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CHEST-2012: High Points and PearlsAlan Brush, MD, FACP, Chief, Anticoagulation Management ServiceHarvard Vanguard Medical AssociatesLanguage: “suggestions” vs. “recommendations”: statements in CHEST-2012 set up as suggestions and recommendations for and against; recommendations have stronger evidence basis. There is general theme of weighing clotting risks of patient against bleeding risk of treatment in all situations. Where there is a clash, the bleeding risk commonly takes precedence; patient preference should be considered foremost when management is not clearly beneficial. However, the patient or responsible caregiver must be part of this decision process.Evidence-based Management of AnticoagulationLoading dose initiation of warfarin: For healthy patients with DVT/PE or otherwise needing LMWH, okay to start with loading dose of 10mg x 2 days; benefit: earlier rise of INR to target range, but consider risks. Although suggested in CHEST-2012, we do not favor this approach, and have already seen some unexpected early INR rises. However, AMS managers will likely see patients discharged from the hospital on these doses.Pharmacogenetic testing: not recommended.Overlap with LMWH: Start warfarin on day 1 or 2 when LMWH used; no reason to wait longer – just delays reaching therapeutic range without increasing safety.Monitoring frequency: For stable patients, may extend INR follow-up date up to 12 weeks per CHEST-2012; we permit up to 8 weeks in the AMS.Management of single out of range result up to 0.5 above or below therapeutic range: if patient previously stable, no change in dose required; brief hold or make-up dose(s) without change in usual dosing often appropriate.Bridging with LMWH for stable patients with single low INR: CHEST-2012 suggests against bridging. Practically speaking this suggestion applies to most patients, with exceptions of highest risk patients (e.g. recently cardioverted, prior event when INR low, and patients with very low INR values and relatively recent event).Use of vitamin K for stable patients with single high INR: CHEST-2012 suggests against routine use of vitamin K unless INR >10) we recommend vitamin K when INR is lower but patient is at high risk of bleeding. Intermediate risk patients may benefit from use of low dose OTC vitamin K (200 mcg). Note current cost issues of prescribed vitamin K; however, not many patients want to take 50 OTC tablets to reach 5 mg dosing! Self-testing and self-management: considered reasonable standard of care when patients demonstrate competence; we will support in a similar fashion to patients tested by VNA and other external services. However, patients relying on self-management should not be part of AMS.Drug interactions to avoid: all NSAIDS and various antibiotics; use antiplatelet agents only when benefit clearly is known or is highly likely to be greater than harm from bleeding, such as patients with mechanical valves, patients with acute coronary syndrome, or patients with recent coronary stents or bypass surgery. Note: all AMS patients taking aspirin require this assessment by AMS clinician. When not clearly indicated, it should be brought to the attention of the PCP and/or AMS consultant.Optimal therapeutic INR ranges: should be 2.0-3.0 for most patients, 2.5-3.5 for certain high-risk patients. Patients awaiting cardioversion should be treated toward the high end of the 2.0-3.0 range. Note: patients wishing some long-term prevention of DVT/PE but unable to test at usual intervals or having increased bleeding risks may in some cases use 1.5-2.0 goal range (note: diverges from CHEST). Aspirin 81mg daily would be even less burdensome for the patient although less effective than this low intensity anticoagulation (). Note: all other ranges require clinical justification beyond clinician personal preference, with rationale documented in chart and approved by AMS physician consultant.Dose Management of Subcutaneous (SC) UFH for DVT/PE: use weight-adjusted dosing (first dose 333 units/kg, then 250 units/kg twice daily) without monitoring; may apply to hemodialysis patients and rare situations when patients unable to afford enoxaparin.Fondaparinux Dose Management by Weight: For patients with VTE and body weight over 100 kg, increase fondaparinux from the usual 7.5 mg to 10 mg daily.VKA-associated major bleeding: when available, patient should receive four-factor prothrombin complex concentrate rather than with plasma, in addition to vitamin 5-10 mg by slow IV injection. Note: if oral vitamin K immediately available, no harm in having the patient take 5 mg right away before going to the ERs, and in fact can only help the situation given potential delays in treatment.Prophylaxis for Higher Risk Patients in the Ambulatory SettingPatients with Cancer but No Other Risk Factors for VTE: CHEST suggests against use of LMWH and recommends against use of VKAs. This management applies regardless of the presence of a central venous catheter.Patients with Solid Tumors and Additional Risk Factors for VTE (e.g. previous venous thrombosis, immobilization, hormonal therapy, and angiogenesis): LMWH or LDUH suggested if bleeding risk low.Chronically immobilized patients residing at home or NH; CHEST suggests against routine use of thromboprophylaxis.Persons Traveling Long-Distance: for long distance travelers at increased risk of VTE, CHEST suggests frequent ambulation, calf muscle exercise, or sitting in an aisle seat when feasible, and use of GCS at 15-30 mm Hg of pressure at the ankle. In the absence of risk factors, CHEST suggests against use of GCS, and in general suggests against use of aspirin and anticoagulants. Persons With Asymptomatic Thrombophilia without previous history of VTE: CHEST recommends against the long-term daily use of mechanical or pharmacologic thromboprophylaxis to prevent VTEPrevention of VTE in Orthopedic Surgery PatientsPatients Undergoing Major Orthopedic Surgery: Total Hip Arthroplasty (THA), Total Knee Arthroplasty (TKA), and Hip Fracture Surgery (HFS): treat at least 10 to 14 days, ideally up to 35 days.TKA/THA: use either LMWH, fondaparinux, apixaban, dabigatran, rivaroxaban, low-dose unfractionated heparin (LDUH), adjusted-dose VKA, aspirin, or an intermittent pneumatic compression device (IPCD); LMWH is preferred option. IPCD in addition to an antithrombotic agent preferred during hospitalization.HFS: same as above, except apixaban, dabigatran, and rivaroxaban not included. When there is increased bleeding risk, IPCD suggested over pharmacologic treatment.When injections and/or IPCD declined or infeasible, apixaban or dabigatran preferred over VKA and rivaroxaban.When all of above declined or contraindicated, no prophylaxis suggested over IVC filter.Patients with Isolated Lower-Leg Injuries Distal to the Knee: Despite need for immobilization, no thromboprophylaxis suggested. Obviously, previous history of the patient should be considered.Perioperative Management of Antithrombotic TherapyInterruption of VKAs before Surgery: VKAs should be stopped 5 days before surgery (longer if high-risk surgery and/or INR starting at higher therapeutic level. Make sure you know the patient’s most recent up to date INR before making a recommendation.Resumption of VKAs after Surgery: VKA should be resumed 12 to 24 hours after surgery assuming adequate hemostasis.Bridging Anticoagulation During Interruption of VKA Therapy:Bridging suggested for high-risk patients, including patients with a mechanical heart valve, high-risk atrial fibrillation, or VTE at high risk for thromboembolism. Note: patients must buy in – those who place a higher value on avoiding bleeding than post-operative thromboembolism may decline bridging.Bridging suggested against for patients with a mechanical heart valve, atrial fibrillation, or VTE at low risk for thromboembolism.Decision based on individual patient and surgery-related factors for patients at intermediate risk for thromboembolism. Note that all of these decisions carry a “suggestion” rather than “recommendation”. Thus, there is room for specific clinical issues and patient preferences to sway the decision.Perioperative Management of VKA-Treated Patients Who Require Minor ProceduresFor minor dental procedure, continuing VKAs with co-administration of an oral prohemostatic agent or stopping VKAs 2 to 3 days before the procedure suggested instead of alternative strategies.For minor dermatologic procedures, continuing VKAs around the time of the procedure and optimizing local hemostasis suggested.For cataract surgery, continuing VKAs around the time of the surgery suggested. MEEI ophthalmologists will perform uncomplicated cataract surgery with an INR below 3.0. Note that complicated surgery, such as combination of glaucoma and cataract surgery, does not fall into this category.Patients taking Aspirin Undergoing a Minor Dental, Dermatologic, or Ophthalmologic Procedure: continuing aspirin suggested for patients requiring secondary prevention of CV disease or at moderate to high risk of CVD; stopping aspirin 7 to 10 days before the procedure suggested for patients at low risk of CVD.Patients Undergoing Coronary Artery Bypass Graft Surgery: continuing aspirin suggested; in patients receiving dual antiplatelet therapy, stopping clopidogrel/prasugrel 5 days before the procedure suggested.Surgical Patients with Coronary Stents: deferring surgery for at least 6 weeks after placement of a bare-metal stent and for at least 6 months after placement of a drug-eluting stent suggested over undertaking surgery within these timeframes. If surgery cannot be deferred for these durations, continuing dual anti-platelet therapy suggested. Patients may decline to continue dual antiplatelet therapy based on potential increased risk of bleeding. Perioperative Use of IV UFH: when used for bridging, IV UFH should be stopped 4 to 6 hours before surgery. Antithrombotic Therapy for VTE DiseaseInitial anticoagulation for patients with acute DVT of the legTreat immediately with LMWH when clinical suspicion is high or when expected delay of diagnostic tests is >4 hours.If clinical suspicion is low, wait for the results of diagnostic tests, assuming results are expected within 24 hoursAnticoagulation in patients with isolated distal DVTIn patients with acute isolated distal DVT of the leg without severe symptoms or risk factors for extension, serial imaging for 2 weeks suggested over initial anticoagulation.In patients with acute isolated distal DVT of the leg and severe symptoms or risk factors for extension, initial anticoagulation suggested over serial imaging.Anticoagulation in patients with extensive superficial vein phlebitis: treatment with prophylactic dose anticoagulation recommended over no treatment, and fondaparinux suggested over LMWH. Patients with acute DVT of the leg treated with LMWH: once daily administration suggested, but only applies when the approved once-daily regimen uses the same daily dose as the twice-daily regimen (i.e., the once-daily injection contains double the dose of each twice-daily injection). This recommendation has no practical application in AMS, since cannot be done with most LMWH options. Unfortunately, this statement has been misunderstood in several anticoagulation management programs. Tinzaparin (Innohep) is the only low molecular weight heparin currently FDA approved for treatment for acute pulmonary embolism that is dosed once daily. Note that fondaparinux (Arixtra), a non-heparin factor Xa inhibitor, is approved for treatment of acute PE and can be dosed once daily.Vena Cava Filters for the initial treatment of patients with DVT:Clinical situationRecommendationDVT with no contraindication to anticoagulation or already on anticoagulationUse anticoagulation without the addition of a filterDVT with contraindication to anticoagulationUse filterDVT with contraindication to anticoagulation that has resolved (e.g. resolution of bleeding risk)Complete conventional course of anticoagulationNote: Having a permanent IVC filter is not in itself an indication for extended course of anticoagulation.Early Ambulation of Patients with Acute DVT In patients with acute DVT of the leg, early ambulation suggested over initial bed rest – at last, the logic of avoiding bedrest, which tends to provoke venous thrombosis, has prevailed over the age-old standard of DVT management!If edema and pain are severe, ambulation may need to be deferred, and compression therapy should be used.Duration of Long-term Anticoagulant TherapyIndicationDuration of anticoagulationProximal DVT of the leg provoked by surgery3 months recommended over shorter period, longer period (6-12 months), or extended therapyProximal DVT of the leg provoked by a nonsurgical transient risk factor3 months recommended over shorter period, longer period (6-12 months) or extended therapy if high bleeding risk; suggested over other options if low or moderate bleeding riskIsolated distal DVT of the leg provoked by surgery or by a nonsurgical transient risk factor3 months suggested over shorter period (if decision to treat has occurred) and recommended over longer period (6-12 months) or extended therapyUnprovoked DVT of the leg (isolated distal or proximal)At least 3 months recommended over shorter duration. Evaluate risks/benefits of extended therapy after 3 monthsFirst VTE that is unprovoked proximal DVT of the leg with low or moderate bleeding riskExtended therapy suggested over 3 months of therapyFirst VTE that is unprovoked proximal DVT of the leg with high bleeding risk3 months of therapy recommended over extended therapyFirst VTE that is unprovoked isolated distal DVT of the leg with low or moderate bleeding risk3 months suggested over extended therapyFirst VTE that is unprovoked isolated distal DVT of the leg with high bleeding risk3 months recommended over extended therapySecond unprovoked VTE with low bleeding riskExtended therapy recommended over 3 months of therapy Second unprovoked VTE with moderate bleeding riskExtended therapy suggested over 3 months of therapySecond unprovoked VTE with high bleeding risk3 months suggested over extended therapyDVT of the leg and active cancer with low or moderate bleeding riskExtended therapy recommended over 3 months of therapyDVT of the leg and active cancer with high bleeding riskExtended therapy suggested over 3 months of therapyNote: in all patients who receive extended anticoagulant therapy, the continuing use of treatment should be reassessed at periodic intervals (e.g., annually).Choice of anticoagulant regimen for long-term therapy without vs with cancer Presence of cancerDuration of anticoagulationNo cancer presentVKA therapy suggested over LMWH for long-term therapy; if not treated with VKA, LMWH suggested over dabigatran or rivaroxaban for long-term therapyPresence of cancerLMWH suggested over VKA therapy; if not treated with LMWH, VKA suggested over dabigatran or rivaroxaban for long-term therapy Other factors involved in the choice of treatment include the individual patient’s tolerance for daily injections, need for laboratory monitoring, treatment costs, and presence or absence of renal dysfunction. Choice of anticoagulant regimen for extended therapy: Use of the same agent used in the first three months suggested for extended therapy. Treatment of patients with asymptomatic DVT of the leg: Treatment of asymptomatic incidentally discovered DVT of the leg should follow same treatment principles as symptomatic pression Stockings and IPCD to Prevent and Treat PTS:Compression stockings suggested for symptomatic DVT of the leg to prevent PTS (post-thrombotic or post-phlebitic syndrome). They should be worn for 2 years, longer if found to be helpful. Note that patients favoring convenience and less concerned with PTS will likely decline stockings. In the presence of PTS, a trial of compression stockings suggested.In the presence of PTS not responsive to compression stockings, a trial of an intermittent compression device suggested. Pharmacologic treatment not recommended.Parenteral Anticoagulation Prior to Receipt of the Results of Diagnostic Work-up for PE Clinical Suspicion of Pulmonary EmbolismSuggested ActionHighTreatment with parenteral anticoagulants suggested over no treatment while awaiting the results of diagnostic testsIntermediateTreatment with parenteral anticoagulants suggested over no treatment if the results of diagnostic tests are expected to be delayed for more than 4 hoursLowAwaiting the results of diagnostic tests, assuming expected within 24 hours, suggested over treatment while awaiting resultsChoice of Initial Parenteral Anticoagulant Regimen in Patients with PEIn patients with acute PE, LMWH or fondaparinux suggested over IV UFH and over SC UFH. In patients with acute PE treated with LMWH, once-daily injections suggested over twice-daily injections, provided that the approved once-daily regimen uses the same daily dose as the twice-daily regimen (i.e., the once-daily injection contains double the dose of each twice-daily injection). Unfortunately, as above, this option does not apply to enoxaparin, so we should NOT be using the once daily enoxaparin regimen for acute treatment of PE.Antithrombotic Therapy for Nonrheumatic (nonvalvular) Atrial Fibrillation CHADS2 ScoreSuggestion or Recommendation0No treatment recommended over anticoagulation or antiplatelet agent; if treatment preferred by patient, aspirin suggested over VKA or combination aspirin plus clopidogrel1Oral therapy recommended over no treatment, and anticoagulation suggested over aspirin or combined aspirin plus clopidogrel≥2Oral anticoagulation recommended over no treatment, aspirin or combined aspirin plus clopidogrelNote: in CHEST-2012, dabigatran suggested over warfarin for all nonvalvular atrial fibrillation situations where anticoagulation recommended! Newer agents were not considered in CHEST-2012, as they had not been approved at the time of the conference.Antithrombotic and Thrombolytic Therapy for Acute Ischemic StrokeConditionRecommendationSuggestionAcute strokeFor IV r-tPA if treatment can be initiated within 3 h, perhaps 4.5 h of symptom onset. For early aspirin 160 to 325 mgFor use of intraarterial r-tPA in patients ineligible for IV tPA if treatment can be initiated within 6 h; against use of mechanical thrombectomyAcute stroke and restricted mobilityFor prophylactic-dose heparin or IPC devices; against use of elastic compression stockingsNoncardioembolic ischemic stroke or TIAFor long-term aspirin (75-100 mg once daily), clopidogrel (75 mg once daily), aspirin/extended release dipyridamole (25 mg/200 mg bid), or cilostazol (100 mg bid) rather than no antiplatelet therapy, oral anticoagulants, combined clopidogrel plus aspirin, or triflusalFor use of clopidogrel or aspirin/extended-release dipyridamole rather than aspirin or cilostazolHistory of stroke or TIA and atrial fibrillationFor oral anticoagulation over no antithrombotic therapy, aspirin, or combined aspirin and clopidogrelVTE, Thrombophilia, Antithrombotic Therapy, and PregnancyConditionRecommendationSuggestionPrevention and treatment of VTE in pregnant womenFor use of LMWH, not UFHPregnant women with acute VTEContinue anticoagulants at least 6 weeks postpartum (and at least total of 3 months)Women with APLA syndrome and three or more pregnancy lossesFor antepartum administration of prophylactic or intermediate-dose UFA or prophylactic LMWH in addition to low-dose aspirin (75-100 mg/d) ................
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