Updates in Diagnosis & Management of VTE Financial - - PDF document

10/19/17 1

TRACY MINICHIELLO, MD CHIEF, ANTICOAGULATION& THROMBOSIS SERVICE- SAN FRANCISCO VAMC PROFESSOR OF MEDICINE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO

Updates in Diagnosis & Management of VTE

— Financial Disclosures-NONE

Objectives

— Approach to subsegmental PE, calf vein DVT and

superficial vein thrombosis

— Determine duration of anticoagulation for VTE — Review options for secondary prevention of VTE — Manage anticoagulation in cancer patients

THESE SHOULD BE AT YOUR FINGERTIPS

Kearon et al. Chest. 2016;149(2):315-352. Doherty et al. JACC 2017

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Volume 41, Issue 1, January 2016 Special Issue: Management of Venous Thromboembolism: Clinical Guidance from the Anticoagulation Forum

Subsegmental PE

A 77 yo man had undergoes colectomy for recurrent bleeding from diverticulosis. On POD # 3 he becomes tachycardic to the 110s. WBC is elevated.The surgical team

• rders an abdominal CT which shows a fluid collection

concerning for early abscess. It also shows an isolated RLL subsegmental PE. A dedicated CTa shows a single isolated RLL subsegmenral PE. Do you anticoagulate this patient?

a)

Sure, it is a PE.

b)

No this is incidental. Let’s pretend we don’t know it is there

c)

Couldn’t you start with an easy question? It is really early.

Isolated Subsegmental PE

Definition: PE shown on CT angiography that

• ccurred in a subsegmental branch but no larger order
• f vessels. The subsegmental PE may involve one or

more than one subsegmental branch Identification of ISSPE has tripled over past decade

Isolated Subsegmental PE

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Isolated Subsegmental PE

IS IT REAL? ISSPE is more likely to be TRUE if….good quality scan, mult defects, centrally located, d-dimer elevated, seen on mult cuts, patient symptomatic vs incidental;high pretest prob of PE Get u/s of bilateral lower extrem (upper if CVC) Consider risk of recurrence-higher if not post op; immobile; active cancer IF high bleed risk –don’t AC: get serial u/s Kearon et al. Chest. 2016;149(2):315-352.

Subsegmental PE

A 77 yo man had undergoes colectomy for recurrent bleeding from diverticulosis. On POD # 3 he becomes tachycardic to the 110s. WBC is elevated.The surgical team

• rders an abdominal CT which shows a fluid collection

concerning for early abscess. It also shows an isolated RLL subsegmental PE. A dedicated CTa shows a single isolated RLL subsegmenral PE. Do you anticoagulate this patient?

a)

Sure, it is a PE.

b)

No this is incidental. Lets pretend we don’t know it is there

c)

Couldn’t you start with an easy question? It is really early.

Incidental PE

A 77 yo man is 2 weeks s/p laproscopic nephrectomy for renal cell CA. He received LMWH for 5 days post

• p but this was discontinued when he developed
• melena. An EGD showed a peptic ulcer. He has a

staging CT which shows no disease but shows a RUL subsegmental pulmonary artery filling defect. Do you anticoagulated this patient?

a) No, that did not go well last time b) Yes, it is a PE c) Easier questions…remember??

Incidental PE in Cancer

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Incidental PE in Cancer

LOCATION RECOMMENDATION

Proximal DVT or main, lobar segmental or multiple subsegmental PE AC for at least 6 months ISSPE with proximal DVT AC for at least 6 months ISSPE with distal DVT or no DVT Case be case;consider risk of bleeding/ recurrent thrombosis, patient preference. If no anticoagulation serial U/S to detect thrombus

Incidental PE

A 77 yo man is 2 weeks s/p laproscopic nephrectomy for renal cell CA. He received LMWH for 5 days post

• p but this was discontinued when he developed
• melena. An EGD showed a peptic ulcer. He has a

staging CT which shows no disease but does show a RUL subsegmental pulmonary artery filling defect. Do you anticoagulated this patient?

a) No, that did not go well last time b) Yes, it is a PE c) Easier questions…remember??

Calf Vein DVT

A 37 year old man presents with right calf pain one week after being kicked in calf during a soccer game. On exam right calf is 2 cm> left. U/S shows DVT in the peroneal vein. What anticoagulation regimen do you recommend?

1.

Rivaroxaban 15 mg BID x 21 days then 20 mg daily to complete 3 months of therapy

• 2. Prophylactic dosing of LMWH or DOAC
• 3. No anticoagulation, return in one week for repeat

ultrasound of lower extremity.

• 4. Um, is that a deep vein? The guy sitting next to me

wants to know.

Also includes gastroc and soleus veins

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Calf Vein DVT-CHEST 2016

Kearon et al. Chest. 2016;149(2):315-352.

Risk factors for extension: d-dimer +, extensive thrombosis close to proximal veins; active cancer, prior VTE, inpatient

Calf Vein DVT-CHEST 2016

AC Forum clinical guidance We suggest treatment of distal DVT with anticoagulation versus

• bservation. We suggest a

duration of therapy 3 months.

Streiff MB et al. J Thromb Thrombolysis. 2016;41:32-67..

Calf Vein DVT

• 1st DVT, no cancer, outpatient only
• 6 weeks LMWH and GCS vs placebo and GCS
• U/S at 3-7 days and 42 days
• Outcome progression to proximal DVT or PE
• No difference in VTE, increased risk of bleeding

Righini et al. Lancet Haematol 2016;3: e556–62

Calf Vein DVT

A 37 year old man presents with right calf pain on week after being kicked in calf during a soccer game. On exam right calf is 2 cm> left. U/S shows DVT in the peroneal vein. What anticoagulation regimen do you recommend?

1.

Rivaroxaban 15 mg BID x 21 days then 20 mg daily to complete 3 months of therapy

• 2. Prophylactic dosing of LMWH or DOAC
• 3. No anticoagulation, return in one week for repeat

ultrasound of lower extremity.

• 4. Um, is that a deep vein? The guy sitting next to me

wants to know.

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A 55 year old woman presents with painful swelling

• ver anterior left thigh. On exam she has a palpable

cord concerning for SVT. She has an u/s which shows thrombosis of the greater saphenous vein extending from the calf proximally and terminating 6 cm from the deep femoral vein. What do you recommend?

a.

Prophylactic fondaparinux

• b. Prophylactic rivaroxaban

c.

Full dose DOAC or warfarin

• d. NSAIDS and ice

Superficial Vein Thrombosis

Superficial Vein Thrombosis –CHEST Guidelines

— Factors that favor the use of AC : extensive SVT;

above the knee, close to saphenofemoral junction; severe symptoms; involvement of the greater saphenous vein; history of VTE or SVT; active cancer; recent surgery

— In patients with superficial vein thrombosis of the

lower limb of at least 5 cm in length, we suggest the use of a prophylactic dose of fondaparinux or LMWH for 45 days over no anticoagulation (Grade 2B).

Kearon C et al. Chest. 2012

CALISTO TRIAL- fonda vs placebo Primary outcome 1% vs 6%

Superficial Vein Thrombosis

• >400 pts symptomatic SVT riva 10 mg v fonda 2.5mg
• Symptomatic above the knee SVT of at least ≥ 5 cm

length + other risk factor (>65 , male,hx VTE , cancer, autoimmune disease, non-varicose veins)

• No difference in primary efficacy outcome
• After 6 weeks 7% recurrence risk in high risk patients

(v 1.2% in CALISTO)

Superficial Vein Thrombosis

Full dose anticoagulation for at LEAST 6 weeks

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A 55 year old woman presents with painful palpable swelling over anterior left thigh. On exam she has a palpable cord concerning for SVT. She has an u/s which shows thrombosis of the greater saphenous vein extending from the calf proximally and terminating 2 cm from the deep femoral vein. What anticoagulant regimen do you recommend?

a.

Prophylactic fondaparinux

• b. Prophylactic rivaroxaban

c.

Full dose DOAC or warfarin

• d. Nsaids and ice

Superficial Vein Thrombosis Duration of Anticoagulation for VTE

A 57 year old man presents with unprovoked PE. He has no other PMHx. He is started on rivaroxaban. How long should he remain on anticoagulation? 1) One year 2) 6 months 3) 3 months 4) Indefinitely 5) At least until I sign out

Risk of VTE Recurrence After Anticoagulation Is Stopped

27

Characteristic Recurrence at 1 y Recurrence at 5 y Major provoked (transient) 1% 3% Minor provoked (transient) 5% 15% Unprovoked 10% 30% Cancer 20% —

Kearon C et al. Blood. 2014;123(12):1794-1801.

• 2. Heit JA. Nat Rev Cardiol. 2015;12(8):464-474.

Major transient risk factors Major surgery, trauma Minor transient risk factors Pregnancy, minor surgery, long- haul air travel, immobilization

Nontransient risk factors Active cancer, severe thrombophilia, inflammatory bowel disease

Risk of VTE Recurrence After AC Is Stopped

28

— Increasing patient age — Increasing BMI — Male gender — Active cancer — Second episode of

unprovoked VTE

— + D-dimer after stopping

anticoagulation

— PE higher risk for recurrent

PE

Independent Predictors of VTE Recurrence1,2

Other Helpful Tools — Age- and sex-adjusted D-

dimer cutoff levels3

— Clinical prediction tools4

¡ DASH ¡ Vienna ¡ Men Continue and HER-

DOO2

• 1. Kearon C et al. Blood. 2014;123:12. 2. Heit JA. Nat Rev Cardiol. 2015;12(8):464-474. 3. Palareti G et al. Int J Lab
• Hematol. 2016;38(1):42-49. 4. Kyrle PA et al. Thromb Haemost. 2012;108:1061-1064.

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Duration of Anticoagulation for VTE: 2016 CHEST and AC Forum Guidelines/Guidance

29

Indication CHEST 20161 AC Forum 20162 1st provoked VTE 3 mo 3 mo (surgical)a ≥3 mo (medical) 1st unprovoked VTE Extendedb Extended 2nd unprovoked VTE Extendedb Extended VTE + cancer Extendedb Extended

aUnless risk factors for recurrence persist bNo scheduled stop date, unless high bleeding risk.

Kearon C et al. Chest. 2016;149(2):315-352. Streiff MB et al. J Thromb

• Thrombolysis. 2016;41:32-67.

VTE and Bleeding Risk: 2016 CHEST Guideline

30

Risk of Major Bleeding After 3 Mo of Anticoagulation, %/y Low (0 risk factors) Moderate (1 risk factor) High (≥2 risk factors) Baseline risk 0.3 0.6 ≥2.5 Increased risk 0.5 1.0 ≥4.0 Total risk 0.8 1.6 ≥6.5

• Age >65 y
• Age >75 y
• Previous bleeding
• Cancer
• Renal or hepatic

failure

• Thrombocytopenia
• Previous stroke
• Diabetes
• Anemia
• Antiplatelet therapy
• Poor anticoagulation

control

• Recent surgery
• Frequent falls
• Alcohol abuse
• NSAID use

Reprinted from Chest, 149(2), Kearon C et al, Antithrombotic Therapy for VTE Disease: CHEST Guideline and Expert Panel Report, 315-352, with permission from the American College of Chest Physicians.

Risk Factors for Bleeding with Anticoagulation

Options for Secondary Prevention of VTE

31

Agent Risk Reduction Regimen None 0% — Full-dose anticoagulation1-3 ~80-90% Warfarin INR 2−3; maintenance dosing dabigatran, rivaroxaban, apixaban, edoxaban Low–dose DOAC₂ ~80% Apixaban 2.5 mg BID Rivaroxaban 10mg QD Low-intensity warfarin3 75% Warfarin INR 1.5−1.9 ASA4 32% 100 mg po daily

• 1. Agnelli G et al. N Engl J Med. 2013;368:699-708. 2. EINSTEIN INVESTIGATORS N Engl J Med 363;26
• 3. Kearon C et al. N Engl J Med. 2003;349:631-639. 4. Brighton TA et al. N Engl J Med. 2012;367:1979-1987.

CHEST 2016: In patients with an unprovoked proximal VTE who are stopping anticoagulant therapy and do not have a contraindication to ASA we suggest ASA ..to prevent recurrent VTE

Agnelli etal NEJM 2013

1.7% 8.8%

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• After 6-12 months of anticoagulation for VTE
• Provoked (~60%) or unprovoked (~40%)
• Clinical equipose about indefinite AC therapy
• One year follow up

Weitz et al. N Engl J Med March 2017

All Provoked VTE Recurrent VTE BLEED Rivaroxaban 20 mg 1.5% 1.4% 1.5% 3.3% Rivaroxaban 10 mg 1.2% 0.9% 1.0% 2.4% ASA 81 mg 4.4% 3.6% 8.8% 2.0%

Weitz et al. N Engl J Med March 2017

ASA for Secondary VTE Prevention

ASA ASA is s no not consi nsider dered ed a rea easo sona nabl ble e al alternat ativ ive to an antico icoag agulan ant therap apy in in pa patients who ho want ext xtended duration th therapy

Duration of Anticoagulation for VTE

A 57 year old man presents with unprovoked PE. He has no other PMHx. He is started on rivaroxaban. How long should he remain on anticoagulation? 1) One year 2) 6 months 3) 3 months 4) Indefinitely 5) At least until I sign out

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DOACS in Cancer

58 yo male presents to ED with chest pain and shortness of breath. CT reveals large bilateral PE. Vitals are stable. He has adenocarcinoma of the lung and is undergoing chemotherapy. Which of the following do you recommend for initial PE treatment?

• a. Enoxaparin
• b. IV UFH-> warfarin
• c. Enoxaparin-> dabigatran
• d. Rivaroxaban 15 mg BID x21 days then 20 mg daily

DOACs and VTE in Cancer

Vedovati et al CHEST 2016

Treatment of Cancer-related VTE

CHEST 2016 VTE + cancer recommendations:2

LMWH over VKA (Grade 2B) (DOAC or VKA okay patients not treated with LMWH)

Bott-Kitslaar Am J Med 2016. Kearon C et al. Chest. 2016.

39

— In case control study

rivaroxaban as effective in cancer v. non cancer patients for VTE

— Mult ongoing RCTs now

DOACS in Cancer

58 yo male presents to ED with chest pain and shortness of breath. CT reveals large bilateral PE. Vitals are stable. He has adenocarcinoma of the lung and is undergoing chemotherapy. Which of the following do you recommend for initial PE treatment?

• a. Enoxaparin
• b. IV UFH-> warfarin
• c. Enoxaparin-> dabigatran
• d. Rivaroxaban 15 mg BID x21 days then 20 mg daily

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Thrombocytopenia Cancer and VTE

Our 58 yo man with new PE, adenoc CA of the lung undergoing chemo has a platelet count of 65 at initiation of low molecular weight heparin but he is on a downward trajectory as expected from chemo infused last week. On HD #3 his platelet count is 42K. You:

— 1) Stop enoxaparin — 2) Switch to half dose enoxaparin — 3) Switch to prophylactic enoxaparin — 4) Transfuse with platelets — 4) Go into an empty room and shout “Why is it ALWAYS

during my shift???””

HIT

O points O points O points O points

Thrombocytopenia Cancer and VTE Thrombocytopenia Cancer and VTE

Our 58 yo man with new PE, adenoc CA of the lung undergoing chemo has a platelet count of 65 at initiation of anticoagulation but he is on a downward trajectory as expected from chemo infused last week. On HD #3 his platelet count is 42K. You:

— 1) Stop enoxaparin — 2) Switch to half dose enoxaparin — 3) Switch to prophylactic enoxaparin — 4) Transfuse with platelets — 4) Go into an empty room and say “Why is it ALWAYS

during my shift???””

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Pulmonary Embolism and Syncope

D-dimer and Wells ~40% ~40%

Pulmonary Embolism and Syncope

• PE identified in 17% of all patients, ~ 25% of those with no clear etiology
• More likely if tachycardia, tachypnea, signs DVT, prior VTE, cancer

and no alternative explanation for syncope

• Get d-dimer and Wells in patients hospitalized for syncope
• ? Incidental
• Rate of in all comers including those not admitted was < 4%
• Average age 76

Take Home Points

— ISSPE-1st is it real? 2nd is there a DVT? 3rd is patient high risk? — Duration of anticoagulation for VTE dictated by status of risk

factors at time of event

— Low dose rivaroxaban or apixaban are options for secondary

prevention of VTE in select patients

— Consider withholding anticoagulation and opting for follow up U/S

in low risk calf vein thrombosis

— 6 weeks of low dose rivaroxaban is an option for treatment of SVT-

consider longer duration if high risk

— Cancer associated VTE should be treated with LMWH-if parenteral

therapy not an option DOAC or warfarin acceptable

— Thrombocytopenia in cancer patients with VTE should prompt

adjustment in anticoagulation regimen or platelet transfusion

— Patients hospitalized for syncope should have pre-test probability of

PE and d-dimer assessed.

WORKSHOP

— IVC filters — Incidental PE — Does this patient need to be bridged? — Thrombophilia work up — Management of patient with recurrent VTE despite

therapeutic anticoagulation

— PICC line thrombosis and more — Heparin-induced thrombocytopenia