PHARMACOLOGY
REVIEW :
Drugs that alter
blood coagulation
Brush up on your knowledge of these potentially
life-saving drugs.
By Amy M. Karch, RN, MS
THE
VASCULAR SYSTEM delivers
oxygen and nutrients to all body
cells and removes waste products
from tissues. This closed system
functions as a pressure system,
with blood flowing continuously
from high-pressure to low-pressure
areas. Injury of a blood vessel
compromises the closed system,
causing blood to flow out of the
injured vessel (now a low-pressure
area). With severe injury to a vessel, the entire circulatory system
may be compromised and the patient could die.
Blood vessel injuries are common, occurring, for instance, when
someone hits the edge of a table,
coughs too hard, or falls down.
They initiate a series of normal reactions that stops blood flow and
maintains balance within the system. The reactions include:
• reflex vasoconstriction
• platelet aggregation
• blood coagulation (clot formation), which causes blood to
solidify
• clot resolution, which returns
blood to the fluid state.
In many clinical situations, drugs
are used to slow or stop this process, with the goal of preventing
tissue damage from the decreased
blood flow that occurs when the
clotting process cuts off blood supply to an area. This article reviews
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American Nurse Today
the processes the body uses to
maintain the cardiovascular system
and discusses the mechanisms of
action, benefits, and risks of drugs
used to alter coagulation. (See Inside the coagulation process.)
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,
CNE: 1.4 contact
hours
CNE
Rx
Rx: 1.4 contact
hours
L EARNING O BJECTIVES
1. Explain the clotting mechanism.
2. Discuss the various drugs that
alter blood coagulation.
3. Describe nursing care for patients
receiving drugs that alter coagulation.
The author and planners of this CNE activity have
disclosed no relevant financial relationships with
any commercial companies pertaining to this activity. See the last page of the article to learn how to
earn CNE credit.
Volume 7, Number 11
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. As a nurse, you 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. (See Classifying
drugs that alter coagulation.)
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
www.AmericanNurseToday.com
Inside the coagulation process
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.
Nursing considerations
When caring for patients receiving
platelet inhibitors, minimize invasive procedures and take other
steps to guard against blood loss.
Be sure to teach about self-care.
Advise them to avoid injury, use a
soft-bristled toothbrush, shave with
an electric razor, and avoid contact
sports. Encourage them to carry or
wear Medic-Alert jewelry that alerts
healthcare providers to platelet inhibitor use. Stress the importance
of telling all healthcare providers
they’re taking a platelet inhibitor—
especially dentists, surgeons, and
others planning an invasive procedure. Caution patients to check
with a physician before taking
other agents that alter coagulation,
including aspirin, nonsteroidal inflammatory drugs, and certain
herbs. Emphasize the need to
avoid excessive dosages, because
no rapid antidote exists for excessive bleeding caused by drug overdose or overreaction. Teach patients about warning signs of
excessive blood loss, and advise
them to report these immediately.
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Platelets
Fibrin
Collagen
Striated muscle
After an injury to a blood vessel, the vessel constricts. With a small injury, constriction
typically seals the open space, allowing blood to flow and helping the vessel to heal.
A larger injury exposes endothelial cells lining the vessel to blood flowing through it,
causing platelets to adhere to the injured area. When a platelet adheres, it releases
chemicals that attract more platelets, in turn drawing even more platelets to the area
in a process called platelet aggregation. Consequently, a platelet plug forms. In some
cases, this is enough to seal the leak and keep pressures stable while the vessel heals.
In more severe injuries, the vessel wall injury activates Hagemann factor, a clotting
factor. Activated Hagemann factor triggers activation of other clotting factors, initiating
the clotting cascade. The cascade ends in conversion of prothrombin to thrombin;
activated thrombin initiates clot formation.
All clotting factors are made in the liver and require vitamin K for their formation.
Calcium is the catalyst that speeds the clotting cascade. Activated thrombin breaks
down fibrinogen into fibrin. An insoluble protein, fibrin forms a clot at the site. The
change of blood from fluid to solid form stops blood flow in the vessel. In this process,
called the intrinsic process, a clot forms within the vessel.
A similar process, the extrinsic process, occurs in blood that has leaked out of the
vessel at the injury site. This process produces a seal within the vessel, along with a
seal outside the vessel. While this allows the vessel wall to seal and heal, it could
interrupt blood flow to tissues beyond that point, causing ischemia or even cell death.
When Hagemann factor is activated and triggers the clotting cascade, it also causes
plasminogen conversion to plasmin. Plasmin dissolves fibrin and returns blood to the
fluid state. This is the body’s clot-dissolving mechanism. Plasminogen, made in the
liver, also is activated by such conditions as stress, fever, and various enzymes. This
process protects against the harmful effects of clot formation.
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
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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-molecularweight 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.
Nursing considerations. Be
aware that in patients with excessive
bleeding caused by anticoagulants,
protamine sulfate can be injected
as a rapid antidote to restore clotting activity. This drug directly reacts with thrombin, freeing it up to
allow clots to form.
Also, know that several serious
to fatal medication errors have occurred when patients have inadvertently received two anticoagulants
at the same time. Such errors are
possible when, for instance, a hospital patient is put on a protocol
that uses an anticoagulant and
then is transferred to another unit,
where she receives an anticoagulant from a different protocol.
Warnings, labels, and effective
communication among nurses at
transfer points can help prevent
this problem.
The major drawback of injectable anticoagulants is that they
must be injected. Some patients
may be discharged on low-molecular-weight heparin to inject themselves; be sure to teach them
proper injection technique and
proper disposal of needles and syringes. Advise patients that they
must have their blood tested frequently to check crucial coagulation indices. Whole blood clotting
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Classifying drugs that
alter coagulation
Drugs that affect blood coagulation
fall into two main categories—
platelet inhibitors and anticoagulants.
Platelet inhibitors
• abciximab (ReoPro)
• anagrelide (Agrylin)
• aspirin
• cilostazol (Pletal)
• clopidogrel (Plavix)
• dipyridamole (Persantine)
• eptifibatide (Integrilin)
• ticagrelor (Brilinta)
• ticlopidine (Ticlid)
• tirofiban (Aggrastat)
Anticoagulants
Anticoagulants may be injectable or
oral.
Injectable anticoagulants
• antithrombin III (Thrombate III)
• argatroban (Acova)
• bivalirudin (Angiomax)
• dalteparin (Fragmin)
• desirudin (Iprivask)
• enoxaparin (Lovenox)
• fondaparinux (Arixtra)
• heparin
Oral anticoagulants
• dabigatran (Pradaxa)
• rivaroxaban (Xarelto)
• warfarin (Coumadin)
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)
Volume 7, Number 11
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
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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. (See
Herbs and other supplements that increase bleeding risk.)
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.
Teach patients to use all tablets
within 60 days of opening the bottle. Instruct them to swallow tablets
whole without cutting, crushing, or
chewing. Advise them to protect
the drug from humidity and light
exposure. Because no antidote exists, caution patients to stay alert
for signs and symptoms of exceswww.AmericanNurseToday.com
Herbs and other
supplements that
increase bleeding risk
The following herbs and supplements may increase the bleeding
risk, especially in patients receiving
drugs that alter coagulation:
•
angelica
•
cat’s claw
•
chamomile
•
chondroitin
•
feverfew
•
garlic
•
ginkgo
•
goldenseal
•
grape seed extract
•
green leaf tea
•
horse chestnut seed
•
psyllium
•
fish oil
•
vitamin E
•
turmeric.
sive 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 af-
fect 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,
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Photo courtesy of MedicAlert® Foundation
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.
Education is important for patients receiving these drugs. (See
Crucial nursing care and patient
education.) Be sure to teach them
how and when to take the prescribed drug, and make sure they
understand safety measures to prevent bleeding.
*
Crucial nursing care and patient education
When caring for patients receiving drugs that alter coagulation, limit invasive
procedures, apply prolonged pressure to puncture sites and wounds, and guard
against activities that may cause bleeding. Evaluate for therapeutic drug effects
and monitor for adverse effects that could put the patient at risk, such as hypersensitivity reactions, gastric hemorrhage, and bleeding.
Monitor clotting tests to ensure therapeutic drug effects and decrease adverse
effects.
• For patients receiving warfarin, prothrombin time should be 1.5 to 2.5 times
the control value, or the International Normalized Ratio (INR) should be 2 to 3.
• For patients receiving heparin, whole blood clotting time should be 2.5 to 3
times the control value, or the activated partial thromboplastin time should be
1.5 to 3 times the control value.
For patients on dabigatran or rivaroxaban, be aware that blood tests aren’t
available to evaluate effectiveness.
If your patient stops or starts a drug that alters coagulation, ask about other
drugs or herbal supplements he or she is taking, because these could cause an interaction. Make sure all healthcare providers know the patient’s receiving the anticoagulant (especially at transfer points) and that the patient’s medical record clearly indicates this information.
Essential teaching points
Educate patients about the drug regimen and required safety measures. Advise
them to use only a soft-bristled toothbrush and an electric razor. If they will be discharged on the drug, teach them how and when to administer it and (with an injectable drug) how to prepare, administer, and dispose of the drug, needles, and
syringes.
Advise patients using dabigatran or rivaroxaban how to store the drug properly.
Instruct them to use it within 60 days of opening the bottle. Caution them not to
stop taking the drug suddenly and to make sure they always have enough tablets
on hand so they don’t run out.
Also teach the patient:
• the importance of carrying or wearing Medical Alert jewelry
• when to return for blood tests to monitor drug effects
• which other drugs, herbs, and other supplements to avoid
• the importance of telling all healthcare providers they’re taking this drug
• what to watch for and report, including prolonged bleeding, easy bruising, and
changes in urine or stool color.
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Volume 7, Number 11
Selected references
Brunton L, Chabner B, Knollman B. Goodman and Gilman’s The Pharmacological
Basis of Therapeutics. 12th ed. New York:
McGraw-Hill; 2010.
Facts & Comparisons. Drug Facts and Comparisons 2012. 66th ed. Philadelphia: Lippincott Williams & Wilkins; 2011.
Hankey GJ, Eikelboom JW. Dabigatran etexilate: a new oral thrombin inhibitor. Circulation. 2011 Apr 5;123:1436-50.
Karch AM. 2012 Lippincott’s Nursing Drug
Guide. Philadelphia: Lippincott Williams &
Wilkins; 2011.
Karch AM. Focus on Nursing Pharmacology.
6th ed. Philadelphia: Lippincott Williams &
Wilkins; 2012.
Mitke M. New alternative to warfarin may
help reduce stroke in patients with AF.
JAMA. 2011 Jan 5:305(1):25-6.
Porth CM. Pathophysiology: Concepts of Altered Health States. 8th ed. Philadelphia:
Lippincott Williams & Wilkins; 2010.
Price MJ, Berger PB, Teirstein et al; GRAVITAS Investigators. Standard- vs high-dose
clopidogrel based on platelet function testing after percutaneous coronary intervention: the GRAVITAS randomized trial. JAMA.
2011 Mar 16:305(11):1079-105.
Shimoli V, Gage BF. Cost-effectiveness of
dabigatran for stroke prophylaxis in atrial
fibrillation. Circuation. 2011:123:2562-70.
Streiff MB, Haut ER. The CMS ruling on venous thromboembolism after total knee or
hip arthroplasty: weighing risks and benefits. JAMA. 2009 Mar 11:301(10):1063-5.
Amy M. Karch is an associate professor of clinical
nursing at the University of Rochester School of
Nursing in Rochester, New York.
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Please mark the correct answer online.
1. Which of the following is among the first
reactions to a blood vessel injury?
a. Prothrombin is converted to thrombin.
b. A blood clot forms.
c. The blood vessel dilates.
d. The blood vessel constricts.
2. Which statement about Hagemann factor is
correct?
a. It is activated when a minor injury to the vessel
wall occurs.
b. It is activated when a more severe injury to the
vessel wall occurs.
c. It stops the clotting cascade.
d. It converts thrombin to prothrombin.
3. During the extrinsic process of blood
coagulation:
a. a seal forms outside the injured blood vessel.
b. platelet aggregation occurs.
c. thrombin breaks up fibrinogen.
d. the clotting cascade is activated.
4. What is the role of plasmin in blood
coagulation?
a. It converts vitamin K to fibrinogen.
b. It converts fibrin to plasminogen.
c. It dissolves the Hagemann factor.
d. It dissolves fibrin.
5. You admit a patient with atrial fibrillation who
is taking clopidogrel. You explain to the student
nurse accompanying you that this drug:
a. stimulates receptors to prevent adhesion.
b. is an anticoagulant.
c. blocks receptors on platelets to prevent
adhesion.
d. is a blood thinner.
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that there is real or implied endorsement of any product, service, or company referred to in this activity nor of any company subsidizing costs related to the activity. This CNE activity does not include any unannounced
information about off-label use of a product for a purpose other than that
for which it was approved by the Food and Drug Administration (FDA).
The planners of this CNE activity have disclosed no relevant financial relationships with any commercial companies pertaining to this CNE.
P URPOSE / GOAL
To provide nurses with the information they need to better
manage patients who are receiving drugs that alter blood
coagulation
L EARNING O BJECTIVES
1. Explain the clotting mechanism.
2. Discuss the various medications that alter blood coagulation.
3. Describe nursing care for patients receiving drugs that alter
coagulation.
6. Which drug may cause cardiovascular problems
if discontinued suddenly?
a. Enoxaparin
b. Cilostazol
c. Dabigatran
d. Bivalirudin
7. To prevent formation of a new blood clot,
which drug might be prescribed?
a. Abciximab
b. Eptifibatide
c. Tirofiban
d. Bivalirudin
8. Your patient with deep vein thrombosis is
receiving an injectable anticoagulant. You explain to
the patient that the drug works by:
a. directly blocking formation of prothrombin from
thrombin.
b. directly blocking formation of thrombin from
prothombin.
c. dissolving the clot.
d. thinning the blood.
9. Which agent is a rapid antidote that may be
given when an anticoagulant causes excessive
bleeding?
a. Ticlopidine
b. Dipyridamole
c. Protamine sulfate
d. Potassium sulfate
10. Your patient just started receiving heparin
because of a pulmonary embolism. Which
laboratory test result would concern you?
a. Activated partial thromboplastin time (APTT) of
2 times the control value
b. APTT of 4 times the control value
c. Whole blood clotting time (WBCT) of 2.5 times
the control value
d. WBCT of 3 times the control value
11. Which statement about a rapid antidote for
excessive bleeding caused by overdose or
overreaction to platelet inhibitors is accurate?
a. No rapid antidote exists for this situation.
b. Vitamin K can be used as a rapid antidote.
c. A rapid antidote is contraindicated in patients
with myocardial infarction.
d. A rapid antidote is contraindicated in patients
with atrial fibrillation.
12. Which drug would you expect the physician to
order for a patient with disseminated intravascular
coagulation?
a. Warfarin
b. Dabigatran
c. Aspirin
d. Heparin
13. Your patient on warfarin experiences minor
abnormal bleeding. Which vitamin may be given to
stimulate the liver to start making clotting factors?
a. Vitamin A
b. Vitamin B
c. Vitamin D
d. Vitamin K
14. Your patient on warfarin therapy describes his
activities at home. Which statement would concern
you?
a. “I stopped taking the garlic pills I used to take.”
b. “I drink chamomile tea every evening to relax.”
c. “I’m using a soft-bristled toothbrush.”
d. “I’m shaving with an electric razor.”
15. Which of the following is a correct instruction
for a patient taking rivaroxaban?
a. Don’t suddenly stop taking the drug.
b. Take it with chondroitin to increase
effectiveness.
c. Use the drug within 30 days.
d. It is acceptable to skip 5 days.
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