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Rapid Fire-Top ArticlesYou Need to Know

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THESE SHOULD BE AT YOUR FINGERTIPS

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

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

Secondary Prevention of VTE

A 57 year old man with DVT 6 months ago possiblymildly provoked (weeks after 4 hour plane flight) is on rivaroxaban 20 mg daily. For ongoing VTE prevention you recommend:1) Continue rivaroxaban 20 mg po daily2) Transition to rivaroxaban 10 mg po daily3) Switch to apixaban 2.5 mg twice daily4) Stop rivaroxaban 5) Stop rivaroxaban. Start ASA 81 mg po daily6) Did you say happy hour?

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

7

Indication CHEST 20161 AC Forum 20162

1st provoked VTE 3 mo 3 mo (surgical)a

≥3 mo (medical)1st unprovoked VTE Extendedb Extended2nd unprovoked VTE Extendedb ExtendedVTE + cancer Extendedb Extended

aUnless risk factors for recurrence persist bNo scheduled stop date, unless high bleeding risk.1. Kearon C et al. Chest. 2016;149(2):315-352. 2. Streiff MB et al. J ThrombThrombolysis. 2016;41:32-67.

Options for Secondary Prevention of VTE

8

Agent Risk Reduction Regimen

None 0% —

Full-dose anticoagulation1-3 ~80-90%

Warfarin INR 2−3; maintenance dosing dabigatran, rivaroxaban,

apixaban, edoxabanLow–dose DOAC₂ ~80% Apixaban 2.5 mg BID

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;263. 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 etalNEJM 2013

1.7%

8.8%

• 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 ProvokedVTE

RecurrentVTE

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

Secondary Prevention of VTE

A 57 year old man with DVT 6 months ago possiblymildly provoked (weeks after 4 hour plane flight) is on rivaroxaban 20 mg daily. For ongoing VTE prevention you recommend:1) Continue rivaroxaban 20 mg po daily2) Transition to rivaroxaban 10 mg po daily3) Switch to apixaban 2.5 mg twice daily4) Stop rivaroxaban 5) Stop rivaroxaban. Start ASA 81 mg po daily6) Did you say happy hour?

“Extending treatment beyond 3 months could be considered

with provoked VTE….The results of this trail cannot be

extended to patients who have an unequivocal indication for

long-term anticoagulation therapy”

What To Do After the Bleed

76 y/o man with CAD (NSTEMI 2006), AFIB CHADS-Vasc=4 on warfarin and ASA is admitted with UGIB. INR is 3.0. He requires 3u PRBCs, vit K and FFP. EGD shows peptic ulcer disease. He is started on high dose PPI therapy, bx for H Pylori done. When should his anticoagulation be restarted?a) Neverb) In two weeksc) In three months d) Let the primary provider deal with this one

What To Do After the Bleed

Witt Hematology 2016

What To Do After the Bleed

76 y/o man with CAD (NSTEMI 2006), AFIB CHADS-Vasc=4 on warfarin and ASA is admitted with UGIB. INR is 3.0. He requires 3u PRBCs, vit K and FFP. EGD shows peptic ulcer disease. He is started on high dose PPI therapy, bx for H Pylori done. When should his anticoagulation be restarted?a) Neverb) In two weeksc) In three months d) Let the primary provider deal with this one

“Two weeks may provide the best balance among GI

bleed recurrence , thromboembolism and

mortality””

DOACs in Extremes of Weight

A 56 year old obese man, BMI 42, weight 155 kg presents with bilateral lower extremity swelling. D-Dimer is elevated prompting bilateral lower extremity ultrasound. Ultrasound shows a DVT in LEFT common femoral, superficial femoral and popliteal vein. He is deemed appropriate for outpatient management of this VTE. What anticoagulant regimen do you recommend?1. Rivaroxaban 15 mg BID x21 days then 20 mg daily2. Apixaban 10 mg BID x 7 days then 5 mg BID3. Enoxaparin bridging to warfarin4. Admission for IV heparin bridging to warfarin5. Do you have Ann Wittkowsky’s cell phone number?

DOACs in Extremes of Weight

• Systematic review of 6 trials of DOACS vs warfarin n VTE• Proportion of patient s classified as high body weight 15-28%• Variability may be related to definition (ie > 90kg vs 100kg)• Very little information on extreme body weight (eg < 40 kg, > 150 kg

Di Minno MN et al. Ann Med. 2015 Feb;47(1):61-8

DOACS AND EXTREMES OF WEIGHT

Minno et al Ann Intern Med 2015Feb;47(1):61-8

HIGH BODY WEIGHT

NORMAL BODY WEIGHT

LOW BODY WEIGHT

DOACs in Obesity

Martin et al Journal of Thrombosis and Haemostasis, 2016 14: 1308–1313

Reduced exposure, lower peaks, shorter t 1/2

ISTH RECOMMENDATIONS:� Recommend standard dosing if BMI< 40 and

weight < 120 kg.� Suggest DOACS not be used if BMI> 40 or

weight > 120 kg� If DOACs used in BMI > 40 or weight> 120 kg

suggest drug specific peak and trough level If level within expected range continue

DOAC; if below suggest warfarin

Martin et al. J Thromb Heamost 2016

DOACs in Extremes of Weight

DOACs in Extremes of Weight

A 56 year old obese man, BMI 42, weight 155 kg presents with bilateral lower extremity swelling. D-Dimer is elevated prompting bilateral lower extremity ultrasound. Ultrasound shows a DVT in LEFT common femoral, superficial femoral and popliteal vein. He is deemed appropriate for outpatient management of this VTE. What anticoagulant regimen do you recommend?1. Rivaroxaban 15 mg BID x21 days then 20 mg daily2. Apixaban 10 mg BID x 7 days then 5 mg BID3. Enoxaparin bridging to warfarin4. Admission for IV heparin bridging to warfarin5. Do you have Ann Wittkowsky’s cell phone number?

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 thrombosis 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.

Also includes gastroc and soleus veins

Calf Vein DVT-CHEST 2016

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

Risk factors for extension: d-dimer +, extensive thrombosisclose 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 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

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 thrombosis 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.

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 6 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

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

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)

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

Superficial Vein Thrombosis

Reducing the Hospital Burden of HIT

� Not uncommon¡ HIT occurs in 5% of those exposed to UFH¡ Risk reduced 10 fold with LMWH

� High morbidity and mortality¡ Thromboembolic complications 20-50%

� Expensive

“Reducing the Hospital Burden of HIT”

McGowan KE, et al. Blood. 2016 Apr 21;127(16):1954-9

Avoid Heparin Protocol

� Systematic replacement of most IV and SQ UFH with SQ LMWH in prophylactic or therapeutic doses (remaining uses of UFH were for hemodialysis, intraoperative use for cardiovascular surgery, ACS)

� Replacement of heparinized saline in arterial and central venous lines with saline flushes

� Modification of order sets to exclude UFH options� Removal of UFH stores from most nursing units.

McGowan KE, et al. Blood. 2016 Apr 21;127(16):1954-9

Avoid Heparin Protocol

McGowan KE, et al. Blood. 2016 Apr 21;127(16):1954-9

~40% reduction in suspected HIT~80% reduction in HIT~80% reduction in HIT related costs

Periprocedural Management of DOACs

A 62 year old man with DM, CAD and aflutter is on dabigatran for stroke prevention. He is to undergo ablation procedure next month. He asks if he will need to stop his dabigatran prior to his procedure. What do you tell him?1) Yes-hold 2 doses prior to the procedure2) No-you don’t have to stop it, just cross your fingers

that it all goes ok.

Raval et al. Circulation. 2017;135:00–00

Calkins et al. N Engl J Med. 2017 Mar 19

Uninterrupted Dabigatran v. Warfarin Ablation

Calkins et al. N Engl J Med. 2017 Mar 19

77% reductionin risk of majorbleeding

Periprocedural Management of DOACs

A 62 year old man with DM, CAD and aflutter is on dabigatran for stroke prevention. He is to undergo ablation procedure next month. He asks if he will need to stop his dabigatran prior to his procedure. What do you tell him?1) Yes-hold 2 doses prior to the procedure2) No-you don’t have to stop it, just cross your fingers

that it all goes ok.

Take Home Points

� Low dose rivaroxaban is an option for secondary prevention of VTE

� If decision is made to restart anticoagulation after GIB in patients on warfarin for AFIB, reinitiate warfarin on day 7-14

� 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

� Uninterrupted dabigatran appears safe in patients undergoing ablation

THE END