thromboembolism q & a cases & controversies · 2018-10-15 · we suggest treatment of...

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Thromboembolism Q & ACases & Controversies

TRACY MINICHIELLO, MDPROFESSOR OF MEDICINECHIEF, ANTICOAGULATION AND THROMBOSIS SERVICESAN FRANCISCO VA MEDICAL CENTER

Central Venous Access Device-Related Upper Extremity DVT

A 62 yo man is admitted with respiratory failure due to community acquired pneumonia. He is hypotensive on admission and is intubated. He requires central access for pressor support . On HD #4 his RUE is swollen and U/S shows DVT in his axillary and brachial veins. How do you manage this DVT?

A) remove the line, start full dose anticoagulation and place new central line in contralateral arm

B) start anticoagulation, do not remove the central line as central access is still needed

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At least 7 days of anticoagulation prior to catheter removal to reduce risk of TEConsider on case be case basis

IVC Filters

A 50 year old man is on warfarin for recurrent VTE. His last VTE event was 8 years ago. He is well controlled with TTR of 85%. H presents with sudden onset LLE swelling and pain and he says it “feels like a DVT”. D-dimer is 1500. Ultrasound shows acute expansile DVT in the distal femoral vein, new since prior U/S one year ago. He is transitioned to LMWH. He is told he needs an IVC filter to prevent PE. a) Yes,it will decrease his risk of PEb) No, it will increase his risk of DVTc) All of the above

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VTE Recurrence on Anticoagulation

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VTE Recurrence on Anticoagulation

Behnood Bikdeli et al. JACC 2017;70:1587-1597

2017 American College of Cardiology Foundation

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IVC Filters

A 50 year old man is on warfarin for recurrent VTE. His last VTE event was 8 years ago. He is well controlled with TTR of 85%. H presents with sudden onset LLE swelling and pain and he says it “feels like a DVY”. D-dimer is 1500. Ultrasound shows acute expansile DVT in the distal femoral vein, new since prior U/S one year ago. He is transitioned to LMWH. He is told he needs an IVC filter to prevent PE. a) Yes,it will decrease his risk of PEb) No, it will increase his risk of DVTc) All of the above

Incidental PE

A 77 yo man is 2 weeks s/p laproscopic nephrectomy for renal cell CA. He received LMWH for 5 days post op 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 subsegmentalpulmonary artery filling defect. Do you anticoagulated this patient?a) No, that did not go well last timeb) Yes, it is a PEc) Not again. Didn’t we just talk about this?

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Should I Treat This Isolated Subsegemental PE?

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

Incidental PE in Cancer

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Should I Treat This Isolated Subsegemental PE?


1st IS IT REAL? good scan, multi defects, central, sx, + d-dimer

2nd Consider risk of recurrence if not treated Hospitalized, reduced mobility, CA, no reversible risk factor

3rd Consider bleeding risk 4th Make an individualized plan High risk recurrence-treat Low cardiopulm reserve or no alternative etiology of sx-

consider treating Low risk recurrence or high bleeding risk- get U/S lower extrem

(& upper if CVC). IF + DVTtreat If NO DVTserial u/s

Incidental PE in CancerLOCATION RECOMMENDATIONProximal 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

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Incidental PE

A 77 yo man is 2 weeks s/p laproscopic nephrectomy for renal cell CA. He received LMWH for 5 days post op 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 timeb) Yes, it is a PEc) Not again. Didn’t we just talk about this?

Calf Vein DVTA 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 therapy2. Prophylactic dosing of LMWH or DOAC3. 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 but is embarrassed to ask.

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Also includes gastroc and soleus veins

Calf Vein DVT-CHEST 2016


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

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Calf Vein DVT-CHEST 2016 AC Forum clinical guidance We suggest treatment of distal DVT with anticoagulation versus observation. 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

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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 therapy2. Prophylactic dosing of LMWH or DOAC3. 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 and is embarrassed to ask.

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???””

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HIT O points

O points

O points

O points


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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???””

Superficial Vein Thrombosis

A 55 year old woman presents with painful 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 6 cm from the deep femoral vein. What do you recommend?a. Prophylactic fondaparinuxb. Prophylactic rivaroxabanc. Full dose DOAC or warfarind. NSAIDS and ice

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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 placeboPrimary outcome 1% vs 6%


• >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)

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Full dose anticoagulationfor at LEAST 6 weeks


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 fondaparinuxb. Prophylactic rivaroxabanc. Full dose DOAC or warfarind. Nsaids and ice

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DOAC for Secondary Cardiovascular Protection

55 year old with stable coronary disease with NSTEMI MI 4 years ago is on ASA 81 mg qd. His primary provider asks if he should now be started on rivaroxaban given the “new data”. You recommend:

1. Change to “low dose” rivaroxaban 5 mg bid

2. Add “very low dose” rivaroxaban 2.5 mg bid

3. Continue ASA 81 mg

COMPASS

Eikelboom JW. N Engl J Med. 2017 Oct 5;377(14):1319-1330. PMID: 28844192

RCT Riva 5 mg BID or Riva 2.5 mg BID + ASA vs ASAStable CAD or PVD1 ◦-Composite death, stroke, MI ;2◦-Major bleeding

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COMPASS

Eikelboom JW. N Engl J Med. 2017 Oct5;377(14):1319-1330. PMID: 28844192

Primary outcome 24% lower with rivaroxaban (2.5mg twice daily) plus aspirin than with aspirinalone (4.1% vs. 5.4%), but the rate of majorbleeding was higher by 70% (3.1% vs. 1.9%).

COMPASS

~ 50% reduction in stroke


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COMPASS

~50% reduction in amputation


Which Patients with CVD May Benefit Most?

Peripheral artery disease High risk population for MALE, CVA

Combination should replace ASA as standard of care

Timing? Voyager PAD study (immediately post re-vascularization)

High risk stable CAD? Polyvascular disease

Disease in more than one vascular bed

RIVAROXABAN 2.5 mg tabsNOT AVAILABLE YET

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DOAC for Secondary Cardiovascular Protection

55 year old with stable coronary disease with NSTEMI MI 4 years ago is on ASA 81 mg qd. His primary provider asks if he should now be started on rivaroxaban given the “new data”. You recommend:

1. Change to “low dose” rivaroxaban 5 mg bid

2. Add “very low dose” rivaroxaban 2.5 mg bid

3. Continue ASA 81 mg

ASA for VTE Prevention in High Risk Ortho Surgery

A 65 year old man with PMHx of obesity (BMI 32, weight 105 kg), HTN, OA has left total knee arthroplasty. Which is the most effective DVT prophylaxis regimen for him?

1. Rivaroxaban 10 mg QHS for 14 days2. Rivaroxaban 10 mg QHS for 5 days- ASA 81 mg daily for 2 weeks3. ASA (81 mg BID to 325 mg BID) QD for 14 days4. Honestly, who knows. But ortho wont listen to me anyway.

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Current ACCP VTE Prophylaxis Guidelines in Orthopedic Surgery

ASA vs Rivaroxaban for VTE prevention after Hip or Knee Arthroplasty

Anderson DR et al. N Engl J Med 2018

Starting on POD#6 ASA is as safe/effective as rivaroxabanFew patients with obesity cancer prior VTEPatients on higher dose ASA had higher bleed rates-use low dose ASA

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ASA for VTE Prevention in High Risk Ortho Surgery

A 65 year old man with PMHx of obesity (BMI 32, weight 105 kg), HTN, OA has left total knee arthroplasty. Which is the most effective DVT prophylaxis regimen for him?

1. Rivaroxaban 10 mg QHS for 14 days2. Rivaroxaban 10 mg QHS for 5 days- ASA 81 mg daily for 2 weeks3. ASA (81 mg BID to 325 mg BID) QD for 14 days4. Honestly, who knows. But ortho wont listen to me anyway.

Dual Therapy with DOACPost PCI in NVAF

A 68 yo man with AFIB, DM, HTN on dabigatran and metoprolol presents with NSTEMI. Cardiac cath shows 90% occlusion in left circumflex, he has PCI with drug eluting stent. You are preparing him for discharge. What antithrombotic regimen should he be discharged on?

1. Triple therapy with dabigatran, clopidigrel and ASA2. Dual therapy with dabigatran and clopidigrel3. Dual therapy with clopidigrel and ASA‐restart dabigatran

after dropping one of the antiplatelet agents4. Whatever cardiology tells me to do

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Dual Therapy with DOAC Post-PCI in NVAF

AFIB and PCI for ACS or CAD110 dabi + P2Y12 inhibitor;150 mg dabi + P2Y 12 inhibitor or triple therapy with warfarin ASA plus P2Y 12 inhibitor1◦ endpoint-major and CRNM bleeding2◦ endpoint composite of TE death or revasculization


15%

27%26%

20%

Dual therapy with dabigatran and P2Y12 inhibitor resulted in lowerrisk of bleeding with non inferior Rates of TE when compared to tripletherapy

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Piccini JP. N Engl J Med. 2017 Oct 19;377(16):1580-1582. PMID: 29045197


AFIB PCI Antithrombotic Therapy

Angiolillo et al. Circulation 2018

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In AF patients requiring OAC undergoing electivePCI/stenting, where bleeding risk is high (HASBLED‡ 3), we suggest triple therapy for 1 month,followed by dual therapy with OAC plus singleantiplatelet (preferably clopidogrel) for 6 months,following which OAC monotherapy can be used(Weak recommendation, low quality evidence).

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A 68 yo man with AFIB, DM, HTN on dabigatran, ASA and metoprolol presents with NSTEMI. Cardiac cath shows 90% occlusion in left circumflex, he has PCI with drug eluting stent. You are preparing him for discharge. What antithrombotic regimen should be discharged on?

1. Triple therapy with dabigatran, Plavix and ASA

2. Dual therapy with dabigatran and Plavix

3. Dual therapy with Plavix and ASA‐restart dabigatran after dropping one of the antiplatelet agents

4. Whatever cardiology tells me to do

DOAC selection, dosing, monitoring

Mr. M is an 80 year old man with CHF, HTN, CKD, and new non valvularAFIB. SCr = 1.4 mg/dL, Wt 70 kg. He has a remote history of GI bleed from gastritis. He is on a PPI. He does not want to use warfarin and is interested in a “new” blood thinner. Which DOAC do you choose for him?

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DOAC Selection in NVAF53Dabigatran Rivaroxaba

nApixaban Edoxaban

MOA FIIa inh FXa inh FXa inh FXa inhAdmin BID

swallow whole

QD*w/ meal*

BID QD

Renal elimination

~80% ~1/3 ~1/4 ~1/2

DrugInteractions

P-gp CYP3A4/P-gp

CYP3A4/ P-gp

P-gp

Other No pill box - - Avoid in CrCl >95 ml/minin AFIB

DOAC Selection in NVAF

*DOACs compared to warfarin; no head-to-head RCTs

54DABI RIVA APIX EDOX

FDA Approval Trial vs. WARF

RE-LY ROCKET-AF ARISTOTLE ENGAGE

Eff: CVA, SEE Superior Noninferior Superior NoninferiorSaf: Maj bleed Similar Similar Superior SuperiorICH Superior Superior Superior SuperiorGI bleed Worse Worse Similar WorseMortality Favorable Favorable Superior Favorable Bleeds in elderly subgroup≥75 yrs

Trend of more major

bleed

Trend of more CR

bleed

Less bleed

Less major,more GI bleed

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DOAC Selection in AF:PBM CFU Algorithm55

DOACS in AFIB Selection Bottom Line

Overall, DOACs perform in most aspects as good or in some cases better than warfarin *Renal function*

Avoid dabigatran in patients with significant impairment or fluctuating or borderline renal function

Avoid edoxaban in patients with very good renal function (CrCl >95 ml/min)

High bleed risk / GI bleed history or high risk –consider apixaban

Drug interactions may guide selection

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Appropriate NVAF DOAC DosingDABI RIVA APIX EDOX

Regulardosing

150 mg BID 20 mg QD 5 mg BID 60 mg QD(CrCl ≤95)

Reduced dosing

75 mg BID 15 mg QD 2.5 mg BID 30 mg QD

Indications for lowerdose:

-CrCl 15-30 ml/min-CrCl 30-50 ml/min +DDI

-CrCl 15-50 ml/min

-2 or more:-SCr ≥1.5-Wt ≤60 kg-Age ≥80 y

-CrCl 15-50 ml/min

Studied clinically

NO Not CrCl <30 ml/min

Not CrCl <25 ml/min or SCr>2.5

Not CrCl <30 ml/min

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NOT THE SAME AS VTE DOSINGTHERE IS EITHER A DOAC “LOAD” OR LMWH LEAD IN FOR ACUTE VTE THERE IS NO RENAL ADUSTMENT FOR VTE EXCEPT EDOXABAN

DOAC selection, dosing, monitoring

Mr. M is an 80 year old man with CHF, HTN, CKD, and new AF. SCr = 1.4 mg/dL, Wt 70 kg. He has a remote history of GI bleed from gastritis. He is on a PPI. He does not want to use warfarin and is interested in a “new” blood thinner. Which DOAC do you choose for him? CHA2DS2-VASc Score = 4; high risk CrCl ~42 ml/min You recommend apixaban 5 mg BID Now what?

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MT1

MT1 lisa can you discuss why you chose 5 mg rather than 2.5 mg and the data on underdosing of DOACs and clinical outcomes here? and maybe highlihgt that he MAY meet dose reduction criteria very soon and perhaps need closer monitoring?Minichiello, Tracy, 1/14/2018

thromboembolism q & a cases & controversies · 2018-10-15 · we suggest treatment of...

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