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Venous Thromboembolism in Rehabilitation Medicine: “the Last Frontier”

March 1, 2002 Medical College of Virginia. Venous Thromboembolism in Rehabilitation Medicine: “the Last Frontier”. Dr. Bill Geerts Sunnybrook & Women’s College HSC University of Toronto. OBJECTIVES. 1. Risks of venous thromboembolism in various

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Venous Thromboembolism in Rehabilitation Medicine: “the Last Frontier”

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  1. March 1, 2002 Medical College of Virginia Venous Thromboembolism in Rehabilitation Medicine: “the Last Frontier” Dr. Bill Geerts Sunnybrook & Women’s College HSC University of Toronto

  2. OBJECTIVES 1.Risks of venous thromboembolism in various patient groups who undergo rehabilitation. 2. Current thromboprophylaxis recommendations for each of these groups in acute care. 3. Published studies of VTE in rehabilitation settings. 4.Thromboprophylaxisstrategies in rehabilitation. 5. Current treatment of acute VTE.

  3. Risk of DVT in Hospitalized Patients Patient group DVT prevalence Medical patients 10-20 % Major gyne/urol/gen surgery 15-40 % Neurosurgery 15-40 % Stroke 20-50 % Critical care patients 15-80 % Hip/knee surgery 40-60 % Major trauma 40-80 % Spinal cord injury 60-80 % Rehabilitation low-high

  4. 6th American College of Chest Physicians Consensus Conference on Antithrombotic Therapy Prevention of Venous Thromboembolism Chest January 2001 Supplement

  5. Mechanical Prophylaxis • Graduated compression stockings • Intermittent pneumatic compression • Venous foot pump

  6. Mechanical Prophylaxis ADVANTAGES DISADVANTAGES • no bleeding • efficacious in moderate • risk patients

  7. Mechanical Prophylaxis ADVANTAGES DISADVANTAGES • no bleeding • efficacious in moderate • risk patients • limited efficacy data • no data related to • routine use • cumbersome • poor compliance • may  mobilization • no long-term use data • no mortality data • cost

  8. Pharmacologic Prophylaxis • Low dose heparin • Adjusted-dose heparin • Low molecular weight heparin • Danaparoid • Hirudin • Pentasaccharide • Oral thrombin inhibitors: ximelagatran • Warfarin

  9. Pharmacologic Prophylaxis ADVANTAGES DISADVANTAGES • proven efficacy • (RRR 60-80%) • broad spectrum of pts • N > 100,000 • multiple agents • ease of use • high compliance • no monitoring (except OAC) • demonstrated cost-effectiveness • mortality reduction

  10. Pharmacologic Prophylaxis ADVANTAGES DISADVANTAGES • proven efficacy • (RRR 60-80%) • broad spectrum of pts • N > 100,000 • multiple agents • ease of use • high compliance • no monitoring (except OAC) • demonstrated cost-effectiveness • mortality reduction • bleeding - GS 0.1% • - ortho 1% • cost (low  high)

  11. Orthopedic Surgery Hip arthroplasty Knee arthroplasty Hip fracture surgery

  12. HIP ARTHROPLASTY - PROPHYLAXIS • prospective trials with mandatory venography No. of No. of Risk Regimen Trials Patients DVT Red’n Control/placebo Grad comp stockings Aspirin Low dose heparin Warfarin Int pneum compress LMW heparin Hirudin 12 4 6 11 13 7 30 3 626 290 473 1016 1828 423 6216 1172 54 % 42 % 40 % 30 % 22 % 20 % 16 % 16 % --- 23 % 26 % 45 % 59 % 63 % 70 % 70 % ACCP CONSENSUS GUIDELINES - CHEST (2001)

  13. Elective hip replacement Recommended: LMWH started 12 hr before surgery, 1A 12-24 hr after surgery, or 4-6 hr after surgery at half the usual high dose or  Warfarin (INR 2-3) 1A Alternative:  adjusted-dose heparin to aPTT > ULN 2A Not recommended: aspirin, LDH, IPC alone 6th ACCP Consensus Conference on Antithrombotic Therapy

  14. KNEE ARTHROPLASTY - PROPHYLAXIS • prospective trials with mandatory venography No. of No. of Risk Regimen Trials Patients DVT Red’n Placebo Aspirin Warfarin Low dose heparin LMW heparin Int pneum compress 6 6 9 2 13 4 199 443 1294 236 1740 110 64 % 56 % 47 % 43 % 31 % 28 % --- 13 % 27 % 33 % 52 % 56 % ACCP CONSENSUS GUIDELINES - CHEST (2001)

  15. Elective knee replacement Recommended: LMWH 1A or Warfarin (INR 2-3) 1A Alternative:  optimal use of IPC 1B Not recommended: aspirin, LDH1C+ 6th ACCP Consensus Conference on Antithrombotic Therapy

  16. HIP FRACTURE - PROPHYLAXIS • prospective trials with mandatory venography No. of No. of Risk Regimen Studies Patients DVT Red’n --- 29 % 44 % 44 % 48 % Control/placebo Aspirin Low dose heparin LMW heparin Warfarin 9 3 2 5 5 381 171 59 437 239 48 % 34 % 27 % 27 % 24 % ACCP CONSENSUS GUIDELINES - CHEST (2001)

  17. Hip fracture surgery Recommended: LMWH 1B or  Warfarin (INR 2-3) 1B Alternative:  Low dose heparin 2B Not recommended: aspirin 2A 6th ACCP Consensus Conference on Antithrombotic Therapy

  18. NEED FOR POST-DISCHARGE PROPHYLAXIS placebo THR R LMWH LMWH (or warfarin) discharge day 6-14 venogram day 30-35 In-hosp In-hosp + 3-4 weeks post-discharge

  19. In-hospital vs Post-discharge LMWH After THR DVT Proximal DVT Author, year Bergqvist, 1996 Planes, 1996 Dahl, 1997 Spiro, 1997 Lassen, 1998 Hull, 2000* COMBINED Patients 223 173 218 435 215 533 1797 Placebo 37 % 19 % 32 % 23 % 12 % 37 % 27 % LMWH 18 % 7 % 19 % 8 % 4 % 20 % 14 % Placebo 24 % 8 % 13 % 13 % 5 % 9 % 12 % LMWH 7 % 6 % 9 % 3 % 1 % 3 % 4 % * In-hospital prophylaxis with warfarin. 6th ACCP Consensus Conference on Antithrombotic Therapy

  20. Extended Duration Prophylaxis: Symptomatic VTE Eikelboom - Lancet (2001)

  21. Trauma

  22. MAJOR TRAUMA PATIENTS ARE THE HIGHEST RISK GROUP FOR THROMBOSIS

  23. Sunnybrook VTE in Trauma Study - 1 • ISS > 9; no prophylaxis given • Prospective; routine bilateral venography • N = 443; mean age 39; ISS 27 DVT PROX DVT All patients 58 % 16 % Major injuries: Face/ chest / abdomen 50 % 15 % Head 54 % 20 % Spine 62 % 27 % L.E. Ortho 69 % 24 % Geerts - NEJM (1994)

  24. Major Trauma Recommended:  Prophylaxis should be used if possible  LMWH as soon as considered safe 1A With high bleeding risk:  initial mechanical prophylaxis (IPC, 1C ES) until LMWH safe High TE risk + suboptimal prophylaxis:  consider screen with DUS 1C IVC Filter:  not for prophylaxis 1C 6th ACCP Consensus Conference on Antithrombotic Therapy

  25. Spinal Cord Injury

  26. ACUTE SPINAL CORD INJURY: LDH + EPC vs LMWH • Randomized trial in 27 acute spinal cord units • C2-T12 SCI ASIA A, B, or C (motor nonfunctional) Acute Phase Rehab Phase No VTE Heparin + IPC Heparin 5000 U Q8H 5000 U Q8H R VTE Enoxaparin Enoxaparin 40 mg once daily 30 mg Q12H No VTE 2 weeks bilateral venography + DUS 8 weeks DUS

  27. SCI Multicenter Trial: Rehabilitation Phase (Weeks 2-8) • Patients who completed Acute Phase without VTE • Routine DUS at start of Rehab Phase + 6 weeks later Heparin Enoxaparin 5000 Q8H 40 mg QD No. 60 59 New VTE 22% 8% DVT 18% 7% PE 3%* 2% Major bleeding 1 0 * 1 fatal

  28. Acute Spinal Cord Injury Recommended:  LMWH 1B If anticoagulants C/I early after injury:  IPC and ES  LMWH2B Possible alternative:  IPC/ES + LMWH/LDH 2B Not recommended:  LDH, ES, IPC alone 1C Rehabilitation phase:  continue LMWH or warfarin (INR2-3) 1C 6th ACCP Consensus Conference on Antithrombotic Therapy

  29. Stroke

  30. Ischemic Stroke Recommended:  LDH, LWMH, danaparoid 1A If anticoagulants contraindicated:  ES or IPC 1C+ 6th ACCP Consensus Conference on Antithrombotic Therapy

  31. Studies of VTE in Rehabilitation

  32. VTE IN REHABILITATION: PROBLEMS 1. Scanty, poor quality data - ??? risk 2. Huge patient variability: underlying conditions, time in acute care, pre-rehab prophylaxis, duration of rehab 3. Some patients have DVT on admission 4. Symptoms/signs: nonspecific, reduced communication 5. Risk often prolonged 6. Often no diagnostic testing on site 7. ? Higher threshold for Dx  larger thrombi/emboli 8. Resource utilization: transportation, diagnostic tests, two hosp beds, interrupts/prolongs rehab, drug costs

  33. GENERAL REHABILITATION Prophylaxis prior to rehab Author, year Method of Dx When screened Prox DVT No. DVT Halvorsen, 1985a Katz, 1995 NS 70 % (various) FgLS  veno IPG  DUS NS on adm (< 6 mos) 150 301 18% --- NS 1%

  34. STROKE REHABILITATION Prophylaxis prior to rehab Method of Dx When screened Prox DVT Author, yr No. DVT Cope, 73 Miyamoto, 80 Sioson, 88 Desmukh, 91 Oczkowski, 92 Pambianco, 95 Harvey, 96 NS NS 21% NS 35 % NS some veno FgLS IPG DUS IPG DUS DUS on adm 10-14 d 45 d 21 d 81 d on adm 25 d 42 141 98 123 93 421 105 40 % 28 % --- 18 % --- 14 % 13 % NS NS 33 % NS 12 % NS NS

  35. TRAUMATIC BRAIN INJURY REHABILITATION Prophylaxis prior to rehab Author, year Method of Dx When screened Prox DVT No. DVT Cifu, 1996 Meythaler, 1996 All (LDH or IPC) none DUS DUS On adm (4-29 d) On adm (< 4 mos) 82 116 18% NS 14 % 8 %

  36. SPINAL CORD INJURY REHAB Prophylaxis prior to rehab Author, year Method of Dx When screened Prox DVT No. DVT Jarrell, 1983 Yelnik, 1991 Gunduz, 1993 LDH 91% all none FgLS + IPG veno veno veno NS on adm (45 d) 80 d 27 d 209 127 87 30 65 % 23 % 14 % 53 % NS NS NS 28 %

  37. VTE in Rehabilitation The best strategy is optimal prophylaxis in the acute care setting

  38. PROPHYLAXIS OPTIONS IN REHAB 1. Mobilization 2. Physiotherapy 3. Low dose heparin 4. Low molecular weight heparins 5. Warfarin

  39. PREVENTING VTE in REHAB: PRINCIPLES • Appropriate prophylaxis MUST start in acute care • Written policy (care pathway) • Simple, universal • Routine prophylaxis for highrisk patients (SCI, • hip and knee surgery, orthopedic trauma) • No prophylaxis (or individual decision) for lower • risk patients (stroke, head injury, amputation, burn) • No routine screening for DVT

  40. Strategies to facilitate effective, safe, efficient, and cost-effective thromboprophylaxis in rehab settings • Written, “approved” and used protocols • Pharmacy involvement • Point of care INR testing • Greater use of LMWH if LOS < 2 weeks • “Education” of referring centers

  41. REHAB PROPHYLAXIS SUMMARY Patient Group Spinal cord injury LE orthop trauma THR TKR Hip fracture Others Duration Until discharge Until discharge 2-4 wks postop (~ til discharge) • Method • Warfarin • (INR 2-3) • Warfarin • (INR 2-3) • LMWH • Warfarin • (INR 2-3) • None • Individualize

  42. ? Post-rehab Prophylaxis Almost never

  43. Treatment of VTE in Rehabilitation

  44. Treatment of Venous Thromboembolism: S/C Low Molecular Weight Heparin is Preferred over IV Heparin 1. At least as efficacious 2. Safer:  bleeding  HIT 3. Reduced all-cause mortality 4. Cheaper 5. No lab monitoring 6. Most can be treated as out-patients

  45. Treatment of DVT/PE LMWH S/C Oral Anticoagulation (INR 2.0 - 3.0) 5-7 d 3 mos-indefinite • 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 • nadroparin (Fraxiparine) 86 U/kg BID • tinzaparin (Innohep) 175 U/kg QD • No lab monitoring or dosage adjustment

  46. INDICATIONS FOR PROLONGED LMWH THERAPY 1. Pregnancy 2. Uncontrolled malignancy 3. High risk of bleeding 4. Warfarin failure 5. Major chemotherapy 6. INR monitoring difficult - poor venous access - geographic inaccessibility - unstable values 7. Need for recurrent invasive procedures 8. PATIENT PREFERENCE

  47. Indications for an IVC Filter Recent PROXIMAL DVT PLUS: 1. Absolute C/I to full anticoagulation 2. Untreatable, major bleeding on anticoag NOT for: PE without proximal DVT Minor bleeding Minor/moderate surgery Primary prophylaxis “Recurrent” VTE/failure of Rx

  48. Vitamin K: Routes & Doses IM  NEVER SC  RARELY (only if NPO) IV  1 mg for MINOR bleeding 10 mg for MAJOR bleeding PO  ROUTE OF CHOICE INR < 9 1 mg INR > 9 2.5-5 mg FFP  Only if major bleeding, surgery imminent

  49. Duration of Anticoagulation 1. RISK FACTOR RESOLUTION 2. NUMBER OF EPISODES OF VTE 3. THROMBOEMBOLISM RESOLUTION 4. BLEEDING RISK 5. PATIENT PREFERENCE INDIVIDUALIZE

  50. Discussion Questions

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