chapter 57
Drugs That Affect Blood Coagulation
Objectives
AFTER STUDYING THIS CHAPTER, THE STUDENT WILL BE ABLE TO:
1. Describe important elements in the physiology
of hemostasis and thrombosis.
2. Discuss potential consequences of blood
clotting disorders.
3. Discuss characteristics and uses of anticoagulant, antiplatelet, and thrombolytic agents.
4. Compare and contrast heparin and warfarin
in terms of indications for use, onset and
duration of action, route of administration,
blood tests used to monitor effects, and
nursing process implications.
5. Teach clients on long-term warfarin therapy
protective measures to prevent abnormal
bleeding.
6. Discuss antiplatelet agents in terms of indications for use and effects on blood coagulation.
7. With aspirin, contrast the dose and frequency
of administration for antiplatelet effects with
those for analgesic, antipyretic, and antiinflammatory effects.
8. Describe thrombolytic agents in terms of indications and contraindications for use, routes
of administration, and major adverse effects.
9. Discuss the use of anticoagulant, antiplatelet,
and thrombolytic drugs in special populations.
10. Describe systemic hemostatic agents for
treating overdoses of anticoagulant and
thrombolytic drugs.
Critical Thinking Scenario
Juan Sanchez, a 56-year-old migrant farmer without health insurance, is admitted to the hospital after an
episode of syncope. He is diagnosed with atrial fibrillation and is started on a calcium channel blocker and
Coumadin. Before his discharge, you are responsible for patient teaching.
Reflect on:
Assessment data that would be helpful to individualize your teaching plan.
Discuss the rationale for use of Coumadin for clients with atrial fibrillation.
Identify side effects of Coumadin therapy.
Consider strategies that might help Mr. Sanchez comply with therapy and experience limited side effects.
OVERVIEW
A
nticoagulant, antiplatelet, and thrombolytic drugs are used
in the prevention and management of thrombotic and thromboembolic disorders. Thrombosis involves the formation
(thrombogenesis) or presence of a blood clot (thrombus) in
the vascular system. Blood clotting is a normal body defense
mechanism to prevent blood loss. Thus, thrombogenesis may
be lifesaving when it occurs as a response to hemorrhage;
however, it may be life threatening when it occurs at other
times, because the thrombus can obstruct a blood vessel and
block blood flow to tissues beyond the clot. When part of a
thrombus breaks off and travels to another part of the body,
it is called an embolus.
832
Atherosclerosis is the basic disease process that often leads
to pathologic thrombosis. It begins with accumulation of lipidfilled macrophages (ie, foam cells) on the inner lining of arteries. Foam cells develop in response to elevated blood lipid
levels and eventually become fibrous plaques (ie, foam cells
covered by smooth muscle cells and connective tissue).
Advanced atherosclerotic lesions also contain hemorrhages,
ulcerations, and scar tissue.
Atherosclerosis can affect any organ or tissue, but often
involves the arteries supplying the heart, brain, and legs.
Over time, plaque lesions become larger and extend farther
into the lumen of the artery. Eventually, a thrombus may
develop at plaque sites and partially or completely occlude
an artery. In coronary arteries, a thrombus may precipi-
CHAPTER 57 DRUGS THAT AFFECT BLOOD COAGULATION
tate myocardial ischemia (angina or infarction) (see Chapter 53); in carotid or cerebral arteries, a thrombus may precipitate a stroke; in peripheral arteries, a thrombus may
cause intermittent claudication (pain in the legs with exercise) or acute occlusion. Thus, serious impairment of blood
flow may occur with a large atherosclerotic plaque or a relatively small plaque with superimposed vasospasm and
thrombosis. Consequences and clinical manifestations of
thrombi and emboli depend primarily on their location and
size.
Normally, thrombi are constantly being formed and
dissolved (thrombolysis), but the blood stays fluid and flow is
not significantly obstructed. If the balance between thrombogenesis and thrombolysis is upset, thrombotic or bleeding disorders result. Thrombotic disorders occur much more often
than bleeding disorders and are emphasized in this chapter;
bleeding disorders may result from excessive amounts of drugs
that inhibit clotting. To aid understanding of drug therapy for
thrombotic disorders, normal hemostasis, endothelial functions
in relation to blood clotting, platelet functions, blood coagulation, and characteristics of arterial and venous thrombosis are
described.
HEMOSTASIS
Hemostasis is prevention or stoppage of blood loss from an
injured blood vessel and is the process that maintains the integrity of the vascular compartment. It involves activation of
several mechanisms, including vasoconstriction, formation
of a platelet plug (a cluster of aggregated platelets), sequential activation of clotting factors in the blood (Table 57–1),
and growth of fibrous tissue (fibrin) into the blood clot to
make it more stable and to repair the tear (opening) in the
damaged blood vessel. Overall, normal hemostasis is a complex process involving numerous interacting activators and
inhibitors, including endothelial factors, platelets, and blood
coagulation factors (Box 57–1).
TABLE 57–1
833
CLOT LYSIS
When a blood clot is being formed, plasminogen (an inactive
protein found in many body tissues and fluids) is bound to fibrin and becomes a component of the clot. After the outward
blood flow is stopped and the tear in the blood vessel repaired, plasminogen is activated by plasminogen activator
(produced by endothelial cells or the coagulation cascade) to
produce plasmin. Plasmin is an enzyme that breaks down the
fibrin meshwork that stabilizes the clot; this fibrinolytic or
thrombolytic action dissolves the clot.
THROMBOTIC AND
THROMBOEMBOLIC DISORDERS
Thrombosis may occur in both arteries and veins. Arterial
thrombosis is usually associated with atherosclerotic plaque,
hypertension, and turbulent blood flow. These conditions
damage arterial endothelium and activate platelets to initiate
the coagulation process. Arterial thrombi cause disease by
obstructing blood flow. If the obstruction is incomplete or
temporary, local tissue ischemia (deficient blood supply) occurs. If the obstruction is complete or prolonged, local tissue
death or infarction occurs.
Venous thrombosis is usually associated with venous stasis. When blood flows slowly, thrombin and other procoagulant substances present in the blood become concentrated in
local areas and initiate the clotting process. With a normal
rate of blood flow, these substances are rapidly removed from
the blood, primarily by Kupffer cells in the liver. A venous
thrombus is less cohesive than an arterial thrombus, and an
embolus can easily become detached and travel to other parts
of the body.
Venous thrombi cause disease by two mechanisms. First,
thrombosis causes local congestion, edema, and perhaps inflammation by impairing normal outflow of venous blood
(eg, thrombophlebitis, deep vein thrombosis [DVT]). Sec-
Blood Coagulation Factors
Number
Name
Functions
I
Fibrinogen
II
III
IV
V
VII
VIII
IX
X
XI
Prothrombin
Thromboplastin
Calcium
Labile factor
Proconvertin or stable factor
Antihemophilic factor
Christmas factor
Stuart factor
Plasma thromboplastin antecedent
XII
XIII
Hageman factor
Fibrin-stabilizing factor
Forms fibrin, the insoluble protein strands that compose the supporting framework of a blood clot. Thrombin and calcium are required for the conversion.
Forms thrombin, which catalyzes the conversion of fibrinogen to fibrin
Converts prothrombin to thrombin
Catalyzes the conversion of prothrombin to thrombin
Required for formation of active thromboplastin
Accelerates action of tissue thromboplastin
Promotes breakdown of platelets and formation of active platelet thromboplastin
Similar to factor VIII
Promotes action of thromboplastin
Promotes platelet aggregation and breakdown, with subsequent release of
platelet thromboplastin
Similar to factor XI
Converts fibrin meshwork to the dense, tight mass of the completely formed clot
834
BOX 57–1
SECTION 9 DRUGS AFFECTING THE CARDIOVASCULAR SYSTEM
HEMOSTASIS AND THROMBOSIS
The blood vessels and blood normally maintain a balance between
procoagulant and anticoagulant factors that favors anticoagulation
and keeps the blood fluid. Injury to blood vessels and tissues
causes complex reactions and interactions among vascular endothelial cells, platelets, and blood coagulation factors that shift
the balance toward procoagulation and thrombosis.
Endothelial Cells
Endothelial cells play a role in all aspects of hemostasis and thrombosis. Normal endothelium helps to prevent thrombosis by producing anticoagulant factors, inhibiting platelet reactivity, and inhibiting
activation of the coagulation cascade. However, endothelium promotes thrombosis when its continuity is lost (eg, the blood vessel
wall is torn by rupture of atherosclerotic plaque, hypertension,
trauma), its function is altered, or when blood flow is altered or
becomes static. After a blood clot is formed, the endothelium also
induces its dissolution and restoration of blood flow.
Antithrombotic Functions
• Synthesizes and releases prostacyclin (prostaglandin I2), which
inhibits platelet aggregation
• Releases endothelium-derived relaxing factor (nitric oxide),
which inhibits platelet adhesion and aggregation
• Blocks platelet exposure to subendothelial collagen and other
stimuli for platelet aggregation
• May inhibit platelet reactivity by inactivating adenosine diphosphate (ADP), a platelet product that promotes platelet aggregation
• Produces plasminogen activators (eg, tissue-type or tPA) in re-
•
sponse to shear stress and such agonists as histamine and thrombin. These activators convert inactive plasminogen to plasmin,
which then breaks down fibrin and dissolves blood clots (fibrinolytic effects).
Produces thrombomodulin, a protein that helps prevent formation of intravascular thrombi by inhibiting thrombin-mediated
platelet aggregation. Thrombomodulin also reacts with thrombin to activate proteins C and S, which inhibit the plasma cascade of clotting factors.
Prothrombotic Functions
• Produces antifibrinolytic factors. Normally, the balance be-
•
•
tween profibrinolysis and antifibrinolysis favors fibrinolysis
(clot dissolution). In pathologic conditions, including atherosclerosis, fibrinolysis may be limited and thrombosis enhanced.
In pathologic conditions, may induce synthesis of prothrombotic factors such as von Willebrand factor. Von Willebrand
factor serves as a site for subendothelial platelet adhesion and
as a carrier for blood coagulation factor VIII in plasma. Several
disease states are associated with increased or altered production of von Willebrand factor, including atherosclerosis.
Produces tissue factor, which activates the extrinsic coagulation
pathway after exposure to oxidized low-density lipoprotein cholesterol, homocysteine, and cytokines (eg, interleukin-1, tumor
necrosis factor–alpha)
Platelets
Platelets (also called thrombocytes) are fragments of large cells
called megakaryocytes. They are produced in the bone marrow
and released into the bloodstream, where they circulate for approximately 7 to 10 days before they are removed by the spleen.
They contain no nuclei and therefore cannot repair or replicate
themselves.
The cell membrane of a platelet contains a coat of glycoproteins that prevents the platelet from adhering to normal endothelium but allows it to adhere to damaged areas of endothelium and
subendothelial collagen in the blood vessel wall. It also contains
receptors for ADP, collagen, blood coagulation factors such as
fibrinogen, and other substances. Breakdown of the cell membrane releases arachidonic acid (which can be metabolized to
produce thromboxane A2) and allows leakage of platelet contents
(eg, thromboplastin and other clotting factors), which function to
stop bleeding.
The cytoplasm of a platelet contains storage granules with
ADP, fibrinogen, histamine, platelet-derived growth factor, serotonin, von Willebrand factor, enzymes that produce thromboxane
A2, and other substances. The cytoplasm also contains contractile
proteins that contract storage granules so they empty their contents and help a platelet plug to retract and plug a hole in a torn
blood vessel.
The only known function of platelets is hemostasis. When
platelets come in contact with a damaged vascular surface, they
become activated and undergo changes in structure and function.
They enlarge, express receptors on their surfaces, release mediators from their storage granules, become sticky so that they adhere to endothelial and collagen cells, and form a platelet
thrombus (ie, a cluster or aggregate of activated platelets) within
seconds. The thrombus blocks the tear in the blood vessel and
prevents further leakage of blood. Platelets usually disappear
from a blood clot within 24 hours and are replaced by fibrin.
Formation of a platelet thrombus proceeds through the phases
of activation, adhesion, aggregation, and procoagulation.
Activation
Platelet activation occurs when agonists such as thrombin, collagen, ADP, or epinephrine bind to their specific receptors on
the platelet cell membrane surface. Activated platelets release von
Willebrand factor, which aids platelet adhesion to blood vessel
walls. They also secrete ADP and thromboxane A2 into the blood.
The ADP and thromboxane A2 activate and recruit nearby platelets.
Adhesion
Platelet adhesion involves changes in platelets that allow them to
adhere to endothelial cells and subendothelial collagen exposed by
damaged endothelium. Adhesion is mediated by interactions between platelets and substances in the subendothelial tissues.
Platelets contain binding sites for several subendothelial tissue proteins, including collagen and von Willebrand factor. In capillaries,
where blood shear rates are high, platelets also can bind indirectly
to collagen through von Willebrand factor. Von Willebrand factor
is synthesized by endothelial cells and megakaryocytes. Although
it contains binding sites for platelets and collagen, it does not normally bind with platelets until they are activated.
Aggregation
Aggregation involves the accumulation of platelets at a site of
injury to a blood vessel wall and is stimulated by ADP, collagen,
thromboxane A2, thrombin, and other factors. It requires the
binding of extracellular fibrinogen to platelet fibrinogen receptors. The fibrinogen receptor is located on a complex of two
glycoproteins (GPIIb and IIIa) in the platelet cell membrane. Although many GP IIb/IIIa complexes are on the surface of each
platelet, they do not function as fibrinogen receptors until the
platelet is activated by an agonist. Each activated GP IIb/IIIa
CHAPTER 57 DRUGS THAT AFFECT BLOOD COAGULATION
BOX 57–1
835
HEMOSTASIS AND THROMBOSIS (Continued)
complex is capable of binding a single fibrinogen molecule.
However, a fibrinogen molecule may bind to receptors on adjacent activated platelets, thus acting as a bridge to connect the
platelets. Activated GP IIb/IIIa complexes can also bind von
Willebrand factor and promote platelet aggregation when fibrinogen is lacking.
Aggregated platelets produce and release thromboxane A2,
which acts with ADP from platelet storage granules to promote
additional GP IIb/IIIa activation, platelet secretion, and aggregate formation. The exposure of functional GP IIb/IIIa complexes is also stimulated by thrombin, which can directly
stimulate thromboxane A2 synthesis and granule secretion without initial aggregation. Collagen stimulates additional aggregation by increasing the production of thromboxane A2 and storage
granule secretion.
Overall, aggregated platelets release substances that recruit
new platelets and stimulate additional aggregation. This activity
helps the platelet plug become large enough to block blood flow
out of a damaged blood vessel. If the opening is small, the platelet
plug can stop blood loss. If the opening is large, a platelet plug and
a blood clot are both required to stop the bleeding.
Procoagulant Activity
In addition to forming a platelet thrombus, platelets also activate
and interact with circulating blood coagulation factors to form
a larger and more stable blood clot. Activation of the previously
inactive blood coagulation factors leads to formation of fibrin
threads that attach to the platelets and form a tight meshwork of a
fully developed blood clot.
More specifically, the platelet plug provides a surface on
which coagulation enzymes, substrates, and cofactors interact at
high local concentrations. These interactions lead to activation
of coagulation factor X and the conversion of prothrombin to
thrombin.
ond, embolization obstructs the blood supply when the embolus becomes lodged. The pulmonary arteries are common
sites of embolization.
DRUGS USED IN THROMBOTIC AND
THROMBOEMBOLIC DISORDERS
Drugs given to prevent or treat thrombosis alter some aspect of
the blood coagulation process. Anticoagulants are widely used
in thrombotic disorders. They are more effective in preventing
venous thrombosis than arterial thrombosis. Antiplatelet drugs
are used to prevent arterial thrombosis. Thrombolytic agents
are used to dissolve thrombi and limit tissue damage in selected
thromboembolic disorders. These drugs are described in the
following sections and in Drugs at a Glance: Anticoagulant,
Antiplatelet, and Thrombolytic Agents.
Anticoagulants
Anticoagulant drugs are given to prevent formation of new
clots and extension of clots already present. They do not dis-
Blood Coagulation
The blood coagulation process causes hemostasis within 1 to
2 minutes. It involves sequential activation of clotting factors that
are normally present in blood and tissues as inactive precursors
and formation of a meshwork of fibrin strands that cements blood
components together to form a stable, dense clot. Major phases include release of thromboplastin by disintegrating platelets and
damaged tissue; conversion of prothrombin to thrombin, which requires thromboplastin and calcium ions; and conversion of fibrinogen to fibrin by thrombin.
Blood coagulation results from activation of the intrinsic or extrinsic coagulation pathway. Both pathways, which are activated
when blood passes out of a blood vessel, are needed for normal hemostasis. The intrinsic pathway occurs in the vascular system; the
extrinsic pathway occurs in the tissues. Although the pathways are
initially separate, the terminal steps (ie, activation of factor X and
thrombin-induced formation of fibrin) are the same.
The intrinsic pathway is activated when blood comes in contact with collagen in the injured vessel wall and coagulation factor XII interacts with biologic surfaces. The normal endothelium
prevents factor XII from interacting with such surfaces. The activated form of factor XII is a protease that starts the interactions
among factors involved in the intrinsic pathway (eg, prekallikrein,
factor IX, factor VIII).
The extrinsic pathway is activated when blood is exposed to
tissue extracts and tissue factor interacts with circulating coagulation factor VII. Activated factors VII and IX both act on factor X
to produce activated factor X, which then interacts with factor V,
calcium, and platelet factor 3. Platelet factor 3, a component of the
platelet cell membrane, becomes available on the platelet surface
only during platelet activation. The interactions among these substances lead to formation of thrombin, which then activates fibrinogen to form fibrin, and the clot is complete.
solve formed clots, improve blood flow in tissues around the
clot, or prevent ischemic damage to tissues beyond the clot.
Heparins and warfarin are commonly used anticoagulants;
danaparoid and lepirudin are newer agents. Clinical indications
include prevention or management of thromboembolic disorders, such as thrombophlebitis, DVT, and pulmonary embolism. The main adverse effect is bleeding.
Heparin
Heparin is a pharmaceutical preparation of the natural anticoagulant produced primarily by mast cells in pericapillary connective tissue. Endogenous heparin is found in
various body tissues, most abundantly in the liver and
lungs. Exogenous heparin is obtained from bovine lung or
porcine intestinal mucosa and standardized in units of biologic activity.
Heparin combines with antithrombin III (a natural anticoagulant in the blood) to inactivate clotting factors IX, X, XI,
and XII, inhibit the conversion of prothrombin to thrombin,
and prevent thrombus formation. After thrombosis has developed, heparin can inhibit additional coagulation by inactivating thrombin, preventing the conversion of fibrinogen to
836
SECTION 9 DRUGS AFFECTING THE CARDIOVASCULAR SYSTEM
Drugs at a Glance: Anticoagulant, Antiplatelet, and Thrombolytic Agents
Generic/Trade Name
Anticoagulants
Heparin
Argatroban (Argatroban)
Bivalirudin (Angiomax)
Indications for Use
Routes and Dosage Ranges
Prevention and management of thromboembolic
disorders (eg, deep vein thrombosis, pulmonary
embolism, atrial fibrillation with embolization)
Adults: IV injection, 5000 units initially, followed by
5000–10,000 units q4–6h, to a maximum dose of
25,000 units/d; IV infusion, 5000 units (loading
dose), then 15–25 units/kg/h
DIC, IV injection, 50–100 units/kg q4h; IV infusion,
20,000–40,000 units/d at initial rate of 0.25
units/kg/min, then adjusted according to aPTT; SC
10,000–12,000 units q8h, or 14,000–20,000 units
q12h
Low-dose prophylaxis, SC 5000 units 2 h before
surgery, then q12h until discharged from hospital or
fully ambulatory
Children: DIC, IV injection, 25–50 units/kg q4h; IV infusion, 50 units/kg initially, followed by 100 units/kg
q4h or 20,000 units/m2 over 24 h
IV continuous infusion 2 mcg/kg/min
Thrombosis prophylaxis or management in heparininduced thrombocytopenia
Clients with unstable angina undergoing PTCA
Dalteparin (Fragmin)
Prophylaxis of DVT in clients having hip replacement surgery; also clients at high risk of thromboembolic disorders who are having abdominal
surgery
Danaparoid (Orgaran)
Prophylaxis of DVT in clients having hip replacement surgery
Prevention and management of DVT and pulmonary
embolism
Management of unstable angina, to prevent
myocardial infarction
Enoxaparin (Lovenox)
Fondaparinux (Arixtra)
Lepirudin (Refludan)
Tinzaparin (Innohep)
Warfarin (Coumadin)
Antiplatelet Agents
Aspirin
Abciximab (ReoPro)
Anagrelide (Agrylin)
Prevention of DVT following hip fracture surgery or
knee or hip replacement
Heparin alternative for anticoagulation of clients
with heparin-induced thrombocytopenia and
associated thromboembolic disorders
Management of DVT, with or without PE; may be
given in conjunction with warfarin
Long-term prevention or management of venous
thromboembolic disorders, including DVT, PE, and
embolization associated with atrial fibrillation and
prosthetic heart valves. May also be used after
myocardial infarction to decrease reinfarction,
stroke, venous thromboembolism, and death
Prevention of myocardial infarction
Prevention of thromboembolic disorders in clients
with prosthetic heart valves or transient ischemic
attacks
Used with PTCA to prevent rethrombosis of treated
arteries
Intended for use with aspirin and heparin
Essential thrombocythemia, to reduce the elevated
platelet count, the risk of thrombosis, and associated symptoms
IV bolus dose of 1 mg/kg followed by 4 h infusion at
rate of 2.5 mg/kg/min
Abdominal surgery, SC 2500 IU 1–2 h before surgery
and then once daily for 5–10 days after surgery
Hip replacement surgery, SC 2500 IU 1–2 h before
surgery and the evening of surgery (at least 6 h after
first dose) and then 5000 IU once daily for 5 days
SC 750 IU twice daily, with first dose 1–24 h before
surgery, then daily for 7–14 days after surgery
DVT prophylaxis in clients having hip or knee replacement surgery, SC 30 mg twice daily, with first dose
within 12–24 h after surgery and continued for
7–10 days
Abdominal surgery, SC 40 mg once daily with first dose
given 2 h before surgery, for 7–10 days
DVT/pulmonary embolism management, outpatients,
SC 1 mg/kg q12h; inpatients, 1 mg/kg q12h or
1.5 mg/kg q24h
Unstable angina 1 mg/kg q12h in conjunction with oral
aspirin (100–325 mg once daily)
SC 2.5 mg daily, with first dose 6–8 h after surgery and
continuing for a maximum of 11 days
IV injection, 0.4 mg/kg over 15–20 sec, followed by
continuous IV infusion of 0.15 mg/kg for 2–10 days
or longer if needed
SC 175 anti-Xa IU/kg daily for at least 6 days and until
adequately anticoagulated with warfarin
PO 2–5 mg/d for 2–3 days, then adjusted according to
the international normalized ratio (INR); average
maintenance daily dose, 2–5 mg
PO 81–325 mg daily
IV bolus injection, 0.25 mg/kg 10–60 min before starting PTCA, then a continuous IV infusion of 10 mcg/min
for 12 h
PO 0.5 mg 4 times daily or 1 mg twice daily initially,
then titrate to lowest dose effective in maintaining
platelet count <600,000/mm3
CHAPTER 57 DRUGS THAT AFFECT BLOOD COAGULATION
837
Drugs at a Glance: Anticoagulant, Antiplatelet, and Thrombolytic Agents (continued)
Generic/Trade Name
Indications for Use
Routes and Dosage Ranges
Cilostazol (Pletal)
Intermittent claudication, to increase walking distance (before leg pain occurs)
Clopidogrel (Plavix)
Reduction of atherosclerotic events (myocardial infarction, stroke, vascular death) in clients with
atherosclerosis documented by recent stroke,
recent myocardial infarction, or established
peripheral artery disease
Prevention of thromboembolism after cardiac valve
replacement, given with warfarin
Same as above
PO 100 mg twice daily, 30 min before or 2 h after
breakfast and dinner; reduce to 50 mg twice daily
with concurrent use of fluconazole, itraconazole,
erythromycin, or diltiazem
PO 75 mg once daily with or without food
Dipyridamole (Persantine)
Dipyridamole and Aspirin
(Aggrenox)
Eptifibatide (Integrilin)
Ticlopidine (Ticlid)
Tirofiban (Aggrastat)
Treprostinil (Remodulin)
Thrombolytic Agents
Alteplase (Activase)
Drotrecogin alfa, activated
(Xigris)
Reteplase, recombinant
(Retavase)
Streptokinase (Streptase)
Tenecteplase (TNKase)
Urokinase (Abbokinase)
Acute coronary syndromes, including clients who
are to be managed medically and those undergoing PTCA
Prevention of thrombosis in clients with coronary
artery or cerebral vascular disease (eg, clients
who have had stroke precursors or a completed
thrombotic stroke)
Acute coronary syndromes, with heparin, for clients
who are to be managed medically or those undergoing PTCA
Acute myocardial infarction
Pulmonary embolism
Pulmonary arterial hypertension
PO 25–75 mg 3 times per day, 1 h before meals
PO 1 capsule (200 mg extended-release dipyridamole/25 mg aspirin) twice daily
IV bolus injection, 180 mcg/kg, followed by continuous
infusion of 2 mcg/kg/min. See manufacturer’s
instructions for preparation and administration.
PO 250 mg twice daily with food
IV infusion, 0.4 mcg/kg/min for 30 min, then
0.1 mcg/kg/min. Patients with severe renal impairment
(creatinine clearance <30 mL/min) should receive
half the usual rate of infusion. See manufacturer’s
instructions for preparation and administration.
Continuous infusion by SC catheter and infusion pump
at initial dose of 1.25 mg/kg/min, increasing by no
more than 1.25 mg/kg/min per week for first 4 wks,
and then by no more than 2.5 mg/kg/min per week
for remaining duration of infusion
Acute ischemic stroke
Acute myocardial infarction
Pulmonary emboli
Reduction of mortality in severe sepsis
IV infusion, 100 mg over 3 h (first hour, 60 mg with a
bolus of 6–10 mg over 1–2 min initially; second hour,
20 mg; third hour, 20 mg)
IV infusion of 24 mcg/kg/h for 96 h
Acute myocardial infarction
IV injection, 10 units over 2 min, repeated in 30 min.
Inject into a flowing IV infusion line that contains no
other medications.
IV 250,000 units over 30 min, then 100,000 units/h
for 24–72 h
Management of acute, severe pulmonary emboli or
iliofemoral thrombophlebitis
Used to dissolve clots in arterial or venous cannulas or catheters
May be injected into a coronary artery to dissolve a
thrombus if done within 6 h of onset of symptoms
Acute myocardial infarction
Coronary artery thrombi
Pulmonary emboli
Clearance of clogged IV catheters
IV bolus dose based on weight, 30 mg (for <60 kg) not
to exceed 50 mg (>90 kg)
IV 4400 units/kg over 10 min, followed by continuous
infusion of 4400 units/kg/h for 12 h
For clearing IV catheters, see manufacturer’s instructions
aPTT, activated partial thromboplastin time; DIC, disseminated intravascular coagulation; DVT, deep vein thrombosis; PE, pulmonary embolism; PTCA, percutaneous
transluminal coronary angioplasty or atherectomy.
fibrin, and inhibiting factor XIII (the fibrin-stabilizing factor).
Other effects include inhibiting factors V and VIII and platelet
aggregation.
Heparin acts immediately after intravenous (IV) injection
and within 20 to 30 minutes after subcutaneous injection. It
is metabolized in the liver and excreted in the urine, primarily as inactive metabolites. Heparin does not cross the pla-
cental barrier and is not secreted in breast milk, making it the
anticoagulant of choice for use during pregnancy and lactation. Disadvantages of heparin are its short duration of action
and the subsequent need for frequent administration, the necessity for parenteral injection (because it is not absorbed
from the gastrointestinal [GI] tract), and local tissue reactions
at injection sites.
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SECTION 9 DRUGS AFFECTING THE CARDIOVASCULAR SYSTEM
Prophylactically, low doses of heparin are given to prevent
DVT and pulmonary embolism in clients at risk for development of these disorders, such as the following:
1. Those with major illnesses (eg, acute myocardial infarction, heart failure, serious pulmonary infections, stroke)
2. Those having major abdominal or thoracic surgery
3. Those with a history of thrombophlebitis or pulmonary
embolism, including pregnant women
4. Those having gynecologic surgery, especially if they
have been taking estrogens or oral contraceptives or
have other risk factors for DVT
5. Those expected to be on bed rest or to have limited
activity for longer than 5 days
Low-dose heparin prophylaxis is either ineffective or
contraindicated in major orthopedic surgery, abdominal
prostatectomy, and brain surgery.
Therapeutically, heparin is used for management of acute
thromboembolic disorders (eg, DVT, thrombophlebitis, pulmonary embolism). In these conditions, the aim of therapy
is to prevent further thrombus formation and embolization.
Heparin is also used in disseminated intravascular coagulation (DIC), a life-threatening condition characterized by widespread clotting, which depletes the blood of coagulation
factors. The depletion of coagulation factors then produces
widespread bleeding. The goal of heparin therapy in DIC is
to prevent blood coagulation long enough for clotting factors
to be replenished and thus be able to control hemorrhage.
Heparin is also used to prevent clotting during cardiac and
vascular surgery, extracorporeal circulation, hemodialysis,
blood transfusions, and in blood samples to be used in laboratory tests.
Contraindications include GI ulcerations (eg, peptic ulcer
disease, ulcerative colitis), blood dyscrasias, severe kidney or
liver disease, severe hypertension, polycythemia vera, and recent surgery of the eye, spinal cord, or brain. It should be used
with caution in clients with hypertension, renal or hepatic disease, alcoholism, history of GI ulcerations, drainage tubes
(eg, nasogastric tubes, indwelling urinary catheters), and any
occupation with high risks of traumatic injury.
Low–Molecular-Weight Heparins
Standard heparin is a mixture of high–and low–molecularweight fractions, but most anticoagulant activity is attributed
to the low–molecular-weight portion. Low–molecularweight heparins (LMWHs) contain the low–molecularweight fraction and are as effective as IV heparin in treating
thrombotic disorders. Indications for use include prevention
or management of thromboembolic complications associated with surgery or ischemic complications of unstable
angina and myocardial infarction. Currently available LMWHs
(dalteparin, enoxaparin, tinzaparin) differ from standard
heparin and each other; they cannot be used interchangeably
(ie, unit for unit).
LMWHs are given subcutaneously and do not require
close monitoring of blood coagulation tests. These characteristics allow outpatient anticoagulant therapy, an increasing
trend. The drugs are also associated with less thrombocy-
Nursing Notes: Apply Your Knowledge
You are caring for a patient who is in traction. He is receiving
5000 units of subcutaneous heparin bid. Discuss the reason why
this patient is receiving heparin and how you will safely administer the medication.
topenia than standard heparin. However, platelet counts should
be monitored during therapy.
Warfarin
Warfarin is the most commonly used oral anticoagulant. It
acts in the liver to prevent synthesis of vitamin K–dependent
clotting factors (ie, factors II, VII, IX, and X). Warfarin is
similar to vitamin K in structure and therefore acts as a competitive antagonist to hepatic use of vitamin K. Anticoagulant
effects do not occur for 3 to 5 days after warfarin is started
because clotting factors already in the blood follow their normal pathway of elimination. Warfarin has no effect on circulating clotting factors or on platelet function.
Warfarin is well absorbed after oral administration. It is
highly bound to plasma proteins (98%), mainly albumin. It is
metabolized in the liver and primarily excreted as inactive
metabolites by the kidneys.
Warfarin is most useful in long-term prevention or management of venous thromboembolic disorders, including DVT,
pulmonary embolism, and embolization associated with atrial
fibrillation and prosthetic heart valves. In addition, warfarin
therapy after myocardial infarction may decrease reinfarction,
stroke, venous thromboembolism, and death. Smaller doses
are being used now than formerly, with similar antithrombotic effects and decreased risks of bleeding.
Like heparin, warfarin is contraindicated in clients with GI
ulcerations, blood disorders associated with bleeding, severe
kidney or liver disease, severe hypertension, and recent surgery
of the eye, spinal cord, or brain. It should be used cautiously
with mild hypertension, renal or hepatic disease, alcoholism,
history of GI ulcerations, drainage tubes (eg, nasogastric tubes,
indwelling urinary catheters), and occupations with high risks
of traumatic injury. In addition, warfarin is contraindicated
during pregnancy.
Other Anticoagulant Drugs
Danaparoid, a heparinoid, is a low–molecular weight,
heparin-like drug derived from porcine mucosa. It has antithrombotic effects and is given subcutaneously to prevent
postoperative thromboembolism in clients having hip replacement surgery, in the management of ischemic stroke,
and as an alternative anticoagulant in clients who cannot tolerate heparin. Although related to heparin and LMWHs, it
does not contain heparin and cannot be used interchangeably
with standard heparin or LMWHs.
CHAPTER 57 DRUGS THAT AFFECT BLOOD COAGULATION
Fondaparinux produces anticoagulant effects by directly
binding to circulating and clot-bound factor Xa, accelerating
the activity of antithrombin and inhibiting thrombin production. It is used in the prevention of DVT in clients having
surgery for hip fracture or joint replacement surgery of the
knee or hip.
Lepirudin, bivalirudin, and argatroban are direct thrombin inhibitors that prevent blood coagulation by inactivating
thrombin. They are used as a heparin substitute for clients who
need anticoagulation but have thrombocytopenia with heparin.
Antiplatelet Drugs
Antiplatelet drugs prevent one or more steps in the prothrombotic activity of platelets. As described previously,
platelet activity is very important in both physiologic hemostasis and pathologic thrombosis. Arterial thrombi, which
are composed primarily of platelets, may form on top of atherosclerotic plaque and block blood flow in the artery. They
may also form on heart walls and valves and embolize to
other parts of the body.
Drugs used clinically for antiplatelet effects act by a variety
of mechanisms to inhibit platelet activation, adhesion, aggregation, or procoagulant activity. These include drugs that block
platelet receptors for thromboxane A2, adenosine diphosphate
(ADP), glycoprotein (GP) IIb/IIIa, and phosphodiesterase.
Thromboxane A2 Inhibitors
Aspirin is a commonly used analgesic–antipyretic–antiinflammatory drug (see Chap. 7) with potent antiplatelet
effects. Aspirin exerts pharmacologic actions by inhibiting
synthesis of prostaglandins. In this instance, aspirin acetylates
cyclooxygenase, the enzyme in platelets that normally synthesizes thromboxane A2, a prostaglandin product that causes
platelet aggregation. Thus, aspirin prevents formation of
thromboxane A2 and thromboxane A2–induced platelet aggregation and thrombus formation. A single dose of 300 to 600 mg
or multiple doses of 30 mg (eg, daily for several days) inhibit
the cyclooxygenase in circulating platelets almost completely.
These antithrombotic effects persist for the life of the platelet
(7 to 10 days). Aspirin may be used long term for prevention
of myocardial infarction or stroke, and in clients with prosthetic heart valves. It is also used for the immediate treatment
of suspected or actual acute myocardial infarction, for transient
ischemic attacks (TIAs), or evolving thrombotic strokes. Adverse effects are uncommon with the small doses used for
antiplatelet effects. However, there is an increased risk of
bleeding, including hemorrhagic stroke. Because approximately 85% of strokes are thrombotic, the benefits of aspirin
or other antiplatelet agents are thought to outweigh the risks of
hemorrhagic strokes (approximately 15%).
Nonsteroidal anti-inflammatory drugs (NSAIDs), including ibuprofen and many other aspirin-related drugs, inhibit
cyclooxygenase reversibly. Their antiplatelet effects subside
when the drugs are eliminated from the circulation and the
839
drugs usually are not used for antiplatelet effects. However,
clients who take an NSAID daily (eg, for arthritis pain) may
not need to take additional aspirin for antiplatelet effects.
Acetaminophen does not affect platelets in usual doses.
Adenosine Diphosphate Receptor Antagonists
Ticlopidine inhibits platelet aggregation by preventing ADPinduced binding between platelets and fibrinogen. This reaction inhibits platelet aggregation irreversibly, and effects
persist for the lifespan of the platelet. The drug is indicated
for prevention of thrombotic stroke in people who have had
stroke precursor events (eg, TIAs) or a completed thrombotic
stroke. Ticlopidine is considered a second-line drug for
clients who cannot take aspirin. The adverse effects (eg, neutropenia, diarrhea, skin rashes) and greater cost make it prohibitive for use by many clients. Contraindications include
active bleeding disorders (eg, GI bleeding from peptic ulcer
or intracranial bleeding), neutropenia, thrombocytopenia, severe liver disease, and hypersensitivity to the drug.
Ticlopidine is rapidly absorbed after oral administration and
reaches peak plasma levels about 2 hours after a dose. It is
highly protein bound (98%), extensively metabolized in the
liver, and excreted in urine and feces. As with other antiplatelet
drugs, there is increased risk of bleeding with ticlopidine.
Clopidogrel is chemically related to ticlopidine and causes
similar effects. It is indicated for reduction of myocardial infarction, stroke, and vascular death in clients with atherosclerosis and reportedly causes fewer or less severe adverse
effects than ticlopidine.
Glycoprotein IIb/IIIa Receptor Antagonists
Abciximab is a monoclonal antibody that prevents the binding of fibrinogen, von Willebrand factor, and other molecules
to GP IIb/IIIa receptors on activated platelets. This action inhibits platelet aggregation.
Abciximab is used with percutaneous transluminal coronary angioplasty or removal of atherosclerotic plaque to prevent rethrombosis of treated arteries. It is used with aspirin
and heparin and is contraindicated in clients who have recently received an oral anticoagulant or IV Dextran. Other
contraindications include active bleeding, thrombocytopenia,
history of a serious stroke, surgery or major trauma within the
previous 6 weeks, uncontrolled hypertension, or hypersensitivity to drug components.
Eptifibatide and tirofiban inhibit platelet aggregation by
preventing activation of GP IIb/IIIa receptors on the platelet
surface and the subsequent binding of fibrinogen and von
Willebrand factor to platelets. Antiplatelet effects occur during drug infusion and stop when the drug is stopped. The
drugs are indicated for acute coronary syndrome (eg, unstable angina, myocardial infarction) in clients who are to be
managed medically or by angioplasty or atherectomy.
Drug half-life is approximately 2.5 hours for eptifibatide
and 2 hours for tirofiban; the drugs are cleared mainly by
renal excretion. With tirofiban, plasma clearance is approxi-
840
SECTION 9 DRUGS AFFECTING THE CARDIOVASCULAR SYSTEM
mately 25% lower in older adults and approximately 50%
lower in clients with severe renal impairment (creatinine
clearance <30 mL/minute).
The drugs are contraindicated in clients with hypersensitivity to any component of the products; current or previous bleeding (within the previous 30 days); a history of
thrombocytopenia after previous exposure to tirofiban; a
history of stroke within 30 days or any history of hemorrhagic stroke; major surgery or severe physical trauma
within the previous month; severe hypertension (systolic
blood pressure >180 mm Hg with tirofiban or >200 mm Hg
with eptifibatide, or diastolic blood pressure >110 mm Hg
with either drug); a history of intracranial hemorrhage, neoplasm, arteriovenous malformation, or aneurysm; a platelet
count less than 100,000 mm3; serum creatinine 2 mg/dL or
above (for the 180 mcg/kg bolus and the 2 mcg/kg/min infusion) or 4 mg/dL or above (for the 135 mcg/kg bolus and
the 0.5 mcg/kg/min infusion); or dependency on dialysis
(eptifibatide).
Bleeding is the most common adverse effect, with most
major bleeding occurring at the arterial access site for cardiac catheterization. If bleeding occurs and cannot be controlled with pressure, the drug infusion and heparin should
be discontinued.
These drugs should be used cautiously if given with other
drugs that affect hemostasis (eg, warfarin, thrombolytics,
other antiplatelet drugs).
Phosphodiesterase Inhibitor
Cilostazol inhibits phosphodiesterase, an enzyme that metabolizes cyclic adenosine monophosphate (cAMP). The inhibition increases intracellular cAMP, which then inhibits
platelet aggregation and produces vasodilation. The drug reversibly inhibits platelet aggregation induced by various
stimuli (eg, thrombin, ADP, collagen, arachidonic acid, epinephrine, and shear stress). It is indicated for management of
intermittent claudication. Symptoms usually improve within
2 to 4 weeks, but may take as long as 12 weeks. The drug is
contraindicated in clients with heart failure.
Cilostazol is highly protein bound (95% to 98%), mainly
to albumin, extensively metabolized by hepatic cytochrome
P450 enzymes, and excreted in urine (74%) and feces. The
drug and two active metabolites accumulate with chronic administration and reach steady state within a few days. The
most common adverse effects are diarrhea and headache.
Miscellaneous Agents
Anagrelide inhibits platelet aggregation induced by cAMP
phosphodiesterase, ADP, and collagen. However, it is indicated only to reduce platelet counts for clients with essential
thrombocythemia (a disorder characterized by excessive
numbers of platelets). Doses to reduce platelet production are
smaller than those required to inhibit platelet aggregation.
Dipyridamole inhibits platelet adhesion, but its mechanism of action is unclear. It is used for prevention of throm-
boembolism after cardiac valve replacement and is given
with warfarin.
Thrombolytic Agents
Thrombolytic agents are given to dissolve thrombi. They
stimulate conversion of plasminogen to plasmin (also called
fibrinolysin), a proteolytic enzyme that breaks down fibrin,
the framework of a thrombus. The main use of thrombolytic
agents is for management of acute, severe thromboembolic
disease, such as myocardial infarction, pulmonary embolism,
and iliofemoral thrombosis.
The goal of thrombolytic therapy is to re-establish blood
flow and prevent or limit tissue damage. Heparin and warfarin
are given after completion of thrombolytic therapy. Thrombolytic drugs are also used to dissolve clots in arterial or
venous cannulas or catheters.
Alteplase, reteplase, and tenecteplase are tissue plasminogen activators used mainly in acute myocardial infarction
to dissolve clots obstructing coronary arteries and re-establish
perfusion of tissues beyond the thrombotic area. The drugs
bind to fibrin in a clot and act locally to dissolve the clot. The
most common adverse effect is bleeding, which may be internal (eg, intracranial, GI, genitourinary) or external (eg, venous
or arterial puncture sites, surgical incisions). The drugs are
contraindicated in the presence of bleeding, a history of stroke,
central nervous system surgery or trauma within the previous
2 months, and severe hypertension.
Streptokinase and urokinase are enzymes that break down
fibrin. They are used mainly to lyse coronary artery clots in
acute myocardial infarction. Streptokinase may also be used to
dissolve clots in vascular catheters and to treat acute, severe,
pulmonary emboli or iliofemoral thrombophlebitis. Urokinase
is recommended for use in clients allergic to streptokinase. As
with other anticoagulants and thrombolytic agents, bleeding is
the main adverse effect.
Drotrecogin alfa (Xigris) is a recombinant version of
human activated protein C that is approved for use in severe
sepsis or septic shock. Severe sepsis is characterized by an
excessive inflammatory reaction to infection, inappropriate
blood clot formation, and impaired breakdown of clots.
Drotrecogin alfa is given for its thrombolytic effects, along
with other therapies for inflammation and infection. The
major adverse effect is bleeding.
Drugs Used to Control Bleeding
Anticoagulant, antiplatelet, and thrombolytic drugs profoundly affect hemostasis, and their major adverse effect is
bleeding. As a result, systemic hemostatic agents (antidotes)
may be needed to prevent or treat bleeding episodes. Antidotes should be used cautiously because overuse can increase
risks of recurrent thrombotic disorders. The drugs are described in this section and in Drugs at a Glance: Systemic Hemostatic Drugs.
CHAPTER 57 DRUGS THAT AFFECT BLOOD COAGULATION
841
Drugs at a Glance: Systemic Hemostatic Drugs
Generic/Trade Name
Indications for Use
Dosage
Aminocaproic acid
(Amicar)
Control bleeding caused by overdoses of thrombolytic agents or bleeding disorders caused by
hyperfibrinolysis (eg, cardiac surgery, blood disorders, hepatic cirrhosis, prostatectomy, neoplastic disorders)
Used in selected clients undergoing coronary artery
bypass graft surgery to decrease blood loss and
blood transfusions
Treatment of heparin overdosage
PO, IV infusion, 5 g initially, followed by 1.0 to 1.25 g/h
for 8 h or until bleeding is controlled; maximum dose,
30 g/24 h
Aprotinin (Trasylol)
Protamine sulfate
Tranexamic acid
(Cyklokapron)
Vitamin K (Mephyton)
Control bleeding caused by overdoses of thrombolytic agents
Prevent or decrease bleeding from tooth extraction
in clients with hemophilia
Antidote for warfarin overdosage
Aminocaproic acid and tranexamic acid are used to
stop bleeding caused by overdoses of thrombolytic agents.
Aminocaproic acid also may be used in other bleeding disorders caused by hyperfibrinolysis (eg, cardiac surgery,
blood disorders, hepatic cirrhosis, prostatectomy, neoplastic disorders). Tranexamic acid also is used for short periods (2 to 8 days) in clients with hemophilia to prevent or
decrease bleeding from tooth extraction. Dosage of tranexamic acid should be reduced in the presence of moderate or
severe renal impairment.
Aprotinin is a natural protease inhibitor obtained from
bovine lung that has a variety of effects on blood coagulation.
It inhibits plasmin and kallikrein, thus inhibiting fibrinolysis,
and inhibits breakdown of blood clotting factors. It is used to
decrease bleeding in selected clients undergoing coronary
artery bypass surgery.
Protamine sulfate is an antidote for standard heparin and
LMWHs. Because heparin is an acid and protamine sulfate is
a base, protamine neutralizes heparin activity. Protamine
dosage depends on the amount of heparin administered during the previous 4 hours. Each milligram of protamine neutralizes approximately 100 units of heparin or dalteparin and
1 mg of enoxaparin. A single dose should not exceed 50 mg.
The drug is given by slow IV infusion over at least 10 minutes (to prevent or minimize adverse effects of hypotension,
bradycardia, and dyspnea). Protamine effects occur immediately and last for approximately 2 hours. A second dose may be
required because heparin activity lasts approximately 4 hours.
Protamine sulfate can cause severe hypotensive and anaphylactoid reactions. Thus, it should be given in settings with
equipment and personnel for resuscitation and management
of anaphylactic shock.
Vitamin K is the antidote for warfarin overdosage. An
oral dose of 10 to 20 mg usually stops minor bleeding and returns the international normalized ratio (INR) (see section on
Regulation of Heparin and Warfarin Dosage, later) to a normal range within 24 hours.
See manufacturer’s literature
Depends on the amount of heparin given within the
previous 4 h
PO 25 mg/kg 3 to 4 times daily, starting 1 d before
surgery, or IV 10 mg/kg immediately before surgery,
followed by 25 mg/kg PO 3 to 4 times daily for 2–8 d
PO 10–20 mg in a single dose
Herbal and Dietary Supplements
Many commonly used herbs and supplements have a profound effect on drugs used for anticoagulation. Multivitamin
supplements may contain 25 to 28 mcg of vitamin K and
should be taken consistently to avoid fluctuating vitamin K
levels. Doses of vitamin C in excess of 500 mg/d may lower
INR and vitamin E in excess of 400 IU/d may increase warfarin effects. Herbs commonly used that may increase the
effects of warfarin include alfalfa, celery, clove, feverfew,
garlic, ginger, ginkgo, ginseng, and licorice. Clients taking
warfarin should be questioned carefully about their use of
herbs as well as vitamin or mineral supplements.
Nursing Process
Assessment
Assess the client’s status in relation to thrombotic and
thromboembolic disorders.
• Risk factors for thromboembolism include:
• Immobility (eg, limited activity or bed rest for more
than 5 days)
• Obesity
• Cigarette smoking
• History of thrombophlebitis, deep vein thrombosis
(DVT), or pulmonary emboli
• Congestive heart failure
• Pedal edema
• Lower limb trauma
• Myocardial infarction
• Atrial fibrillation
• Mitral or aortic stenosis
• Prosthetic heart valves
• Abdominal, thoracic, pelvic, or major orthopedic
surgery
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SECTION 9 DRUGS AFFECTING THE CARDIOVASCULAR SYSTEM
• Atherosclerotic heart disease or peripheral vascular
disease
• Use of oral contraceptives
• Signs and symptoms of thrombotic and thromboembolic
disorders depend on the location and size of the thrombus.
• DVT and thrombophlebitis usually occur in the legs.
The conditions may be manifested by edema (the affected leg is often measurably larger than the other) and
pain, especially in the calf when the foot is dorsiflexed
(Homans’ sign). If thrombophlebitis is superficial, it
may be visible as a red, warm, tender area following the
path of a vein.
• Pulmonary embolism, if severe enough to produce
symptoms, is manifested by chest pain, cough, hemoptysis, tachypnea, and tachycardia. Massive emboli
cause hypotension, shock, cyanosis, and death.
• Disseminated intravascular coagulation (DIC) is usually manifested by bleeding, which may range from petechiae or oozing from a venipuncture site to massive
internal bleeding or bleeding from all body orifices.
Nursing Diagnoses
• Ineffective Tissue Perfusion related to thrombus or embolus or drug-induced bleeding
• Acute Pain related to tissue ischemia
• Impaired Physical Mobility related to bed rest and pain
• Ineffective Coping related to the need for long-term prophylaxis of thromboembolic disorders or fear of excessive bleeding
• Anxiety related to fear of myocardial infarction or stroke
• Deficient Knowledge related to anticoagulant or antiplatelet drug therapy
• Risk for Injury related to drug-induced impairment of
blood coagulation
Planning/Goals
The client will:
• Receive or take anticoagulant and antiplatelet drugs
correctly
• Be monitored closely for therapeutic and adverse drug effects, especially when drug therapy is started and when
changes are made in drugs or dosages
• Use nondrug measures to decrease venous stasis and prevent thromboembolic disorders
• Act to prevent trauma from falls and other injuries
• Inform any health care provider when taking an anticoagulant or antiplatelet drug
• Avoid or report adverse drug reactions
• Verbalize or demonstrate knowledge of safe management
of anticoagulant drug therapy
• Keep follow-up appointments for tests of blood coagulation and drug dosage regulation
• Avoid preventable bleeding episodes
Interventions
Use measures to prevent thrombotic and thromboembolic
disorders.
• Have the client ambulate and exercise legs regularly,
especially after surgery.
• For clients who cannot ambulate or do leg exercises, do
passive range-of-motion and other leg exercises several
times daily when changing the client’s position or performing other care.
• Have the client wear elastic stockings. Elastic stockings
should be removed every 8 hours and replaced after inspecting the skin. Improperly applied elastic stockings
can impair circulation rather than aid it. For clients on bed
rest, intermittent pneumatic compression devices can also
be used.
• Avoid trauma to lower extremities.
• Maintain adequate fluid intake (1500–3000 mL/day) to
avoid dehydration and hemoconcentration.
• Assist clients to promote good blood circulation (eg, exercise) and avoid situations that impair circulation (eg,
wearing tight clothing, crossing the legs at the knees, prolonged sitting or standing, bed rest, and placing pillows
under the knees when in bed).
For the client receiving anticoagulant therapy, implement safety measures to prevent trauma and bleeding.
• For clients who cannot ambulate safely because of
weakness, sedation, or other conditions, keep the call
light within reach, keep bedrails elevated, and assist in
ambulation.
• Provide an electric razor for shaving.
• Avoid intramuscular injections, venipunctures, and arterial punctures when possible.
• Avoid intubations when possible (eg, nasogastric tubes,
indwelling urinary catheters).
For the client receiving tirofiban or eptifibatide:
• Monitor the femoral artery access site closely. This is the
most common site of bleeding.
• Avoid invasive procedures as much as possible (eg, arterial and venous punctures, intramuscular injections, urinary catheters, nasotracheal suction, nasogastric tubes).
If venipuncture must be done, avoid sites where pressure
cannot be applied (eg, subclavian or jugular veins).
• While the vascular sheath is in place, keep clients on complete bed rest with the head of the bed elevated 30 degrees
and the affected limb restrained in a straight position.
• Discontinue heparin for 3 to 4 hours and be sure the activated clotting time is less than 180 seconds or the activated
partial thromboplastin time (aPTT) is below 45 seconds
before removing the vascular sheath.
• After the vascular sheath is removed, apply pressure to the
site and observe closely. For outpatients, be sure there is
no bleeding for at least 4 hours before hospital discharge.
For the client receiving a thrombolytic drug or a revascularization procedure for acute myocardial infarction:
• Monitor closely for bleeding.
• Assist the client and family to understand the importance
of diligent efforts to reverse risk factors contributing to
coronary artery disease (eg, diet and perhaps medication
CHAPTER 57 DRUGS THAT AFFECT BLOOD COAGULATION
to lower serum cholesterol to below 200 mg/dL and lowdensity lipoprotein cholesterol to below 130 mg/dL,
weight reduction if overweight, control of blood pressure
if hypertensive, avoidance of smoking, stress reduction
techniques, exercise program designed and supervised by
a health care provider).
• Assist the client and family to understand the importance
of complying with medication orders to prevent reinfarction and other complications, and continued medical supervision.
Evaluation
• Observe for signs and symptoms of thromboembolic disorders or bleeding.
• Check blood coagulation tests for therapeutic ranges.
• Observe and interview regarding compliance with instructions about drug therapy.
• Observe and interview regarding adverse drug effects.
PRINCIPLES OF THERAPY
Drug Selection
Choices of anticoagulant and antiplatelet drugs depend on the
reason for use and other drug and client characteristics.
1. Heparin is the anticoagulant of choice in acute venous
thromboembolic disorders because the anticoagulant
effect begins immediately with IV administration.
2. Warfarin is the anticoagulant of choice for long-term
maintenance therapy (ie, several weeks or months)
because it can be given orally.
3. Aspirin has long been the most widely used antiplatelet
drug for prevention of myocardial reinfarction and arterial thrombosis in clients with TIAs and prosthetic heart
valves. However, clopidogrel may be more effective
than aspirin.
4. When anticoagulation is required during pregnancy,
heparin is used because it does not cross the placenta.
Warfarin is contraindicated during pregnancy.
5. Various combinations of antithrombotic drugs are used
concomitantly or sequentially (eg, abciximab is used
with aspirin and heparin; thrombolytic drugs are usually followed with heparin and warfarin).
Regulation of Heparin
and Warfarin Dosage
Heparin dosage is regulated by the activated partial thromboplastin time (aPTT), which is sensitive to changes in blood
clotting factors, except factor VII. Thus, normal or control
values indicate normal blood coagulation; therapeutic values
indicate low levels of clotting factors and delayed blood coagulation. During heparin therapy, the aPTT should be maintained at approximately 1.5 to 2.5 times the control or
843
baseline value. The normal control value is 25 to 35 seconds;
therefore, therapeutic values are 45 to 70 seconds, approximately. With continuous IV infusion, blood for the aPTT may
be drawn at any time; with intermittent administration, blood
for the aPTT should be drawn approximately 1 hour before a
dose of heparin is scheduled. Monitoring of aPTT is not necessary with low-dose standard heparin given subcutaneously
for prophylaxis of thromboembolism or with the LMWHs
(eg, enoxaparin).
Warfarin dosage is regulated according to the INR, for
which therapeutic values are 2.0 to 3.0 in most conditions. An
average daily dose of 4 to 5 mg maintains a therapeutic INR;
stopping warfarin returns an elevated INR to normal in
approximately 4 days in most clients.
The INR is based on prothrombin time (PT). PT is sensitive
to changes in three of the four vitamin K–dependent coagulation factors. Thus, normal or control values indicate normal
levels of these factors; therapeutic values indicate low levels of
the factors and delayed blood coagulation. A normal baseline
or control PT is approximately 12 seconds; a therapeutic value
is approximately 1.5 times the control, or 18 seconds.
When warfarin is started, PT and INR should be assessed
daily until a stable daily dose is reached (the dose that maintains PT and INR within therapeutic ranges and does not cause
bleeding). Thereafter, PT and INR are determined every 2 to
4 weeks for the duration of oral anticoagulant drug therapy. If
the warfarin dose is changed, PT and INR are needed more
often until a stable daily dose is again established.
For many years, the PT was used to regulate warfarin
dosage. PT is determined by adding a mixture of thromboplastin and calcium to citrated plasma and measuring the time
(in seconds) it takes for the blood to clot. However, values vary
among laboratories according to the type of thromboplastin
and the instrument used to measure PT. The INR system standardizes the PT by comparing a particular thromboplastin with
a standard thromboplastin designated by the World Health
Organization. Advantages of the INR include consistent values among laboratories, more consistent warfarin dosage with
less risk of bleeding or thrombosis, and more consistent reports
of clinical trials and other research studies. Some laboratories
report both PT and INR.
Warfarin dosage may need to be reduced in clients with
biliary tract disorders (eg, obstructive jaundice), liver disease
(eg, hepatitis, cirrhosis), malabsorption syndromes (eg, steatorrhea), and hyperthyroidism or fever. These conditions increase anticoagulant drug effects by reducing absorption of
vitamin K, decreasing hepatic synthesis of blood clotting factors, or increasing the breakdown of clotting factors. Despite
these influencing factors, however, the primary determinant
of dosage is the PT and INR.
Warfarin interacts with many other drugs to cause increased,
decreased, or unpredictable anticoagulant effects (see Nursing
Actions). Thus, warfarin dosage may need to be increased or
decreased when other drugs are given concomitantly. Most
drugs can be given if warfarin dosage is titrated according to
the PT or INR and altered appropriately when an interacting
drug is added or stopped. INR or PT measurements and vigi-
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SECTION 9 DRUGS AFFECTING THE CARDIOVASCULAR SYSTEM
CLIENT TEACHING GUIDELINES
Drugs to Prevent or Treat Blood Clots
General Considerations
✔ Antiplatelet and anticoagulant drugs are given to people
who have had, or who are at risk of having, a heart attack,
stroke, or other problems from blood clots. For prevention of a heart attack or stroke, you are most likely to be
given an antiplatelet drug (eg, aspirin, clopidogrel) or warfarin (Coumadin). For home management of deep vein
thrombosis, which usually occurs in the legs, you are
likely to be given heparin injections for a few days, followed by warfarin for long-term therapy. These medications help to prevent the blood clot from getting larger,
traveling to your lungs, or recurring later.
✔ All of these drugs can increase your risk of bleeding, so
you need to take safety precautions to prevent injury.
✔ To help prevent blood clots from forming and decreasing
blood flow through your arteries, you need to reduce risk
factors that contribute to cardiovascular disease. This
can be done by a low-fat, low-cholesterol diet (and medication if needed) to lower total cholesterol to below
200 mg/dL and low-density lipoprotein cholesterol to
below 130 mg/dL; weight reduction if overweight; control
of blood pressure if hypertensive; avoidance of smoking;
stress reduction techniques; and regular exercise.
✔ To help prevent blood clots from forming in your leg veins,
avoid or minimize situations that slow blood circulation,
such as wearing tight clothing; crossing the legs at the
knees; prolonged sitting or standing; and bed rest. For example, on automobile trips, stop and walk around every
1 to 2 hours; on long plane trips, exercise your feet and
legs at your seat and walk around when you can.
✔ Following instructions regarding these medications is extremely important. Too little medication increases your
risk of problems from blood clot formation; too much
medication can cause bleeding.
✔ While taking any of these medications, you need regular
medical supervision and periodic blood tests. The blood
tests can help your health care provider regulate drug
dosage and maintain your safety.
✔ You need to take the drugs as directed; avoid taking
other drugs without the health care provider’s knowledge and consent; inform any health care provider (including dentists) that you are taking an antiplatelet or
anticoagulant drug before any invasive diagnostic tests
or treatments are begun; and keep all appointments for
continuing care.
How Can You Avoid This Medication Error?
Helen Innes is admitted to your medical unit for management of
bacterial pneumonia. She has been on oral antibiotics for 7 days
but her respiratory condition has not improved. In addition to her intravenous antibiotics, you administer her usual dose of Coumadin
that she takes for a history of pulmonary emboli. When you document the medications given, you notice that her international normalized ratio (INR) is 6.
✔ With warfarin therapy, you need to avoid walking barefoot;
avoid contact sports; use an electric razor; avoid injections when possible; and carry an identification card,
necklace, or bracelet (eg, MedicAlert) stating the name of
the drug and the health care provider’s name and telephone number. Also, avoid large amounts of certain
vegetables (eg, broccoli, brussels sprouts, cabbage,
cauliflower, chives, collard greens, kale, lettuce, mustard
greens, peppers, spinach, turnips, and watercress), tomatoes, bananas, or fish; these foods contain vitamin K and
may decrease anticoagulant effects.
✔ For home management of deep vein thrombosis, both
warfarin and enoxaparin (Lovenox) are given for 3 months
or longer. With Lovenox, you need an injection, usually
every 12 hours. You or someone close to you may be instructed in injecting the medication, or a visiting nurse
may do the injections, if necessary.
Even if a nurse is not needed to give the injections, one
will usually visit your home each day to perform a finger
stick blood test. The results of this test determine your
daily dose of warfarin. Once the blood test and the warfarin dose stabilize, the blood tests are done less often
(eg, every 2 weeks).
✔ Report any sign of bleeding (eg, excessive bruising of the
skin, blood in urine or stool). If superficial bleeding occurs, apply direct pressure to the site for 3 to 5 minutes
or longer if necessary.
Self-Administration
✔ Take aspirin with food or after meals, with 8 oz of water,
to decrease stomach irritation. However, stomach upset
is uncommon with the small doses used for antiplatelet
effects. Do not crush or chew coated tablets (long-acting
preparations).
✔ Take cilostazol (Pletal) 30 minutes before or 2 hours
after morning and evening meals for better absorption
and effectiveness.
✔ Take ticlopidine (Ticlid) with food or after meals to decrease GI upset. Clopidogrel (Plavix) may be taken with or
without food.
✔ With Lovenox, wash hands and cleanse skin to prevent infection; inject deep under the skin, around the navel, upper
thigh, or buttocks; and change the injection site daily. If excessive bruising occurs at the injection site, rubbing an ice
cube over an area before the injection may be helpful.
lant observation are needed whenever a drug is added to or
removed from a drug therapy regimen containing warfarin.
Thrombolytic Therapy
1. Thrombolytic therapy should be performed only by experienced personnel in an intensive care setting with
cardiac and other monitoring devices in place.
CHAPTER 57 DRUGS THAT AFFECT BLOOD COAGULATION
2. All of the available agents are effective with recommended uses. Thus, the choice of a thrombolytic agent
depends mainly on risks of adverse effects and costs.
All of the drugs may cause bleeding. Alteplase may act
more specifically on the fibrin in a clot and cause less
systemic depletion of fibrinogen, but this agent is very
expensive. Streptokinase, the least expensive agent,
may cause allergic reactions because it is a foreign protein. Combination therapy (eg, with alteplase and streptokinase) may also be used.
3. Before a thrombolytic agent is begun, INR, aPTT,
platelet count, and fibrinogen should be checked to establish baseline values and to determine if a blood coagulation disorder is present. Two or 3 hours after
thrombolytic therapy is started, the fibrinogen level can
be measured to determine that fibrinolysis is occurring.
Alternatively, INR or aPTT can be checked for increased values because the breakdown products of fibrin exert anticoagulant effects.
4. Major factors in decreasing risks of bleeding are selecting recipients carefully, avoiding invasive procedures
when possible, and omitting anticoagulant or antiplatelet
drugs while thrombolytics are being given. If bleeding
does occur, it is most likely from a venipuncture or invasive procedure site, and local pressure may control it.
If bleeding cannot be controlled or involves a vital
organ, the thrombolytic drug should be stopped and fibrinogen replaced with whole blood plasma or cryoprecipitate. Aminocaproic acid or tranexamic acid may also
be given.
5. When the drugs are used in acute myocardial infarction,
cardiac dysrhythmias may occur when blood flow is reestablished. Therefore, antidysrhythmic drugs should
be readily available.
Use in Children
Little information is available about the use of anticoagulants in children. Heparin solutions containing benzyl alcohol as a preservative should not be given to premature
infants because fatal reactions have been reported. When
given for systemic anticoagulation, heparin dosage should
be based on the child’s weight (approximately 50 units/kg).
Safety and effectiveness of LMWHs (eg, enoxaparin) have
not been established in children.
Warfarin is given to children after cardiac surgery to prevent thromboembolism, but doses and guidelines for safe,
effective use have not been developed. Accurate drug administration, close monitoring of blood coagulation tests,
safety measures to prevent trauma and bleeding, avoiding interacting drugs, and informing others in the child’s environment (eg, teachers, babysitters, health care providers) are
necessary.
Antiplatelet and thrombolytic drugs have no established
indications for use in children.
845
Use in Older Adults
Older adults often have atherosclerosis and thrombotic disorders, including myocardial infarction, thrombotic stroke,
and peripheral arterial insufficiency, for which they receive
an anticoagulant or an antiplatelet drug. They are more likely
than younger adults to experience bleeding and other complications of anticoagulant and antiplatelet drugs. For example, aspirin or clopidogrel is commonly used to prevent
thrombotic stroke, but both drugs increase risks of hemorrhagic stroke.
With standard heparin, general principles for safe and effective use apply. With LMWHs, elimination may be delayed
in older adults with renal impairment and the drugs should be
used cautiously. They should also be used with caution in
clients taking a platelet inhibitor (eg, aspirin, clopidogrel)
to prevent myocardial infarction or thrombotic stroke or an
NSAID for arthritis pain. NSAIDs, which are commonly
used by older adults, also have antiplatelet effects. Clients
who take an NSAID daily may not need low-dose aspirin for
antithrombotic effects.
With warfarin, dosage should be reduced because impaired liver function and decreased plasma proteins increase
the risks of bleeding. Also, many drugs interact with warfarin
to increase or decrease its effect, and older adults often take
multiple drugs. Starting or stopping any drug may require
that warfarin dosage be adjusted.
Use in Renal Impairment
Most anticoagulant, antiplatelet, and thrombolytic drugs may
be used in clients with impaired renal function. For example,
heparin and warfarin can be used in usual dosages, and
thrombolytic agents (eg, streptokinase and urokinase) may be
used to dissolve clots in IV catheters or vascular access sites
for hemodialysis. Dosage of LMWHs should be reduced in
clients with severe renal impairment (creatinine clearance
<30 mL/minute) because they are excreted by the kidneys
and elimination is slowed. In addition, home management of
DVT with LMWHs and warfarin is contraindicated in clients
with severe renal impairment. Guidelines for the use of other
drugs include the following:
• Anagrelide may be given to clients with renal impairment (eg, serum creatinine <2 mg/dL) if potential benefits outweigh risks. Clients receiving this medication
should be monitored closely for signs of renal toxicity.
• Cilostazol is probably safe to use in clients with mild or
moderate renal impairment. However, severe renal impairment alters drug protein binding and increases blood
levels of metabolites.
• Clopidogrel does not need dosage reduction in clients
with renal impairment.
• Danaparoid is excreted mainly by the kidneys and
dosage may need to be reduced in clients with severe
renal impairment. Monitor serum creatinine during
therapy.
846
SECTION 9 DRUGS AFFECTING THE CARDIOVASCULAR SYSTEM
• Eptifibatide does not need dosage reduction in clients
with mild to moderate renal impairment. No data are
available for clients with severe impairment or those on
hemodialysis.
• Lepirudin is excreted by the kidneys and may accumulate in clients with impaired renal function. Dosage
should be reduced.
• Ticlopidine may be more likely to cause bleeding in
clients with renal impairment because the plasma drug
concentration is increased and elimination is slower.
• Tirofiban clearance from plasma is decreased approximately 50% in clients with severe renal impairment
(eg, creatinine clearance <30 mL/minute), including
those receiving hemodialysis. Dosage must be reduced
by approximately 50%.
Use in Hepatic Impairment
Little information is available about the use of most anticoagulant, antiplatelet, and thrombolytic drugs in clients with impaired liver function. However, such drugs should be used very
cautiously because these clients may already be predisposed to
bleeding because of decreased hepatic synthesis of clotting factors. Additional considerations include the following:
• Warfarin is more likely to cause bleeding in clients with
liver disease, because of decreased synthesis of vitamin K.
In addition, warfarin is eliminated only by hepatic metabolism and may accumulate with liver impairment.
• Low–molecular-weight heparins are contraindicated for
home management of DVT in clients with severe liver
disease because of high risks of excessive bleeding.
• Anagrelide is metabolized in the liver and may accumulate with hepatic impairment. Clients with evidence
of impairment (eg, bilirubin or aspartate aminotransferase more than 1.5 times the upper limit of normal)
should receive anagrelide only if potential benefits
outweigh potential risks. When anagrelide is given,
clients should be closely monitored for signs of hepatotoxicity.
• Clopidogrel is metabolized in the liver and may accumulate with hepatic impairment. It should be used
cautiously.
• Dipyridamole is metabolized in the liver and excreted
in bile.
Home Care
Antiplatelet agents and warfarin are used for long-term prevention or management of thromboembolism and are often
taken at home. For prevention, antiplatelet agents and warfarin
are usually self-administered at home, with periodic office or
clinic visits for blood tests and other follow-up care.
For home management of DVT, warfarin may be selfadministered, but a nurse usually visits, performs a finger stick
INR, and notifies the prescriber, who then prescribes the appropriate dose of warfarin. Precautions are needed to decrease
risks of bleeding. The risk of bleeding has lessened in recent
years because of lower doses of warfarin. In addition, bleeding during warfarin therapy may be caused by medical conditions other than anticoagulation.
Heparin may also be taken at home. Standard heparin may
be taken subcutaneously, but LMWHs for home management
of venous thrombosis are becoming standard practice. Enoxaparin is approved by the Food and Drug Administration for
outpatient use. Daily visits by a home care nurse may be
needed if the client or a family member is unable or unwilling to inject the medication. Platelet counts should be done
before and every 2 to 3 days during heparin therapy. Heparin
should be discontinued if the platelet count falls below
100,000 or to less than half the baseline value.
Most home management regimens involve a structured
protocol. Clients and family members should be educated
about the disorder (usually DVT), including the potential
consequences of either overcoagulation or undercoagulation,
and the need for blood tests.
The home care nurse needs to assess clients in relation to
knowledge about prescribed drugs and ability and willingness
to comply with instructions for taking the drugs, obtaining
blood tests when indicated, and taking safety precautions. In
addition, assess the environment for risk factors for injury. Interventions vary with clients, environments, and assessment
data, but may include reinforcing instructions for safe use of
the drugs, assisting clients to obtain laboratory tests, and teaching how to observe for signs and symptoms of bleeding.
CHAPTER 57 DRUGS THAT AFFECT BLOOD COAGULATION
NURSING
ACTIONS
847
Drugs That Affect Blood Coagulation
NURSING ACTIONS
RATIONALE/EXPLANATION
1. Administer accurately
a. With standard heparin:
(1) When handwriting a heparin dose, write out “units”
rather than using the abbreviation “U.”
This is a safety precaution to avoid erroneous dosage. For example, 1000 U (1000 units) may be misread as 10,000 units.
(2) Check dosage and vial label carefully.
Underdosage may cause thromboembolism, and overdosage may
cause bleeding. In addition, heparin is available in several concentrations (1000, 2500, 5000, 10,000, 15,000, 20,000, and
40,000 units/mL).
(3) For SC heparin:
(a) Use a 26-gauge, 1⁄2-inch needle.
To minimize trauma and risk of bleeding
(b) Leave a small air bubble in the syringe to follow
dose
Locks drug into subcutaneous space and minimizes trauma
(c) Grasp a skinfold and inject the heparin into it, at a
90-degree angle, without aspirating.
To give the drug in a deep subcutaneous or fat layer, with minimal
trauma
(d) Do not massage site after injection
(4) For intermittent IV administration:
(a) Give by direct injection into a heparin lock or tubing injection site.
These methods prevent repeated venipunctures.
(b) Dilute the dose in 50 to 100 mL of any IV fluid
(usually 5% dextrose in water).
(5) For continuous IV administration:
This is usually the preferred method because it maintains consistent serum drug levels and decreases risks of bleeding.
(a) Use a volume-control device and an infusioncontrol device.
To regulate dosage and flow rate accurately
(b) Add only enough heparin for a few hours. One
effective method is to fill the volume-control set
(eg, Volutrol) with 100 mL of 5% dextrose in water
and add 5000 units of heparin to yield a concentration
of 50 units/mL. Dosage is regulated by varying the
flow rate. For example, administration of 1000 units/h
requires a flow rate of 20 mL/h.
Another method is to add 25,000 units of heparin
to 500 mL of IV solution.
To avoid inadvertent administration of large amounts. Whatever
method is used, it is desirable to standardize concentration of
heparin solutions within an institution. Standardization is safer,
because it reduces risks of errors in dosage.
b. With low–molecular-weight heparins:
(1) Give by deep SC injection, into an abdominal skin fold,
with the patient lying down, using the same technique as
standard heparin. Do not rub the injection site.
To decrease bruising
(2) Rotate sites.
c. After the initial dose of warfarin, check the international
normalized ratio (INR) before giving a subsequent dose. Do
not give the dose if the INR is above 3.0. Notify the health care
provider.
The INR is measured daily until a maintenance dose is established,
then periodically throughout warfarin therapy. An elevated INR
indicates a high risk of bleeding.
d. Give ticlopidine with food or after meals; give cilostazol
30 min before or 2 h after morning and evening meals; give
clopidogrel with or without food.
e. With eptifibatide, tirofiban, and thrombolytic agents,
follow manufacturers’ instructions for reconstitution and
administration.
These drugs require special preparation and administration techniques.
(continued )
848
SECTION 9 DRUGS AFFECTING THE CARDIOVASCULAR SYSTEM
NURSING ACTIONS
RATIONALE/EXPLANATION
2. Observe for therapeutic effects
a. With prophylactic heparins and warfarin, observe for the
absence of signs and symptoms of thrombotic disorders.
b. With therapeutic heparins and warfarin, observe for decrease or improvement in signs and symptoms (eg, less edema
and pain with deep vein thrombosis, less chest pain and respiratory difficulty with pulmonary embolism).
c. With prophylactic or therapeutic warfarin, observe for an
INR between 2.0 and 3.0.
Frequency of INR determinations varies, but the test should be
done periodically in all clients taking warfarin.
d. With therapeutic heparin, observe for an activated partial
thromboplastin time of 1.5 to 2 times the control value.
e. With anagrelide, observe for a decrease in platelet count.
Platelet counts should be done every 2 days during the first week
of management and weekly until a maintenance dose is reached.
Counts usually begin to decrease within the first 2 wk of therapy.
f. With aspirin, clopidogrel, and other antiplatelet drugs, observe for the absence of thrombotic disorders (eg, myocardial
infarction, stroke)
g. With cilostazol, observe for ability to walk farther without
leg pain (intermittent claudication).
Improvement may occur within 2 to 4 wk or take as long as 12 wk.
3. Observe for adverse effects
a. Bleeding:
Bleeding is the major adverse effect of anticoagulant drugs. It may
occur anywhere in the body, spontaneously or in response to minor
trauma.
With eptifibatide and tirofiban, most major bleeding occurs at the
arterial access site for cardiac catheterization.
(1) Record vital signs regularly.
Hypotension and tachycardia may indicate internal bleeding.
(2) Check stools for blood (melena).
Gastrointestinal (GI) bleeding is fairly common; risks are increased
with intubation. Blood in stools may be bright red, tarry (blood that
has been digested by GI secretions), or occult (hidden to the naked
eye but present with a guaiac test). Hematemesis also may occur.
(3) Check urine for blood (hematuria).
Genitourinary bleeding also is fairly common; risks are increased
with catheterization or instrumentation. Urine may be red (indicating fresh bleeding) or brownish or smoky gray (indicating old
blood). Or bleeding may be microscopic (red blood cells are visible only on microscopic examination during urinalysis).
(4) Inspect the skin and mucous membranes daily.
Bleeding may occur in the skin as petechiae, purpura, or ecchymoses. Surgical wounds, skin lesions, parenteral injection sites,
the nose, and gums may be bleeding sites.
(5) Assess for excessive menstrual flow.
b. Other adverse effects:
(1) With heparin, tissue irritation at injection sites, transient alopecia, reversible thrombocytopenia, paresthesias,
and hypersensitivity
These effects are uncommon. They are more likely to occur with
large doses or prolonged administration.
(2) With warfarin, dermatitis, diarrhea, and alopecia
These effects occur only occasionally. Warfarin has been given for
prolonged periods without toxicity.
(3) With anagrelide, adverse cardiovascular effects (eg,
tachycardia, vasodilation, heart failure)
These effects are most likely to occur in clients with known heart
disease.
(4) With clopidogrel and ticlopidine, GI upset, skin rash,
neutropenia, and thrombocytopenia
Neutropenia and thrombocytopenia are more likely to occur with
ticlopidine than clopidogrel.
(continued )
CHAPTER 57 DRUGS THAT AFFECT BLOOD COAGULATION
NURSING ACTIONS
c. With thrombolytic drugs, observe for bleeding with all uses
and reperfusion dysrhythmias when used for acute myocardial
infarction.
849
RATIONALE/EXPLANATION
Bleeding is most likely to occur at sites of venipuncture or other
invasive procedures. Reperfusion dysrhythmias may occur when
blood supply is restored to previously ischemic myocardium.
4. Observe for drug interactions
a. Drugs that increase risks of bleeding with anticoagulant,
antiplatelet, and thrombolytic agents:
These drugs are often used concurrently or sequentially to decrease risks of myocardial infarction or stroke.
(1) Any one of these drugs in combination with any other
drug that affects hemostasis
(2) A combination of these drugs
b. Drugs that increase effects of heparins:
(1) Antiplatelet drugs (eg, aspirin, clopidogrel, others)
(2) Warfarin
Additive anticoagulant effects and increased risks of bleeding
(3) Parenteral penicillins and cephalosporins
Some may affect blood coagulation and increase risks of bleeding
c. Drugs that decrease effects of heparins:
(1) Antihistamines, digoxin, tetracyclines
These drugs antagonize the anticoagulant effects of heparin.
Mechanisms are not clear.
(2) Protamine sulfate
The antidote for heparin overdose
d. Drugs that increase effects of warfarin:
(1) Analgesics (eg, acetaminophen, aspirin and other nonsteroidal anti-inflammatory drugs)
(2) Androgens and anabolic steroids
Mechanisms by which drugs may increase effects of warfarin include inhibiting warfarin metabolism, displacing warfarin from
binding sites on serum albumin, causing antiplatelet effects, inhibiting bacterial synthesis of vitamin K in the intestinal tract,
and others.
(3) Antibacterial drugs (eg, aminoglycosides, erythromycin,
fluoroquinolones, isoniazid, metronidazole, penicillins,
cephalosporins, trimethoprim-sulfamethoxazole, tetracyclines)
(4) Antifungal drugs (eg, fluconazole, ketoconazole,
miconazole), including intravaginal use
(5) Antiseizure drugs (eg, phenytoin)
(6) Cardiovascular drugs (eg, amiodarone, beta blockers,
loop diuretics, gemfibrozil, lovastatin, propafenone, quinidine)
(7) Gastrointestinal drugs (eg, cimetidine, omeprazole)
(8) Thyroid preparations (eg, levothyroxine)
e. Drugs that decrease effects of warfarin:
(1) Antacids and griseofulvin
May decrease GI absorption
(2) Carbamazepine, disulfiram, rifampin
These drugs activate liver metabolizing enzymes, which accelerate the rate of metabolism of warfarin.
(3) Cholestyramine
Decreases absorption
(4) Diuretics
Increase synthesis and concentration of blood clotting factors
(5) Estrogens, including oral contraceptives
Increase synthesis of clotting factors and have thromboembolic
effect
(6) Vitamin K
Restores prothrombin and other vitamin K–dependent clotting factors in the blood. Antidote for overdose of warfarin.
f. Drug that may increase or decrease effects of warfarin:
(1) Alcohol
Alcohol may induce liver enzymes, which decrease effects by accelerating the rate of metabolism of the anticoagulant drug. However, with alcohol-induced liver disease (ie, cirrhosis), effects may
be increased owing to impaired metabolism of warfarin.
(continued )
850
SECTION 9 DRUGS AFFECTING THE CARDIOVASCULAR SYSTEM
NURSING ACTIONS
RATIONALE/EXPLANATION
g. Drugs that increase effects of cilostazol:
(1) Diltiazem
(2) Erythomycin
(3) Itraconazole, ketoconazole
Nursing Notes: Apply Your Knowledge
Answer: Low-dose subcutaneous heparin is administered prophylactically to prevent deep vein thrombosis, which is associated
with prolonged immobility. Activated partial thromboplastin time
(aPTT) levels may be assessed before beginning therapy, but routine aPTT assessment and dosage adjustments are not required for
low-dose heparin therapy. When giving the injection, take care to
prevent trauma and subsequent bruising. A small, 26-gauge
1
⁄2-inch needle is used. Leave a small air bubble in the syringe to
follow the dose and lock the heparin into the subcutaneous space.
The area is cleansed and grasped firmly and the needle is inserted
at a 90-degree angle. Do not aspirate or rub the area because this
fosters bruising. Avoid injections within 2 inches of incisions or
the umbilicus and any areas that are scarred or abnormal. Although
research indicates that various sites (abdomen, arms, and legs) can
be used, the preferred site is the abdomen. Observe and report any
signs of bleeding.
How Can You Avoid This Medication Error?
Answer: Ms. Innes’ INR is too high, which could significantly increase her risk for bleeding. Therapeutic INR levels are usually
between 2 and 3. Before giving anticoagulants, it is important to
check lab work (activated partial thromboplastin time for heparin,
prothrombin time or INR for Coumadin) to determine whether the
dose should be administered. For Ms. Innes, antibiotic therapy
may have interfered with the synthesis of vitamin K in the intestine, thus increasing the risk of bleeding. Notify Ms. Innes’ physician. Because no signs of bleeding have been noted, he or she
may decrease the Coumadin dosage.
Review and Application Exercises
1. What are the major functions of the endothelium, platelets,
and coagulation factors in hemostasis and thrombosis?
2. What are the indications for use of heparin and warfarin?
3. How do heparin and warfarin differ in mechanism of
action, onset and duration of action, and method of administration?
4. List interventions to protect clients from anticoagulantinduced bleeding.
5. When is it appropriate to use protamine sulfate as an
antidote for heparin?
These drugs inhibit the main cytochrome P450 enzyme (CYP3A4)
that metabolizes cilostazol. Grapefruit juice also inhibits drug
metabolism and should be avoided.
6. When is it appropriate to use vitamin K as an antidote for
warfarin?
7. How do antiplatelet drugs differ from heparin and warfarin?
8. For what conditions are antiplatelet drugs indicated?
9. When is it appropriate to use a thrombolytic drug?
10. How do aminocaproic acid and tranexamic acid stop
bleeding induced by thrombolytics?
11. Compare and contrast nursing care needs of clients
receiving anticoagulant therapy in hospital and home
settings.
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