1. Deep Vein Thrombosis and Pulmonary Embolism prophylaxis in Asian general surgical patients: is it necessary?  AMY KOK Caritas Medical Centre

2. Introduction  Importance  Incidence  Current practice and guidelines  Review of prophylactic methods  Applicable to our patients?

3. Introduction  General surgical patients  Fatal PE ~1%  DVT ~24%  10% hospital deaths attributed to PE Venous thromboemobolism (VTE): A Major Source of Mortality and Morbidity

4. Consequence of unprevented DVT  Calf (46%)/thigh (67%)/pelvis(77%)  PE  50% untreated DVT  PE  50-80% untreated PE  associated with DVT Clinicopathological pattern of PTE in Chinese autopsy patient:comparison with caucasian series Pathology 1997

5. Literature review –prophylaxis works!  New England Journal of Medicine 1988 and 1999  Prophylaxis can reduce: PE by 50% DVT by 2/3 No increase in bleeding Long term mortality reduction VTE: The most common preventable cause of hospital death

6. Incidence in Caucasian  USA  100 per 100,000  UK  48 per 100,000 DVT  23 per 100,000 PE (12% mortality)  Australia  30,000 new cases  2,000 death per year 3 rd most common vascular disorder

7. Incidence in Asia  Study shows that incidence of 1 st time VTE of Asian  3-5x lower HOWEVER…

8. Incidence in Asia is increasing  Hong Kong  16.6 per 100,000 population  3 per 10,000 hospital admissions  4.7%  1.8% (PE death) (91-97)  Asia  17.1 per 100,000 DVT  3.9 per 100,000 PE  Japan and Singapore: 2x increase in DVT (91  97)  Epidemiology of VTE in a Chinese population Br J Surg 2004;91:424-8  Pulmonary thromboembolism and venous thrombosis in the Chinese Clin Ortho 1980;150:253-60

9. Guidelines for VTE Prophylaxis

10. Modalities of prophylaxis  Mechanical  Graduated compression stockings  Intermittent pneumatic compression  Venous foot pump  Pharmacological  Unfractionated heparin  Low-molecular weight heparin  Pentasaccharide  Aspirin

11. Mechanical prophylaxis  Graduated compression stockings (GCS)  Intermittent pneumatic compression (IPC) devices  Venous foot pump (VFP)  Aim:  Increase venous outflow  Reduce stasis within leg veins

12. Mechanical prophylaxis  Recommendation:  High risk for bleeding (Grade 1A)  Adjunct to anticoagulant prophylaxis (Grade 2A)  Proper use of and optimal adherence (Grade 1A) Data from Geerts WH, Bergqvist, Pineo G, et al. Prevention of venous thromboembolism. Chest 2008; 133:381S-435S

13. Aspirin  NO significant benefit  Inferior results  NOT recommended alone for VTE in any patient group (Group 1A)

14. Unfractionated heparin  Effective:  General and orthopedics surgery  Reduce VTE by 50-70%  Minor bleeding events:  6.3% vs 4.1% (statistically significant)

15. Low molecular weight heparin  Examples:  Enoxaparin  Fraxiparin  Effective:  General and Orthopedic surgery

16. General surgery  General recommendation:  Avoid dehydration  Early mobilization  Leg elevation  Stop Oral contraceptive pills or Hormone replacement therapy 4 weeks beforehand  Consider regional anaesthesia

17. General surgery  Low Risk (Grade 1A)  Minor Surgery < 40 No additional risk factors (cancer, history of VTE)  Recommendation  No specific prophylaxis; early mobilization 8th ACCP GUIDELINE

18. General surgery  Moderate Risk (Grade 1A)  Minor Surgery: with additional risk factors  Nonmajor surgery: 40-60 years with no risk factors  Major surgery: < 40 with no risk factors  Recommendation  Heparin (5,000 units Q12H, start 1-2 hrs preop till discharge)  Enoxaparin (40mg sc 1-12 hrs preop followed by 40mg sc Q24H 12hrs postop till discharge) 8th ACCP GUIDELINE

19. General surgery  High Risk (Grade 1A)  Non-major surgery: > 60 yr or have additional risk factors  Major Surgery: > 40 or have additional risk factors  Recommendation  Heparin (5,000 units Q8H, start 1-2 hrs preop till discharge)  Enoxaparin (40mg sc 1-12 hrs preop followed by 40mg sc Q24H 12hrs postop till discharge ) 8th ACCP GUIDELINE

20. General surgery  Highest Risk (Grade 1C)  Major surgery: >40 + prior VTE, cancer or hypercoagulable state  Recommendation  Heparin or LMWH +  Intermittent pneumatic compression sleeves till discharge 8th ACCP GUIDELINE

21. Special consideration  Extended VTE prophylaxis (selected high risks patients) Recommendation Extend prophylaxis for 28-30days (Grade 2A) Enoxaparin 40mg sc Q24H  High bleeding risk Recommendation Optimal use of mechanical thromboprophylaxis (Grade 1A) Subsituted or added on pharmacological thromboprophylaxis when bleeding risks decreased (Grade IC) Prolonged prophylaxis in abdominal and pelvic cancer reduced DVT 12 to 5% Bergqvist NEJM 2002

22. General Surgery  Laparoscopic surgery  Longer general anasthesia  Pneumoperitoneum and reverse Trendelenburg position reduces venous return

23. Laparoscopic surgery Rates of VTE is LOW

24. General Surgery  Laparoscopic surgery  Recommendation  No risk factors – aggressive early mobilization (Grade1A)  Risk factors – Heparin, LMWH, IPC or GCS (Grade 1C) 8th ACCP GUIDELINE

25. Bariatric Surgery  Reported incidence: varied!  Unknown: optimal regimen, dosage, timing and duration  Recommendation  Routine thromboprophylaxis with Heparin, LMWH or fondaparinux + IPC National Bariatric Surgery Registry

26. Guidelines for VTE Prophylaxis in Asia  HK:  Guideline for orthopedics and ICU patients  Japan:  Japanese guidelines for prevention of VTE 2004 Decrease in perioperative VTE  Korea:  Korean guidelines for the prevention of VTE  Malaysia:  Prophylaxis of VTE, clinical guideline

27. JAPAN

28. Korean guidelines for prevention of VTE 2010

29. Hong Kong  NO unique guideline for general surgery  Guidelines for ICU, neurosurgery and orthopedics patients

30. Hong Kong  TMH/PMH  ICU

31. Guideline in Hong Kong  Step 1: Identify high risk surgical procedures or injury  Step 2: other VTE risk factors  Step 3: Risk stratification  Step 4: Assess bleeding risk or contraindication  Step 5: Select appropriate thromboprophylaxis  Step 6: Reassess

32. Bring home message  Do not ignore venous thromboembolism (VTE)  Incidence is rising in Asian population  Prophylaxis and Guidelines with reference to other Asian countries should be considered  Further RCT required

33.  Thank you

37. Risk factors for DVT  Stasis  Surgery, trauma, immobility, paresis  Increasing age  Pregnancy and postpartum  Heart or respiratory failure  Obesity  Vessel Injury  Previous DVT  Smoking  Varicose veins  Central venous catheterization  Hypercoagulability  Increasing age  Malignancy  Cancer therapy  Estrogen therapy (OCP or HRT)  Acute medical illness  Inflammatory bowel disease  Nephrotic syndrome  Myeloproliferative disorders  Paroxysmal nocturnal hemoglobinuria  Inherited or acquired thrombophilia

38. Chinese population  NOT UNCOMMON!  Annual incidence of VTE in HK Chinese  16.6 events per 100,000 population  3 per 10,000 hospital admissions  Autopsy study in adult HK Chinese population  PE: 0.75%  Postoperative incidence (120940 surgical operations)  DVT: 0.13%  PE: 0.04%  Epidemiology of VTE in a Chinese population Br J Surg 2004;91:424-8  Pulmonary thromboembolism and venous thrombosis in the Chinese Clin Ortho 1980;150:253-60

39. Chinese population  Incidence of DVT after colorectal surgery in a chinese population  Open surgery 38.9%  Laparoscopic surgery 50%  Study showed 41.7% developed asymptomatic postop DVT in postop colorectal cancer patients in HK  Noted increase prevalence in HK  DVT 2.6-17%  PE 0.75-4.5%  INCIDENCE OF DEEP VEIN THROMBOSIS AFTER COLORECTAL SURGERY IN A CHINESE POPULATION ANZ J. Surg.(2001)71, 637–640

40. Chinese population  Prevalence of DVT in different surgery  Orthopedic surgery 53.3%  Neurosurgery 10%  General surgery 8.5%  Colorectal surgery 4%

41.  Surgical patients:  Anaesthetic time >90mins  Anaesthetic time >60mins + operation involves pelvis or lower limb  Acute surgical admission with inflammatory or intraabdominal condition  Expected reduced mobility  Any VTE risks factors

43. Mechanism of Heparin Unfractionated heparin inactivates both Factor IIa and Xa LMWH has increased affinity for Factor Xa Fondiparinux is only a pentasaccharide sequence

45. Bleeding risk  Acute bleeding  Acquired bleeding disorders eg acute liver failure  Concurrent use of anticoagulant eg warfarin  Acute stroke  Thrombocytopenia (Plt <75)  Untreated inherited bleeding disorders (eg hemophilia)

46. Major bleeding  Death  Decrease in Hb >/=2  Transfusion of at least 2 units  Bleeding from retroperitoneal, intracranial or intraocular site

47. Contraindication for mechanical prophylaxis  Suspected or proven peripheral arterial disease  Peripheral arterial bypass grafting  Peripheral neuropathy or other causes of sensory impairment  Allergy  Severe leg edema  Major limb deformity  Local skin condition eg dermatitis, gangrene etc

48. New oral anticoagulants  Factor Xa inhibitors: apixaban and rivaroxaban  Factor IIa inhibitors: dabigatran  No need for routine coagulation monitoring  No major food interactions  Limited drug-drug interactions  Trial on orthopedic surgery