Relapse risk: Mr Ariel Sharon is in hospital after suffering a second stroke. (AFP)

The life-threatening stroke that Israeli Prime Minister Ariel Sharon suffered early this month has focused attention on the treatment of strokes, in particular the use of anti-coagulants and clot-dissolving drugs.

The use of such drugs is among the most potentially dangerous therapies in medicine and one of the most controversial. The full story of Sharon’s case is not known because his family and doctors have released limited information. But questions have been raised about whether the drugs he received for a less severe stroke in December, caused by a blood clot, may have contributed to his huge stroke on January 4.

The use of anti-coagulants and clot dissolvers is controversial, in part because their benefits must be weighed against their risks. Drugs like tissue plasminogen activator, or TPA, for example, can be lifesaving if given within a few hours after the onset of an ischaemic stroke but lethal if started only a few hours later. Though many people call TPA an anti-coagulant, it is a different type of drug that dissolves clots.

TPA can allow patients to survive the first few days after a stroke begins ? a period during which many patients would almost surely die without such therapy. But the trade-off is that many of them are left paralysed, unable to speak and suffering from intellectual impairments.

Heparin, a short-acting anti-coagulant, is given to prevent a recurrent stroke, not to dissolve the offending clot. But giving it can be dicey in the early stages of a stroke because it can help turn a mild ischaemic stroke into a devastating bleeding one.

“It is hard to imagine that a single treatment can shift so radically from making you better and saving your life, to one that could kill you,” said Dr Lee H. Schwamm, director of acute stroke care at the Massachusetts General Hospital in Boston.

In addition, clinical trials have not been able to determine for which types of strokes anti-coagulant drugs are effective. And the drugs need to be closely monitored. The anti-coagulant Coumadin was originally developed as a rat poison. Patients given Coumadin must be given frequent tests to ensure that the amounts they receive are safe and effective. One patient might need 1 milligram a day while others might need seven mg for the same ailment, and in long-term care the dose may have to be changed after treatment has begun.

Decisions about anti-coagulation are difficult and often frightening for patients, who often have little understanding of the potential risks. They can also be frightening for doctors. But the need for such decisions has increased with the improvement in imaging techniques like CT scans and MRIs.

Researchers have developed drugs that block the action of platelets that help the blood to clot, adding to old standbys like aspirin, heparin and Coumadin. (Anti-coagulants are often called blood thinners, but this is a misnomer because the drugs don’t change the thickness of blood. They alter the blood’s ability to clot). Deciding which anti-coagulant to use and for how long is a highly complex process. The selection depends on the root cause of a stroke, which can vary from trauma to underlying heart and blood-system ailments. The decision often has to be made in the first hours after a stroke, before permanent damage has set in, which is why patients are urged to get to a hospital immediately.

Ischaemic strokes account for a vast majority of strokes. They occur because the brain is starved of oxygen and other vital nutrients from a clot that forms in a brain artery or that breaks off from a larger artery elsewhere in the body and travels to lodge in a brain artery.

Also, a long-term buildup of fats in the walls of brain arteries can narrow the vessels and reduce flow to critically low levels, causing an ischaemic stroke.

Some 15 to 20 per cent of strokes are from blood that leaks from an artery into the brain. This haemorrhagic type of stroke has a high death rate because it is the least treatable form. A genetically engineered form of a clotting substance in the blood known as Factor VII has shown promise in preventing further bleeding if it is given within the first four hours of a haemorrhagic stroke.

The two categories make it imperative to use CT and MRI scans in the initial care. The distinction between ischaemic and haemorrhagic strokes is critical because drugs like TPA and urokinase can rapidly reverse the damage from an ischaemic stroke, but giving them for a haemorrhagic stroke is like pouring gas on a fire.

“Often, it is forgotten that the goal of anti-coagulation is not to treat a stroke that has just occurred, but to prevent a recurrent stroke” or a first stroke, said Dr David S. Liebeskind, associate director of the University of California, Los Angeles, Stroke Center in California.

In recent years, doctors have increasingly relied on clinical trials to decide whether to prescribe a particular drug or therapy. When clinical studies offer clear findings about the benefits and risks of a particular treatment, that can be a straightforward exercise. Among the few clear indications for long-term use of anti-coagulant drugs are a heart rhythm abnormality known as atrial fibrillation, a prosthetic heart valve and inherited or acquired abnormalities of the blood clotting system.