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24-1
CHRONIC ANTICOAGULATION
To Bridge or Not to Bridge,
That is the Question. . . . . . . . . . . . . . . . . . . . . . . . . . . . Level III
Mikayla L. Spangler, PharmD, BCPS
CASE SUMMARY
A 53-year-old woman with a past medical history of recurrent
deep vein thrombosis (DVT) × 2 (most recent 4 months ago) and
antiphospholipid syndrome presents for follow-up evaluation of
her chronic warfarin therapy and instructions for anticoagulation
management during her colonoscopy procedure scheduled in
2 weeks. Her international normalized ratio (INR) is therapeutic
today. The reader is asked to consider periprocedural bridging
options for her colonoscopy and recommend an appropriate bridging protocol for the patient. Once the plan is made, an appropriate
monitoring and follow-up plan must be devised, and education
about bridge therapy should be reviewed with the patient. In addition, the patient has also been using a high dose (800 mg TID) of
ibuprofen for osteoarthritis pain in the last 2.5 weeks.
QUESTIONS
Problem Identification
1.a. Create a list of this patient’s drug-related problems.
• Periprocedural management of anticoagulation is needed for
pending colonoscopy procedure.
• Drug interaction between ibuprofen and warfarin must be
addressed.
• Calcium supplementation dose is too low for postmenopausal
woman not receiving hormone therapy; vitamin D deficiency
not present.
1.b. What questions would you ask this patient to assess her current warfarin therapy?
Questions to identify the presence of factors that may
affect the INR value:
• What dose of warfarin are you currently taking? (Verify dose
and color of tablet.)
• Have you started any new medications recently, including
prescription, over-the-counter (OTC), and alternative therapies (eg, St. John’s wort, ginkgo, and garlic)? It is important to
ask patients about OTC medications and alternative therapies.
Patients will often forget to mention these agents because they
have not been prescribed. However, they can have a substantial
impact on warfarin therapy.
• Have you stopped taking any medications? This may be important as the warfarin dose could have been previously adjusted
for a drug–drug interaction. If the interacting medication is no
longer present, the INR could increase or decrease. A common
example of this is when a patient who has been previously stabilized on a specific warfarin regimen discontinues his or her
daily multivitamin containing vitamin K.
• Have you taken any extra doses of warfarin recently?
Questions to assess for signs and symptoms
of hemorrhage or thromboembolism:
• Have you had any episodes of bleeding, unexplained bruises,
or bruises that do not seem to heal?
• Have you noticed any pain, redness, warmth, or swelling in
your legs? Have you noticed any chest pain or shortness of
breath?
1.c. What signs or symptoms might she experience if she developed a venous thromboembolism (VTE)?
• Symptoms of a DVT include unilateral (or bilateral) pain,
erythema, tenderness, swelling, and discoloration in one or
more extremities. Symptoms of a pulmonary embolism (PE)
include dyspnea, pleuritic chest pain, cough, tachypnea, and
tachycardia.
• Signs: Low (subtherapeutic) INR. In this case the INR is currently 2.8, which is within the target range of 2.0–3.0.1
1.d. What is her risk of thromboembolism during interruption
of warfarin therapy?
• According to the 2012 Chest guidelines, her DVT 4 months
ago and the fact that it was her second DVT would normally
only put her in the moderate risk for thromboembolism category. However, the patient is in the high-risk category for
perioperative thromboembolic risk due to her severe thrombophilia, antiphospholipid syndrome (Table 24-1).2
1.e. What are the risks of using nonsteroidal anti-inflammatory
drugs (NSAIDs) in combination with warfarin?
• Although NSAIDs may not necessarily increase the INR when
used in combination with warfarin, they do increase the risk of
bleeding, and their concomitant use counts as a risk factor for
anticoagulant-related bleeding.1,3 NSAIDs also can be a cause
of gastric bleeding and this is one of the most common sites for
bleeding related to warfarin therapy.4 Due to increased risk of
bleeding with NSAIDs, low-dose acetaminophen is preferred
over NSAIDs for management of pain and ibuprofen should
be discontinued. Ms Heartly can reduce the number of risk
factors for bleeding from one (moderate risk) to zero (low risk)
when she discontinues use of ibuprofen.3
Desired Outcome
2.What are the goals of anticoagulation therapy in this patient?
• Minimize the risk of recurrent DVT and PE chronically and
surrounding the colonoscopy procedure.
• Minimize adverse effects (eg, bleeding) associated with
anticoagulation.
• For patients with antiphospholipid syndrome and a history of
VTE, a target INR range of 2.0–3.0 is recommended. The INR
should be maintained within this range to ensure adequate
anticoagulation and minimize adverse effects.1
Therapeutic Alternatives
3a. What are the options for extended therapy of venous
thromboembolism?
The 2016 update to the Chest guidelines recommends nonvitamin K oral anticoagulants (NOACs) as first-line therapy for
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Chronic Anticoagulation
Beth Bryles Phillips, PharmD, FCCP, BCPS
• Have you missed any warfarin doses?
CHAPTER 24
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• Have you had any recent changes in your diet (ie, alteration
in consumption of vitamin K-containing foods, or alcohol
intake)? Have you started any new dietary or OTC supplements such as SlimFast, Boost, Ensure, or Viactiv?
24-2
TABLE 24-1 Thromboembolic Risk After Interruption of Warfarin Therapy2,3
SECTION 2
Warfarin Indication
Cardiovascular Disorders
Risk Stratum
Mechanical Heart Valve
Atrial Fibrillation
Venous Thromboembolism
High
Any mitral valve prosthesis
Any caged ball or tilting disc aortic valve prosthesis
Multiple mechanical heart valves
Stroke, TIA, or cardioembolic eventa
CHADS2 score 5–6
Recent (<3 mo) stroke or TIA
Severe valvular heart disease
Moderate
Bileaflet aortic valve +AF, prior stroke or TIA, HTN, DM,
CHF, age >75
CHADS2 score 3–4
Low
Bileaflet aortic valve without AF, prior stroke or thromboembolic event, or known intracardiac thrombus
CHADS2 score 0–2 (assuming
no prior stroke or TIA)
Recent (<3 mo) VTE
Severe thrombophilia (eg, protein C, S, or antithrombin
deficiency, antiphospholipid syndrome, homozygous
for factor V Leiden or prothrombin gene mutation, or
multiple abnormalities)
VTE within past 3–12 mo
Nonsevere thrombophilia (eg, heterozygous factor V
Leiden or prothrombin gene mutation)
Recurrent VTE
Active cancer (treated <6 mo or palliative)b
Single VTE occurred >12 mo ago and no other RF
TIA, transient ischemic attack; AF, atrial fibrillation; HTN, hypertension; DM, diabetes mellitus; CHF, chronic heart failure; mo, months; RF, risk factor; VTE, venous thromboembolism.
a
The 2012 Chest guidelines specify “recent” stroke or TIA as having occurred within the past 6 months.
b
A recent review article lists active cancer in the high-risk category.3
most patients with VTE. Vitamin K antagonists, such as warfarin,
are preferred in patients with severe chronic kidney disease, coronary heart disease, history of gastrointestinal bleed, nonadherence,
or in cases where a reversal agent may be needed.3 The guidelines
also note that patient preference and shared decision-making
should be considered when choosing treatment. In this case, Ms
Heartly does not have an indication for warfarin as the preferred
therapy. However, this therapy is appropriate for her due to patient
preference.
3b. What are the options for periprocedural management of
anticoagulation?
• Decisions regarding periprocedural management of anticoagulation are based on the risk of thromboembolism during
subtherapeutic or no anticoagulation when warfarin is held
prior to and after the procedure, as well as the risk of bleeding
associated with the procedure. (See Question 1.d. for thromboembolic risk.) Procedures and surgeries are generally considered low risk if the bleeding rate is <1.5%, and high risk if the
bleeding rate is >1.5%.5 Warfarin therapy may be continued
uninterrupted throughout the procedure with the use of other
measures to control bleeding if the risk of bleeding is very low
compared with the risk of thromboembolism (eg, tooth extraction, minor dermatologic procedures, or cataract removal).
During procedures in which there is a significant bleeding
risk, warfarin therapy must be held prior to and sometimes
after the procedure to minimize risk. In these cases, alternative
anticoagulation should be used in patients who have a high
risk of thromboembolism.2 In patients with a moderate risk
for thromboembolism, the individual thrombotic and periprocedural bleeding risks must be considered by both the patient
and clinician to determine whether alternative anticoagulation
is appropriate.2,5 “Bridging” is the term used to describe the
process of administering alternative anticoagulation, such as a
low-molecular-weight heparin (LMWH), to a patient with the
intent of providing therapeutic anticoagulation until a therapeutic INR is obtained with warfarin therapy.
• A recent randomized, double-blind, placebo-controlled noninferiority trial compared enoxaparin to placebo for periprocedural management of anticoagulation in patients with
atrial fibrillation needing interruption in warfarin therapy.
No difference was found in the rate of thromboembolism
within 30 days after the procedure between the two groups.
However, patients receiving enoxaparin did have a higher rate
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
of bleeding compared to patients who did not get bridged.
Although the results of this study raise important questions
about the safety of bridging patients in need of interruption
of anticoagulation, it is important to note that (a) the study
was only conducted in patients with atrial fibrillation and not
recurrent VTE or thrombophilia, and (b) <3% of patients studied were at high risk for thromboembolism while the rest of
the patients were at low or moderate risk.6 Given Ms Heartly’s
indication for anticoagulation and the fact she is considered
high risk, bridging would be appropriate for this patient.
• The Chest guidelines recommend the use of therapeutic-dose
drug regimen for patients needing bridge therapy. This may
include any FDA-approved LMWH, where dosing is weightbased (eg, enoxaparin 1 mg/kg BID or 1.5 mg/kg daily; or
dalteparin 100 IU/kg BID or 200 IU/kg daily), or IV unfractionated heparin (UFH) to attain an activated partial thromboplastin time (aPTT) 1.5–2 times the control aPTT.2 Patients
with heart valve replacements and atrial fibrillation should be
given enoxaparin 1 mg/kg BID while patients with VTE may
be prescribed enoxaparin 1.5 mg/kg daily. However, patients
weighing more than 100 kg would have difficulty administering a once-daily dose due to the lack of prefilled syringes in
doses >150 mg.
• The benefits of LMWH include a rapid onset of action following initiation and a rapid dissipation in anticoagulant effect
following discontinuation. Additionally, routine laboratory
monitoring is not required for most patients. Although the
risk is considerably lower with LMWH compared with UFH,
heparin-induced thrombocytopenia may occur in high-risk
patients. Monitoring platelet count is only suggested for
patients whose risk for HIT is >1% based on clinician judgment. According to the Chest guidelines, patients receiving
LMWH have a risk for HIT of ≤1%, and, therefore, monitoring
is not suggested.7 Specific patient-related concerns include the
fact that LMWH are injectable medications, and some patients
may be opposed to this type of administration or find it difficult. Additionally, LMWHs are expensive and insurance may
cover only part or none of the cost of therapy.
• Although bridging is routinely provided with LMWH, special
circumstances may arise in which alternatives are needed. UFH
may be the preferred product for patients with chronic kidney
disease and CrCl <30 mL/min.8 Additionally, IV UFH may
be used in hospitalized patients who need bridging therapy,
24-3
• In this patient, bridging therapy surrounding her colonoscopy
is recommended due to her high thromboembolic risk and the
potential for high bleeding risk if polypectomy is performed.
LMWHs are a good option for her as she will be treated as an
outpatient and has no contraindications to therapy. Enoxaparin 150 mg subcutaneously Q 24 H may be used (1.5 mg/kg ×
96.3 kg = 144 mg). Since enoxaparin is available in a 150-mg
syringe, the dose should be rounded up.
Optimal Plan
4.a. Based on today’s laboratory result, what is your recommendation for this patient’s warfarin therapy?
• Given the patient’s stable warfarin dose of 2.5 mg Tue and Sat,
5 mg 5 days per week for at least the previous 3 months, and
the fact that the patient has had no changes in the parameters
that may affect the INR (including missing or taking additional
warfarin doses, changes in dietary habits, medications, and
overall health), it would be appropriate to have Ms Heartly
continue on her current warfarin dose until she is to discontinue it (5 days prior) for the colonoscopy procedure.
• Once Ms Heartly has the colonoscopy, it is recommended
that she restart her warfarin therapy at her current dose
12–24 hours after the procedure.2
4.b.How should the plan for periprocedural management of
anticoagulation be implemented?
• Ms Heartly should discontinue her warfarin 5 days prior to her
colonoscopy procedure.2 Enoxaparin 150 mg subcutaneously
should be given once daily in the morning for 4, 3, and 2 days
prior to the colonoscopy. (It should be noted that some clinicians may choose to delay starting enoxaparin until the INR is
<2.0.) On the day prior to the procedure, Ms Heartly should
administer one half of the enoxaparin dose (0.5 mL).2 Following
the procedure, if there is no bleeding present, Ms Heartly should
restart her warfarin at her regular dose that evening, and she
should restart enoxaparin on the day following the procedure.2
However, if bleeding should occur, the use of enoxaparin, and
Outcome Evaluation
5.How will you monitor this patient’s warfarin therapy?
• Follow-up with the patient shortly after her colonoscopy procedure to ensure her INR is increasing at an appropriate level.
Efforts should focus on obtaining and maintaining the target
INR (2.5, range: 2.0–3.0). Patients with subtherapeutic INRs
are at an increased risk of recurrent thromboembolism. It is
important to note that although the patient’s risk of a recurrent thromboembolism is increased, it does not mean that the
patient will have a recurrent thromboembolism. Patients may
develop a recurrent thromboembolism with therapeutic INRs
and may have no evidence of a recurrent thromboembolism
with very low INRs (eg, 1.0). Patients with a supratherapeutic
INR are at an increased risk of bleeding.
• Because warfarin has a narrow therapeutic window and many
factors can alter a patient’s response to therapy, the INR should
be monitored on a routine basis. On initiation of therapy, it is
wise to monitor the INR frequently until the patient has been
stabilized on a therapeutic warfarin dose. After the patient has
been stabilized (ie, at least two documented steady-state therapeutic INRs on the same dose), the monitoring interval may
be extended to 4 weeks. Although the most recent guidelines
suggest monitoring intervals may be extended up to 12 weeks
in stable patients (ie, therapeutic INR values for at least
3 months), this is a low-level recommendation and based on
weak evidence.1 In this case, the patient’s INRs were stable and
therapeutic on the same warfarin dose. She required follow-up
sooner than 1 month due to the colonoscopy procedure.
• Monitor for signs and symptoms of thromboembolism as discussed in Question 1.b.
• Educate patients about common sites of bleeding and instruct
them to notify their provider or clinic if any signs or symptoms
of bleeding occur. Common sites include bleeding from the
nose and gums (often after brushing teeth), and blood in the
stool or urine (it is usually more difficult to detect blood in
the urine, but the urine may turn a rusty color). In addition,
tell patients to watch for unexplained bruises and bruises that
do not seem to heal. At each appointment, ask patients if they
have noticed any symptoms of bleeding.
Patient Education
6.a. What information should this patient know regarding her
upcoming bridging therapy for her colonoscopy procedure?
• Taking warfarin therapy during your colonoscopy procedure
can increase your risk of bleeding complications associated
with the procedure. For this reason, you will need to stop
warfarin several days before the colonoscopy to give warfarin
a chance to get out of your system.
• While you are off warfarin, you could develop another blood
clot if you were not treated with another medication. This is
why you have been given instructions to start the enoxaparin
injections.
• Please refer to the following instructions to administer
enoxaparin:
✓Wash your hands.
✓Position yourself in a way that allows you to see your abdomen (belly button).
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Chronic Anticoagulation
• Elective surgical procedures such as colonoscopy should generally be postponed in patients with a VTE until after warfarin
therapy is completed. However, in a patient with recurrent
VTE, and low to moderate bleeding risk, extended warfarin
therapy is recommended.3 A colonoscopy with or without a
biopsy is considered a low-risk procedure for bleeding. Therefore, discontinuation of warfarin may not be necessary. However, a colonoscopic polypectomy, which may be indicated
during a colonoscopy, is considered a high-risk procedure for
bleeding.2,10 It is unpredictable if a patient will require colonic
polyp removal prior to the colonoscopy procedure. It is possible to perform a diagnostic colonoscopy procedure with a
follow-up colonoscopic polypectomy if necessary and if bleeding is a concern at the time of colonoscopy. This would allow
a first look without placing the patient at risk for bleeding or
thromboembolism when temporarily discontinuing warfarin
and possibly adding bridge therapy. However, due to the
preparation involved and inconvenience of the procedure,
most patients elect to discontinue warfarin and prepare for
potential polypectomy rather than chance having a second
colonoscopy performed.
possibly warfarin, should be delayed. Follow-up for the INR is
recommended shortly after to determine when the enoxaparin
should be discontinued. Enoxaparin should be continued for at
least 5 days and until the INR is therapeutic.5
CHAPTER 24
where close monitoring of aPTTs is feasible. Although studies and guideline recommendations are lacking, dabigatran,
rivaroxaban, apixaban, edoxaban, and fondaparinux could
theoretically be used for bridging. The long half-life associated
with fondaparinux presents a challenge in this setting due to
need for rapid dissipation of effect prior to the procedure.9
2
24-4
SECTION 2
✓Choose an area at least 2 in away from your belly button on
the right or left side. Clean the area with an alcohol swab and
let dry.
✓Gently make a fold (“pinch an inch”) in the skin in the area
of injection with your nondominant hand.
✓Inject the needle at a 90° angle (straight into the skin) while
holding the syringe in your dominant hand.
✓Press the plunger with your thumb until it is completely
empty.
Cardiovascular Disorders
✓Pull the needle straight out and release the skin fold.
✓Point the needle down and away from you or others and
push down on the plunger for the safety shield.
✓Place the used syringe in the sharps container.
• You may notice some pain and bruising at the injection site.
This is normal. As the bruises heal, they may turn yellow. If
you notice bruises that seem to be getting worse or not healing,
tell your provider.
• You may bleed more easily while using this medication.
6.b.What information should this patient know about her
warfarin therapy, especially to minimize subtherapeutic
or supratherapeutic INRs and potential hemorrhagic and
thromboembolic complications?
• Warfarin is an oral anticoagulant, which means it decreases the
body’s ability to make clots. It is also sometimes called a blood
thinner. Although warfarin does not actually “thin” the blood,
it does help prevent new clots from forming.
• Laboratory monitoring: This drug requires close monitoring of
blood tests to minimize the chances of developing a new blood
clot or bleeding. The prothrombin time measures how long it
takes your blood to form a clot. To standardize the prothrombin time test between laboratories, another test called the INR
is also reported. The goal is to keep your INR between 2.0 and
3.0. If the INR is above 3.0, you are at an increased risk of
bleeding. If the INR is below 2.0, you are at an increased risk
of developing another clot. Due to a number of factors that can
influence your response to warfarin therapy, you will need to
be monitored, and your INR will need to be checked approximately every 2–4 weeks. Once your INR is stable and within
the target range, follow-up can generally occur every 4 or more
weeks. However, if your INR is outside the target range or as
other medical conditions dictate, you may need earlier followup in 1–2 weeks.
• Warfarin dose: Because we want your blood tests to stay within
a certain range, your warfarin dose will probably be changed in
response to those results. It is important to know exactly what
warfarin dose you are taking at all times. It is a good idea to
keep a medication list on your person. As your warfarin dose
changes, the color of your tablet(s) may also change. Each tablet strength of warfarin is a different color. It is important to
remember the color of tablet you are taking at any given time.
• Drug–drug interactions: Many medications can interact with
warfarin and cause you to be at an increased risk of bleeding
or for developing a clot. It is important that you inform all of
your healthcare providers that you are taking warfarin. This
includes physicians, pharmacists, nurses, and dentists. Both
prescription and nonprescription medications can interact
with warfarin. It is important that you do not take any OTC
products containing aspirin unless specifically instructed by
your physician. In addition, you should not take ibuprofen
(eg, Motrin IB and Advil), naproxen (eg, Aleve), or ketoprofen
(eg, Orudis KT) without asking your physician or pharmacist.
If you have a headache or need a pain reliever, acetaminophen
(eg, Tylenol) is a safer option, but you should even limit how
much of this you use. You should check with your pharmacist
before taking any nonprescription medications, herbal medications, dietary supplements, vitamins, or other alternative
therapies, because they may also interact with warfarin.
• Drug–food interactions: Certain foods can alter your response
to warfarin therapy. These foods contain a relatively large
amount of vitamin K and include dark green leafy vegetables,
certain meats, oils, mayonnaise, and nutrition products. It is
important that you keep your intake of these foods consistent.
You should not drastically change your intake of these foods
from week to week. Alcohol can also alter your response to
warfarin. You should consult your physician before drinking
alcohol while taking warfarin. It is preferable to limit alcohol
intake to one or two alcoholic beverages per day unless you
have been instructed by your primary care provider to avoid
alcohol altogether.
• Side effects: Call your physician immediately if you experience
any abdominal pain or swelling, back pain, coughing up blood,
or vomiting of blood (this may look like coffee grounds), as
these symptoms might indicate internal bleeding from warfarin. You should also tell your physician if you notice a blue or
purple color and pain in the toes.
• Medical alert bracelet: It is a good idea to get a medical alert
bracelet for anticoagulants. This will notify healthcare providers that you are taking warfarin in the event that you are unable
to tell them yourself.
• Proper storage: Your warfarin should be kept in a cool (room
temperature), dry place that is out of the reach of children.
Refrigerators and bathroom cabinets are not good places to
keep medicines due to the humidity.
■■ FOLLOW-UP QUESTION
1.Based on this information, what are your recommendations
for her warfarin and LMWH therapy?
• The INR is now within the therapeutic range; however, you
will need to obtain a second therapeutic INR on a separate day
before enoxaparin can be discontinued. It appears that the current warfarin dose has increased the INR nicely over the past
7 days and this dose should be continued.
• Adherence: It is very important that you take your warfarin
dose every day. Even if you miss one dose, your blood tests
will show a difference. If you do forget to take a dose 1 day, you
should not take an extra dose the next day to “catch up.” In the
event that you happen to forget a dose, it is important to notify
your physician or pharmacist, so that he or she is aware of the
missed dose and can instruct you on what to do.
1.Ms Heartly has been diagnosed with hypothyroidism. Although
her TSH is within normal range at this time, how would
untreated hypothyroidism affect the INR?
• Administration time: It is important that you take your warfarin dose at the same time every day, preferably in the afternoon
or evening.
Patients with untreated hypothyroidism can be difficult to anticoagulate despite significant increases in the warfarin dose due to
a lower rate of metabolism of the vitamin K-dependent clotting
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
■■ ADDITIONAL CASE QUESTION
24-5
REFERENCES
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Chronic Anticoagulation
1. Holbrook A, Schulman S, Witt DM, et al. Evidence-based management
of anticoagulant therapy. Chest 2012;141:e152S–e184S.
2. Douketis JD, Spyropoulos AC, Spencer FA, et al. Perioperative management of antithrombotic therapy. Chest 2012;141:e326S–e350S.
3.Kearon C, Akl EA, Omelas J, et al. Antithrombotic therapy for
VTE disease: Chest Guideline and Expert Panel Report. Chest
2016;149:315–352.
4. Ageno W, Gallus AS, Wittkowsky A, et al. Oral anticoagulant therapy:
antithrombotic therapy and prevention of thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice
Guidelines. Chest 2012;141:e44S–e88S.
5. Baron TH, Kamath PS, McBane RD. Management of antithrombotic
therapy in patients undergoing invasive procedures. N Engl J Med
2013;368:2113–2124.
6.Douketis JD, Spyropoulos AC, Kaatz S, et al. for the BRIDGE
investigators. Perioperative bridging anticoagulation in patients with
atrial fibrillation. N Engl J Med 2015;373:823–833. doi: 10.1056/
NEJMoa1501035.
7. Linkins L, Dans AL, Moores LK, et al. Treatment and prevention of
heparin-induced thrombocytopenia. Chest 2012;141:e495S–e530S.
8. Garcia DA, Baglin TP, Weitz JI, Samama MM. Parenteral anticoagulants. Chest 2012;141:e24S–e43S.
9. Garwood CL, Gortney JS, Corbett TL. Is there a role for fondaparinux
in perioperative bridging? Am J Health Syst Pharm 2011;68:36–42.
10.ASGE Standards of Practice Committee, Anderson MA, BenMenachem T, et al. Management of antithrombotic agents for endoscopic procedures. Gastrointest Endosc 2009;70:1060–1070.
CHAPTER 24
factors. Once thyroid replacement therapy is initiated, the patient
should be monitored closely for an increase in the INR.