ANTICOAG & THROMBOSIS CASES

Transcription

1 ANTICOAG & THROMBOSIS CASES Tracy Minichiello, M.D. Professor of Medicine University of California, San Francisco Chief, SF VA Anticoagulation & Thrombosis Service Disclosures I have nothing to disclose 1

2 QUESTIONS Catheter related thrombosis-pull the line? Thrombophilia work up-do we still do those? QUESTIONS How do we treat this patient with recurrent VTE while ON anticoagulation? Does this patient need an IVC filter? Does ANY patient need an IVC filter Should this patient with AFIB/VTE/ mechanical valve be bridged perioperatively and how? 2

3 Catheter- Associated DVT A 55 year old woman being treated for osteomyelitis of the spine develops right upper extremity swelling. U/S reveals a DVT in the subclavian and axillary vein. She has a PICC line in that arm. She needs 4 more weeks of antibiotics.you start anticoagulation. Do you need to pull the line? a. Yes b. No Upper Extremity DVT Remove catheter (after 7 days of anticoagulation if possible) if: Infection Malfunction AC contraindicated AC failed Cath not needed Kucher N. N Engl J Med

4 Upper Extremity DVT AC Forum A similar approach may be considered for cancer patients Catheter- Associated DVT A 55 year old woman being treated for osteomyelitis of the spine develops right upper extremity swelling. U/S reveals a DVT in the subclavian and axillary vein. She has a PICC line in that arm. She needs 4 more weeks of antibiotics.you start anticoagulation. Do you need to pull the line? a. Yes b. No 4

5 IVC Filters A 68 year old woman falls and fractures her hip. She is in CHF on admission so OR time is delayed. On HD #3 she becomes acutely short of breath and is found to have PE and DVT. How do you manage her anticoagulation perioperatively? IVC Filters PREPIC STUDY 12 days 2 years 2 years Filter No Filter 1% 5% 20% 11% 3.4%(ns) 6.3% PREPIC 8 yr FOLLOW UP PE HR 0.32 DVT HR 1.52 No survival benefit PREPIC STUDY GROUP, Circulation 2005; Decousus NEJM

6 PREPIC IVC Filters Most retrievable IVC filters are not removed, in real-world practice Recent meta analysis found only 1/3 devices actually retrieved Filter complications are serious: fracture, embolization, thrombosis 6

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8 IVC Filter A 68 year old woman falls and fractures her hip. She is in CHF on admission so OR time is delayed. On HD #3 she becomes acutely short of breath and is found to have PE and DVT. How do you manage her anticoagulation perioperatively? Take Home Points-IVC Filters Retreivable IVC filters are not without complications-risk benefit should be assessed carefully in each case Once placed prophylactic anticoagulation should be started as soon as possible Make retrieval plans for device prior to DC so not inadvertently left in place 8

9 VTE Recurrence on Anticoagulation A 33 year old woman diagnosed with left lower extremity DVT 3 months ago maintained on warfarin present with complaints of pleuritic chest and shortness of breath. A CT angio of the chest reveals new bilateral segmental pulmonary emboli. VTE Recurrence on Anticoagulation She reports compliance with her warfarin therapy and has an INR of 2.5 at the time of admission. She is admitted to your service for recurrent VTE. How do you manage this? 9

10 VTE Recurrence on Anticoagulation A 65 year old man with adeno CA of the lung on chronic dalteparin for cancer associated VTE that occurred 3 months ago develops SOB and chest pain and is found to have recurrent PE. What anticoagulation regimen do you recommend now? A) rivaroxaban B) warfarin with goal inr 3 4 C) IVC filter C) Higher doses of dalteparin VTE Recurrence on Anticoagulation 1 st IS THIS A TRUE RECURRENCE? Treatment Factors Within 1 st month of therapy Adherence VKA sub therapeutic AC prescribed incorrectly On DOAC and problem med AC dose reduced Patient Factors Is there cancer Is this APLS Is this HIT Is this antithrombin def Myeloproliferative d/o PNH Dysfibrinogenemia Structural 10

11 VTE Recurrence on Anticoagulation Warfarin failure Transition to LMWH for at least a month Do not change to DOAC if reasonable TTR-DOACS noninferior to warfarin for VTE recurrence- NOT superior AC forum says increase target INR or 3-4 or LMWH DOAC failure Transition to LMWH for at least a month AC Forum says consider transition to warfarin LMWH failure Increase dosing by 25-35% Change to BID dosing Follow anti-xa levels VTE Recurrence While on LMWH 11

12 Management Algorithm of Recurrent VTE in Cancer Lee A Y Y et al Blood 2013;122: by American Society of Hematology VTE Recurrence on Anticoagulation She reports compliance with her warfarin therapy and has an INR of 2.5 at the time of admission. She is admitted to your service for recurrent VTE. How do you manage this? 12

13 Thrombophilia Work up A 55 year old man presents with large unprovoked PE. Do you send a thrombophilia work up? a) Yes b) No c) Are we still doing those? American Society of Hematology, 2015 ASH:Thrombophilia is not associated with Risk of VTE Recurrence N = 474 HR = 1.3 (95% CI, ) Christiansen et al. JAMA 2005;293(19):

14 American Society of Hematology, 2015 ASH: Thrombophilic Defects Are Not Associated with a Higher Risk of Recurrent VTE Kearon C et al. Blood 2008;112: Impact of Acute Thrombosis & Anticoagulation on Thrombophilia Testing test Acute VTE Heparin Warfarin Anticardiolipin antibodies Lupus anticoagulant May be elevated May be prolonged no effect prolonged no effect prolonged Protein C, S decreased No effect decreased Antithrombin level decreased decreased increased Factor VIII level increased no effect no effect 14

15 DOAC and Thrombophilia Testing Mani et al White Paper Siemans 2013 When to CONSIDER Work up for Laboratory Thrombophilia Women of childbearing years Patients with suspicion for APLS Strong family history of VTE Patients with recurrent VTE Thrombosis in weird places Results will influence therapy IF done prefer to do when out of acute phase (after 3 months/except when high suspicion for APLS) 15

16 MORE IMPORTANTLY Conditions Associated with VTE IBD Behcets HIT DIC ITP Myeloproliferative d/o Nephrotic syndrome PNH OSA Wegners SLE Buergers RA Autoimmune disease Hyperthyroidism Hyperhomocyseinemia Celiac Sickle cell/sickle trait Thrombophilia Work up A 55 year old man presents with large unprovoked PE. Do you send a thrombophilia work up? a) Yes b) No c) Are we still doing those? 16

17 Case 69 yo man with CKD CrCl 35 ml/min, GERD, DM, HTN admitted with new AFIB and CHF. What anticoagulant do you recommend? DOAC?-if so which? Warfarin? If so why? Choosing a DOAC for AFIB 17

18 DABIGATRAN RIVAROXABAN APIXABAN Dosing 150 mg BID 20 mg once daily 5 mg BID Caps cannot be crushed or opened Must be taken with meal None Renal impairment Primarily renal elimination Significant renal elimination Minor renal elimination Avoid if CrCl <30 ml/min (Reduced dose available for CrCl ml/min but not studied clinically and not recommended) Avoid if CrCl 50 ml/min if on interacting drugs dronedarone or ketoconazole Avoid if CrCl <30 ml/min (not studied) Reduced dose to 15 mg/day if CrCl ml/min Avoid if SCr >2.5 or CrCl <25 ml/min Reduced dose to 2.5 mg BID, if 2 out of 3: SCr 1.5 mg/dl 80 yrs, wt 60 kg Drug interactions **Consult AC Forum Clinical Guidance, EHRA Practical Guide and Univ. of Washington AC Service website for comprehensive guidance Prodrug is substrate of P-gp AVOID use P-gp inducers (e.g., rifampin, St. John s Wort)- reduced dabigatran effect Caution with P-gp inhibitors (e.g., dronedarone, ketoconazole); AVOID if concurrent renal impairment CYP3A4, P-gp substrate AVOID use with strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin) reduced rivaroxaban effect AVOID use with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir and ritonavir combinations)- increased rivaroxaban effect CYP3A4, P-gp substrate AVOID use with strong CYP3A4 inducers (e.g., rifampin, carbamazepine, phenytoin) reduced apixaban effect Reduced dose of apixaban by 50% with strong CYP3A4 inhibitors (e.g., ketoconazole, itraconazole, ritonavir, and ritonavir combinations) increased apixaban effect Switching from WARF Start DOAC when INR <2-2.5 Switching to WARF Start warfarin and overlap with dabigatran; CrCl >50 ml/min, overlap 3 days CrCl ml/min, overlap 2 days CrCl ml/min, overlap 1 day Start warfarin and stop rivaroxaban 3 days later Start warfarin and stop apixaban 3 days later Missed doses Take a forgotten dose up until 6 h after the scheduled intake. For patients with a high stroke risk and low bleeding risk, this can be extended up till the next scheduled dose. Take a forgotten dose up until 12 h after the scheduled intake. If that is not possible anymore, the dose should be skipped and the next scheduled dose should be taken. Take a forgotten dose up until 6 h after the scheduled intake. For patients with a high stroke risk and low bleeding risk, this can be extended up till the next scheduled dose. Periprocedural management See SFVA/UCSF GUIDELINES FOR THE PERI-PROCEDURAL MANAGEMENT OF ADULTS TAKING DOACS Which of these patients should receive bridge therapy postoperatively yo man AFIB CHADS-Vasc =4 on warfarin s/p L hip fracture repair year old man on warfarin for recurrent VTE, last event June 2012 s/p bowel resection year old man on warfarin with mechanical mitral valve s/p bowel resection 4. All of the above 18

19 Perioperative Anticoagulation Does anticoagulation need to be stopped? How many days prior does anticoagulation need to be stopped? Which agent What is renal function Should this patient be bridged? When should anticoagulation be started post operatively American College of Chest Physicians 2012 Guidelines CHADS2: validated to estimate YEARLY incidence of thromboembolism with temporary anticoagulant interruption Clinical translation: Low (CHADS0-2: <5%) no bridging Moderate (CHADS2 3-4: 5-10%) sometimes bridged High (CHADS2 5-6 :>10%) usually bridged Rose et al. Circ Cardiovasc Qual Outcomes

20 CHEST 2012 The suggested thromboembolic risk stratification shown in Table 1 is based largely on indirect evidence from studies outside of the perioperative setting involving patients with a mechanical heart valve, chronic atrial fibrillation, or VTE who either were not receiving anticoagulation (ie, placebo instead of a VKA in patients with chronic atrial fibrillation) or were receiving less-effective treatment (eg, ASA instead of VKA in patients with a mechanical heart valve. TO BRIDGE OR NOT TO BRIDGE Patient: Thrombotic Risk Procedure: Elective CHADS2/ CHA2DS2- VASc VTE history Bleeding Risk 20

21 TO BRIDGE OR NOT TO BRIDGE Nonzero risk of thromboembolism if anticoagulation interrupted absolute risk: small Expert opinion: no study demonstrates a net benefit of bridging?prevent thromboembolism?prevents more problems than it causes: bleeding Rose et al. Circ Cardiovasc Qual Outcomes

22 The BRIDGE Trial N Engl J Med 2015 Jun 22 [EPUB] PMID: The BRIDGE Trial Mean CHADS2=2.3 Very few high risk N Engl J Med 2015 Jun 22 [EPUB] PMID:

23 Patient: Thrombotic Risk Procedure: Emergent/Urgent BRIDGING IN VTE Use of bridge therapy was associated with hazard ratio of 17.2 for clinically-relevant bleeding (95% CI ) No difference in recurrent VTE even with high risk patients No difference in bleed between full dose and prophylactic dose JAMA Intern Med May 26: [EPUB] PMID:

24 Systematic Review of Bridging Cohort Studies Bridge therapy associated with 3 fold increaed risk of bleeding No in TE with heparin bridge regardless of dose of LMWH use Low int dose of LMWH associated with lower risk of bleed Siegal D. Circulation Sep 25;126(13): Summary of recent literature Majority of patients with AF experience net harm from bridging Should only be offered after careful consideration and for highly selected patients Patients should be informed that the practice of bridging in nonevidence-based: expert opinion Ideally, goal is to prevent a thromoboembolic event recent studies demonstrate greatly increased risk of bleeding: fold no study demonstrated a reduction in thromboembolism from bridging RE-LY analysis: strongly suggests that bridging is not needed with DOAC therapy Rose et al. Circ Cardiovasc Qual Outcomes

25 2017 ACC Expert Consensus Periprocedural Management ofac American College of Cardiology Foundation Patients Who May Benefit From Bridge Therapy Patients with any thromboembolism during past interruptions of anticoagulation, or while on therapeutic anticoagulation Patients with CVA or TIA within past 3 months Patients with recent (within 1 month) evidence of mural thrombus or left atrial appendage clot Patients with a mitral mechanical valve Patients with older caged ball or tilting disc mechanical valves Patients with VTE within the past 3 months Patients with VTA and a properly diagnosed hypercoaguable state (antiphospholipid syndrome, Proctein C/S deficiency, antithrombin 3 deficiency) Rose et al. Circ Cardiovasc Qual Outcomes

26 Case #1 Which of these patients should receive bridge therapy perioperatively? 75 yo man CHADS2=4 on warfarin s/p left hip fracture repair. 50 year old man on warfarin for recurrent VTE. last event June 2012 s/p bowel resection 65 year old man with mechanical mitral valve on warfarin s/p bowel resection Bridging 65 year old man on with mechanical mitral on warfarin s/p bowel resection. You restart full dose bridge therapy 1. on POD#0 with IV heparin, no bolus 2. on POD#1 with IV heparin, no bolus 3. no sooner than POD#2 with IV heparin, no bolus 4. Why did this issue have to come up on my shift? 26

27 ACCP Guidelines 4.4. In patients who are receiving bridging anticoagulation with therapeutic-dose SC LMWH and are undergoing high-bleedingrisk surgery We suggest resuming therapeutic-dose LMWH 48 to 72h after surgery instead of resuming LMWH within 24 h after surgery (Grade 2C) Douketis JD. Chest Feb;141(2 Suppl):e326S-50S. PMID: Risk of Bleeding with Bridging after Major Surgery Dunn AS, Spyropoulos AC, Turpie AG. J Thromb Haemost Nov;5(11): PMID:

28 Resumption of DOACs Bridging 65 year old man on with mechanical mitral on warfarin s/p bowel resection. You restart full dose bridge therapy 1. on POD#0 with IV heparin, no bolus 2. on POD#1 with IV heparin, no bolus 3. no sooner than POD#2 with IV heparin, no bolus 28

29 Periop Anticoagulation An 80 yo woman is s/p fall and ORIF of the hip. She was on apixaban preoperatively for NVAF. Cr Cl is ~ 60 ml/min. When should she take her last dose of apixaban? a. 1 day pre op b. 2 days pre op c. 3 days preop d. 4 days pre op 29

30 Periop Anticoagulation An 80 yo woman is s/p fall and ORIF of the hip. She was on apixaban preoperatively for NVAF. Cr Cl is ~ 60 ml/min. When would you stop her anticoagulation preoperatively should she take her last dose of apixaban? a. 1 day pre op b. 2 days pre op c. 3 days preop d. 4 days pre op Resuming Anticoagulation After Surgery An 80 yo woman is s/p fall and ORIF of the hip. She was on apixaban preoperatively for NVAF. When would you resume her full intensity anticoagulation therapy post operatively for stroke prevention? a. Evening of surgery b. Post op day #1 c. No sooner than post op day #2 or 3 30

31 Resumption of DOACs post operatively DOACs have rapid onset of anticoagulant effect (~1 4 hours) Analogous to using LMWH Caution with resuming too soon Timing of resumption dependent on type of procedure Low bleed risk: resume 24 hours post op High bleed risk: resume NO SOONER THAN hours post op May consider step up approach Lower or prophylactic dose of DOAC for initial hours; If/when tolerated, increase to treatment dose DOAC Spyropolous AC, et al. Blood 2012; 120(15): Resumption of DOACs Anticoagulation FULLY therapeutic within 1-2 hours Only dabigatran has a reversal agent 31

32 Bridging When would you resume her full intensity anticoagulation therapy for stroke prevention? a. Evening of surgery b. Post op day #1 c. No sooner than post op day #2 or 3** ** remember if you restarted warfarin without a bridge post op pateint would not be fully anticoagulated until POD# risks of full dose anticoagulation on POD#2-3 may outweigh benefits. May opt to wait until 5+ days post op in many cases. Take Home Points BRIDGING Periprocedural bridge therapy is associated with marked increased risk of bleeding Consider on a case by case basis for highest risk patients Early resumption of full dose anticoagulation after major surgery associated with higher bleed rates Periop DOAC management dictated by renal function and procedure bleeding risk 32

33 Take Home Points Catheter-associated VTE does not mandate catheter removal and requires 3 months of anticoagulation once catheter is removed Risk stratify each patient to determine IF calf vein thrombosis needs treatment Analyze risks and benefits of anticoagulation in each case of islolated subsegmental PE Take Home Points Recurrent VTE while on anticoagulation requires detailed review to assure it is anticoagulation failure and exploration for APLS cancer and consider structural defect MPO Thrombophilia testing not routinely recommended. If sent result more reliable after acute phase. 33

34 Take Home Points Consider ASA for secondary prevention of recurrent VTE in patients with unprovoked events who are not candidates for ongoing anticoagulation Work with GI during index hospitalization to determine safe time frame to restart anticoagulation after GIB 34

35 Key Literature Kearon et al. Antithrombotic Therapy for VTE Disease. CHEST 2012;141(2) (Suppl):e419s-e494s Aujesky d etl al. outpatient versus inpatient treatment of acute pulmonary embolism: a international open labeled randomised non inferiority trial Lancet 2011; 378:41-48 Iorio et al.risk of recurrence after a first episode of symptomatic venous thromboembolism provoked by a transient risk factor: a systematic reviewarch Intern Med Oct 25;170(19): Kyrle, PA. Clinical scores to predict recurrence risk of venous thromboembolism. Thromb Haemost Dec;108(6): DeWilde et al Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled triallancet 2013; 381: Key Literature Becattini et al Aspirinfor Preventing the Recurrence of Venous Thromboembolism. N Engl J Med 2012; 366:1959 Brighton TA et al Low-Dose Aspirin for Preventing Recurrent Venous Thromboembolism..NEngl J Med 2012; 367: Kucher N. Upper Extremity DVT.N Engl J Med 2011;364: Lamberts M et al. Circulation. 2014;129: