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. Anticoagulants 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
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, antiplatelet
agents, or fibrinolytic (clot-dissolving) medications for treating heart attacks. Intravenous heparin
is given (usually with aspirin or an antiplatelet 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 anticoagulant 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 anticoagulation. The goal is to
keep the patient's APPT level in a safe range and to avoid abnormally high
APPT levels that signify excessive anticoagulation and a greater risk of
bleeding. If there is bleeding, heparin has the advantage of having a short duration
of action and its anticoagulant effects disappear rapidly
after stopping the intravenous infusion.
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 to 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 to 12 hours. They are not used in place of intravenous heparin in
patients undergoing PTCA or stenting.
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 anticoagulant effect. Warfarin's anticoagulant 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 anticoagulation. 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 anticoagulation 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 anticoagulation 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 anticoagulation in the event of serious bleeding.
Direct thrombin inhibitors are newer oral anticoagulants that have recently been introduced, such as rivaroxaban (Xarelto) and dabigatran (Pradaxa), which don't require the monitoring and dietary restrictions of warfarin, and their role is under investigation.