Deep Vein Thrombosis
increased risk of DVT; estrogen plus pro-
BASIC INFORMATION
DEFINITION
Venous thromboembolism is any thromboem-
bolic event occurring within the venous system.
Deep vein thrombosis (DVT) is the development
of thrombi in the deep veins of the extremities
or pelvis.
SYNONYMS
DVT
Venous thromboembolism (VTE) (VTE includes
DVT and pulmonary embolism [PE])
Deep venous thrombosis
VTE
ICD-10CM CODES
I82.401 Acute embolism and thrombosis of
unspecified deep veins of right lower
extremity
I82.402 Acute embolism and thrombosis of
unspecified deep veins of left lower
extremity
I82.403 Acute embolism and thrombosis
of unspecified deep veins of lower
extremity, bilateral
I82.621 Acute embolism and thrombosis of
deep veins of right upper extremity
I82.622 Acute embolism and thrombosis of
deep veins of left upper extremity
I82.623 Acute embolism and thrombosis of
deep veins of upper extremity, bilateral
EPIDEMIOLOGY &
DEMOGRAPHICS
• Annual incidence of VTE is 0.1% to 0.27%,
affecting up to 5% of the population during
their lifetimes.
• The risk of recurrent thromboembolism is
higher among men than women.
• In the U.S., there are approximately 900,000
DVT events annually. About 5% to 15% of
persons with untreated DVT die from pulmo-
nary embolism.
• Venous thromboembolism occurs in nearly 2
cases per 1000 pregnancies and is a leading
cause of maternal mortality and morbidity
PHYSICAL FINDINGS & CLINICAL
PRESENTATION
• Pain and swelling of the affected extremity
• In lower extremity DVT: leg pain on dorsiflex-
ion of the foot (Homans’ sign)
• Physical examination may be unremarkable
in early DVT
ETIOLOGY
The etiology is often multifactorial (prolonged
stasis, coagulation abnormalities, vessel wall
trauma). The following are risk factors for DVT:
• Prolonged immobilization (>3 days)
• Postoperative state
• Trauma to pelvis and lower extremities for
lower extremity DVT; central line placement
for upper extremity DVT
• Birth control pills, high-dose estrogen
therapy; conjugated equine estrogen but
not esterified estrogen is associated with
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409
gestin is associated with doubling the risk
of venous thrombosis. The use of bevaci-
zumab is also significantly associated with
an increased risk of developing DVT in cancer
patients receiving this drug.
• Visceral cancer (lung, pancreas, alimentary
tract, genitourinary tract)
• Occult cancer is detected in 1 in 20 patients
within a year of receiving a diagnosis of
unprovoked VTE
• Age >60 yr
• History of thromboembolic disease
• Hematologic disorders (e.g., factor V Leiden
mutation [FVL], antithrombin III deficiency,
protein C deficiency, protein S deficiency,
heparin cofactor II deficiency, sticky platelet
syndrome, G20210A prothrombin mutation,
lupus anticoagulant, dysfibrinogenemias,
anticardiolipin antibody, hyperhomocystein-
emia, concurrent homocystinuria, high levels
of factors VIII, XI, and single nucleotide poly-
morphisms [SNPs] such as CYP4V2)
• Pregnancy and early puerperium
• Obesity (BMI >30)
• Congestive heart failure
• Surgery, fracture, or injury involving lower leg
or pelvis
• Plaster cast immobilization
• Surgery requiring >30 min of anesthesia
• Gynecologic surgery (particularly gynecologic
cancer surgery)
• Recent travel (within 2 wk, lasting ≥2 hr).
Every 2 hr spent traveling increases VTE risk
by 18%.
• Smoking and abdominal obesity
• Central venous catheter or pacemaker insertion
• Superficial vein thrombosis (10% risk of DVT
within 3 mo), varicose veins
• Collagen vascular disease
• Nephrotic syndrome
• Myeloproliferative disorders
• Testosterone therapy
• Long-term exposure to particulate air pollu-
tion is also associated with altered coagula-
tion function and DVT risk.
TABLE 1  Wells Scoring Scheme for Pre-Test Probability of Deep Vein
Thrombosis*
Clinical Feature
Risk Factors
Active cancer
Paralysis, paresis, or recent plaster immobilization of the lower extremities
Recently bedridden >3 days or major surgery, within 4 weeks
Signs
Localized tenderness along the distribution of the deep venous system
Entire leg swollen
Asymmetric calf swelling (>3 cm difference, 10 cm below tibial tuberosity)
Asymmetric pitting edema
Collateral superficial veins (nonvaricose)
Alternative Diagnosis
Alternative diagnosis as likely or more likely than deep venous thrombosis
*Interpretation of score: high probability if 3 points or more, moderate probability if 1 or 2 points, and low probability if 0 points or less.
From Wells PS, et al.: Value of assessment of pretest probability of deep-vein thrombosis in clinical management. Lancet.
350:1795–1798, 1997 in McGee S: Evidence-based physical diagnosis, ed 4, Philadelphia, 2018, Elsevier.
DIAGNOSIS D
DIFFERENTIAL DIAGNOSIS
• Postphlebitic syndrome
• Superficial thrombophlebitis
• Ruptured Baker’s cyst
• Cellulitis, lymphangitis, Achilles tendinitis
• Hematoma
• Muscle or soft tissue injury, stress fracture
• Varicose veins, lymphedema
• Arterial insufficiency
and Disorders
Diseases
• Abscess
• Claudication
• Venous stasis
WORKUP
• The clinical diagnosis of DVT is inaccurate.
Pain, tenderness, swelling, or color changes
are not specific for DVT.
I
• Clinical prediction rules can be used to
establish pretest probability of DVT. The Wells
prediction rules for DVT and for pulmonary
embolism are described in Table 1. These
rules perform better in younger patients
without a history of DVT and in those without
comorbidities. In younger patients without
associated comorbidities and a low pretest
probability using Wells criteria and a negative
high-sensitivity D-dimer test, the diagnosis of
DVT can be reasonably excluded.
• Compression ultrasonography (CUS; Fig. E1)
is preferred as the initial study to diagnose
DVT in patients with intermediate to high pre-
test probability. An initial negative test limited
to the proximal leg should be repeated after
5 days (if the clinical suspicion of DVT per-
sists) to exclude DVT that is propagating
proximally from the calf. Comprehensive
ultrasonography (whole-leg CUS) is a more
extensive test that examines the deep veins
from the inguinal ligament to the level of the
malleolus. Literature reports indicate that it
may be safe to withhold anticoagulation after
negative results on comprehensive duplex
ultrasonography in nonpregnant patients with
Points
1
1
1
1
1
1
1
1
−2
410 Deep Vein Thrombosis
a suspected first episode of symptomatic
DVT of the leg.
LABORATORY TESTS
• Laboratory tests are not specific for DVT.
Baseline prothrombin time (INR), partial
thromboplastin time, and platelet count
should be obtained on all patients before
starting anticoagulation. D-dimer testing is
sensitive but not specific for DVT. A negative
result (D-dimer <0.5 mcg/ml) can exclude
the diagnosis in a patient with low probability
of DVT, but a positive result (≥0.5 mcg/ml)
mandates additional testing with venous
ultrasonography.
• Use of D-dimer assay by ELISA is useful in the
management of suspected DVT. The combi-
nation of a normal D-dimer study on presen-
tation together with a normal compression
venous ultrasound is useful to exclude DVT.
DVT can be ruled out in patients who are
clinically unlikely to have DVT and who have
a negative D-dimer test. Compressive ultra-
sonography can be safely omitted in such
patients.
• Laboratory evaluation of young patients
with DVT, patients with recurrent thrombosis
without obvious causes, and those with a
family history of thrombosis should include
protein S (both total and free PS), protein C,
fibrinogen, antithrombin III level, lupus anti-
coagulant, anticardiolipin antibodies, anti-b2
glycoprotein1, factor V Leiden, factor VIII,
factor IX, and fasting plasma homocysteine
levels. HIT antibody may also be useful in the
correct context (heparin exposure and abrupt
onset of unexplained decrease in platelet
count, whether thrombocytopenic or not). It
is important to remember that the lupus anti-
coagulant assay and antithrombin, protein C,
protein S, and dysfibrinogenemia testing can-
not be properly interpreted if the patient is
already on warfarin, whereas anticardiolipin
antibody test, prothrombin G20210A factor
VII:C, factor V Leiden, and PT polymorphism
can be performed when the patient is on
warfarin.
IMAGING STUDIES
• Compression ultrasonography (CUS) is gen-
erally preferred as the initial study because
it is noninvasive and can be repeated serially
(useful to monitor suspected acute DVT); it
offers good sensitivity for detecting proximal
vein thrombosis (in the popliteal or femoral
vein). Its disadvantages are poor visualiza-
tion of deep iliac and pelvic veins and poor
sensitivity in isolated or nonocclusive calf
vein thrombi. Whole-leg compression ultra-
sound can generally exclude proximal and
distal DVT in a single evaluation. Withholding
anticoagulation following a single negative
whole-leg CUS is associated with a relatively
low risk of venous thromboembolism (3.5%
of inpatients will develop DVT) during a 3-mo
follow-up.
• Contrast venography is the gold standard for
evaluation of DVT of the lower extremity. It
is, however, invasive and painful. Additional
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disadvantages are the increased risk of phle-
bitis, new thrombosis, renal failure, and
hypersensitivity reaction to contrast media;
it also gives poor visualization of the deep
femoral vein in the thigh and the internal iliac
vein and its tributaries.
• Magnetic resonance direct thrombus imag-
ing (MRDTI) is an accurate noninvasive test
for diagnosis of DVT. It is particularly useful
in suspected DVT patients with leg casts,
which prevent CUS, and in pregnant patients
with positive D-dimer and negative CUS.
Current limitations are its cost and lack of
widespread availability.
TREATMENT
NONPHARMACOLOGIC THERAPY
• Gradual resumption of normal activity.
Immobility promotes stasis and propagation
of DVT. Patients should get up and walk as
tolerated. The theoretical risk that ambulation
may dislodge thrombi in the legs, precipitat-
ing PE, is unfounded.
• Patient education on anticoagulant therapy
and associated risks.
ACUTE GENERAL Rx
• Initial treatment of DVT requires therapeu-
tic doses of heparin (low-molecular-weight
heparin [LMWH] or unfractionated). LMWH is
preferred due to ease of administration, less
hemorrhage, and significantly fewer deaths.
Unfractionated heparin is recommended in
patients with renal insufficiency because
LMWH is predominantly excreted in the
urine.
• LMWH is generally administered for 5 to 7
days. Recommended dose of enoxaparin is
1 mg/kg q12h SC. Once-daily fondaparinux,
a synthetic analogue of heparin, is also as
effective and safe as twice-daily enoxapa-
rin in the initial treatment of patients with
symptomatic DVT. Once systemic antico-
agulation is initiated, vitamin K antagonist
warfarin or oral factor V inhibitors are initi-
ated. Preferred alternatives to warfarin may
include the oral factor Xa inhibitors rivar-
oxaban, apixaban, edoxaban, or dabigatran,
a direct oral thrombin inhibitor. These new
anticoagulants are noninferior to warfarin,
do not require periodic lab monitoring, and
have a relatively low bleeding risk. They are
preferred agents for extended treatment
of venous thromboembolism if cost is not
a significant issue. When using warfarin,
it is normally started on the same day as
heparin and is titrated to maintain an INR
between 2 and 3. Warfarin therapy at 10 mg
daily for 2 days may be initiated in healthy
patients with acute DVT. This higher dose
helps achieve therapeutic INR sooner and
decreases LMWH doses needed as com-
pared to the 5 mg/day dose. After ≥5 days,
heparin is stopped and warfarin is con-
tinued as monotherapy. Long-term LMWH
may be preferable to warfarin in patients
with cancer or those whose INR is difficult
to control.
• Outpatient treatment of DVT is appropriate
for patients without thrombophilic condi-
tions or substantial comorbidity. Exclusions
from outpatient treatment of DVT include
patients with potential high complication
risk (e.g., hemoglobin <7, platelet count
<75,000, guaiac-positive stool, recent cere-
brovascular accident or noncutaneous sur-
gery, noncompliance).
• Compression stockings are effective in
reducing the incidence of postthrombotic
syndrome and should be used starting within
1 mo of proximal DVT and continued for at
least 1 yr after diagnosis.
• Insertion of an inferior vena cava filter to
prevent pulmonary embolism is recom-
mended in patients with contraindications
to anticoagulation (e.g., hemorrhagic stroke,
active internal bleeding, pregnancy), HIT in
a patient with an active VTE/PE, recurrent
PE despite adequate anticoagulant therapy,
emergent surgery in patient with DVT, pres-
ence of free-floating iliofemoral thrombus,
lower IVC thrombosis (incipient embolization),
and chronic pulmonary (thromboembolic)
hypertension with limited pulmonary reserve.
Table 2 summarizes indications for IVC filter
placement.
• Thrombolytic therapy (streptokinase) can be
used in rare cases (unless contraindicated)
in patients with extensive iliofemoral venous
thrombosis and a low risk of bleeding. There
are concerns about hemorrhagic complica-
tions related to the large doses of thrombo-
lytics required in systemic thrombolysis for
DVT (2% to 10% risk of major hemorrhagic
complications).
• Other treatment modalities for DVT include
surgical thrombectomy and catheter-directed
thrombolysis (CDT). Thromboreduction by
surgical thrombectomy is effective but inva-
sive and expensive. CDT is also invasive,
carries a bleeding risk, and will generally
require ICU admission.
CHRONIC Rx
• The optimal duration of anticoagulant therapy
varies with the cause of DVT and the patient’s
risk factors. The risk of recurrence is low
if VTE is provoked by surgery, intermedi-
ate if provoked by a nonsurgical risk factor,
and high if unprovoked. These risks should
determine whether patients with VTE should
undergo short-term vs. indefinite treatment.
• Therapy for 3 mo is generally satisfactory
in patients with reversible risk factors (low-
risk group). A high D-dimer level measured
after 3 mo of anticoagulation in patients
with unprovoked DVT should favor a longer
duration of therapy. The American College of
Chest Physicians Guidelines suggests that
patients with first unprovoked VTE receive
indefinite anticoagulation unless their bleed-
ing risk is high.
• The risk of recurrence in patients with a first
unprovoked VTE who have negative D-dimer
results is not low enough to justify stopping
anticoagulant therapy in men but may be
low enough in some cases to justify stopping
 Deep Vein Thrombosis 411

TABLE 2  Indications for IVC Filter Placement

Indications for IVC Filter Placement Examples
D
1. DVT and contraindication to anticoagulation (A) Hemorrhage while on anticoagulation.
2. DVT and failure of anticoagulation (A) Recurrent DVT or PE despite anticoagulation, inability to achieve or maintain
adequate anticoagulation.
3. DVT and low cardiopulmonary reserve or high mortality risk from Severe pulmonary hypertension, right heart failure, known large right-to-left
possible PE (R) shunt.
4. Populations with very high risk for PE (R) Some postbariatric, orthopedic or neurosurgical patients or multitrauma
patients. Patients with expected prolonged immobilization.
5. High risk for life-threatening PE (R) Large, unstable (free-floating) IVC clot

and Disorders
Diseases
6. DVT and high fall risk (R)
7. Prophylaxis during catheter-directed thrombolysis of DVT (R)

There are two absolute indications for IVC filter placement: first, if the patient is at risk for PE (i.e., DVT) but for whatever reason he/she is not a candidate for systemic anticoagulation (i.e., hemorrhage);
and second, if the patient developed a PE, new DVT, or an extension of DVT while on proper anticoagulation. There are a number of relative indications for filter placement. They are presented in
rows 3 through 7. In every case the decision to place a filter compels careful consideration of the risks and benefits and may require multidisciplinary input. (A), Absolute; DVT, deep vein thrombo-
sis; IVC, inferior vena cava; PE, pulmonary embolism; (R), relative.
From Cameron JL, Cameron AM: Current surgical therapy, ed 12, Philadelphia, 2017, Elsevier.
therapy in women who were taking estrogen
at the time of initial VTE.1
• Anticoagulation for 6 mo is recommended for
patients with idiopathic venous thrombosis
or medical risk factors for DVT (intermediate-
risk group). About 20% of patients with
unprovoked venous thromboembolism have
a recurrence within 2 yr after the withdrawal
of oral anticoagulant therapy. Use of daily
low-dose aspirin after discontinuation of
anticoagulant treatment may provide a mod-
est reduction in DVT risk.
• Indefinite anticoagulation is necessary in
patients with DVT associated with active
cancer; long-term anticoagulation is also
indicated in patients with inherited throm-
bophilia (e.g., deficiency of antithrombin III,
protein C or S antibody), high factor VIII
levels, antiphospholipid antibody, and those
with recurrent episodes of idiopathic DVT
(high-risk group). Long-term anticoagulation
should also be considered in the presence of
comorbidities such as paroxysmal nocturnal
hemoglobinuria (PNH), SLE (especially with
nephrotic syndrome), some myeloprolifera-
tive disorders, IBD, and Cushing’s syndrome.
• Measurement of D-dimer after withdrawal
of oral anticoagulation may be useful to
estimate the risk of recurrence in selected
patients. In patients with a first unprovoked
DVT, positive D-dimer test results after ces-
sation of anticoagulation predict recurrence,
regardless of test timing or patient’s age.
Patients with a first spontaneous DVT and a
D-dimer level <250 mg/ml after withdrawal
of oral anticoagulation have a low risk of DVT
recurrence. Risk is lower in women than in
men. In patients who have completed at least
3 mo of anticoagulation for a first episode of
unprovoked DVT and after approximately 2
yr of follow-up, a negative D-dimer result is
associated with a 3.5% annual risk of recur-
rent disease, whereas a positive D-dimer
result is associated with an 8.9% annual
1 Kearon
C, et al: D-Dimer testing to select patients
with a first unprovoked venous thromboembolism
who can stop anticoagulant therapy: a cohort study.
Ann Intern Med 162:27–34, 2015.
risk for recurrence. Hence, elevated D-dimer
levels would be an indication for prolonged
therapy (for 1 or 2 more yr at a minimum).
• The presence of residual thrombosis on
ultrasonography when warfarin therapy
is discontinued is also associated with an
increased risk for subsequent recurrent DVT;
a recent trial showed that tailoring the dura-
tion of anticoagulation on the basis of the
persistence of residual thrombi on ultraso-
nography may reduce the rate of recurrent
DVT. Additional trials are needed before this
approach can be adapted for all patients.
• Patients with DVT and pulmonary embolism
are at high risk of recurrence whenever anti-
coagulation is discontinued; therefore, many
experts recommend prolonged anticoagula-
tion in this population group, especially if
other risk factors for recurrence are present.
PEARLS &
CONSIDERATIONS
COMMENTS
•  The prevalence of occult cancer is low
among patients with a first unprovoked
venous embolism. Routine screening with CT
of the abdomen and pelvis does not provide
a clinically significant benefit.2
• When using heparin, there is a risk of hep-
arin-induced thrombocytopenia (HIT) (with
unfractionated more so than with LMWH).
Platelet count should be obtained initially and
repeated every 3 days while on heparin.
• ISOLATED DEEP VEIN THROMBOSIS OF
THE CALF: The American College of Chest
Physicians Guidelines suggest (1) anticoagu-
lation in patients with severe symptoms or
risk factors for proximal extension, and (2)
repeat sonogram in 2 weeks in lower risk
patients and anticoagulation only in those
patients whose DVTs extend proximally.
• PROPHYLAXIS OF DVT: Recommended in all
patients at risk (e.g., low-molecular-weight
2 
CarrierM, Lazo-Langner A, Shivakumar S et al.:
Screening for occult cancer in unprovoked venous
thromboembolism, N Engl J Med 373:697–704, 2015.
I
heparin [enoxaparin 30 mg SC bid or
fondaparinux 2.5 mg SC daily] after major
trauma, postsurgery of hip and knee; enoxa-
parin 40 mg SC qd post–abdominal sur-
gery in patients with moderate to high DVT
risk; gradient elastic stockings alone or
in combination with intermittent pneumatic
compression [IPC] boots following neuro-
surgery). Graduated compression stockings
(GCSs) are effective for preventing air-travel-
related DVT and in reducing the risk of
DVT in patients hospitalized for conditions
other than stroke. The type of GCSs is also
important because proximal DVT occurs
more often in patients with stroke who
wear below-knee stockings than in those
who wear high-length stockings. The new
oral anticoagulants (rivaroxaban, apixaban,
etc.) are effective for thromboprophylaxis
after THR and TKR. However, their clinical
benefits over LMWH are marginal and they
are more expensive. Betrixaban is the first
FDA-approved once-daily oral direct factor
Xa inhibitor for prophylaxis of VTE in adults
hospitalized for an acute medical illness
with risk factors for VTE and moderately or
severely restricted mobility.
• RECURRENT THROMBOEMBOLISM: The risk
of recurrent venous thromboembolism in het-
erozygous carriers of factor V Leiden and a
first spontaneous venous thromboembolism
is similar to that of non-carriers of factor
V Leiden; therefore, heterozygous patients
should receive secondary thromboprophy-
laxis for a similar length of time as patients
without factor V Leiden.
• POSTTHROMBOTIC SYNDROME: Approxi-
mately 20% to 50% of patients with DVT
develop postthrombotic syndrome charac-
terized by leg edema, pain, venous ectasia,
skin induration, and ulceration. Patients
with extensive DVT and those with more
severe postthrombotic manifestations 1
month after DVT have poorer long-term
outcomes. Recent trials have shown that
compression stockings after DVT do not
prevent postthrombotic syndrome.
• Exercise following DVT is reasonable because
it improves flexibility of the affected leg and

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412 Deep Vein Thrombosis
does not increase symptoms in patients with
postthrombotic syndrome.
• Previously undiagnosed cancer is frequent in
patients with newly diagnosed DVT. A cancer
screening strategy should be considered in
all patients with unprovoked venous throm-
boembolism.
• UPPER EXTREMITY DVT: It is less com-
mon than lower extremity DVT and is seen
more frequently in patients requiring cen-
tral venous catheters or wires. It confers
risk for mortality, recurrent thromboem-
bolic events, and postthrombotic syndrome
similar to that of lower extremity DVT. It is
classified as primary upper extremity DVT
(Paget-Schroetter syndrome), defined as
a thrombus in the axillary and subclavian
veins in absence of identifiable thrombosis
risk factors. It accounts for 20% of upper
extremity DVT cases and may be due to
an underlying anatomic abnormality at
the thoracic outlet in combination with
local hypercoagulability due to venous
stretching or perivascular fibrosis from
recurrent venous compression. Secondary
upper extremity DVT is defined as any DVT
related to a predisposing factor (e.g., inser-
tion of central venous catheter, wires, or
other devices, malignancy). In patients with
secondary upper extremity DVT removal of
the catheter is not routinely recommended
but is warranted if there is a catheter
malfunction or infection, if anticoagulation
therapy is contraindicated or has failed,
or if the catheter is no longer needed.
Anticoagulation therapy in upper extremity
DVT consists of use of vitamin K antago-
nists, except in patients with cancer, for
whom LMWH is preferred. Optimal dura-
tion of anticoagulation treatment in upper
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extremity DVT is 3 to 6 mo (including in
those in whom a central catheter has been
removed).
• DVT THERAPY IN PREGNANCY: Vitamin K
antagonists such as warfarin are contrain-
dicated in pregnancy. Low-molecular-weight
heparins are safe and effective. Typical
agents used in pregnancy include dalteparin
(200 IU per kilogram of body weight daily or
100 IU per kilogram twice daily) or enoxapa-
rin (1.5 mg per kilogram daily or 1 mg per
kilogram twice daily).
• REVERSAL OF ANTICOAGULATION: Vitamin
K (1 mg PO or 2 mg IV) can be used to
reverse elevated INR (3 to 6) from warfa-
rin when elective or urgent procedures are
needed. The administration of vitamin K
can take more than 24 hr to fully restore
vitamin K dependent coagulation factors II,
VII, IX, and X. The American College of Chest
Physicians recommends the following guide-
lines for managing elevated INRs or bleeding
in patients receiving vitamin A antagonist
therapy:
1. INR between 4.5 and 10 and no signifi-
cant bleeding: omit dose and monitor the
next day, routine use of vitamin K is not
recommended
2. INR >10 and no significant bleeding: hold
vitamin K antagonist, give 5 to 10 mg
orally of vitamin K. Monitor the next day
and use additional vitamin K if necessary.
Resume therapy at lower dose when INR
therapeutic.
3. Serious bleeding at any elevation of INR:
hold vitamin K antagonist and supple-
ment with prothrombin complex concen-
trates (PCC). Give vitamin K (10 mg by
slow IV infusion over 30 min to reduce the
risk of anaphylaxis). Vitamin K1 can be
repeated every 12 hr. PCC composition in
the United States (3-factor PCC) includes
clotting factors II, IX, and X but minimal
amounts of factor VII (unlike PCC products
available outside of the United States
[4-factor PCC], which have a significant
amount of factor VII). In order to replace
the low factor VII, some clinicians in the
United States will also give fresh frozen
plasma (FFP) in addition to vitamin K
and PCC in patients with life-threatening
warfarin-related bleeding.
• SPECIFIC REVERSAL AGENTS FOR NON–
VITAMIN K ANTAGONIST ANTICOAGULANTS
• Idarucizumab, an antibody fragment given
at a dose of 5 g IV, has been shown to
completely reverse the anticoagulant effect
of dabigatran within minutes.
•  The anticoagulant activity of factor Xa
inhibitors apixaban, rivaroxaban, and
edoxaban can be rapidly reversed with IV
administration of andexanet alfa.
SUGGESTED READINGS
Available at ExpertConsult.com
RELATED CONTENT
Deep Vein Thrombosis (DVT) (Patient Information)
Antiphospholipid Antibody Syndrome (Related
Key Topic)
Hypercoagulable State (Related Key Topic)
Postthrombotic Syndrome (Related Key Topic)
Pulmonary Embolism (Related Key Topic)
Upper Extremity Deep Vein Thrombosis (Related
Key Topic)
AUTHOR: FRED F. FERRI, M.D.
Deep Vein Thrombosis
SUGGESTED READINGS
Adams S, et al.: Comparative effectiveness of new oral anticoagulants and stan-
dard thromboprophylaxis in patients having total hip or knee replacement, Ann
Int Med 159:275–284, 2013.
Agnelli G, et al.: Apixaban for extended treatment of venous thromboembolism, N
Engl J Med 368:699–708, 2013.
Antithrombotic therapy and prevention of thrombosis 9th ed: American College of
Chest Physicians evidence-based clinical practice guidelines, Chest 141(Suppl
2), 2012.
Baccarelli A, et al.: Exposure to particulate air pollution and risk of deep vein
thrombosis, Arch Intern Med 168(9):920, 2008.
Becattini C, et al.: Aspirin for preventing the recurrence of venous thromboembo-
lism, N Engl J Med 366:1959–1967, 2012.
Brighton TA, et al.: Low-dose aspirin for preventing recurrent venous thromboem-
bolism, N Engl J Med 367:1979–1987, 2012.
Buller HR: Fracture XI antisense oligonucleotide for prevention of venous throm-
bosis, N Engl J Med 372:232–240, 2015.
Chan WS, et al.: A red blood cell agglutination D-dimer test to exclude deep
venous thrombosis in pregnancy, Ann Intern Med 147:165–170, 2007.
Cohen AT, et al.: Rivaroxaban for thromboprophylaxis in acutely ill medical
patients, N Engl J Med 368:513–523, 2013.
Connolly SJ, et al.: Andexanet alfa for acute major bleeding associated with factor
Xa inhibitors, N Engl J Med 375(12):1131–1141, 2016.
Douketis J, et al.: Patient-level meta-analysis: effect of measurement timing,
threshold, and patient age on ability of D-dimer testing to assess recur-
rence risk after unprovoked venous thromboembolism, Ann Intern Med
153:523–531, 2010.
Galioto NJ, et al.: Recurrent venous thromboembolism, Am Fam Phys 83(3):293–
300, 2011.
Greer IA: Pregnancy complicated by venous thrombosis, N Engl J Med 373:540–
547, 2015.
Iorio A, et al.: Risk of recurrence after a first episode of symptomatic venous
thromboembolism provoked by a transient risk factor, Arch Intern Med
170(19):1710–1716, 2010.
Johnson SA, et al.: Risk of deep vein thrombosis following a single negative
whole-leg compression ultrasound, JAMA 303(5):438–445, 2010.
Kahn SR, et al.: Compression stockings to prevent post-thrombotic syndrome: a
randomized placebo-controlled trial, Lancet 383(9920):880–888, 2014.
Kucher N: Deep-vein thrombosis of the upper extremity, N Engl J Med 364:861–
869, 2011.
Landerfeld CS: Noninvasive diagnosis of deep vein thrombosis, JAMA 300:1696,
2008.
Downloaded for Fitria Halid (fitriahalid20@gmail.com) at Universitas Muslim Indonesia from ClinicalKey.com by Elsevier on October 16, 2018.
For personal use only. No other uses without permission. Copyright ©2018. Elsevier Inc. All rights reserved.
412.e1
Lassen MR, et al.: Apixaban versus enoxaparin for thromboprophylaxis after hip
replacement, N Engl J Med 363:2529, 2010.
Linkins LA, et al.: Selective D-dimer testing for diagnosis of a first suspected
episode of deep venous thrombosis, Ann Intern Med 158:93–100, 2013.
Mai C, Hunt D: Upper-extremity DVT: a review, Am J Med 124:402–407, 2011.
Pautas E, et al.: Reversal of overanticoagulation in very elderly hospitalized
patients with an INR above 5.0: 24 hour INR response after vitamin K admin-
istration, Am J Med 124:527–533, 2011.
Pollack CV, et al.: Idarucizumab for dabigatran reversal, full cohort analysis, N Engl
J Med 377:431–441, 2017.
Pollack CV, Reilly PA, Eikleboom J, et al.: Idarucizumab for dabigatran reversal,
N Engl J Med 373:511–520, 2015.
Righini M, et al.: Anticoagulant therapy for symptomatic calf deep vein throm-
bosis (CACTUS): a randomised, double-blind, placebo-controlled trial, Lancet
Haematol 3(12):e556–e562, 2016.
Sevestre MA, et al.: Outcomes for inpatients with normal findings on whole-leg
ultrasonography: a prospective study, Am J Med 123:158–165, 2010.
Siegal DM, et al.: Andexanet Alfa for the Reversal of Factor Xa Inhibitor Activity,
N Engl J Med 373:2413–2424, 2015.
Spandorfer J, Galanis T: In the Clinic. Deep venous thrombosis, Ann Intern Med
162:ITC1, 2015.
Stein PD, et al.: Home treatment of deep venous thrombosis according to comor-
bid conditions, Am J Med 129:392–397, 2016.
Sweeney J: Venous thromboembolism: duration, IVC filters, and hypercoagulable
workup. Medicine & Health, Rhode Island 94(4):99–104, 2011.
The CLOTS, Trial Collaboration: Thigh-length versus below-knee stockings for
deep venous thrombosis prophylaxis after stroke, Ann Intern Med 153:553–
562, 2010.
The EINSTEIN, Investigators: Oral rivaroxaban for symptomatic venous thrombo-
embolism, N Engl J Med 363:2499, 2010.
Ullinjian A: Safety and feasibility of a diagnostic algorithm combining clinical
probability D-dimer testing and ultrasonography for suspected upper extrem-
ity deep venous thrombosis: a prospective management study, Ann Int Med
160:451–457, 2014.
Van ES, et al.: Screening for occult cancer in patients with unprovoked venous
thromboembolism, Ann Int Med 167:410–417, 2017.
Wells PS, et al.: Diagnosis of venous thromboembolism: 20 years of progress, Ann
Int Med 168:131–140, 2018.
Wells PS, et al.: Treatment of venous thromboembolism, JAMA 311(7):717–728,
2014.
Wilbur J, Shian B: Deep venous thrombosis and pulmonary embolism: current
therapy, Am Fam Physician 95(5):295–302, 2016.
Deep Vein Thrombosis 412.e2

FIG. E1  Doppler ultrasound appearance of deep vein thrombosis. The superficial femoral vein is filled
with echogenic material representing thrombus, and no flow can be identified in the vein on Doppler evaluation.
Flow can be identified in the adjacent artery on color Doppler evaluation (arrows). (From Crawford MH, DiMarco
JP, Paulus WJ [eds.]: Cardiology, ed 2, St. Louis, 2004, Mosby.)

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