and microcirculatory systems relies on an integrated system of enzymatic reactions on cell surfaces. Specifically, coagulation begins on tissue-factor-bearing cells, where just enough thrombin is generated to cause platelet activation, coagulation protein assembly, and then a burst of thrombin generation. Evidence derived from pathology specimens, clinical trials, and epidemiologic studies shows that thrombin generation and its subsequent effects on vascular surfaces, endothelial cells, endocardial surfaces, platelets, and coagulation proteases contribute to the clinical expression of disease in cardiovascular disorders including atherosclerotic coronary artery disease, atrial fibrillation, and venous thromboembolism.