Indications for drugs that alter coagulation

In certain clinical situations—for instance, coronary artery disease, immobility, atrial fibrillation,
and joint replacement—interfering with coagulation helps prevent clots that could impede blood
flow and cause tissue damage or death. Patients with coronary artery disease, for example, have
narrowed vessels. An immobile patient loses the protective massaging of veins caused by muscle
fiber contractions; also, blood pools and doesn’t return to the heart efficiently. With atrial
fibrillation, blood pools in the heart’s auricles and may clot. The artificial parts of a hip or knee
replacement initially may damage a blood vessel, leading to clotting.

All drugs that alter coagulation interfere with the normal protective reflexes. A physician need to
be aware of the dangers of eliminating these reflexes, which could include serious or even fatal
bleeding episodes. Drugs that alter coagulation include platelet inhibitors and anticoagulants.

Platelet inhibitors

Platelet inhibitors are often the first line of defense in preventing vascular clots; they don’t affect
clots that already have formed. These drugs block platelets’ ability to adhere and aggregate to
form the platelet plug—the first step in sealing the vascular system and preventing blood loss
into body tissues.

Current platelet inhibitors include abciximab (ReoPro), anagrelide (Agrylin), aspirin, cilostazol
(Pletal), clopidogrel (Plavix), dipyridamole (Persantine), eptifibatide (Integrilin), ticlopidine
(Ticlid), ticagrelor (Brilinta), and tirofiban (Aggrastat). These drugs are used to treat
cardiovascular diseases in which vessels become occluded, as well as to maintain venous and
arterial grafts and prevent cerebrovascular occlusion. They’re also given as adjuncts to
thrombolytic therapy in treating myocardial infarction (MI) and preventing post-MI reinfarction.
Ticagrelor, released in 2011, is indicated only to prevent thromboembolic events in acute
coronary syndrome. Its black-box warning cites the risk of excessive bleeding and dangers of
sudden withdrawal, which can trigger an acute cardiovascular event.

Most platelet inhibitors block receptors on platelets to prevent adhesion; anagrelide prevents
platelet formation in the bone marrow. Bleeding (including bleeding caused by toothbrushing
and excessive bleeding after injury) is the most common adverse effect. Easy bruising also may
occur.

Anticoagulants

Although commonly called blood thinners, anticoagulants don’t actually thin the blood. Like
platelet inhibitors, they don’t dissolve clots that have already formed but they can prevent
formation of new clots. In patients with clots, deep vein thrombosis, or occluded vessels that
have caused an MI or a stroke, clot prevention is crucial, because new clot formation may
compound the patient’s problem. Anticoagulants fall into two categories—injectable and oral.
Injectable anticoagulants

These agents act rapidly to directly block formation of thrombin from prothombin. Clotting
changes occur rapidly after injection. Injectable anticoagulants in current use include
antithrombin III (Thrombate III), argatroban (Acova), bivalirudin (Angiomax), desirudin
(Iprivask), fondaparinux (Arixtra), heparin (generic), and the low-molecular-weight heparins
dalteparin (Fragmin) and enoxaparin (Lovenox).

Indications for injectable anticoagulants include acute treatment and prevention of venous
thrombosis and pulmonary embolism, treatment of atrial fibrillation with embolization,
prevention of clotting in blood samples and in dialysis and venous tubing, and diagnosis and
treatment of disseminated intravascular coagulation.

Whole blood clotting time must be maintained at 2.5 to 3 times the control value, or activated
partial thromboplastin time (APTT) must be maintained at 1.5 to 3 times the control value. Be
sure to provide other protective measures and cover the same teaching topics as for patients
receiving platelet inhibitors.

Oral anticoagulants

Previously, warfarin (Coumadin) was the only oral anticoagulant available. In recent years, two
new oral anticoagulants have been approved by the Food and Drug Administration. Dabigatran
(Pradaxa) is a direct thrombin inhibitor; rivaroxaban (Xarelto) inhibits activated thrombin. Both
stop the coagulation process.

Warfarin Warfarin blocks the liver’s use of vitamin K to produce clotting factors. It’s commonly
prescribed for chronic conditions that might involve problems with clot formation, such as
coronary artery disease, atrial fibrillation, knee or hip replacement, and immobility.

However, warfarin has several disadvantages. For one, it takes time to deplete already-formed
clotting factors; clot formation may not decrease until 48 to 72 hours after warfarin therapy
begins. Also, if the patient receives too much warfarin and is bleeding, no precise antidote exists.
Although vitamin K can be injected to trigger the liver to resume making clotting factors,
clotting activity may not return for 48 to 72 hours. In severe overdose and bleeding, blood
products containing clotting factors may be given to stop the bleeding; however, the liver still
needs time to restore a normal level of clotting factors.

Traditionally, warfarin was the only oral anticoagulant patients could take at home. In light of its
slowness in halting clot formation, warfarin therapy usually is started while the patient is still
receiving an injectable anticoagulant; the latter drug is withdrawn when warfarin kicks in. Also,
warfarin may interact with many other drugs and certain herbal supplements. What’s more, its
effects may be altered by changes in the liver or in vitamin K production by the normal intestinal
flora.

Patients on warfarin need to have frequent blood tests to evaluate its effectiveness and allow
dosage adjustment, if needed. The desired prothrombin time (PT) is 1.5 to 2.5 times the control
value; the desired International Normalized Ratio (INR) is 2 to 3. If a drug is added to or
removed from the patient’s regimen, warfarin dosage may need to be adjusted. As with any drug
used to alter coagulation, be sure to provide education and support.

Dabigatran. This drug was approved in 2010 for prevention of stroke and blood clots in patients
with nonvalvular atrial fibrillation. Rather than affecting clotting-factor formation, it inhibits
activation of a clotting factor, which stops the clotting cascade. Dabigatran has become the drug
of choice for preventing clots in patients with chronic nonvalvular atrial fibrillation. It interacts
with few drugs and its effects aren’t altered directly by liver function changes, so patients don’t
need frequent blood testing to guide dosages. Because its half-life is 12 to 17 hours, the drug’s
effects linger after the patient stops taking it.

Because no antidote exists, caution patients to stay alert for signs and symptoms of excessive
bleeding, such as excessive bruising, easy bleeding from minor injuries, and bleeding from
toothbrushing. Stress that they shouldn’t stop taking the drug suddenly, because cardiovascular
problems could result.

Rivaroxaban. This drug was approved in 2011 to prevent deep vein thrombosis after knee or hip
replacement surgery and to reduce stroke risk in patients with nonvalvular atrial fibrillation. It
affects clot formation by inhibiting activated clotting factor. It has a shorter half-life than
dabigatran (5 to 9 hours), so it clears from the body faster and its effects don’t last as long. No
specific antidote exists.

Caution patients not to stop taking rivaroxaban suddenly because this may cause sudden reversal
of effects, triggering a stroke. Inform them that combining rivaroxaban with other drugs or herbs
that affect coagulation could lead to excessive bleeding.

Ensuring patient safety

Patient safety is a major concern for patients receiving drugs that affect coagulation because
they’re at risk for excessive bleeding. Take the following measures to protect patients from
injury and minimize invasive procedures:

 Help consolidate required blood withdrawals so the patient has fewer chances to bleed.
 Clearly document in the chart that the patient is on this drug, to alert other caregivers that
invasive procedures could lead to blood loss.
 Use compression dressings over areas that could bleed.
 Check all drugs and supplements the patient is taking for their potential to alter
coagulation, which could lead to more bleeding
 At least once during each shift, assess patients carefully for signs and symptoms of
bleeding.
 Evaluate clotting-test results to help determine the drug’s therapeutic dosage, if
appropriate.
 To help prevent or check for possible interactions, ask patients about all drugs, herbs, and
other supplements they’re taking.
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