Transcript Deep Vein Thrombosis

Deep Vein Thrombosis
Physical Examination
GEN
Somewhat overweight, Caucasian man who appears
comfortable. Cooperative, A & O 3, normal affect.
VS
BP 132/76, P 75 regular, R 16, T 98.3°F, O sat 97/ra;
Wt 194 lb, Ht 6'0″
SKIN
Warm, dry, normal color. No rash or induration.
HEENT
Pupils equal and reactive to light. EOM intact.
Mucous membranes moist and pink
x
2
PATIENT PRESENTATION
CHIEF COMPLAINT
"I'm having pain in my leg."
HISTORY OF PRESENT ILLNESS
(HPI)
Rodney Cross is a 48-year-old man who presents to h
is primary care physician
because of pain in his right leg. He states that he
awoke with the pain 3 days ago and
that it has been continuous, although it hurts more
when he walks. The pain is located
behind his right knee and extends down into his cal
f. He rates the pain intensity as
3/10 at this time. The patient denies CP and SOB. H
e denies recent travel, immobility,
and leg injury. The patient did start
pravastatin
40 mg daily for treatment of
dyslipidemia approximately 3 months prior to this v
isit. He stopped the pravastatin 3
days ago because he thought it might be causing his
leg pain, but the pain has
continued.
PAST MEDICAL HISTORY (PMH)
Hypertension
Dyslipidemia
Graves' disease with thyroid ablation
Gout
Left ankle fracture 9 years ago that required a cast
but no surgery
Remote history of depression
PAST SURGICAL HISTORY (PSH)
Left herniorrhaphy about 10 years ago Pilonidal
cyst excision in remote past.
FAMILY HISTORY
Father died at age 81 of liver failure. Mother, one
brother, and son all alive and well
No family history of venous thromboembolism or
clotting disorders
SOCIAL HISTORY (SH)
Married, one adult child. Drinks one to two
alcoholic beverages daily. Smokes one
cigar per month, no cigarettes. Denies illicit drug
use.
Medications:
Allopurinol 300 mg po once daily
Hydrochlorothiazide 12.5 mg once daily
Lisinopril 10 mg once daily
Levothyroxine 150 mcg po once daily
Pravastatin 40 mg po once daily (discontinued 3
days ago)
All
NKDA
ROS
Constitutional: No chills, no fatigue.
Eyes: No eye pain or changes in vision.
ENT(ears,nose,throat): No sore throat.
Skin: No pigmentation changes, no nail changes.
Cardiovascular: No CP, palpitations, or syncope.
Respiratory: No cough, SOB, wheezing, or stridor.
GI: No abdominal pain, nausea, diarrhea, or
vomiting.
Musculoskeletal: No neck pain, back pain, or
injury.
Neurologic: No dizziness, headache, or focal
weakness.
Psychiatric/behavioral: Remote history of
depression. Not a current problem
Physical Examination
GEN (General)
Somewhat overweight, Caucasian man who appears
comfortable. Cooperative, A & O x 3, normal affect
VS( Vital signs)
BP 132/76, P 75 regular, R 16, T 98.3°F, O2 sat 97/ra;
Wt 194 lb, Ht 6'0″
SKIN
Warm, dry, normal color. No rash or induration.
HEENT (Head Eye Ear Nose Throat)
Pupils equal and reactive to light. EOM(extra occular
Movement) intact. Mucous membranes moist and
pink
NECK
Normal range of motion with no meningeal signs
LUNGS/THORAX
Breath sounds normal, no respiratory distress
CV
RRR, no rubs, murmurs, or gallops
ABD
Nontender, no masses, no distension, no
peritoneal signs
MS/EXT
Upper extremities: Normal by inspection, no CCE,
normal ROM(Range of motion).
Lower extremities: Right calf tight, warm to touch,
and tender with 1+ pretibial pitting edema. LLE
(Left lower extrremity) without redness,
warmth, and swelling. Lower extremity pulses
and sensation are normal bilaterally. Normal
ROM.
NEURO
Glasgow coma scale of 15, no focal motor deficits,
no focal sensory deficits
Labs
Na 140 mEq/L(Normal)
WBC 5.9 x 1o^3/L
(Normal)
K 3.9 mEq/L (Normal)
RBC 4.28 x 10^6/L
(Normal)
Cl 103 mEq/L(Normal)
Hgb 13.5 g/dL (Normal)
CO2 27 mEq/L
Hct 39.3%(Normal)
BUN 10 mg/dL (Normal)
MCV 92.0 fL(Normal)
SCr 0.84 mg/dL(Normal)
MCHC 34.4 g/dL
(Normal)
Glucose 88 mg/dL (Normal ,
controlled)
RBC dist 14.3
(Normal)
Uric acid 5.0 mg/dL(Normal)
Platelets 175 x 103/L
(Normal)
Labs
CK 117 IU/L
(Creatinine Kinase 60-117)
Mean platelet volume 7.2 fL
(7.5-11.5)
Granulocytes, electronic 51.0%
Lymphocytes, electronic 38.2%
(20-40%)
Monocytes, electronic 8.4%
(2-8%)
Eosinophils, electronic 1.9%
(1-4%)
Basophils, electronic 0.5%
(0.5-1%)
INR 1.0(Normal)
Lower extremity venous duplex ultrasonography:
"Acute DVT of right distal superficial femoral,
popliteal, and peroneal veins. No compression or
flow in these vessels."
(Note to reader: The "superficial femoral
vein" is actually a deep vein, in spite of
its name. Use of the name "femoral vein"
is preferred because it is less confusing.
However, the name "superficial femoral
vein" is still encountered, as it is in this
patient's venous duplex report.)
Assessment
Acute DVT in right distal femoral, popliteal, and
peroneal veins
CLINICAL PEARL
Current evidence does not clearly establish the
appropriate duration of anticoagulation therapy for
many patients with DVTs. A decision must therefore
be based on a careful comparison of the benefits of
continuing anticoagulation (primarily a decreased
risk of DVT recurrence and potential sequelae)
versus the risk of adverse events (primarily
bleeding) in each patient
Questions
Problem Identification
1.a. Create a list of this patient’s
medication-related problems.
• Drug therapy needed for newly diagnosed DVT
in right lower extremity.
• Drug therapy needed for dyslipidemia.
(Note: This problem results from the patient’s
discontinuation of pravastatin. No lipid data are
presented in this case. Identification of this
problem therefore assumes the previous
assessment that lipid-lowering therapy is needed
was correct. This potential problem is identified
here for completeness, but the reader is not
asked to address it.)
1.b. What subjective and objective findings
support the diagnosis of a lower extremity
DVT?
• The patient presents with unilateral pain, swelling,
warmth, and tenderness in his right calf. This
clinical presentation suggests a DVT, which is
confirmed by the absence of compressibility and
flow in the proximal deep veins of his right leg.
• The absence of CP and SOB; normal vital signs,
including a normal respiratory rate; normal
lungs/thorax and cardiovascular physical exam,
including the absence of an accentuated S2; and
normal O2 saturation in room air all suggest that a
PE has not occurred.
• The unilateral nature of the patient’s symptoms
along with a normal CK argues against statinrelated myopathy as the cause of this patient’s
problem.
Desired Outcome
2. What are the short- and long-term goals of
pharmacotherapy for this patient’s DVT?
• The short-term therapeutic goal is to quickly, safely,
and effectively anticoagulate this patient to prevent
extension of his DVT and minimize the risk
of embolization while minimizing his bleeding risk.
• The long-term goals are to maintain safe and
effective anticoagulation for an adequate period of
time to permit DVT resolution and to prevent the
development of postthrombotic syndrome. In
addition, careful consideration should be given to
the need for long-term anticoagulation therapy to
prevent recurrence of venous thromboembolism.
Therapeutic Alternatives
3. What therapeutic alternatives are available for the
pharmacologic management of this patient’s DVT?
• Oral warfarin therapy is the treatment of choice for chronic
anticoagulation of this patient, with a targeted international
normalized ratio (INR) of 2.5 (acceptable range: 2.03.0).1 However, establishing effective anticoagulation
with warfarinrequires several days to weeks.
• Concurrent use of a rapid-acting anticoagulant is therefore
indicated until that goal is achieved (INR ⩾2.0 × 2 days). Four
main options are available for this purpose in this
patient: subcutaneous LMWH; UFH; weight-adjusted, fixeddose subcutaneous UFH; and subcutaneous fondaparinux.
✓ Recent guidelines recommend the use of LMWH for the
initial treatment of DVT in the absence of PE because
current evidence demonstrates that LMWH is associated
with lower mortality, a lower incidence of adverse events
(both bleeding and HIT), and a cost saving or costeffectiveness.1Current evidence suggests that this initial
treatment with LMWH may occur on an outpatient basis,
although patients in studies addressing this issue have been
highly selected.1 Based on information available at this point
in his care, Mr Cross is a candidate for concurrent
outpatient therapy with LMWH (short-term) and warfarin.
✓ A decision to use IV UFH in this patient would require his
hospitalization until his INR is therapeutic and stable.
IV heparin therapy would be started with an 80 Units/kg bolus
followed by an 18 Units/kg/h infusion. The infusion rate would
traditionally be adjusted based on measurement of the
patient’s activated partial thromboplastin time, with
prolongation of the activated partial thromboplastin time to an
extent that would correspond to plasmaheparin levels of 0.30.7 IU/mL anti-Xa activity.1
✓ Recent data support the possibility of using weight-adjusted, fixed-dose subcutaneous UFH rather than LMWH
in the treatment of acute DVTs.2 In a randomized study of
708 patients with acute venous thromboembolism, an initial
subcutaneous UFH dose of 333 Units/kg followed by 250
Units/kg every 12 hours was as safe and effective as LMWH.
While the reduced cost of this approach and ability to avoid
hospitalization are appealing, the findings need to be
confirmed by other investigators before the routine use of
weight-adjusted, fixed-dose subcutaneous UFH can be
advocated. However, this approach is included as a treatment
option in the 2008 ACCP guidelines.1
✓ The final option for the acute treatment of this
patient is fondaparinux, a relatively new anticoagulant
that inhibits thrombin formation by binding
toantithrombin III and potentiating factor Xa
inactivation. Fondaparinux is approved for the initial
treatment of acute DVTs, including its use on an
outpatient basis in the absence of PE. The dosage
regimen for this 88-kg patient would be 7.5 mg
subcutaneously once daily for at least 5 days and until
the INR is at goal (2.0-3.0). The place of fondaparinux
relative to UFH and LMWH in the treatment of DVTs
with or without PE is an active area of research.3
• Consideration of more aggressive treatment strategies, including catheterdirected thrombolysis, thrombectomy, and placement of an inferior vena cava
filter, is not warranted in this patient.1
• Consideration should be given to recommending the patient wear compression
stockings to minimize the risk of postthrombotic syndrome.1 Available data
suggest that wearing either custom-fit or over-the-counter compression
stockings with an ankle pressure gradient of 30-40 mm Hg starting within 1 week
to 1 month of an acute DVT and continuing for at least 2 years reduces the
incidence of postthrombotic syndrome by approximately half.1
• Dabigatran etexilate, an oral direct thrombin inhibitor, may provide an
alternative to warfarin for the treatment of acute DVTs in the United States in
the near future.4,5 Dabigatran was approved by the U.S. FDA in October 2010 for
prevention of stroke and embolism in patients with atrial fibrillation. It was not
approved for treatment of DVT at the time of this writing.
class of anticoagulant drugs which act directly upon Factor
X in the coagulation cascade, without using antithrombin as
a mediator.[1]
Direct factor Xa inhibitors are being used clinically.
Clinical trials have shown promise for these compounds
as substitutes for the currently administered vitamin
K antagonists or low molecular weight heparin. Those
trials demonstrated efficacy and safety against warfarin
for stroke prevention in atrial fibrillation and against lowmolecular-weight heparin for treatment and secondary
prevention of venous thromboembolism or for initial
treatment and prevention of venous thromboembolism in
patients undergoing hip or knee replacement.[2]
Optimal Plan
4. Design a treatment plan for the initial management of this
patient’s DVT. Be sure to include dosage form, dose,
schedule, and duration of therapy for each
drug that is part of the plan.
• Start the patient on concurrent subcutaneous LMWH and
oral warfarin therapies. At our institution, the LMWH would
be enoxaparin, 1 mg/kg every 12 hours. Since this patient’s
body weight is 88 kg, the ideal dose would be 88 mg every
12 hours, which would be rounded to 90 mg for practical
purposes. Unfortunately, enoxaparinis not marketed in 90-mg
prefilled syringes; it is available in 80- and 100-mg prefilled
syringes. One must therefore choose either to round the dose
up or down or to have the patient (or caregiver) expel 10 mg
from a 100-mg syringe. Expelling part of the syringe contents
can be difficult and lead to dosing errors, so we generally try
to avoid this approach. We would choose a dose of 100 mg
every 12 hours as a practical option for this patient.
✓ Enoxaparin 1.5 mg/kg subcutaneously once daily might
also be considered, although this regimen is not FDAapproved for outpatient use and may be associated with a
higher risk of recurrent VTE.6
✓ There is no need for dose adjustment for either decreased
kidney function (estimated creatinine clearance =112
mL/min using ideal body weight of 73.8 kg or 121 mL/min
using adjusted body weight of 79.6 kg) or liver function
(hepatic function panel not available, but findings on
history and physical exam do not suggest liver disease and
baseline INR was 1.0).
• Continue this enoxaparin dosage regimen for at least 5 days
and until the patient’s INR is ⩾2.0 for 2 consecutive days.
✓ Equivalent regimens of dalteparin (200 U/kg per day
subcutaneously divided into once or twice daily injections
with a maximum of 18,000 U per dose) or tinzaparin (175
anti-Xa U/kg subcutaneously once daily) could also be
used.
• Also start the patient on warfarin with instructions to take one
5-mg tablet by mouth daily. The duration of warfarin therapy
is difficult to determine at this point. Current ACCP guidelines
recommend anticoagulation for at least 3 months for patients
with an unprovoked DVT.1 The guidelines recommend a riskbenefit assessment at that point. Long-term anticoagulation
therapy is recommended for patients with a first, unprovoked,
proximal DVT who do not have significant risk factors for
bleeding and who do have good monitoring available. The
thrombophilia testing completed at baseline will help guide
the decision in this patient.
Outcome Evaluation
5. Design a monitoring plan for this patient’s DVT therapy.
Be sure to include monitoring for both safety and efficacy.
• Mr Cross should visit his primary care physician or an
anticoagulation clinic approximately 3 days after his visit to
the ED.
• Assess the patient for the following:
✓ Continuing signs and symptoms of DVT and/or PE (see the
section “Problem Identification”), with the expectation that
DVT-related findings should be stable or improving and no
new findings consistent with a PE should be present;
✓ Signs and symptoms of bleeding (see the section “Patient
Education”) or other medication-related adverse effects;
✓ Adherence to the anticoagulation regimen;
✓ Adherence to dietary recommendations;
✓ Alcohol consumption;
✓ Changes in over-the-counter, herbal, or prescription
medications; and
✓ INR response.
• Do not monitor this patient’s platelet count since he has not
received heparin and does not have a history of HIT.1
• Increase the warfarin dose if the patient has been adherent
and his INR has not changed significantly (e.g., INR <1.5).
Decrease the warfarin dose if the patient’s INR has increased
too rapidly (e.g., INR >1.9).
• Reinforce or extend the initial patient education (see the
section “Patient Education”), as appropriate.
• Assess the patient at approximately 2- to 5-day intervals until
a stable INR within the targeted range of 2.0-3.0 is achieved,
at which point you should stop theenoxaparin. Recommended
minimum duration of enoxaparin therapy is 5 days. Use of
less frequent visits (e.g., 1 week to 10 days) tends to extend the
time toenoxaparin discontinuation.
• Assess the patient approximately 1 week after discontinuation
of enoxaparin to assure that his INR is stable and therapeutic.
If it is, assess the patient at 1-month intervals as long as the
INR is stable and there is no recurrence of venous
thromboembolic symptoms.
Patient Education
6. What education should be provided for this
patient to optimize the probability
of therapeutic success while minimizing the risk
of adverse events?
General information:
• You have blood clots in several veins in your right leg.
This is called deep vein thrombosis or DVT. Symptoms
of a DVT include pain, swelling, redness, and warmth in
the affected leg.
• It is important that your DVT is treated properly to
prevent a piece of a blood clot in your leg from breaking
off and traveling to your lungs. If this happens, it is
called a pulmonary embolism or PE. Symptoms of a PE
include chest pain and shortness of breath. Get medical
attention if you develop these symptoms because a PE
can be life-threatening.
• Effective treatment of your DVT will also decrease the
risk of your developing a condition known as
postthrombotic syndrome, which would be a long-term
problem with pain, swelling, and possibly open sores on
your leg.
• Treatment of your DVT will include two medicines that
are called anticoagulants. Anticoagulants decrease the
ability of your blood to clot. They are used to treat or
prevent harmful blood clots. The two anticoagulants you
will be using areenoxaparin (or Lovenox)
and warfarin (frequently called Coumadin). You will only
need to use the enoxaparin until the warfarin is
providing effective anticoagulation.
Enoxaparin:
• Enoxaparin is an anticoagulant that is used to treat or prevent harmful
blood clots. It is available as the brand name Lovenox. Lovenox must be
given by injection under your skin, preferably in your stomach area.
• You will be injecting 100 mg of Lovenox twice each day (about every 12
hours). The syringes you receive from the pharmacy will have that
amount of Lovenox in each syringe. You should use the following steps
to give these injections in your stomach area (Note: Pictures or
diagrams should be used to explain this procedure to the patient, and
the patient should be asked to demonstrate the technique once he
understands how to do it.):
1. Wash your hands with soap and water.
2. Sit so you can see your stomach. It may be helpful to recline slightly.
3. Choose an injection site. It should be on the lower part of your
stomach area, below your ribs and above your hip bones, and at least
2 in away from your belly button, incision sites, or scars. Alternate
the injection sites between your right and left sides, and try not to use
the same site twice.
4. Clean the injection site with an alcohol wipe and let it dry.
5. Prepare the syringe you are going to use for the
injection. Hold the syringe in your right hand if you are righthanded, or left hand if you are left-handed. Remove the needle
cover with your other hand. Do not push any liquid or air from
the syringe before giving the injection. Do not touch the exposed
needle or allow it to touch anything else.
6. Gently pinch the injection site to form a skin fold between the
thumb and forefinger of your free hand.
7. Insert the needle straight into the skin fold. The full length of the
needle should be inserted at a 90˚ angle to the skin.
8. Push the entire contents of the syringe into the skin fold. Do not
pull back on the plunger.
9. Remove the needle by pulling it straight out of the skin and then
release the skin fold. Do not rub the injection site since that will
increase bruising.
10. Point the used syringe away from you and others, and then
push on the plunger to activate the safety shield. Dispose of the
empty syringe in a puncture-proof container. Store the container
of used syringes away from children.
• If you forget to inject a dose of Lovenox, inject it as soon as you
remember unless it is almost time for your next dose and then
resume your normal schedule. If it is almost time for your next
dose, skip the forgotten dose and resume your normal schedule.
• You may experience some discomfort/pain/stinging or redness at
the injection site.
• The most common side effects of Lovenox are related to bleeding.
Call us or seek emergency medical care, as appropriate, if you
experience any of the following: bleeding from your gums or
nose, bruising easily, coughing up blood, red or dark brown
urine, red or black stools, vomiting of blood (may look like coffee
grounds), or bleeding from cuts or wounds that does not stop.
• Allergic reactions to Lovenox are rare, but might include itching
or hives; swelling of your face, hands, mouth, or throat; chest
tightness; or trouble breathing. Please let us know if you
experience any other symptoms that you think might be related
toLovenox, including nausea, diarrhea, confusion, excessive
bruising, pain, redness, swelling, or a lump at an injection site.
Warfarin:
• Warfarin is an anticoagulant that is used to treat or prevent
harmful blood clots. It is sometimes called a “blood thinner,”
although it does not really “thin” your blood.Warfarin is
available as a generic or by brand names such
as Coumadin andJantoven.
• You will be taking 5-mg warfarin tablets. You will start by taking
one 5-mg tablet at about the same time each day. I recommend
that time be in the evening since you will be able to more quickly
adjust your dose of warfarin when you have your INR checked,
but the most important thing is to pick a time of the day when
you will remember to take it each day. You may
take warfarin either with or without food.
• If you miss or forget to take a dose, take that dose as soon as you
can if it is within 12 hours of when you were supposed to take it.
Skip the dose if more than 12 hours have passed. Please make a
note of any missed or skipped doses so that you can tell me and
your doctor about them at your next appointment.
• It
is likely that your dose of warfarin will need to be adjusted up or down
to make sure you are taking the right dose. We will use a test called an
“INR” to measure how much effect warfarin is having on your blood’s
ability to clot. A normal INR is 1.0. The higher the INR is, the longer it
takes for your blood to clot. Our goal is to maintain your INR between
2.0 and 3.0. Lower INRs put you at risk of another DVT or pulmonary
embolism, while higher INRs put you at greater risk of bleeding. We will
measure your INR frequently at first (every few days to a week). Once
your INR is stable and at goal, we will measure your INR once a month.
• Many prescription, over-the-counter, and herbal medicines can change
the effectwarfarin has on your blood clotting. These interactions can
either make warfarinmore effective (and increase your risk of bleeding)
or make it less effective (and increase your risk of another clot or
pulmonary embolism). Make sure that all of your health care providers
know that you take warfarin so they can take that into consideration
when prescribing a new drug or discontinuing or changing the dose of a
drug you are currently taking. One group of medicines to be cautious
with is the anti-inflammatory drugs such as aspirin, ibuprofen,
and naproxen. These medicines can cause stomach bleeding, which can
be dangerous when you are taking warfarin. Please discuss your need
for these medicines with your physician before taking them.
• Warfarin will work best and be safest when the amount of vitamin
K in your diet is relatively consistent. You should avoid big
changes (either up or down) in your vitamin K intake. Foods that
contain large amounts of vitamin K include broccoli, Brussels
sprouts, cabbage, lettuce (other than iceberg), greens, and
spinach.
• Drinking alcohol may affect your warfarin therapy. It is safest to
avoid alcoholwhile you are taking warfarin. If this is not possible,
intake should be limited to no more than one or two drinks per
day.
• The most common side effects of warfarin are related to bleeding.
Call us or seek emergency medical care, as appropriate, if you
experience any of the following: bleeding from your gums or
nose; bruising easily; coughing up blood; red or dark brown
urine; red or black stools; vomiting of blood (may look like coffee
grounds); sudden, severe headaches, possibly accompanied by
symptoms such as vision changes, slurred speech, or muscle
weakness; or bleeding from cuts or wounds that does not stop.
Also call us or seek medical care if you experience purple
discoloration of your toes or soles of your feet, or develop skin
sores.
• Allergic reactions to warfarin are rare, but might include
itching or hives; swelling of your face, hands, mouth, or
throat; chest tightness; or trouble breathing. Please let us
know if you experience any other symptoms that you think
might be related towarfarin.
• You are likely to bleed more easily while you are
taking warfarin. Lifestyle changes can help minimize the
risk of bleeding. Do not engage in contact sports or other
activities that increase your risk of bruises, cuts, or injuries.
Be careful when using sharp objects, and brush and floss
your teeth gently.
• Please let us know any time you are going to be undergoing
medical, surgical, or dental testing or procedures. It may be
necessary to stop your warfarin therapy before such
procedures.
• Finally, it is recommended that you wear a medical alert
bracelet and/or carry an ID card that would let emergency
caregivers know you are taking warfarin.
Follow-Up Questions
1.a. Identify the patient’s anticoagulation therapyrelated drug therapy problem(s), and design treatment
and monitoring plans for managing each problem you
identify.
• Anticoagulation therapy-related problem: patient is
taking warfarin for treatment of his DVT and has not yet
achieved the therapeutic range. His INR has increased to 1.7
after 3 days of treatment. The patient should be closely
questioned to try to identify any anticoagulation therapy-related
problems. Assuming issues are identified, the plan would be to:
✓ Continue enoxaparin therapy.
✓ Maintain current warfarin dose. Some might advocate a
small warfarindose decrease with this magnitude of initial
response to avoid overshooting the targeted INR, but we
would likely continue 5 mg warfarin daily with careful
monitoring.
✓ See the patient in 2-3 days to assess his response to the
continued dose of 5 mg warfarin daily, as well as to perform an
overall assessment as outlined above.
1.b. Identify the patient’s anticoagulation therapyrelated drug therapy problem(s), and design treatment
and monitoring plans for managing each problem you
identify.
• Anticoagulation therapy-related problem: patient may have
experienced an adverse event, hematuria, possibly related to
anticoagulation with warfarin for treatment of his DVT. Given
that this is an isolated event and the patient’s INR is within
the therapeutic range, the plan would be to:
✓ Check a standard urine dipstick, microscopic urine, and
culture and sensitivity to rule out a urinary tract infection and
microscopic hematuria.
✓ Obtain a urology consult to rule out other kidney or bladder
causes of hematuria if no urinary tract infection is identified.
✓ Continue current warfarin dosage regimen.
✓ See the patient in 1 month to reassess, including measurement
of INR. Instruct patient to call if hematuria or any other
symptom of bleeding occurs before that visit.
.
• In this patient, the standard urine dipstick was negative (clear
appearance, yellow color, specific gravity =1.020, pH 5.5,
and glucose, bilirubin, ketones, blood, protein, nitrites, and
leukocyte esterase all negative). The microscopic urine was also
negative (white blood cells, red blood cells, and bacteria all
absent). The culture of a clean catch urine was reported as
negative. The patient was therefore referred to a urologist
• The patient was seen by the urologist after his episode
of hematuria. The urologist’s history and physical exam revealed
no new findings. A urinalysis was negative for blood, nitrites,
and leukocyte esterase. A renal ultrasound revealed “no evidence
of any hydronephrosis, tumors, stones, or other abnormalities.”
Urine cytology was negative. The urologist’s recommendation
was for “further observation.”
• This patient therefore appears to have experienced an isolated
episode of hematuria while on warfarin with a therapeutic INR
and no other identifiable cause. He has not experienced a
recurrence after over 2 years of observation.
1.c. Identify this patient’s anticoagulation therapyrelated drug problem(s), and design a treatment and
monitoring plan for each problem that you identify.
Be sure to specify the anticipated duration of his
anticoagulation therapy.
• Anticoagulation therapy-related problem: the patient is
taking warfarin for treatment of his DVT and has exceeded
the targeted INR range of 2.0-3.0. Possible causes include
a drug interaction with simvastatin and a change in
analytic method used to measure the prothrombin time.
• Available data suggest that simvastatin may increase the
INR in patients takingwarfarin, but pravastatin does not.79 These data and the time frame of the patient’s switch
from pravastatin to simvastatin are consistent with his
increased INR caused by the initiation
of simvastatin therapy.
• A second factor that possibly contributed to the increased
INR relates to a change in the analytic method used to
measure it. The INR from the previous month was
measured on a venous blood sample by the clinical lab
using a STA-R Evolution (Stago Diagnostica, Inc). The INR
from this visit was measured using a CoaguChek XS (Roche
Diagnostics). Substantial intermethod variability in the
measurement ofINRs exists. In our experience, the
CoaguCHek XS systematically measures high INRs higher
than the STA-R Evolution.
• The plan for managing this patient’s warfarin therapy was the
following:
✓ Hold warfarin dose × 1 and then decrease warfarin maintenance
dose to 2.5 mg 5 days per week and 5 mg 2 days per week (e.g.,
2.5 mg on Monday, Wednesday, Thursday, Friday, and Sunday
and 5 mg on Tuesday and Saturday). This is a 10% dose decrease
from 25 to 22.5 mg per week. A further dose decrease may be
required depending on the INR response.
✓ Repeat lupus anticoagulant studies to confirm presence of lupus
anticoagulants. A dilute Russell’s viper venom time (dRVVT),
dRVVT Confirm if dRVVT elevated, and StaClot LA would be
most helpful since patient is currently taking warfarin. These
tests will help guide the decision regarding duration of this
patient’s anticoagulation therapy. If the repeat tests are positive,
this patient meets the diagnostic criteria for antiphospholipid
syndrome.10 These criteria require the detection of lupus
anticoagulant antibodies (or other antiphospholipid antibodies)
on at least two occasions at least 12 weeks apart.
✓ As noted previously, current ACCP guidelines recommend
long-term anticoagulation therapy for patients such as Mr
Cross with a first, unprovoked, proximal DVT who do not
have significant risk factors for bleeding and who do have
good monitoring available.1 If repeat testing for lupus
anticoagulants is positive, this recommendation would be
strengthened since the presence of lupus anticoagulants is
known to significantly increase the risk of VTE
recurrence.1 Mr Cross does not have an antithrombin
III, protein C, or protein S deficiency or a factor V Leiden
or prothrombin G-20210-A mutation, any of which would
further increase his risk of VTE recurrence.
✓ See the patient in 2 weeks to reassess, including
measurement of INR. Instruct patient to call if any signs or
symptoms of bleeding occur before that visit. Some might
choose to see the patient sooner (e.g., 7-10 days) to assess
the response to the decreased warfarin dose and the
possibility of an ongoing simvastatin interaction.
✓ In this patient, lupus anticoagulant studies were repeated
several months after the patient’s initial presentation. The
partial thromboplastin time was elevated beyond any effect
expected from warfarin and the dRVVT/dRVVT Confirm
and StaClot LA were again positive. A decision to
anticoagulate this patient indefinitely was therefore made
with a targeted INR of 2.5 (acceptable range: 2.0-3.0).
Current guidelines recommend a higher target of 3.0
(acceptable range: 2.5-3.5) only in lupus anticoagulant
patients who have a VTE recurrence while their INR
is therapeutic or have additional risk factors for VTE
events.11
THE END