DVT, PE and the Orthopaedic surgeon Inspire MediLaw The Principal Hotel April 2019

1. DVT, PE and the Orthopaedic surgeonInspire MediLawThe Principal HotelApril 2019 Graham M. Lawson Consultant Orthopaedic Surgeon Spire Murrayfield Hospital Royal Infirmary of Edinburgh St John’s Hospital Livingston

2. Disclosures • If only!

3. AIMS • AETIOLOGY • ASSOCIATION WITH LOWER LIMB ARTHROPLASTY • SCALE OF THE PROBLEM • CHARNLEY • PRESENT DAY • PHARMACOLOGIC PROPHYLAXIS • IMPROVEMENTS IN PRACTICE • GUIDELINES

4. Virchow’s Triad

5. Deep Vein Thrombosis

6. Deep Vein Thrombosis

7. Association with orthopaedic surgery • Major lower limb surgery • Duration of surgery • Use of tourniquet • Embolic phenomena • Prolonged immobilisation • Historical

8. The long term results of low-friction arthroplasty of the hip performed as a primary intervention (BOA 1970) • 582 primary THR • 32 (5.5%) DVT • 19 (3.2%) non-fatal PE • 8 (1.4%) fatal PE • 4 (0.7) other deaths

9. Pulmonary embolism and its prophylaxis following the Charnley total hip replacementJohnson et al ClinOrthopRelat Res 1977 • 1962 – 1973 • 7,959 THRs • 7.89% non fatal PE • 1.04% fatal PE • Early cohort (No prophylaxis) • 15.2% non fatal PE • 2.3% fatal PE

10. Venous Thrombosis & EmbolismLowe JBJS 1981 • “After the operation of hip replacement arthroplasty, dvt in the legs and pelvis can be detected in 30 -50% of cases and PE in 10% carrying a mortality of 1-2%” • “Knee replacement fares no better and dvt has recently been found in 80%” • Venography, Radio-labelled fibrinogin

11. Major orthopaedic surgery on the leg and thromboembolism-Prophylaxis now or negligence claims laterParker-Williams & Vickers BMJ 1991 • DVT and PE are both more likely after surgery for a fractured hip, which has a 7.5% mortality from PE • Low dose subcut heparin conferred a clear advantage in reducing fatal PE in patients over 40 having elective major general surgery

12. Prevention of PE and DVT with low dose aspirin-Pulmonary Embolism Prevention (PEP) trialLancet 2000 • 1992 -1998 • 13,356 # NOF • (4088 THR) • 160mg aspirin v placebo • Aspirin group 6679 pts • 105 (1.6%) PE & DVT • Placebo group 6677 pts • 165 (2.5%) PE & DVT • Aspirin prevented 4 fatal PE per 1000 pts

13. Guidelines • “While clinical guidelines help health professionals in their work, they do not replace their knowledge and skills”NICE . • “Following a guideline is never mandatory. Guidelines are not binding and are not enforced.” US Dept Vet Affairs

14. Same evidence different answers! NICE SIGN AAOS AOA ACCP

15. Venous thromboembolsim:reducing the risk • NICE clinical guideline 92 (Jan 2010) • Elective hip and knee replacement • “Choose any one of: • Dabigatranetexilate • Fondaparinux sodium • LMWH • Rivaroxaban • UFH (for patients with renal failure)”

16. Clotting Cascade

17. The Players LMWH Direct Thrombin Inhibitor Dagibatranetexolate BoehringerIngelheim Some issues with increased risk of MI • Dalteparin • Pfizer • Enoxaparin • Sanofi • A more manageable and controllable form of heparin • HIT syndrome

18. The Players Inhibitor of activated factor X Platelet inhibitor Aspirin Boots, Tesco, Co-op Stops platelets sticking together to form a clot • Rivaroxoban • Bayer • Apixaban • Bristol-Myers Sqibb • Oral but irreversible

19. The Players Vitamin K antagonists • Warfarin

20. Prevention & Management of venous thromboembolismSIGN 122 December 2010 • “A meta-analysis of aspirin for prophylaxis of VTE in general or orthopaedic surgery reported significant reductions in risks of asymptomatic DVT (26% v 35%), PE (0.6% v 1.6%) and fatal PE (0.2% v 0.6%) with a non-significant trend to lower mortality” • “There is a paucity of robust direct comparisons between aspirin and other pharmacological methods. In the absence of evidence from such studies..... The use of aspirin as the sole agent for VTE prophylaxis is not appropriate”

21. Prevention & Management of venous thromboembolismSIGN 122 December 2010 • Chair Haematologist • Consultant for Sanofi (Clexane), Baxter HC, Astra Zeneca anti-thrombotic products • Cardiologist • Consultancy with a number of pharma companies • Haematologist • Consultancy Bayer (rivoroxoban) Boerhinger (dabigatron) • General Surgeon • Shares in Glaxo Smith Kline • Orthopaedic Surgeon • Anaesthetist • Vascular surgeon • General surgeon • Orthopaedic Surgeon • Haematologist • Gynaecolgist • Haematologist

22. There is hope! 2011 AAOS NICE Guideline 89 (2018) Hospital acquired DVT or PE Elective THR LMWH then aspirin Elective TKR Aspirin of 14 days • Preventing venous thrombo-embolic disease in patients undergoing elective hip and knee arthroplasty. • Aspirin: • Is as effective as the rest • Is cheaper • Has less bleeding risk

23. The influence of Pharma • Differences in reported outcomes in Industry funded vsNonfunded studies assessing thromboprophylaxis after total joint arthroplasty • J Parvezi et al J Arthroplasty 2018 • “NICE has thus far relied on historical data and predominantly industry-sponsored trials to provide evidence for VTE prophylaxis in joint replacements” • Deehan et al Bone Joint Res 2014

24. Meanwhile? • Death rate from PE following joint replacement surgery. • 1569 patients • 1362 THR • 207 TKR • 6 fatal PE (0.38%) • No pharmacological prophylaxis • Dennyson et al 1996 J R CollSurgEdin

25. Meanwhile? • Mortality and fatal PE after primary THR • 2090 THRs (1873 full notes) • 19 (0.91%) Deaths • 4 (0.19%) fatal PE • Fatal PE rate • Proph. 3/1226 (0.24%) • No Proph 1/667 (0.15%) • Gregg et at JBJS 1997

26. Developments in practice Day of surgery admission Regional / spinal anaesthesia

27. Developments in practice TED stockings Intra-op calf compression

28. Developments in practice A-V Impulse foot pumps Early mobilisation

29. Risk Assessment • Previous VTE • Thrombophilia • Family Hx of VTE • Active Cancer • Age >60 • Obesity BMI>30 • Hormone Therapy OCP or HRT • Combined anaesthesia surgery time >90 mins • Lower limb surgery & anaesthesia time >30 mins • Post-operative immobility

30. Mechanical prophylaxis &: Standard DVT risk Moderate Risk

31. Mechanical prophylaxis &: High Risk • Warfarin (Historical) • Dalteparin • Prophylaxis dose • Treatment dose • Haematologist

32. CONSENT • Risks of DVT/PE • Individual’s Options • Personalised plan • Risks of plan • Document discussion • Patient copy

33. Incidence of Pulmonary Embolus (Absolute Risk) (Total Excess mortality around 0.5%)

34. Bleeding and PE BenefitAll Active Therapies (Absolute risk) Nice 2010

35. Risks of pharmacological prophylaxis • Haematoma and dehisence

36. So Where are we know? • At 90days post total joint replacement: • DVT rate ~ 3% • PE rate ~ 1% • Fatal PE rate 0.1% • Mortality rate ~ 0.3-0.4%

37. Olmsted County, Minnesota, USA1966 - 1990

38. Conclusions • Major improvement in VTE rates over last 40 years – multi-factorial • Anaesthesia, surgery, rehab, mechanical proph. • Pharmacological prophylaxis • Link between DVT and PE unclear & complex • Aspirin in favour once more • No scientific paper has been able to show a reduction in fatal PE rate with pharmacological prophylaxis

39. Major orthopaedic surgery on the leg and thromboembolism-Prophylaxis now or negligence claims laterParker-Williams & Vickers BMJ 1991 • Is it negligent to omit a treatment that has no scientifically proven benefit?