Désiré Collen (b. 1943)
A delicate balance exists between the ability of the body to control bleeding by forming a clot and the formation of a clot within blood vessels (thrombus) that can interfere with normal blood flow. Blocking blood flow in arteries that supply the heart can cause a myocardial infarction (MI), or heart attack. Similarly, in an ischemic stroke—the most common type of stroke—blood flow to the brain is blocked, markedly reducing the supply of oxygen and glucose and resulting in the death of brain tissue. In Western countries, heart attack and stroke are the leading causes of death, and stroke is second only to Alzheimer’s disease as the most common cause of neurological damage.
Drugs can prevent clotting in blood vessels by decreasing clot formation (warfarin) or by interfering with the clumping of platelets (aspirin, Plavix). While these approaches are effective, ongoing heart attacks and strokes require the immediate restoration of blood flow to forestall long-lasting or permanent disability or even death. The odds of surviving after and recovering from a heart attack are greatly improved when blood flow returns within three hours of the time a heart attack begins. To limit the damage and disability associated with strokes, treatment should also begin within three hours of the first symptoms.
Thrombolytic drugs (clot-busters) are used to actively break up or dissolve existing blood clots that interfere with blood flow in the heart, brain, lungs (pulmonary embolism), or deep veins in the leg (deep-vein thrombosis). Normally, after an injury, a fibrin clot forms, plugging an injured blood vessel. Bleeding stops, the blood vessel is repaired, and the clot is dissolved by a natural thrombolytic chemical. This chemical—the enzyme tPA (tissue plasminogen activator)—plays an essential role in the biological process by promoting the conversion of inactive plasminogen to active plasmin, which breaks down the fibrin clot. The medical potential of natural tPA as a clot-buster drug was first recognized in 1980 by the Belgian physician-biochemist Désiré Collen.
Approved in some countries in 1987 for treating stroke and in the United States in 1996, commercial tPA (rtPA; Alteplase), manufactured by recombinant DNA technology, is the most effective and widely used thrombolytic drug.
SEE ALSO Aspirin (1899), Heparin (1916), Warfarin (1940), Biologic Drugs (1982), Plavix (1997), Pradaxa (2010).
A clot blocking the blood flow in the coronary artery is shown here. In an emergency, tPA can be used to dissolve the clot.