Surgical Foundations January 27, 2015 Venous Thromboembolism: a review for surgeons Bill Geerts, MD, FRCPC Thromboembolism Consultant, Sunnybrook HSC Professor of Medicine, University of Toronto National Lead, VTE.
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Surgical Foundations January 27, 2015 Venous Thromboembolism: a review for surgeons Bill Geerts, MD, FRCPC Thromboembolism Consultant, Sunnybrook HSC Professor of Medicine, University of Toronto National Lead, VTE Prevention, Can. Pat. Safety Institute Executive, Thrombosis Canada Objectives 1. Patrhogenesis of VTE and risk factors 2. Investigation of suspected DVT, PE 3. The new oral anticoagulants (NOACs) 4. Management of VTE 5. Management of massive DVT, PE 6. Warfarin reversal 7. Perioperative management of anticoagulated patients 8. Prevention of VTE in surgical patients Objectives 1. Pathogenesis of VTE and risk factors 2. Investigation of suspected DVT, PE 3. The new oral anticoagulants (NOACs) 4. Management of VTE 5. Management of massive DVT, PE 6. Warfarin reversal 7. Perioperative management of anticoagulated patients 8. Prevention of VTE in surgical patients Thrombosis 101 Fibrin Blood vessel wall RBCs Platelets Venous Thromboembolism (VTE) = 1. Deep vein thrombosis (DVT) 2. Pulmonary embolism (PE) Risk factors Small DVT Big DVT PE Death Deep vein thrombosis (DVT) Thrombus in one or more deep veins - legs >>> arms - portal, mesenteric, splenic, cerebral, renal Proximal DVT Distal or calf DVT - Distal to popliteal - Posterior tibial, peroneal veins - Most calf DVT asymptomatic - Rarely lead to PE Superficial thrombosis - Not DVT; don’t lead to PE - Popliteal iliac veins - Lead to >90% of PE Risk factor(s) Calf DVT 80-90% 10-20% Resolves spontaneously PROXIMAL DVT rare >50% Pulmonary embolism Death What Causes the Blood to Clot when it Should (and Shouldn’t)? Activation of coagulation Venous stasis THROMBOSIS Injury to the blood vessel wall Virchow’s Triad Risk Factors for VTE Major surgery Previous VTE Trauma – major, local leg Family history of VTE Cancer (some) Thrombophilia: - Factor V Leiden - Prothrombin 20210A - Deficiency of AT, Pr C, Pr S - Antiphospholipid antibody Cancer treatments Immobilization – bedrest, stroke, paralysis Acute medical illness Acute infection Acute or chronic inflammatory diseases Estrogen, pregnancy, postpartum Increased age Obesity Etc Risk of DVT in Hospital Patients Varies no prophylaxis + routine screening for asympt DVT Spinal Cord Injury Major trauma High risk THR, TKR, HFS Gen surg Gyne / Urol Neurosurg Moderate risk Medical 0 10% 20% 30% 40% 50% 60% 70% 80% 90% 100% Geerts – Chest 2008;133:381S VTE Risk Factors in General Surgery Procedure-related: Cancer > benign Open > laparoscopic GA > regional anesthesia Duration of procedure Patient-related: Age Previous VTE Obesity Reduced mobility Infection Whenever a patient develops DVT or PE, ask the question: “Why did this happen?” 70 yo woman with breast cancer 3 years ago, on tamoxifen, family history of VTE who develops acute DVT after a hernia repair DVT Why did this happen? VTE is often multifactorial age hernia repair Triggering factor DVT + FH, ?coag abnormality Predisposing factors tamoxifen ? Genetic factor Objectives 1. Pathogenesis of VTE and risk factors 2. Investigation of suspected DVT, PE 3. The new oral anticoagulants (NOACs) 4. Management of VTE 5. Management of massive DVT, PE 6. Warfarin reversal 7. Perioperative management of anticoagulated patients 8. Prevention of VTE in surgical patients D-dimer (“D-dummer”) Formed by effect of plasmin on fibrin plasmin Increased in VTE Fibrin FDPs (incl D-dimer) Also increased: after surgery trauma cancer acute infection inflammatory disease liver disease uncomplicated pregnancy healthy elderly etc Generally useless; may be misleading NEVER done on inpatients or patients at high risk of having a positive result Virtually no role in surgical patients Investigation of Suspected DVT ultrasonography (“Duplex scan”) = very accurate for proximal DVT Doppler Less accurate for pelvic, calf DVT Compression Doppler Ultrasound (“Doppler” or “Duplex Scan”) Suspected DVT in a Hospitalized Patient Proximal Doppler ultrasound Proximal DVT Negative for prox DVT Treat Continue DVT prophylaxis Diagnostic Tests for PE D-dimer (“D-dummer”) Not for in-patients, postop, trauma, etc Ventilation/Perfusion (V/Q) Scan Rules out PE if perfusion is normal BUT 60% of scans are nondiagnostic Consider in: young with normal CXR, renal failure, severe contrast allergy Tests for DVT Doppler ultrasound (DUS) Diagnostic Test of Choice for most Patients with Suspected PE CT pulmonary angiogram (CTPA) = very accurate for PE (?too sensitive) Requires contrast, a lot of radiation Suspected PE CTPA No PE Definite PE Consider alternate diagnosis Treat Objectives 1. Pathogenesis of VTE and risk factors 2. Investigation of suspected DVT, PE 3. The new oral anticoagulants (NOACs) 4. Management of VTE 5. Management of massive DVT, PE 6. Warfarin reversal 7. Perioperative management of anticoagulated patients 8. Prevention of VTE in surgical patients Traditional Anticoagulants XII 1. INDIRECT inhibitors of coagulation 2. MULTIPLE SITES of action XI IX VII VIII X AT heparin LMWH AT warfarin V II fibrinogen fibrin THROMBUS The new/novel oral anticoagulants (NOACs) apixaban (Eliquis®) dabigatran (Pradaxa®) [edoxaban (Savaysa®)] rivaroxaban (Xarelto®) New Oral Anticoagulants (NOACs) XII 1. DIRECT inhibitors of coagulation 2. SINGLE SITES of action XI IX VII VIII X heparin LMWH warfarin V Oral IIa inhibitors dabigatran (Pradaxa) II fibrinogen Oral Xa inhibitors rivaroxaban (Xarelto) apixaban (Eliquis) edoxaban (Savaysa) fibrin THROMBUS NOACs: Advantages Property Advantages Rapid onset of action No need for IV/SC anticoag Less variability in anticoagulant effect Fixed dose (or limited options) No routine lab monitoring Convenient for patients, docs Relatively rapid offset of action Simplifies pre-procedure Mx Relatively inexpensive Generally affordable All of the above Potential for greater/longer use fewer thromboemboli Approved in Canada Today apixaban dabigatran rivaroxaban Orthopedic prophylaxis # Stroke prevention in AF # # VTE treatment Other indications # 6mo No No Med/surg thromboprophylaxis Mechanical heart valves Cancer, pregnancy No # ODB supported Laboratory Monitoring of New OAC Poor correlation between standard coag tests (PT, PTT) and drug level Major variability in reagent/analyzer Timing of the test is critical 0 24 Assessment of “reversal” dabigatran rivaroxaban apixaban aPTT PT / INR none Monitoring of blood level (limited avail) dabigatran rivaroxaban Hemoclot test Anti-Xa Management of Bleeding on New Oral Anticoagulants 1. No specific antidotes for any 2. No human reversal of bleeding studies Management of Bleeding in Patients Receiving a New Anticoagulant 1. Don’t use: Plasma, vitamin K, cryoprecipitate 2. GET HELP! (or a good lawyer) 3. Develop/use a local hospital policy Patient with bleeding on dabigatran When was last dose? CBC, creatinine aPTT If aPTT >40 sec, consult TE or Transfusion Medicine Moderate-severe Bleeding* Mild bleeding Local hemostatic measures Hold 1 or more doses of dabigatran Manage bleeding (compression, surgery) Fluid diuresis Transfuse RBCs or platelets if needed (follow Sunnybrook guidelines) Oral charcoal if dose <2 hrs before Life-threatening Bleeding* Contact Transfusion Medicine Tranexamic acid (1 G IV followed by 1 G infusion over 8 hours) Hemodialysis might be helpful Consider FEIBA* *50-100 IU/kg Objectives 1. Pathogenesis of VTE and risk factors 2. Investigation of suspected DVT, PE 3. The new oral anticoagulants (NOACs) 4. Management of VTE 5. Management of massive DVT, PE 6. Warfarin reversal 7. Perioperative management of anticoagulated patients 8. Prevention of VTE in surgical patients Treatment of DVT/PE: 3 options LMWH injections 1 once a day ↓ ↓ ↓ ↓ ↓ ↓ warfarin (INR 2.0-3.0) 5-7 days Low Molecular Weight Heparin injections once a day 2 ↓ ↓ ↓ ↓ ↓ ↓↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ 3 Direct oral anticoagulant (rivaroxaban, apixaban, dabigatran) Treatment of DVT/PE: 3 options LMWH injections 1 once a day ↓ ↓ ↓ ↓ ↓ ↓ warfarin (INR 2.0-3.0) 5-7 days 2 Low Molecular Weight Heparin injections once a day ↓ ↓ ↓ ↓ ↓ ↓↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ pregnancy, most cancer-associated VTE, high bleeding risk LMWH Initial Treatment of VTE Subcutaneous LMWH: - dalteparin (Fragmin) 100 U/kg BID or 200 U/kg QD - enoxaparin (Lovenox) 1 mg/kg BID or 1.5 mg/kg QD - tinzaparin (Innohep) 175 U/kg QD No lab monitoring or dosage adjustment - except in patients with moderate renal impairment Use pre-filled syringes (and round up) - e.g. for 74 kg use enoxaparin 120 mg not 111 mg Obesity: - Use actual body weight (no maximum) - e.g. for 150 kg use enoxaparin 150 mg BID Injection of LMWH Patients do their own injections No need for CCAC IV Heparin is Occasionally Preferred over LMWH 1. Unstable patient 2. Severe renal insufficiency 3. Anticipated invasive procedure(s) requiring interruption of anticoagulation 4. Peri-thrombolytic therapy i.e. very uncommon Treatment of DVT/PE: 3 options LMWH injections 1 once a day ↓ ↓ ↓ ↓ ↓ ↓ warfarin (INR 2.0-3.0) 5-7 days 2 Low Molecular Weight Heparin injections once a day ↓ ↓ ↓ ↓ ↓ ↓↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ ↓ 3 pregnancy, cancer-associated VTE, high bleeding risk Direct oral anticoagulant (rivaroxaban, apixaban, dabigatran) Other Acute Management Issues In patients with proven acute DVT or PE: Don’t In investigate for PE or DVT PE, don’t order echocardiogram Don’t order hypercoagulability testing Don’t advise stopping the BCP Don’t look for occult cancer Don’t scare the hell outta the patient Treatment of VTE Anticoagulation Recurrent VTE 0 VTE 3 mos Time Treatment of VTE Anticoagulation surgery trauma pregnancy medical illness Recurrent VTE 0 VTE 3 mos Time provoked Duration of Treatment for VTE Provoked (transient, reversed risk) duration 3 months Individualized Treatment Duration Anticoagulation unprovoked VTE active cancer ongoing risk factor high risk thrombophilia male Recurrent VTE 0 VTE 3 mos Time provoked Duration of Treatment for VTE Provoked (transient, reversed risk) duration 3 months Unprovoked indefinite* Continuing risk (unresolved cancer, AT deficiency, APLA) indefinite* *Periodic reassessment re: 1) New patient risk factors for bleeding, thrombosis 2) New knowledge 3) Patient preference For most patients like you . . . (i.e. unprovoked VTE) Continue anticoagulation for now . . . And we will reassess this decision together periodically Post-thrombotic Syndrome Treatment: 1. prevent recurrent DVT 2. support stockings Objectives 1. Pathogenesis of VTE and risk factors 2. Investigation of suspected DVT, PE 3. The new oral anticoagulants (NOACs) 4. Management of VTE 5. Management of massive DVT, PE 6. Warfarin reversal 7. Perioperative management of anticoagulated patients 8. Prevention of VTE in surgical patients 34 yo woman with phlegmasia after spine # Day after catheter thrombolysis 53 yo woman with massive PE after ankle # Day after presentation with massive PE Indications for Catheter-Directed Thrombectomy/Thrombolysis I. In DVT, with extensive clot and severe symptoms (“big clot, can’t walk”) 2. In PE with hypotension, overt right heart failure (increased mortality) Treatment of choice for massive DVT and massive PE Single Indication for an IVC Filter Recent PROXIMAL DVT PLUS an absolute C/I to full anticoagulation NOT for: - PE without proximal DVT - “Recurrent” VTE/failure of Rx - Primary prophylaxis - Etc IVC Filters 1. Only if indicated (recent proximal DVT + absolute contraindication to therapeutic anticoagulation) 2. Only use retrievable filters 3. Anticoagulate the patient as soon as safe 4. When patient anticoagulated, have the filter removed Objectives 1. Pathogenesis of VTE and risk factors 2. Investigation of suspected DVT, PE 3. The new oral anticoagulants (NOACs) 4. Management of VTE 5. Management of massive DVT, PE 6. Warfarin reversal 7. Perioperative management of anticoagulated patients 8. Prevention of VTE in surgical patients Vitamin K: Routes & Doses IM NEVER SC NEVER PO ROUTE OF CHOICE - 1 INR < 5 1 - 2 mg INR > 5 2.5 - 5 mg IV ROUTE OF CHOICE - 2 1 mg for MINOR bleeding 10 mg for MAJOR bleeding Warfarin Reversal FFP NEVER PCC For major bleeding or reversal need urgent (Octaplex®, Beriplex®) ** Always give vitamin K too Objectives 1. Pathogenesis of VTE and risk factors 2. Investigation of suspected DVT, PE 3. The new oral anticoagulants (NOACs) 4. Management of VTE 5. Management of massive DVT, PE 6. Warfarin reversal 7. Perioperative management of anticoagulated patients 8. Prevention of VTE in surgical patients Surgery in Patients Requiring Long-term Anticoagulants 1. Thrombosis risk versus 2. Bleeding risk Need to individualize the approach Surgery in Patients Requiring Long-term Anticoagulants PRE-operative consideration 1. Thrombosis risk versus 2. Bleeding risk Need to individualize the approach POST- operative consideration For each case, ask 4 questions 1. Does anticoagulation need to be reversed at all? 2. If so, how long should anticoagulation be stopped before the procedure? 3. Should bridging with LMWH be done? 4. When can anticoagulant be restarted after the procedure (and how)? Peri-procedure Management of Warfarin: 3 Options Option Stop warfarin 1 No Bridge with LMWH No 2 Yes No 3 Yes Yes Peri-procedure Management of Anticoagulation: 3 Options 1 Very Low Bleeding Risk Procedure 2 Low TE Risk 3 High TE Risk Bridge Procedure Anticoagulation in Patients Requiring 1 Surgery with Very Low Bleeding Risk warfarin 3.0 INR 2.0 No anticoagulant reversal 1.5 1.0 -5 INR -4 -3 -2 -1 OR DAYS 1 2 3 4 5 6 1 Patients with Very Low Bleeding Risk don’t reverse warfarin Cataract surgery Most dental procedures Upper GI endoscopy + biopsy Colonoscopy without polypectomy Removal of most skin lesions Thora-, para-, arthro- centesis 2 Anticoagulation in Usual (i.e. low) TE Risk Patients Requiring Surgery warfarin warfarin 3.0 ? DVT prophylaxis INR 2.0 1.5 1.0 -5 INR -4 -3 -2 -1 OR DAYS 1 2 3 4 5 6 “Usual” (i.e. low) TE Risk 2 Patients interrupt, don’t bridge Atrial fibrillation (most) DVT/PE >3 months ago Mechanical aortic valve with no additional risks Most “miscellaneous” reasons for anticoagulation 3 Higher TE Risk Patients Requiring Surgery “Bridge” warfarin warfarin 3.0 full-dose LMWH INR LMWH: prophylactic dose, intermediate or full-dose 2.0 1.5 1.0 -5 INR -4 -3 -2 -1 OR DAYS 1 2 3 4 5 6 3 “Higher” Risk TE Patients → Bridging Anticoagulation DVT All <3 months ago mechanical mitral valves Mechanical aortic valve with additional risk factors Special cases: e.g. lawyer, AF, Grade IV LV, TIA after colonoscopy Pre-Procedure Stopping of NOACs (apixaban, dabigatran, rivaroxaban) Renal Function (CrCL, mL/min) Half-life (hours) How far in advance of procedure should NOAC be stopped? ≥50 10-15 2 days 30 – 49 15-20 2-3 days <30 * More than 25 4-5 days (check aPTT or INR first) + get help * Use of NOAC contra-indicated Post -Procedure Use of DOACs Ask yourself: “Is it OK that the patient be fully anticoagulated 2 hours after 1st dose?” 1 “Yes”: Restart DOAC at therapeutic doses 2 3 -5 -4 -3 -2 -1 OR “No”: DVT prophylaxis with LMWH or prophylactic dose of DOAC 1 DAYS “No” Delay restart of DOAC at therapeutic doses 2 3 Restart DOAC at therapeutic doses 4 5 6 Objectives 1. Pathogenesis of VTE and risk factors 2. Investigation of suspected DVT, PE 3. The new oral anticoagulants (NOACs) 4. Management of VTE 5. Management of massive DVT, PE 6. Warfarin reversal 7. Perioperative management of anticoagulated patients 8. Prevention of VTE in surgical patients Rationale for Thromboprophylaxis 60% of all VTE in the population is hospital-acquired Most hospital-acquired VTE are preventable – effectively, safely and inexpensively Thromboprophylaxis is standard of care for most hospitalized patients Who Should Get VTE Prophylaxis? After most surgery: - major general surgery - thoracic surgery - major gynecologic surgery - major urologic surgery - major orthopedic surgery All major trauma Most surgical patients in hospital Prevention of VTE in Nonorthopedic Surgical Patients M. Gould, et al Chest – 2012;141:e227S Prevention of VTE in Orthopedic Surgery Patients Y. Falck-Ytter, et al Chest – 2008;141:2278S 9th ACCP Guidelines on Antithrombotic Therapy Thromboprophylaxis in Surgery (2015) Patient Group Surgery: general, Options LMWH Duration Discharge gyne, thoracic, urol Major orthopedics rivaroxaban LMWH LMWH 2-6 weeks Major trauma LMWH discharge High bleeding risk mechanical - Hip, knee replacement - Hip fracture 2-6 weeks Until LMWH can start LMWH = low molecular weight heparin (dalteparin, enoxaparin, tinzaparin) VTE and Surgery: Do’s 1. Order prophylaxis for (almost) all patients. 2. Use rivaroxaban (or LMWH) as Rx of VTE: - rivaroxaban 15 mg PO BID x 3 wks 20 mg QD - dalteparin 200 U/kg SC QD - enoxaparin 1 mg/kg SC BID (or 1.5 mg/kg QD) 3. Most VTEs can be treated as outpatients 4. Use long-term LMWH instead of warfarin or NOAC for many cancer patients 5. Consider catheter-directed therapy for massive DVT/PE VTE and Surgery: Don’ts 1. Get excited about tiny filling defects called “clots” or small PE 2. Order hypercoagulability testing for unexplained VTE 3. Order an IVC filter unless recent PROXIMAL DVT and anticoagulation not possible 4. Forget to order prophylaxis for (almost) all patients VTE: Summary - 1 DVT and PE (VTE) are common VTE is a multicausal disease Risk factors include genetic, acquired, situational – Was the VTE provoked or unprovoked? Investigation of VTE: DVT: Doppler U/S PE: CTPA VTE: Summary - 2 Treatment of VTE: 1. LMWH warfarin 2. LMWH alone (cancer, pregnancy) 3. DOAC Duration of Rx: Provoked VTE 3 months Unprovoked VTE indefinite (periodic review of benefits vs risks) Thromboprophylaxis: LMWH for most