Transcript Intravenous Warfarin as an Alternative for Anticoagulation

King Faisal Specialist Hospital
and Research Center
(2007-1428)
Presented by:
Supervised by:
Manar Lashkar
Samah Al-shehri
Pharm.D candidates
Dr.Mohammad Elfaour
1
Introduction
Oral
isCollege
the standard
of
The warfarin
American
of Chest
Achieving
a therapeutic
INR
may
be
care
for patients
requiring
long-term
Physicians
recommends
treating
complicated
by(ACCP)
many
factors,
such as
anticoagulation due to venous
these
patients
with
oral
warfarin
to
drug-drug
interactions,
drug-food
thromboembolic disease.
maintain an
interactions,
andinternational
inadequate normalized
ratio (INR)
of 2.0–3.0.
absorption
of drugs.
2
Introduction

Normally Warfarin sodium is
completely absorbed after oral
administration with peak
concentration generally attained
within the first 4 hours.
3
Introduction



Patients with Crohn's disease may have
reduced absorption of warfarin in the small
bowel due to loss of effective surface area
secondary to:
chronic inflammation
ulcerative lesions
resection
4
Introduction

So, the usual alternative
outpatientWhat
anticoagulation
is
about
achieved by subcutaneous
low
if
molecular weight heparin (LMW
LMW heparin
heparin) e.g. enoxaparin and
is contraindicated?!
tinzaparin.
5
Introduction
In cases like pyoderma gangrenosum
(which is a complication of Crohn’s disease
that causes tissue to become necrotic
causing
deep
ulcers
and
worsened
by
What
is
the
alternative?!
subcutaneous injections),
oral warfarin and SC LMW heparin
are not useful…

6
Intravenous Warfarin as
an Alternative for
Anticoagulation
In this presentation we will discuss a case report published
in Pharmacotherapy Journal in 2007 that describes the
successful use of intravenous warfarin in a patient with
upper extremity thrombosis who was resistant to oral
warfarin and cannot tolerate the SC LMW heparin.
7
Case Report

Patient information:
A 27-year-old, 40-kg, Caucasian woman
Complain:
Malnourishment secondary to end-stage Crohn's
disease.
Blocked central venous catheter line that had been
inserted 6 weeks earlier for administration of
total parenteral nutrition (TPN).
8
Case Report

Medical History:
Multiple surgical procedures, including a colectomy
with a primary closure for her Crohn's disease.
Pyoderma gangrenosum
•
•
Drug administration on admission:
•
•
•
•
•
Hydromorphone IV
Dimenhydrinate IV
Furosemide IV
Total parenteral nutrition
Sublingual lorazepam
9
Case Report

Lab results:
Hepatic transaminase levels and platelet count
were within normal limits and remained stable
throughout her admission.
 Diagnostic tools:
Doppler ultrasonography confirmed that the
patient had developed an upper extremity
thrombosis extending from the right jugular
to the subclavian vein, secondary to her
central line.
10
Thromboembolic Treatment

New central line was inserted, and
anticoagulation with an intravenous heparin
infusion along with oral warfarin was started.
11
So
oral warfarin
should be discontinued
INR
Oral Daily Warfarin Doses (mg)
High doses of warfarin
were potentially
Warfarin
Next doses failed to
The
dangerous if sudden INR
producewas
a significant
patient
still
patient did
increase vitamin
in the patient's absorption were to occur
receiving
respond to
KINR
10 mg/week INR
in remained
therapy
subtherapeutic
her TPN
Vitamin K discontinued
Day
12
Since
LMW heparin was
contraindicated
due to her history of
pyoderma gangrenosum
IV heparin was not an
option for outpatient
management of the
thrombus
An alternative anticoagulant was required
The decision was made to use IV warfarin
The hospital's purchasing group ordered IV warfarin
on hospital day 28; it arrived the next morning
Therapy was started
13
IV
warfarin
was
The
patient
began
to
The
patient
achieved
started
atto5 warfarin.
mg INR
respond
her therapeutic
dose.
INR
IV Daily Warfarin Doses (mg)
Warfarin
INR
The patient stabilized on
4mg/day IV warfarin and
was discharged.
Heparin DC
Day
14
Discussion
15
Warfarin Resistance


1) Hereditary.. very rare
2) Acquired: more common
 Poor compliance.
 Exogenous vit. K intake.
 Increased warfarin clearance (intrinsic
or due to enzyme inducers)
 Decreased warfarin absorption.
16
Determining Warfarin Resistance Cause
in our Case
x
x
x
x
x
Hereditary


The patient was in the
inpatient setting.
Achievement therapeutic INR
while receiving warfarin
intravenously.
Poor Compliance
Vitamin K intake
Drug-drug Interactions


vitamin K was removed from
the TPN.
Increased clearance
Patient drugs were reviewed.
Decreased absorption
17
Pharmacological Facts

Warfarin is an anticoagulant that inhibits
activation of vitamin K–dependent clotting
factors II, VII, IX, and X and proteins C
and S.

So, it works on the extrinsic clotting
system which is measured by the INR.
18
Pharmacological Facts


It is completely absorbed from the GIT and its
effect is produced within 36–72 hours and lasts
from 4–6 days.
Intravenous warfarin, approved for use the FDA,
provides an alternative administration route for
patients who cannot receive the oral formulation
and cannot use subcutaneous low-molecularweight heparins due to adverse effects
19
But is there any differences
between IV and oral warfarin??
vs
20
Coumadin® for Injection

Pharmacologically:

The efficacy and toxicity of IV warfarin is similar
to that of the oral form and it is monitored by
INR, prothrombin time and hemoglobin levels

Pharmacokinetically:

It should provide the patient with the same
concentration of an equal oral dose.

But maximum plasma concentration will be
reached earlier.
21
Coumadin® for Injection

However, the full anticoagulant effect of a dose of
warfarin may not be achieved until 72-96 hours after
dosing.

So, IV warfarin should not provide any increased
biological effect or earlier onset of action.

Warfarin for injection should be administered as a slow
bolus over 1–2 minutes into a peripheral vein.

It is not to be given intramuscularly and is not approved
for direct intravenous push.
22
Coumadin® for Injection

However, clinical experience, including the
experience with our patient, suggests that it can
be administered as a direct intravenous push
injection without complications.

The vial must be reconstituted with 2.7 mL of
sterile water for Injection to yield 2mg/mL. So,
net contents 5.4 mg of warfarin lyophilized
powder.

It must be protected from light.
23
Coumadin® for Injection

After reconstitution, COUMADIN® for Injection is
chemically and physically stable for 4 hours at
room temperature.

It does not contain any antimicrobial
preservative.

The vial is not recommended for multiple use
and unused solution should be discarded.
24
Conclusion
In this complicated patient who was resistant to
oral warfarin and unable to receive
subcutaneous low-molecular-weight heparin,
therapeutic anticoagulation was achieved with
intravenous warfarin.
Further clinical experience and reports are
needed to better understand the role of
intravenous warfarin in anticoagulation
management.
25
Criticism

The title was interesting and useful in our clinical
practice. (Intravenous Warfarin as an Alternative for
Anticoagulation)

The case follows a standard format
(Introduction, description of the case, discussion
and references).

The case described clearly and it stated the
clinical importance for reporting this case.
26
Criticism

The patient data were reported
adequately.

The treatment plan was appropriate for the
problem and other options were
discussed .

The author indicates direction for future
management of similar cases.
27
Criticism
However, the article doesn’t state the
exact date of patient admission and
the hospital name and place.
28
References

Gellatly R. Intravenous Warfarin as an Alternative for Anticoagulation.
Pharmacotherapy. 2007;27(6):933-935

Buller HR, Agnelli G, Hull RD, Hyers TM, Prins MH, Raskob GE. The
seventh ACCP conference on antithrombotic and thrombolytic therapy:
antithrombotic therapy for venous thromboembolic disease. Chest
2004;126(3):401S–28.

DiDomenico RJ. Coagulants and anticoagulants. In: Anderson PO,
Knoben JE, Troutman WG, eds. Handbook of clinical drug data, 10th ed.
New York: McGraw-Hill Companies, Inc., 2002:615–17.

Porter RS, Sawyer WT. Warfarin. In: Evans WE, Schentag JJ, Jusko WJ,
eds. Applied pharmacokinetics: principles of therapeutic drug
monitoring, 3rd ed. Vancouver, WA: Applied Therapeutics, Inc.,
1992:31-1–31-46.
29
References



Hulse ML. Warfarin resistance: diagnosis and
therapeutic alternatives. Pharmacotherapy
1996;16(6):1009–17.
Brophy DF, Ford SL, Crouch MA. Warfarin resistance in a
patient with short bowel syndrome. Pharmacotherapy
1998;18(3):646–9.
Brystol-Myers Squibb Canada, Inc. Coumadin (warfarin
sodium) product monograph. Montreal, Quebec,
Canada; 2005.
30
Manar Lashkar
Samah Al-shehri
31