DRUGS AFFECTING COAGULATION OBJECTIVES

1. Define the following terms:

Anticoagulant substances that keep blood from clotting; prevent blood blots from forming or extending; dont break
down existing clots; given IV, SC, or PO
Clot thrombus; results from excessive coagulation (hypercoagulation)
Clotting cascade series of steps initiated by tissue damage and platelet activation, which mobilize clotting factors that
are circulating in the blood. Active clotting factors work with Ca++ to form fibrin, which signals completion of blood
coagulation and end of blood loss. End result is formation of a stable blood clot.
Occurs over 2 pathways: (one or both may be activated in response to injury)
o Intrinsic clotting factors in blood activated by damage to blood vessel
o Extrinsic clotting factors activated by damaged tissue
Clotting factor plasma protein that causes blood clotting; inactive in blood until mobilized by injury
Coagulation blood aggregation, clotting
Embolus (embolism) any undissolved matter carried in a blood or lymph vessel to another location where it lodges and
occludes the vessel
Fibrin an insoluble protein that stabilizes the temporary plug formed by platelets to seal the injured vessel
Fibrinolysis process of breaking down a formed clot
Hemophilia uncontrollable bleeding due to genetic deficiencies of normal clotting factors
Hemostasis series of events to slow blood flow, stop blood loss at injury site, and prevent extensive blood loss when the
body begins bleeding
INR (Interational Normalized Ratio) standardized unit developed to measure therapeutic levels of warfarin;
determined by math equation and reflects pts PT compared w/ standardized PT value
(Activated) Partial thromboplastin time (aPTT) Plasmin activated plasmin lyses the blood clot about 1-2 days after bleeding stops
Platelets (thrombocytes) fragmented cells that assist in blood clotting and clot formation
Prothrombin time (PT) Thrombin converts fibringogen (factor I) to fibrin, and also activated factor XIII (a fibrin-stabilizing factor); thrombin is
converted from prothrombin (factor II)

Thromboembolism fragment of a thrombus that breaks off, travels through bloodstream and lodges in a vessel to
occlude blood flow
Thrombus blood clot; arterial thrombi consist of mostly platelet aggregated held together with thin fibrin strands, and
venous thrombi consist of mostly RBCs, a large amount of fibrin, and few platelets
Vitamin K fat-soluble vitamin that is continually produced in GI tract; absorption depends on amount of fat and bile
o deficiency of vitamin K normal clotting factors made bleeding risk in pts on warfarin
o infants more susceptible b/c intestinal flora inactive at birth
o high levels decrease warfarin effectiveness

2. Describe the pharmacotherapeutics, pharmacokinetics, pharmacodynamics, adverse effects, CPVs, and nursing
management of the prototype anticoagulants, heparin and warfarin.
ANTICOAGULANTS
HEPARIN - parenteral
Prevents conversion of prothrombin thrombin
Affects fibrin, prevents formation of stable clot
Low dose therapy is prophylactic
aPTT:
o 1:1 is normal clotting time
o No standardized number look at effect and see if clotting time is longer
o Therapeutic aPTT = 1.5-2X control (ie, control = 12 sec, then therapeutic aPTT = 18-24 sec)
o If aPTT is > 2X control risk for adverse effects (ie, bleeding)
Pharmacotherapeutics
Prevent extension of blood clot for DVT and pulmonary embolisms
SHORT-TERM prophyaxis post-operatively
NOT recommended as adjunct for ischemic strokes
Continuous IV infusion needed to achieve full anticoagulation, but bolus is given initially, followed by continuous infusion
Low risk for recurrent thrombosis (ie, risk factor reversible, like surgery) give anticoagulation therapy for 3 months

High risk for recurrent thrombosis (ie, no apparent risk factors or persistent risk factors like cancer) give anticoagulation
therapy for 6 months to indefinitely
Pharmacokinetics
Administered IV or SC
Onset of action: IV immediate; SC 20-60 min
Half-life = 1-2 hrs (full therapeutic effect occurs at steady state, so need to know half-life to determine steady state;
important for when you take aPTT)
Destroyed by gastric acid not absorbed from GI tract
Pharmacodynamics
Rapidly promotes inactivation of factor X (factor X blocks prothrombin thrombin)
Limits formation of stable clot by affecting fibrin
Prolongs clotting time w/o affecting bleeding time
No effect on already formed blood clots
Contraindications/CPVs
Thrombocytopenia, bleeding disorders, active bleeding other than DIC
Allergies to beef or pork
Pre-existing prolonged bleeding time
High activity level and susceptibility to injury
Safe for pregnant women
Adverse Effects
Bleeding
Heparin-induced thrombocytopenia (HIT) life-threatening! D/C heparin, let platelet count get back to normal, and treat
thrombosis with LEPIRUDIN (Refludan) and ARGATROBAN (Argatroban)
OD GIVE ANTIDOTE = PROTAMINE SULFATE (dont give protamine sulfate too fast b/c can cause hypotension,
bradycardia, dyspnea, and anaphylaxis; only used when pt is symptomatic and bleeding out; otherwise, D/C infusion and
wait for clotting time to decrease)
Nursing Management

Monitor aPTT to confirm therapeutic lengthening of clotting time, ie, 1.5-2X control aPTT (ie, if aPTT control time = 30
sec, therapeutic level = 45-60 sec)
Measure aPTT 6-8 hrs (ie, 4-5 half-lives) AFTER infusion to ensure steady state reached
Check aPTT each time dose is changed
Notify MD/NP if aPTT too low/high
Dont disrupt infusion; Insert new lines asap b/c will lose therapeutic effect
Monitor for signs of bleeding gums, nose, stool, vagina, urine, IV sites
Check aPTT, hematocrit, platelet count before starting therapy
Use IV pump
Dont administer other drugs in heparin line!
Give protamine sulfate if active bleeding occurs

WARFARIN (Coumadin) oral

PT measured against a control, reading will vary
Thrombus/embolus
Mechanical Heart Valve
PT (sec)
1.4-1.6X control
1.5-1.7X control
INR
2-3
2.5-3.5
Pharmacotherapeutics
Given after heparin therapy to finish tx for DVP or PE (thrombus/embolism PT = 1.4-1.6X control, or INR = 2-3)
Prophylaxis for LONG-TERM risk of thrombus formation (mitral vale replacement, hypercoagubility) PT = 1.51.7X control, or INR = 2.5-3.5
Prophylaxis for pts w/ Atrial fibrillation (at high risk for cardioembolic stroke)
Pharmacokinetics
Binds to albumin in plasma
Peak action occurs in 1-9 hrs
Therapeutic (anticoag) effects occur in 24 hrs
Steady state/max effect occurs 3-4 days after dosing beings

Pharmacodynamics
Competitively blocks vitamin K, prevents activation of prothrombin and other factors (doesnt affect already
activated factors need 3-4 days to achieve steady state and max effect)
Metabolized through P-450 pathway (if pt metabolizes poorly, > therapeutic effect of warfarin)
Low pre-op Hgb response to warfarin
Contraindications/CPVs
Active bleeding, open wounds, GI tract ulcerations, bleeding disorders (hemophilia, thrombocytopenia)
Patients undergoing surgery where hemorrhage is possible (spinal, eye, GI, cranial, arterial bypass grafting) usually D/C
7 days before surgery
Vitamin K deficiency (increases bleeding/hemorrhage risk and decreases synthesis of normal clotting factors) caused by:
o poor dietary intake
o obstructed bile duct
o long-term antibiotic therapy which affects normal GI flora (decreased vitamin K synthesis)
Newborns deficient in vitamin K b/c intestinal flora inactive at birth
**NOT for Pregnant women fetal warfarin syndrome defects
Older adults more sensitive to effects of warfarin
Diet high in vitamin K decreases effectiveness of warfarin
Interacts w/ a lot of drugs
Adverse Effects
Bleeding
Hemorrhage
Nausea, vomiting, diarrhea, abdominal cramps
Fetal warfarin syndrome
Nursing Management
DONT drastically increase dietary vitamin K intake therapeutic effect
NO ASPIRIN or ACETAMINOPHEN & NO EXTRA
Give initial loading dose to reach therapeutic range faster; follow with maintenance dose
Give dose at 6:00 PM to allow for early morning blood draws for PT or INR

OD GIVE ANTIDOTE = VITAMIN K

3. Apply the principles of drug therapy for coagulation problems to their effects on the clotting cascade.

4. Explain and differentiate the onset of action, lab tests, and antidotes associated with these two prototype drugs.
HEPARIN
WARFARIN
Onset of action
IV: immediate
24 hrs
SC: 20-60 sec
Lab Tests
-aPTT (1.5-2X control aPTT)
-blood draws for PT and INR
-hematocrit
-platelet count
Tx/Prophylaxis of thrombus or embolus:
PT: 1.4-1.6X control time
INR: 2-3
Prophylaxis for mech. heart valves:
PT: 1.5-1.7X control time
INR: 2.5-3.5
Antidotes
Protamine sulfate
Vitamin K
5. State the expected aPTT, PT, and/or INR for selected conditions related to thrombus and embolus formation.
WARFARIN
Thrombus/embolus
Mechanical Heart Valve
PT (sec)
1.4-1.6X control
1.5-1.7X control
INR
2-3
2.5-3.5
6. Compare and contrast the pharmacotherapeutics, pharmacokinetics, pharmacodynamics, adverse effects, CPVs, and
nursing management of the anticoagulant enoxaparin, with the prototype anticoagulants heparin and warfarin.
ANTICOAGULANT

ENOXAPARIN (Lovenox)
Low MW heparin
Limited effect on thrombin
Less interaction w/ platelets
Very predictable dose response
Dont need to constantly monitor aPTT
Pharmacotherapeutics
Reduce death, MI, and emergency revascularization in pts w/ Q-wave MI
Longer half-life, only administer SC 1X/day good for long-term therapy
A good F/U for initial heparin therapy
Pharmacokinetics
Most absorbed after SC
Widely distributed
Pharmacodynamics
Affects activated factor X (decreases aPTT)
Affects clotting factor C and antithrombin
Limited effects on thrombin
Adverse Effects
Bleeding, but less than heparin
CPVs (same as heparin)
Thrombocytopenia, bleeding disorders, active bleeding other than DIC
Allergies to beef or pork
Pre-existing prolonged bleeding time
High activity level and susceptibility to injury
Safe for pregnant women
Nursing Management
Teach patients how to self-administer
Take drug on time

Follow regular dosage schedule

Get follow-up blood analyses done as recommended
Safety clear pathways, remove loose scatter rugs, wear nonskid footwear, obtain adequate lighting, use handrails

7. Describe the pharmacotherapeutics, pharmacodynamics, adverse effects, CPVs, and nursing management of aspirin
when used for antiplatelet effects.
8. Compare and contrast the pharmacotherapeutics, pharmacodynamics, adverse effects, CPVs, and nursing
management of clopidogrel and aspirin.
ANTIPLATELETS
ASPIRIN
Anti-inflammatory effects (peripheral inhibition of prostaglandin synthesis; other mediators of inflammation)
Anti-thrombotic effects (inhibits prostaglandin responsible for platelet aggregation)
Pharmacotherapeutics
Prevents MI & stroke (Give w/i 24-48 hrs of onset)
Adjunct in revascularization procedures
Decrease incidence of coronary heart disease in those w/ increased risk (ie, men > 40 y/o, postmenopausal women, HTN,
DM, smoking, hyperlipidemia, obesity, family hx)
Prophylaxis against thromboembolic complications in CV disease (MI and TIA = transient ischemic attack)
Atrial fibrillation to prevent stroke (noncardioembolic)
Pharmacodynamics
Irreversibly inhibits platelet COX and synthesis of thromboxane A (vasoconstrictor that facilitates platelet aggregation) for
the life of the platelet
Adverse Effects
Bleeding
GI ulceration and bleeding
Hemorrhagic stroke
neutropenia
Contraindications/CPVs

Peptic ulcer disease, bleeding disorders, pts on anticoagulant therapy

Gout
Renal/liver impairment or disease
Children < 16 y/o w/ varicella or flu-like illness Reye syndrome (swelling in brain, intracranial pressure, seizures)
Pregnant and lactating women (pregnancy category D)
asthma

Nursing Management
NEVER give to pregnant women in 3rd trimester b/c high risk of maternal hemorrhage and adverse fetal effects
NEVER give to children < 16 y/o w/ flu-like symptoms (Reye syndrome)
Caution for pts > 60 y/o
Ask about OTCs, smoking, alcohol
Give with milk or food to relieve GI distress
Get CBC, platelet count, liver/renal function tests for pts on long-term therapy
CLOPIDOGREL (Plavix)
Pharmacotherapeutics
Prevent atherosclerotic events in patients who have had/are at risk for MI, stroke, vascular death, peripheral artery disease
(PAD)
Manage acute coronary syndrome (post-MI w/ elevated QT)
Prevent thrombosis post coronary stent
Reduce platelet adhersion/aggregation
Pharmacodynamics
Irreversibly modifies platelet ADP receptor inhibits binding of ADP to platelet receptor inhibits platelet aggregation
prolongs bleeding time
Adverse Effects
Bleeding
GI distress: abdominal pain, indigestion, diarrhea, nausea (but not ulcers or GI bleeding like w/ aspirin)

 neutropenia
Contraindications/CPVs
peptic ulcers or intracranial hemorrhage
platelet function
liver function
CV status
Neuron status
Children < 18 y/o, pregnancy and lactation
Nursing Management
Take with food to relieve GI distress
Check WBCs if signs of infection
D/C 7 days before surgery to prevent excessive bleeding
Apply pressure on wounds until bleeding stops
Avoid behaviors that may lead to injury
Make home environment more fall proof
9. Describe the pharmacotherapeutics, pharmacokinetics, pharmacodynamics, adverse effects, CPVs, and nursing
management of thrombolytics (prototype: alteplase recombinant).
10. Describe the pharmacotherapeutics, pharmacodynamics, adverse effects, CPVs, and nursing management of
streptokinase.
THROMBOLYTICS
ALTEPLASE RECOMBINANT
Drug of choice for CVA
Fewer systemic effects
Tissue plasminogen activator (tPA)
Converts plasminogen to plasmin when fibrin is present; attaches directly to fibrin in clot (ie, must have fibrin to work)

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Pharmacotherapeutics
Acute evolving MI from acute coronary artery thrombus (initiate at onset of symptoms)
Acute ischemic stroke (ONLY drug to treat this; must initiate w/i 3 hrs of onset of stroke and after IC bleeding has been
ruled out by CT scan)
Massive pulmonary embolism
Pharmacokinetics
IV for immediate effect
Rapid clearance 80% cleared w/i 10 min after infusion has completed
Pharmacodynamics
Binds to fibrin in a clot and converts trapped plasminogen to plasmin fibrinolysis (break down of clot)
Adverse Effects
Bleeding (but less than streptokinase)
Contraindications/CPVs
Active internal bleeding, evidence of IC bleeding on pre-tx evaluation, suspicion of subarachnoid hemorrhage
Recent (w/i last 2 months) stroke
IC surgery or sever head trauma
Intraspinal surgery or trauma
IC neoplasm
Seizure at onset of stroke
Arteriovenous malformation or aneurysm
Severe uncontrolled HTN (systolic BP 180 or diastolic BP 110)
Co-Anticoagulant therapy (heparin), Co-antiplatelet therapy (aspirin)
Current pregnancy or delivery of child w/i last 10 days
Older adults more susceptible to IC bleeding
Nursing Management
IV pump
NO invasive procedures
Monitor for:

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o signs of bleeding
o VS changes (fever, arrhythmias, hypotension)
o blood work abnormalities
o respiratory problems (bronchospasm)
Lab values: hematocrit, Hgb level, platelet count, PT, aPTT
Reconstitute in sterile water
Dont shake or agitate too much
Infuse over 90 min (recommended) or over 3-hrs, or accelerated
Cardiac monitor during and after tx (when MI)
Check RR, dyspnea, pulse ox, ABGs (when pulmonary embolism)
Check BP closely (when acute ischemic stroke)

STREPTOKINASE
BREAKS DOWN formed blood clots
Indications
Treat acute evolving MI
Treat acute evolving thrombotic CVA
pulmonary embolism
acute, extensive DVT
arterial thrombosis
opens occluded arteriovenous catheters (w/ lower doses)
How it works:
activates plasminogen and acts w/ plasminogen to convert plasminogen to plasmin (dissolves fibrin, fibrinogen, and other
clot-forming proteins)
fibrin NOT needed for plasminogen activation

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Adverse Effects
severe bleeding GIVE ANTIDOTE = AMINOCAPROIC ACID
life-threatening bleeding (b/c it changes fibrin throughout body) blood transfusion
allergic reactions: fever, chills (in 30% of pts)
hypotension
CPVs
Nursing Management
IV pump
NO invasive procedures
Monitor for:
o signs of bleeding
o VS changes (fever, arrhythmias, hypotension)
o blood work abnormalities
o respiratory problems (bronchospasm)
11. List the life-threatening adverse effects of each of the anti-coagulants, anti-platelet agents, and thrombolytics.
12. List measures to prevent, minimize, and treat these life-threatening effects.
Life-threatening Adverse Effect
ANTICOAGULANTS
Heparin
Warfarin
ANTI-PLATELETS
Aspirin

Heparin-induced thrombocytopenia
(HIT)
Fetal warfarin syndrome
Salicylate Poisoning

Prevent/Minimize/Tx
D/C heparin, wait for platelet count to get back to normal, treat
any thrombosis. Administer lepirudin (Refludan) and argatroban
(Argatroban)
Dont give to pregnant women
No antidote (gastric emptying, give activated charcoal, life
support)

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Clopidogrel
THROMBOLYTICS
Alteplase Recombinant
Streptokinase

Neutropenia or bleeding?
Bleeding
Severe bleeding

Dont give to pregnant women or to women that have delivered

w/i past 10 days. Caution w/ older adults b/c more likely to have
IC bleeding.
blood transfusion

13. Prepare teaching plans for patients receiving specific anti-coagulant therapy at home.
14. Apply nursing management principles to case studies of patients receiving home coagulation therapy.

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