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November 26, 2009
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Heart Attack Treatment (cont.)

Anti-coagulants

Coagulants (clotting factors) are proteins produced by the liver. Clotting factors are responsible for "cementing" clumps of platelets together to form a stronger and larger clot. Anti-coagulants such as intravenous or subcutaneous heparin, subcutaneous low molecular weight heparin, and oral warfarin (Coumadin), prevent the formation of blood clots either by inhibiting the production of clotting factors or by interfering with the action of the clotting factors.

Heparin. Heparin prevents the formation and growth of blood clots by inhibiting the action of clotting factors that cement the clumps of platelets together. Heparin is given either intravenously or as a subcutaneous (under the skin) injection.

Heparin commonly is given intravenously, usually with aspirin, anti-platelet agents, or fibrinolytic (clot-dissolving) medications for treating heart attacks. Intravenous heparin is given (usually with aspirin or an anti-platelet agent) to patients with heart attacks who are undergoing PTCA with or without stenting. Heparin also is given to patients who are at risk of developing blood clots within the chambers (atria and ventricles) of the heart. (For example, patients with atrial fibrillation can develop blood clots in the atria. Patients with large heart attacks and major damage to the heart muscle also can develop blood clots in the ventricles.) Heparin's anti-coagulant effect is fast acting (beginning shortly after the start of the infusion) and dose-related (greater with higher doses). The duration of heparin treatment for heart attacks is approximately 48 hours.

Heparin's major side effect is bleeding, and the most serious bleeding complication is intracranial hemorrhage (bleeding into the brain). The risk of bleeding is higher with higher doses. Thus, patients receiving heparin will undergo frequent blood testing to measure APPT levels. The APPT level is a measure of the degree of anti-coagulation. The goal is to keep the patient's APPT level in a safe range and to avoid abnormally high APPT levels that signify excessive anti-coagulation and a greater risk of bleeding. If there is bleeding, heparin has the advantage of having a short duration of action and its anti-coagulant effects disappears rapidly after stopping the intravenous infusion.

Low molecular weight heparin. Low molecular weight heparins such as enoxaparin (Lovenox) and dalteparin (Fragmin), are sub-fractions of heparin with longer-lasting effects than heparin. They can be given every 12-24 hours as subcutaneous injections (like insulin). Studies have shown enoxaparin and dalteparin to be equivalent to intravenous heparin in patients with many conditions such as heart attacks, unstable angina, and blood clots in the veins or arteries of the lungs. The effects of low molecular weight heparins generally wear off after 6-12 hours. They are not used in place of intravenous heparin in patients undergoing PTCA or stenting.

Warfarin. Warfarin (Coumadin) prevents the formation of blood clots by inhibiting the production of clotting factors by the liver. Warfarin must be taken orally and is slow acting; it can take days to achieve an adequate anti-coagulant effect. Warfarin's anti-coagulant effect is dose-related, that is, its effect is greater with larger doses.

Because of its slow onset of action, Coumadin is not commonly used immediately for the treatment of heart attacks. Instead, it is used orally on a long-term basis in selected patients after heart attacks to prevent blood clots. For example, patients with atrial fibrillation or patients with major damage to ventricular muscle will take warfarin daily on a long-term basis to prevent blood clots in the atria and ventricles, respectively. Warfarin also is commonly used to prevent blood clots in veins of the legs in patients who are likely to develop them.

The risk with warfarin is abnormal bleeding, and the risk of bleeding is higher with higher doses. Thus, patients on warfarin should have their blood tested frequently (often weekly) to measure their prothrombin time and INR. Like APPT, the prothrombin time and INR measure the degree of anti-coagulation. The goal of treatment is to keep the prothrombin time and INR in a safe range, avoiding excessively high prothrombin time and INR levels that indicate too much anti-coagulation and a greater risk of bleeding. The effects of warfarin may be increased or decreased greatly by many other medications or foods, and it is crucial to review these medications and foods with the doctor.

Warfarin has a long duration of action, and its anti-coagulation effect can last several days after it is stopped. Therefore, transfusions of clotting factors and/or vitamin K (to stimulate the liver to produce the clotting factors depleted by treatment with warfarin) must be given to reverse the anti-coagulation in the event of serious bleeding.



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