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© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
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© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
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© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
in the clinicDeep Venous Thrombosis
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
DVT versus VTE
DVT refers to Deep Venous Thrombosis, which is the focus of this material
VTE refers to Venous ThromboEmbolism
VTE includes DVT plus the embolic consequences of DVT
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
Should clinicians screen specific types of patients for DVT?
No evidence supports using ultrasound in:
Hospitalized medical patients
Orthopedic surgery patients
Limited evidence supports using ultrasound in:
Asymptomatic nonambulatory neurosurgery patients
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
Which hospitalized medical patients should receive prophylaxis and what should be used?
Assess VTE risk with Padua Prediction Score
Assess bleeding risk with IMPROVE model
Independent bleeding risk factor: Gastroduoduodenal ulcer bleeding w/in 3 mo admission
Independent bleeding risk factor: Platelets <50,000/µl
High VTE risk + low bleeding risk: pharmacologic prophylaxis
UFH, LMWH, or fondaparinux
High VTE risk + high bleeding risk: mechanical prophylaxis
Intermittent pneumatic compression or graduated compression stockings
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
Risk Factor Points
Active Cancer 3
Previous VTE with exclusion of superficial vein thrombosis 3
Reduced Mobility 3
Already known thrombophilic condition of antithrombin, protein C or S, factor V Leiden, antiphospholipid syndrome
3
Recent (< 1 month) trauma and/or surgery 2
Elderly age (> 70 y) 1
Heart and/or Respiratory failure 1
Acute myocardial Infarction or ischemic stroke 1
Acute Infection or rheumatologic disorder 1
Obesity (BMI > 30) 1
Ongoing hormonal treatment 1
High risk is defined by a cumulative score ≥4 and low risk <4
Risk Factor Guide for VTE in Hospitalized Medical Patients
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
Which pregnant patients should receive prophylaxis, and what methods should be used?
Consider screening for thrombophilia when: Patient had VTE unrelated to a known risk factor
First-degree relative has high-risk thrombophilia
Base pharmacologic VTE prevention on: Personal and family (first-degree relative) Hx of VTE
Whether patient has a known thrombophilia
LMWH preferred over UFH in pregnancy
Oral thrombin and Xa inhibitors not recommended prenatally or during breastfeeding
VTE prevention methods vary by pregnancy subgroups
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
Risk factors Antepartum Postpartum LMWH
Personal history of VTE related to temporary risk factors (not pregnancy or estrogen related), no thrombophilia
Vi gilance LMWH x 6 weeks
Personal history of idiopathic VTE or VTE related to pregnancy or estrogen
LMWH LMWH x 6 weeks
No personal or family history of VTE and patient has low risk thrombophiliaa
Vigilance Vigilance
No personal history of VTE but has family history of VTE and patient has low risk thrombophilia
Vigilance LMWH x 6 weeks
No personal or family history VTE and patient has high risk thrombophilia
Vigilance LMWH x 6 weeks
No personal history of VTE but has family history of VTE and patient has high risk thrombophilia
LMWH LMWH x 6 weeks
Suggested VTE Prevention Methods in Subgroups of Pregnant Patients
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
Which patients with thrombophilic disorders should receive prophylaxis, and what methods should be used?
Inherited thrombophilias
Factor V Leiden, prothrombin G20210A, protein C and S deficiency
Acquired thrombophilias
Estrogen use, cancer, the antiphospholipid antibody syndrome, sepsis
Prophylaxis is not recommended to prevent thrombosis in patients with thrombophilia who do not have a Hx of VTE
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
How should physicians counsel patients about prevention during prolonged immobility associated with travel?
Patients at high risk for travel-associated VTE
Prior VTE, recent surgery, pregnancy, active cancer
Known thrombophilic disorder, morbid obesity
Prevention for patients at high risk
Graduated compression stockings
Frequent ambulation
Maintaining hydration
Sitting in an aisle seat
Consider pharmacologic prophylaxis on individual basis
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
CLINICAL BOTTOM LINE: Prevention...
Risk factor assessment models determine individual risk
Screening for DVT in most settings is not advised
LMWH preferred to UFH for prevention in medical patients
Intermittent pneumatic compression preferred to heparin when bleeding risk is elevated in medical or non-orthopedic surgical patients
Several different agents can be used for prevention in patients undergoing total hip or knee replacement
For heparin use in pregnancy, LMWH is preferred
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
What signs and symptoms should lead
clinicians to suspect DVT?
Always use a formal prediction rule if VTE is suspected
Wells score
Primary Care Rule
Combine the results from the prediction rule with the results from D-dimer testing to determine next steps
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
Modified Wells Clinical ScoreDVT unlikely (score ≤1) or DVT likely (score ≥2)
Active cancer (treatment ongoing, within 6 mo, or palliative) = 1
Paralysis, paresis, or recent plaster immobilization of lower extremities = 1
Recently bedridden >3 d or major surgery ≤12 wk requiring general or regional anesthesia = 1
Localized tenderness on distribution of deep venous system = 1
Entire leg swollen = 1
Calf swelling 3 cm larger than asymptomatic side (measured 10 cm below tibial tuberosity) = 1
Pitting edema confined to the symptomatic leg = 1
Collateral superficial veins (nonvaricose) = 1
Previously documented DVT = 1
Alternative diagnosis at least as likely as DVT = –2
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
Primary Care RuleVery low risk (score ≤3) or increased risk (score ≥4)
Male = 1
Use of hormonal contraceptives = 1
Active cancer in past 6 mo = 1
Surgery in previous month = 1
Absence of leg trauma = 1
Distention of collateral leg veins = 1
Difference in calf circumference ≥3 cm = 2
Abnormal D-dimer assay result = 6
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
What is the role of D-dimer testing?
Combine D-dimer testing with assessment of pre-test probability to safely exclude DVT
Testing can r/o VTE in ED, outpatient practice
Enzyme-linked immunoassays: sensitivity, specificity
Whole-blood agglutination assays: sensitivity, specificity
Sensitivity and specificity suboptimal in:
Pregnant women
Patients receiving anticoagulation therapy
Prolonged clinical symptoms of DVT, prior DVT, or cancer
D-dimer levels normally increase with age
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
What is the role of venous ultrasonography?
Proximal ultrasonography
Examines only the common and popliteal veins
Whole-leg ultrasonography
Examines entire deep vein system, including calf veins
Avoids repeated testing
But may identify more patients with isolated, calf vein DVT
Both methods associated with acceptable 3-month incidence of VTE after negative results
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
What is the role of other types of testing?
CT venography and MRI
Uncertain role in diagnosis
Not recommended as first-line diagnostic tests
Except in cases when ultrasonography cannot be
performed (lower-extremity casting; severe edema)
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
How should a pregnant patient be evaluated for suspected DVT?
Compression ultrasound should be the initial test
Follow-up ultrasonography is recommended for patients with a normal result on initial testing
Thrombosis in the iliac veins
Suggestive symptoms include whole-leg edema or discomfort in the flank, back, or buttock
Evaluate pelvic vessels with ultrasonography and/or MRI
D-dimer assays have decreased specificity during pregnancy, but results become reliable by 3rd trimester in most women
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
What other diagnoses should clinicians consider?
Venous insufficiency (venous reflux)
Superficial thrombophlebitis
Muscle strain, tear or trauma
Leg swelling in a paralyzed limb
Baker’s cyst
Cellulitis
Lymphedema
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
Imaging is nondiagnostic
Recurrent DVT is suspected
Post-thrombotic syndrome occurs in 20%-50% of patients with symptomatic DVT, and differentiating post-thrombotic syndrome from recurrent DVT can be challenging
Criteria for diagnosing recurrent DVT are lacking, especially in venous segments with residual abnormalities
Suspicion for DVT should be high despite negative testing
When should clinicians consider consulting a specialist?
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
What other underlying conditions and clinical manifestations should clinicians look for?
Cancer
3.5%-10% diagnosed with cancer within 12 months of VTE
Benefit of an extensive screening protocol has not been established
Tailor cancer screening to age, symptoms, risk factors
Recurrent VTE
There is no consensus on which, if any, patients should be tested for thrombophilia
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
CLINICAL BOTTOM LINE: Diagnosis... To stratify a patient’s risk for thrombosis
Use a clinical prediction rule Combine the results with a sensitive D-dimer assay Whole-leg ultrasound may limit the need for repeat testing
but will identify more patients with isolated calf vein thrombi In patients diagnosed with DVT
Extensive cancer screening strategy and thrombophilia testing is controversial
Consult a specialist when Recurrent VTE is possible Imaging studies are nondiagnostic or negative, particularly if
the suspicion for thrombosis is high
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
How should clinicians decide whether to treat patients on an oupatient or inpatient basis?
Most people with VTE can be safely treated as outpatients
With LMWH treatment
Outcome is better at home than in hospital
Consider admitting patients who have difficulty managing outpatient treatment
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
What local measures should clinicians recommend?
Compression therapy
Conflicting data on efficacy for reducing risk for post-thrombotic syndrome
Early ambulation
Not associated with increased risk for PE in patients with acute DVT
May lead to more rapid resolution of limb pain
Has the potential to decrease the frequency and severity of post-thrombosis syndrome
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
When should clinicians start anticoagulants?
If there is a high probability of VTE before testing plus a low risk for bleeding
Initiate short-acting anticoagulant while awaiting results of diagnostic work-up
If the diagnosis is acute proximal DVT
Initiate parental anticoagulant, apixaban, or rivaroxaban immediately unless these drugs are contraindicated
If vitamin k antagonist is chosen for long-term therapy, start it on same day as parental anticoagulant
If the diagnosis is isolated calf vein thrombosis
Initiate anticoagulation immediately, especially if the risk for proximal propagation is high and the risk for bleeding is low
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
Which anticoagulants should clinicians use?
LMWH, dalteparin, enoxaparin, or
tinzaparin
IV or SC UFH
Coumarin derivatives
Apixaban
Rivaroxaban
IV direct thrombin inhibitors (lepirudin,
bivalirudin, argatroban)
Oral direct thrombin inhibitor (dabigatran
etexilate)
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
Some novel oral anticoagulants can be used immediately
Others should not be used until patient is treated with a parenteral anticoagulant ≥5 days
Anticoagulants for use during initial phase
Rivaroxaban, apixaban
Fondaparinux, IV or SC heparin, LMWH
Anticoagulants for long-term and extended use
Dabigatran, edoxaban
Vitamin K antagonist
Rivaroxaban, apixaban
LMWH
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
How should clinicians monitor anticoagulation?
Heparin
Use aPTT to adjust the dose of UFH but not LMWH
Vitamin K antagonists
Evidence lacking on specific dosing-algorithms
Consider lower initial doses for the elderly
Monitor with INR every 4 weeks once the level of anticoagulation stable
Home monitoring is safe and effective in motivated patients who demonstrate competency
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
When should clinicians stop anticoagulation?
Reversible risk factor
Pregnancy, hormonal therapy, surgery, temporary immobilization
Treat for 3 months
Unprovoked or recurrent VTE or active cancer
Extended anticoagulation with no prespecified stopping point (if bleeding risk is low)
Reevaluate risks and benefits annually
Recurrence risk may be higher when D-dimer levels are elevated 1 mo after anticoagulation discontinued
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
What options are available for patients who cannot use anticoagulants?
Anticoagulant contraindications
Active bleeding
Recent surgery or recent hemorrhagic stroke
Inferior vena cava filters
May be used in acute VTE when anticoagulation is absolutely contraindicated
May increase risk for recurrent DVT
Use usually requires an absolute contraindication to anticoagulation
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
When should clinicians use thrombolysis?
Anticoagulant therapy alone is usually recommended instead of thrombolysis
Thrombolysis increases the risk for bleeding
Consider thrombolytic therapy for patients who
Have iliofemoral DVT or impending venous gangrene and a low risk for bleeding
Are more concerned about preventing post-thrombosis syndrome and less concerned about bleeding
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
What treatment modifications are needed in pregnancy and in other hypercoagulable states?
Novel oral anticoagulants are contraindicated
LMWH therapy preferred over warfarin and UFH
When VTE develops in pregnancy, continue treatment for 3 mo or until 6 wk after delivery, whichever is longer
Warfarin may be used postpartum and during lactation
Initial management of acute VTE same in patients with thrombophilia as in those without
Consider extended course for patients with first episode of VTE and thrombophilia who have other persistent risk factors or who have had a life-threatening thrombosis
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
How should clinicians treat the post-thrombotic syndrome?
It occurs in 20%-50% of patients following DVT and is characterized by recurrent pain and swelling with ulceration and signs of stasis skin changes
Consider the possibility of recurrent DVT
Advise patients to elevate their feet whenever possible
Use graduated compression stockings (20-40mm Hg)
Contraindications include severe peripheral arterial disease and open wounds
Out-patient pneumatic compression is reserved for patients who don’t respond to foot elevation and stockings
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
When should clinicians consider consulting a specialist?
Recurrent idiopathic VTE
Recurrent VTE while on anticoagulation
Complications necessitating alternatives to anticoagulation
Management of DVT in pregnant patients
© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.
CLINICAL BOTTOM LINE: Treatment... Most DVT can be treated with LMWH outside the hospital
LMWH + VKA results in less recurrence than UFH + VKA
NOACs are as effective as LMWH+VKA, and the bleeding risk is lower
Data conflict on elastic compression stockings to prevent PTS
Treat patients with reversible risk factor for 3 months
Treat longer if the bleeding risk is low and VTE is unprovoked, recurrent, or accompanied by active malignancy
Only use IVC filters when anticoagulation is contraindicated
Consider thrombolytic therapy when there is a low risk of bleeding and either massive iliofemoral DVT or impending venous gangrene
Manage most patients with thrombophilia like those without it