Updates in Diagnosis & Management of VTE

Transcription

1 Updates in Diagnosis & Management of VTE TRACY MINICHIELLO, MD CHIEF, ANTICOAGULATION& THROMBOSIS SERVICE-SAN FRANCISCO VAMC PROFESSOR OF MEDICINE UNIVERSITY OF CALIFORNIA, SAN FRANCISCO Financial Disclosures-NONE 1

2 Objectives Determine duration of anticoagulation for VTE Review options for secondary prevention of VTE Identify patients who should have thrombophilia evaluation and interpret testing Manage anticoagulation in cancer patients THESE SHOULD BE AT YOUR FINGERTIPS Kearon et al. Chest. 2016;149(2): Doherty et al. JACC

3 Volume 41, Issue 1, January 2016 Special Issue: Management of Venous Thromboembolism: Clinical Guidance from the Anticoagulation Forum Duration of Anticoagulation for VTE A 57 year old man presents with pleuritic chest pain. D-dimer is elevated and CT chest shows bilateral lobal PE. There are no identifiable provoking factors. 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 3

4 Risk of VTE Recurrence After Anticoagulation Is Stopped Characteristic Recurrence at 1 yr Recurrence at 5 yr Major provoked 1% 3% (transient) Minor provoked 5% 15% (transient) Unprovoked 10% 30% Cancer 20% ~20% in those with medically provoked VTE Major transient risk factors Major surgery, trauma Minor transient risk factors Pregnancy, minor surgery, longhaul air travel, immobilization, medical illness Nontransient risk factors Active cancer, severe thrombophilia, inflammatory bowel disease Kearon C et al. Blood. 2014;123(12): Heit JA. Nat Rev Cardiol. 2015;12(8): Risk of VTE Recurrence After AC Is Stopped Independent Predictors of VTE Recurrence 1,2 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 Other Helpful Tools Age- and sex-adjusted D- dimer cutoff levels 3 Clinical prediction tools 4 DASH Vienna Men Continue and HER- DOO2 1. Kearon C et al. Blood. 2014;123: Heit JA. Nat Rev Cardiol. 2015;12(8): Palareti G et al. Int J Lab Hematol. 2016;38(1): Kyrle PA et al. Thromb Haemost. 2012;108:

5 Duration of Anticoagulation for VTE: 2016 CHEST and AC Forum Guidelines/Guidance Indication CHEST AC Forum st provoked VTE 3 mo 3 mo (surgical) a 3 mo (medical) 1st unprovoked VTE Extended b Extended 2nd unprovoked VTE Extended b Extended VTE + cancer Extended b Extended a Unless risk factors for recurrence persist b No scheduled stop date, unless high bleeding risk. Kearon C et al. Chest. 2016;149(2): Streiff MB et al. J Thromb Thrombolysis. 2016;41: VTE and Bleeding Risk: 2016 CHEST Guideline Risk of Major Bleeding After 3 Mo of Anticoagulation, %/y Low (0 risk factors) Moderate (1 risk factor) High ( 2 risk factors) Baseline risk Increased risk Total risk Risk Factors for Bleeding with Anticoagulation 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, , with permission from the American College of Chest Physicians. 10 5

6 ASA for Secondary VTE Prevention ASA is not considered a reasonable alternative to anticoagulant therapy in patients who want extended duration therapy Simes et al. Circulation. 2014;130: ) 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

7 Weitz et al. N Engl J Med March 2017 All Provoked VTE Recurrent VTE BLEED Rivaroxaban 1.5% 1.4% 1.5% 3.3% 20 mg Rivaroxaban 1.2% 0.9% 1.0% 2.4% 10 mg ASA 81 mg 4.4% 3.6% 8.8% 2.0% 8.8% 1.7% Agnelli etal NEJM

8 UNPROVOKED VTE All patients get 3-6 months of FULL intensity anticoagulation for VTE At 3-6 months determine candidacy for secondary prevention ~50% will develop recurrent VTE if off anticoagulation Case fatality rate of VTE is ~4% in all comers but closer to 9% in those who present with PE Case fatality rate of bleeding is ~10% Case by case decision consider continuation in all if not Secondary high bleeding Prevention risk. Options Most compelling Do not use in dose low reduced bleed risk DOAC: Low patients dose DOAC*** and in those with PE Obesity Full dose anticoagulation ASA Cancer Recurrent VTE on AC Duration of Anticoagulation for VTE A 57 year old man presents with pleuritic chest pain. D-dimer is elevated and CT chest shows bilateral lobal PE. There are no identifiable provoking factors. 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 8

9 Thrombophilia Testing Should he have a thrombophilia work up for this unprovoked VTE event? Yes No More coffee, please? Thrombophilia Testing No current guidance/.guidelines EXCEPT ASH Choosing Wisely Campaign- do not test in provoked VTE Results of thrombophilia testing should RARELY affect clinical decisions about VTE treatment-no strong influence on recurrence risk beyond stratification based on clinical presentation Can help explain why Can be of interest to family members Current tests are insufficient for identifying inherited VTE risk 9

10 Who should we suspect harbors thrombophilia? Connors JM. N Engl J Med 2017;377: Thrombophilia Tests. Connors JM. N Engl J Med 2017;377:

11 Summary of Recommendations Regarding Testing for Thrombophilia. Connors JM. N Engl J Med 2017;377: Algorithm for Selecting Patients with a First Venous Thromboembolism (VTE) for Thrombophilia Testing. Splanchnic vein thrombosis Cerebral vein thrombosis Connors JM. N Engl J Med 2017;377:

12 Antiphospholipid Antibody Syndrome Antiphospholipid Antibody Syndrome WHY- risk of recurrence off AC much higher; at risk for arterial disease, bridge therapy; DOACs generally avoided WHO- arterial and venous events, unexpected arterial events, recurrent thrombosis ON anticoagulation, underlying autoimmune d/o, prolonged aptt WHAT-send Lupus anticoagulant, Beta 2 glycoprotein antibodies and anticardiolipin antibodies (IgG & Ig M) WHEN-LAC-don t do it on anticoagulation; antibodies you can send anytime IF POSITIVE- must repeat in 12 weeks-high rate of transient positivity LAC most predicative of 1 st and recurrent VTE, triple positives at highest risk 12

13 Thrombophilia Testing Should he have a thrombophilia work up for this unprovoked VTE event? Yes No More coffee, please? DOACS in Cancer 58 yo male with adeno of the lung, undergoing chemotherapy presents to ED with pleuritic chest pain and shortness of breath. He is hemodynamically stable. CT reveals bilateral PE. Which of the following do you recommend for PE treatment? 1. Enoxaparin warfarin 2. Enoxaparin edoxaban 3. Enoxaparin 4. Rivaroxaban 15 mg BID x21 days then 20 mg daily 5. Remember the good old days when there was only one option??? 13

14 Treatment of Cancer-related VTE Bott-Kitslaar Am J Med Kearon C et al. Chest CHEST 2016 VTE + cancer recommendations: 2 LMWH over VKA (Grade 2B) (DOAC or VKA okay patients not treated with LMWH) DOACs and Cancer Raskob et al NEJM

15 Hokusai VTE Cancer Raskob et al. NEJM 2017 Hokusai- Recurrent VTE 11.3% 7.9% Raskob et al. NEJM 2017 Treatment duration 211 days-edoxaban 184 days-dalteparin 15

16 Hokusai- VTE Cancer Major Bleeding Higher rates of UGIB with edoxaban Mainly in patients with GI malignancy Similar rates of severe bleeding 6.9% 4.0% Raskob et al. NEJM 2017 Hokusai- VTE Bleeding SELECT D-riva vs LMWH for cancer..similar results Agent VTE recurrence Bleeding ESOPH CA Riva 4% 4% 36% LMWH` 11% 6% 11% Young et al J Clinical Oncology

17 ISTH DOACS in CANCER GUIDEDANCE We suggest the use of specific DOAC for active cancer patients with an acute VTE, low risk of bleeding & no drug drug interactions with current systemic therapy. LMWHs constitute an acceptable alternative. Currently,edoxaban and rivaroxaban are the only DOACs that have been compared with LMWH in RCTs in cancer Inform patients regarding potential reduction in recurrence but higher bleeding ISTH DOACS in CANCER GUIDEDANCE We suggest the use of LMWHs for cancer patients with acute diagnosis of VTE and a high risk of bleeding (GI cancers with intact primary, cancers at risk of bleeding from the GU tract, bladder, or nephrostomy tubes, active GI mucosal abnormalities such as duodenal ulcers, gastritis, esophagitis, or colitis.) Specific DOACs (edoxaban and rivaroxaban) are acceptable alternatives if there are no drug drug interactions with current systemic therapy. 17

18 DOACS in Cancer 58 yo male with adeno of the lung, undergoing chemotherapy presents to ED with pleuritic chest pain and shortness of breath. He is hemodynamically stable. CT reveals bilateral PE. Which of the following do you recommend for PE treatment? 1. Enoxaparin warfarin 2. Enoxaparin edoxaban 3. Enoxaparin 4. Rivaroxaban 15 mg BID x21 days then 20 mg daily 5. Remember the good old days when there was only one option??? VTE Recurrence on Anticoagulation A 65 year old man with unprovoked PE that occurred 3 months ago develops SOB and chest pain and is found to have recurrent PE. He is on warfarin. His INR is 2.0. What anticoagulation regimen do you recommend now? A) rivaroxaban B) warfarin with goal inr 3-4 C) IVC filter D) Low molecular weight heparin E) Honestly, why me? 18

19 VTE Recurrence on Anticoagulation Shulman Blood 2017 VTE Recurrence on Anticoagulation 1 st -is it REAL? D-dimer DOAC-acute VTE vs AFIB No dose reduction for renal insufficieny with DOAC except edox Warfarin overlap 1 in 3 may have cancer MPO-JAK 2 Other exon mutations APLS-beware the INR Shulman Blood 2017 PNH-hemolysis cytopenias and clots in weird places 19

20 VTE Recurrence on Anticoagulation Shulman Blood 2017 NOTICE-NO MENTION OF IVC FILTER! CHEST 2016:VTE Recurrence While on AC 20

21 Anticoagulation in Recurrent VTE in APLS Increase INR to Add ASA to usual intensity warfarin? Add statin Consider hydroxychloroquine LMWH-case reports:some good, some not so good Fondaparinux-limited data VTE Recurrence on Anticoagulation A 65 year old man with unprovoked PE that occurred 3 months ago develops SOB and chest pain and is found to have recurrent PE. He is on warfarin. His INR is 2.0. What anticoagulation regimen do you recommend now? A) rivaroxaban B) warfarin with goal inr 3-4 C) IVC filter D) Low molecular weight heparin 21

22 Take Home Points 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 Cancer associated VTE can be treated with DOACs-tumor type, concomitant medication and bleeding risk should guide therapy Thrombophilia evaluation for select patient, not during acute thrombosis Recurrent VTE on AC requires first confirmation of new thrombosis, consideration of factors related to the anticoagulant and investigation into diseases associated with high risk of failure and possible change in AC regimen WORKSHOP IVC filters Does this patient need to be bridged? Superficial Vein thrombosis Calf vein thrombosis Management of patient with recurrent VTE despite therapeutic anticoagulation ASA for DVT prophylaxis PICC line thrombosis and more Heparin-induced thrombocytopenia 22