Blood clot dissolving agent

Blood clots are masses of blood cells that have clumped together because of disease or injury. In cases of damage, blood platelets (roundish disks associated with clotting found in mammal blood) mass (gather together) to stop bleeding. The platelets release clot-promoting chemicals and cause a clot to form.

Blood Clots

A blood clot in a vessel is called a thrombus, and it is called an embolus when part of it detaches and travels through the bloodstream, where it can lodge in a blood vessel and block blood flow. A thrombus can form where the body has been injured, where blood vessels are damaged by arteriosclerosis (hardening and/or narrowing of the arteries), or where blood stagnates (chronic bedrest can cause blood to stagnate, or pool, in one location). The thrombus can then block ever greater portions of the blood vessel. Blood flow can become blocked when a blood vessel gets obstructed by blood clots or other foreign matter in the bloodstream. Foreign matter could include air bubbles, fat globules from a broken bone, or fatty sub-stances accumulating on the inside wall of an artery (arteriosclerosis). As blood flow beyond the clot of blood or foreign matter is reduced or cut off, the part of the body thus deprived of oxygen may become damaged. If the brain becomes damaged, a stroke may result. If the heart muscle becomes damaged, a heart attack may result.

Over half of the cardiovascular (heart and blood vessel)-related deaths in the United States are caused by heart attacks, known as acute myocardial infarctions (MI). Strokes, known as cerebrovascular accidents (CVA), are the third-ranking cause of death in the United States (after heart disease and cancer). A clot that stops blood flow to the brain causes 80 percent of all strokes.

New Medicines Dissolve Clots

Many strategies have been developed to prevent these deposits from forming in patients who are prone to them. One approach is to use anti-coagulants (substances that prevent the blood-clotting factors in the blood from becoming active). Anticoagulants—including aspirin, warfarin, and heparin—thin the blood (reduce the stickiness of blood), which helps prevent clots from forming in the first place.

Until recently, however, there were very few therapies that were able to break down clots that had already formed. Scientists have now developed several substances that can reduce existing clots. These new treatments were first used for heart attack patients, and have recently being used to treat stroke victims.

This process of dissolving blood clots that already exist is called thrombolysis. Three groups of thrombolytic agents are available, including enzymes, which act directly upon the fibrin strands within the clot, plasma activator agents, which increase plasma activator activity, and plasminogen activators, such as streptokinase, urokinase, and tissue plasminogen. All these drugs digest clots by increasing the amount of plasmin (plasmin dissolves clots) in the blood. To produce plasmin, the substance plasminogen must first be activated. Plasminogen is converted into plasmin by certain enzymes known as plasminogen activators.

Streptokinase has been used since about 1960. Researchers use streptococci bacteria to produce this drug. Although streptokinase is the least expensive activator, some negative side effects, such as immune responses, have been experienced by patients. Urokinase is found naturally in humans, especially in the urine. Thus, no negative immune response is associated with its use. This therapy is usually administered in small doses and combined with other drugs, because it is difficult to purify, and therefore rather expensive.

Tissue Plasminogen Activator Aids Heart Attack and Stroke Victims

Tissue plasminogen activator (tPA) is currently the most expensive drug for dissolving blood clots. It is unique because it activates only fibrin-bound plasminogen and thus targets the clot site. tPA in human blood is produced in very small amounts by vascular endothelial cells. Since about 1980, when tPA was first purified from human uterine tissue, it has enjoyed widespread use among American physicians. Lately, researchers have even used cloning technology to recombine the genes that encode human tPA. Cloning is transferring the genetic material from one organism into another organism, such as a virus or bacteria, which is called a host. The host reproduces, new generations of offspring, called clones, that are identical genetically. Scientists have cloned hamster genes to produce tPA in large quantities. This should help make the drug more affordable.

Each of these thrombolytic agents shows great promise in reducing the severity of heart attacks. More recent studies of using tPA for certain stroke victims show significant reduction of brain injury if given within three to six hours of the start of the stroke. This is very exciting, because until now no treatment has served to limit the damage caused by stroke. However, studies are ongoing to define which patients will benefit from tPA, because tPA given to the wrong type of stroke patient could start an episode of severe bleeding.

[See also Gene ]