Who should get long term anticoagulation for PE/DVT

Financial Disclaimer: against the drug companies

● My financial interests are only as a purchaser of insurance and a taxpayer

○ Concern about prices

● Physician and caring person

○ Concern about impoverishing the needy

○ Concerned about truth and advertising

Goals of the talk

○ A framework for deciding on which patients might need prolonged anticoagulation

○ what are the guidelines for prolonged anticoagulation

○ what are the problems in applying those guidelines

○ methods for increasing the Predictive Value of the decision

Framework

Balancing Risk

Anticoagulate • Bleeding

Don’t anticoagulate • Pulmonary

embolism

Principle: Risk vs Risk

● Risk of failure to anticoagulate

○ Massive pulmonary embolism ○ Other thrombotic complication

○ Risk of anticoagulation

○ Bleeding ○ Treatment complication

Risk Decay

Most patients with acute venous thromboembolism (VTE) require anticoagulation for a minimum of three months

○ Risk decay curve

with some patients requiring longer finite periods of 6 to 12 months.

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TABLE 55.16 DURATION OF ANTICOAGULATION

IN VENOUS THROMBOEMBOLIC DISEASE

Wintrobe's Clinical Hematology

Disease Duration

Situational DVT or PE (transient risk factors)

3 mo

Unprovoked DVT or PE 3 mo (minimum)/indefinite

Recurrent unprovoked DVT or PE

Indefinite

DVT with ongoing risk factorsa Long-term/indefinite

Massive PE Long-term/indefinite

Calf vein DVT 3 mo

DVT, deep venous thrombosis; PE, pulmonary embolism.

a For example, malignancy, antiphospholipid antibody syndrome, or natural anticoagulant deficiency.

Timing of anticoagulation initiation

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PATIENTS LIKELY TO BENEFIT

● Unprovoked proximal DVT ● Symptomatic PE ● Recurrence with anticoagulation ● Recurrence without anticoagulation ● Recurrent unprovoked VTE ● Active cancer

○ Khorana score

Categorization of patients as having provoked or unprovoked venous thromboembolism: guidance from the SSC of ISTH

Journal of Thrombosis and Haemostasis, Volume: 14, Issue: 7, Pages: 1480-1483, First published: 15 April 2016, DOI: (10.1111/jth.13336)

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guidelines

Recent Guideline ASH: Guidelines for management of venous thromboembolism – Optimal

management of anticoagulation therapy (2018)

American College of Chest Physicians (CHEST): Guideline and expert panel

report on antithrombotic therapy for VTE disease (2016)

ISTH: Guidance for the categorization of patients as having provoked or

unprovoked venous thromboembolism (2016)

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TABLE 55.16 DURATION OF ANTICOAGULATION

IN VENOUS THROMBOEMBOLIC DISEASE

Disease Duration

Situational DVT or PE (transient risk factors)

3 mo

Unprovoked DVT or PE 3 mo (minimum)/indefinite

Recurrent unprovoked DVT or PE Indefinite

DVT with ongoing risk factorsa Long-term/indefinite

Massive PE Long-term/indefinite

Calf vein DVT 3 mo

DVT, deep venous thrombosis; PE, pulmonary embolism.

a For example, malignancy, antiphospholipid antibody syndrome, or natural anticoagulant deficiency

Figure 1. Simplified schema of the management of venous thromboembolism. DASH indicates elevated D-dimer post anticoagulation, age <50 years at initial VTE, male sex, and hormone use in women at initial VTE; DVT, deep vein thrombosis; HERDOO-2, hyperpigmentation, edema or redness of affected leg, elevated d-dimer while on anticoagulation, obesity with body mass index >30, and age ≥65 years; PE, Pulmonary embolism; USG, ultrasonography; VTE, venous thromboembolism. *Superficial femoral and popliteal veins are proximal veins.

DOI: (10.1177/1076029616652727) An Algorithmic Approach to Management of Venous Thromboembolism

DASH score ● D dimer

○ 1 month after stopping anticoagulation

● Age

○ Less than 50

● Sex

○ Male

● Hormone

○ Estrogen

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Table. HERDOO2 Scoring

Predictor Scoring

H Hyperpigmentation 1 point total, if any one of these criteria is present

E Edema

R Redness of either leg

D D-dimer ≥ 250 μg/L while anticoagulated

1 point

O Obesity with BMI ≥ 30 kg/m2 1 point

O Older age, i.e. ≥ 65 years 1 point

problems in applying the guidelines

Things that are not clear ● What constitutes provoked?

○ Airline flight

○ Cast immobilization

● How to calculate the balance of risks

○ Apps

● Which anticoagulant

○ Heparinoids

○ NOACs

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Airline flight: UpToDate

Provoked VTE with transient risk factor

VTE provoked by a nonsurgical trigger (eg, oral contraceptive pill, long flight, pregnancy), the risk of VTE recurrence is estimated to 5 percent at one year and 15 percent at five years (approximately 2.5 percent per year after the first year)

Airline Flight Risk Recent publications report the risk of venous thromboembolism (VTE) is increased 1.5 to 3 fold (Timp 2015), by approximately two fold (Cannegieter 2006; WRIGHT project 2007), or four fold (Kuipers 2007), following long-haul travel.

Kuipers and colleagues also reported that the "absolute risk of a symptomatic event within 4 weeks of flights longer than 4 h is 1/4600 flights" and "the risk of severe pulmonary embolism (PE) occurring immediately after air travel increases with duration of travel, up to 4.8 per million in flights longer than 12 h" (Kuipers 2007).

Low molecular weight heparin for prevention of venous thromboembolism in patients with lower-limb immobilization.

● Moderate-quality evidence showed LMWH reduced DVT when immobilization of the lower limb was required

○ when compared with no prophylaxis or placebo.

● Low-quality evidence showed no clear differences in PE between the LMWH and control groups,

● less symptomatic VTE in the LMWH groups. ● The quality of the evidence was downgraded due to risk of bias and

imprecision.

Predictive Value

How to decide ● Sum of all risks ● Physiologic understanding ● Aversions

○ Risk

○ cost

How is the decision made ● Kahneman system I

○ Risk aversion ○ Ineffables

● System II ○ Quantitative analysis

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Goals of the talk

○ A framework for deciding on which patients might need prolonged anticoagulation

○ what are the guidelines for prolonged anticoagulation

○ what are the problems in applying those guidelines

○ methods for increasing the Predictive Value of the decision

Low molecular weight heparin for prevention of venous thromboembolism in patients with lower-limb immobilization.

rationale for extending anticoagulation indefinitely

● based upon long-term epidemiologic studies of recurrence risk after cessation of a conventional course of anticoagulation

● as well as randomized trials and meta-analyses that suggest that anticoagulation for prolonged periods successfully reduces the rate of VTE recurrence

Airline flight: UpToDate PATIENTS UNLIKELY TO BENEFIT

We and others agree that indefinite anticoagulation is unlikely to benefit the populations described below, provided that

persistent risk factors, which would elevate the risk of recurrence, are absent [3-5]. (See 'Assess additional risk factors'

below.)

Provoked VTE with transient risk factor — For most patients who have a provoked VTE with transient medical or surgical

risk factors, we recommend anticoagulation for three to six months rather than periods of longer or shorter duration. For

those with a VTE provoked by a transient surgical risk factor, the risk of VTE recurrence is estimated to be 1 percent at one

year and 3 percent at five years (approximately 0.5 percent per year after the first year) [3-5,7,8]. For those with a VTE

provoked by a nonsurgical trigger (eg, oral contraceptive pill, long flight, pregnancy), the risk of VTE recurrence is

estimated to 5 percent at one year and 15 percent at five years (approximately 2.5 percent per year after the first year) [3-

5,7,8].

issues

● How to decide

○ Sum of all risks

○ Physiologic understanding

○ Aversions

■ Risk

■ cost

● Things that are not clear

● Which anticoagulant

Earlier anticoagulation impact

Incidence and mortality of venous thrombosis: a population-based study

Journal of Thrombosis and Haemostasis, Volume: 5, Issue: 4, Pages: 692-699, First published: 02 April 2007, DOI: (10.1111/j.1538-7836.2007.02450.x)

rationale for extending anticoagulation indefinitely

● long-term epidemiologic studies ● of recurrence risk ● after cessation of a conventional course of anticoagulation

● randomized trials and meta-analyses ● suggest that anticoagulation for prolonged periods ● reduces the rate of VTE recurrence

DASH score Application

● previously diagnosed with VTE ● completed a 3-6 month course of anticoagulation ● DASH Scores ≤1 are associated with 3.1% annual recurrence

○ may be low enough to consider discontinuing anticoagulation.

● DASH Scores ≥2 are at high risk for recurrent VTE

○ may require long-term anticoagulation.

● https://www.mdcalc.com/dash-prediction-score-recurrent-vte#use-cases

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UNPROVOKED VTE

No provoking risk factor (transient or persistent)

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Total follow-up# Periods of follow-up after VT

0–0.49 years

0.50–2.99 years

≥ 3 years

Total population

92 804 1 1 1 1

Idiopathic† 373 2.57 (2.17–3.04)

4.36 (3.12–6.08)

1.83 (1.44–2.32)

1.24 (0.87–1.75)

Secondary‡ 236 1.97 (1.52–2.57)

4.85 (3.07–7.66)

1.05 (0.68–1.63)

1.09 (0.68–1.75)

Cancer¶ 131 12.73 (10.59–15.29)

33.78 (26.41–43.21)

7.29 (5.25–10.13)

2.48 (1.24–4.95)

Categorization of patients as having provoked or unprovoked venous thromboembolism: guidance from the SSC of ISTH

VTE PROVOKED BY A TRANSIENT RISK FACTOR*

Major transient risk factor during the 3 months before diagnosis ofVTE

A risk factor is considered ‘major’ if it has been shown to beassociated with:

(1)half the risk of recurrent VTE after stopping anticoagulant ther-apy (compared with if there was no transient risk factor), whenthe risk factor occurred up to 3 months before the VTE†;or

(2)a greater than10-fold increase in the risk of having a first VTE.

Examples:

•Surgery with general anesthesia for greater than 30 min.

•Confined to bed in hospital (only ‘bathroom privileges’) for atleast 3 days with an acute illness.

•Cesarean section

Minor (yet important) transient risk factor during the 2 months before diagnosis of VTE A risk factor is considered ‘minor’ if it has been shown to be associated with:

(1)half the risk of recurrent VTE after stopping anticoagulant therapy (compared with if there was no transient risk factor), when the risk factor occurred up to 2 months before the VTE †;or

(2)a 3 to 10-fold increase in the risk of having a first VTE.

Examples:•Surgery with general anesthesia for less than 30 min.

•Admission to hospital for less than 3 days with an acute illness.

•Estrogen therapy.

•Pregnancy or puerperium.

•Confined to bed out of hospital for at least 3 days with an acuteillness.

•Leg injury associated with reduced mobility for at least 3 days

VTE PROVOKED BY A PERSISTENT RISK FACTOR

Active cancer

Cancer is considered active if any of the following apply:(1)has not received potentially curative treatment; or

(2)there is evidence that treatment has not been curative (e.g. recurrent or progressive disease)‡;or

(3)treatment is ongoing.

On-going non-malignant condition associated with at least a 2-fold riskof recurrent VTE after stopping anticoagulant therapy

Example:Inflammatory bowel disease.

Cochrane Systematic Review - Intervention Version published: 14 September 2016

Compression stockings for preventing deep vein thrombosis in airline passengers

Eleven randomised trials (n = 2906) were included in this review

Sixteen of 1804 people developed superficial vein thrombosis

There were no symptomless DVTs

No deaths, pulmonary emboli or symptomatic DVTs were reported.

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• D-dimer abnormal • Measured ~1 month after stopping anticoagulation

• Age ≤50 years

• Male patient

• Hormone use at VTE onset (if female)

DASH score

HERDOO2

● Women ≥18 years old with unprovoked VTE. ● Patients diagnosed 5–7 months before enrollment. ● On heparin or low molecular weight heparin (LMWH) for ≥5 days and oral

anticoagulation for 5–7 months after the event. ● Without recurrent VTE during the treatment period. ● Noncompressible segment on compression ultrasound of popliteal (or more

proximal) leg vein, high-probability V/Q scan, or segmental (or larger) artery filling defect on spiral CT.

● Exclusion criteria: ● Leg fracture. ● Lower-extremity plaster cast. ● Immobilization for >3 days.

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