Coagulation: In medicine, the clotting of blood. The process by which the blood clots to form solid masses, or clots. More than 30 types of cells and substances in blood affect clotting. The process is initiated by blood platelets. Platelets produce a substance that combines with calcium ions in the blood to form thromboplastin, which in turn converts the protein prothrombin into thrombin in a complex series of reactions.