Long-term anticoagulation is important in the treatment of many cardiac conditions. Intracardiac thrombi can form and lead to devastating consequences as a result of obstruction of blood flow and peripheral embolization.
Treatment for intracardiac thrombi involves the use of anticoagulants
for both primary and secondary prevention of thrombosis and embolization.
There are, however, risks associated with the use of these agents,
and an understanding of the risks and benefits of anticoagulant
therapy for various cardiac conditions is important.
These agents affect the coagulation protein cascade to reduce thrombosis. Their greatest use is in primary and secondary prevention
of intravascular and intracardiac thrombosis and embolization.
Unfractionated heparin (UFH) binds to antithrombin III, markedly
increasing the effect of antithrombin III in neutralizing thrombin.
It also inhibits the activation of factors IX and X. The effectiveness
of UFH varies greatly from person to person due to its interactions with
a number of plasma proteins and the endothelium. Monitoring the
effects of full dose UFH on hemostasis is mandatory. Routinely,
the activated partial thromboplastin time (aPTT) is used to monitor
the effects of UFH, which should be titrated to 1.5–2.0
times greater than control. In certain situations, a higher level
of anticoagulation is needed, ie, during coronary interventions.
In those instances, the activated clotting time (ACT) is used to
monitor its effect, and the dose of UFH is adjusted to keep the
ACT 250–300 seconds or greater. When given intravenously,
the effects of UFH are immediate. It is usually given as a bolus,
followed by a continuous infusion. It may also be given subcutaneously.
The effects of UFH will dissipate within 6 hours. Protamine can
be given to reverse its effects more quickly. UFH can be given subcutaneously
in smaller doses, which will not affect the aPTT, for primary prevention
of deep venous thrombosis in certain high-risk situations.
Low-molecular-weight heparins (LMWHs) are breakdown products of UFH. They have a greater affect on factor X than on thrombin.
Low-molecular-weight heparins bind less to plasma proteins than UFH
and therefore, the dosing is more predictable. They are more resistant
to neutralization by platelet factor 4 than UFH and have less inhibitory
affect on platelet function than UFH. Low-molecular-weight heparins
have a more predictable affect on coagulation than UFH and laboratory
monitoring is usually not necessary. Monitoring the effects of LMWHs
is difficult, since the commonly used tests for anticoagulation are
not helpful and activated factor Xa levels need to be measured.
Low-molecular-weight heparins are usually administered subcutaneously
twice daily. They are not easily reversed by protamine. Low-molecular-weight
heparin can also be given in smaller doses for the primary prevention of deep venous thrombosis in certain high-risk situations.
Oral Vitamin K Antagonists
Coumarins, or vitamin K antagonists, are the mainstay of oral anticoagulants and have been used for more than 50 years. Warfarin is the most commonly used oral anticoagulant. It blocks the conversion of vitamin K to the active moiety, vitamin K epoxide, which is necessary for the synthesis of factors II, VII, IX, X and proteins C and S. The half-life of warfarin is about 40 hours. It is nearly completely absorbed when given orally and binds to albumin. Its effect on hemostasis
is quite variable from person to person and sometimes, for the same
person at different times. Warfarin’s effect can be influenced
by dietary factors, liver disease, congestive heart failure, hypermetabolic
states, and numerous drug interactions. Monitoring the anticoagulant
effect of warfarin is mandatory. The prothrombin time (PT) is now
standardized to an international thromboplastin reagent and is reported as
the international normalized ratio (INR), which is used to monitor
the effects of warfarin and adjust its dose. Warfarin therapy may
be started without a loading dose. It usually takes several days
for the optimal or target INR to be achieved. During initiation
of therapy, there may be a brief paradoxical hypercoagulable state
due to the inhibition of proteins C and S (anticoagulant factors) before
the inhibition of the coagulant factors. For this reason, UFH or
LMWH may be used as a bridge until a therapeutic INR is achieved. During initiation of warfarin therapy, the INR should be checked frequently
until a stable dose of warfarin that achieves the target INR is found. Subsequently, the INR should be monitored at least once a month and more frequently if the dose needs to be adjusted. Monitoring
can be done by an individual care provider or through a warfarin clinic. The latter tends to be more organized and efficient. Point of care monitoring of INR is now available and can be done at home. If
warfarin needs to be stopped, the INR will normalize in about 3–4 days. If its anticoagulant effect needs to be reversed more quickly, vitamin K can be administered subcutaneously or, preferably, by the oral route. The INR will usually correct in 1–2 days if vitamin K is given. If it is necessary to reverse the effects of warfarin more quickly, fresh frozen plasma or prothrombin concentrate can be given.
Risks of Anticoagulant Therapy
Bleeding is the most common serious adverse effect seen with the use of anticoagulant agents. Bleeding complications are more likely to occur in patients who are older; who have a history of
previous stroke or gastrointestinal tract bleeding; who have had
a recent myocardial infarction; who have anemia, renal insufficiency,
serious concurrent illness, or diabetes; or who drink alcohol excessively
or take aspirin (Table 29–1). Intracranial hemorrhage is perhaps the most feared complication of anticoagulant
therapy. Intracranial hemorrhage that occurs without anticoagulation usually presents
suddenly, with rapid progression to the maximal neurologic deficit. Intracranial
hemorrhage that occurs while a patient is receiving anticoagulant therapy
is more devastating, with continued bleeding and progressive neurologic
deterioration. In such situations, reversal of ...