© copyright annals of internal medicine, 2015 ann int med. 162 (5): itc5-1. * for best viewing:...

© Copyright Annals of Internal Medicine, 2015Ann Int Med. 162 (5): ITC5-1.

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in the clinicDeep Venous Thrombosis


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


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


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


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

Sankey Williams

Should only patients with high risk be considered for prophylaxis? This information also does not explain how to combine the risk for VTE with the risk for bleeding to decide whether or not the patient should have prophylaxis – it should. Should the IMPROVE model be included with this table?


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


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


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


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


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


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


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


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


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


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


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)


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


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


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?


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


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


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


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


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


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)


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


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


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


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


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


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


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


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


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

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