Ven ous T h romboemboli sm Risk in Medical Patients

1. Venous ThromboembolismRisk in Medical Patients Dr. H. Gül ÖNGEN İstanbul University Cerrahpaşa Medical Faculty Pulmonology Department

2. Epidemiology of VTE • In the general population • Different countries • Recent studies • (VITEA, IMPROVE, ENDORSE) • Medical VTE risks • Gender and sex • Medical risk factors and their relative weight

3. VTE is a multifactorial disease Acute infections Cancer Pregnancy Congenital thrombophilia Age THROMBOSIS A multifactorial accident Smoking HIT Diabetes Antiphospholipids Hypertension Hyperlipidaemia Others

4. DVT and PE as one disease ! • Symptomatic DVT is often associated with asymptomatic PE. • Symptomatic PE is often associated with asymptomatic DVT

5. Major PE remain undiagnosed untill autopy ! • 1964-1977 • Coon1 : % 84 • Goldhaber2 : % 70 Mean: % 77 ‘PE is most comman preventable cause of death among hospitalized medical patients.’ ‘PE is often a cause of unexpected death’ 1Coon WW.Arch Surg. 1976;111:398-402 2Goldhaber SZ.etal Am J Med.1982;73:822-6

6. Epidemiology of VTE • Mortality Symptomatic PE • initial presentation is death in ¼ of patients1 • Risk of early death among patients with symptomatic PE is 18-fold high compared to patients with DVT alone2 • Risk of death is high among elderly patients 1Heit JA J Thromb Thorombolysis. 2006:21:23-9 2Heit JA.et al.Arch Intern Med. 1999:159:445-53

7. Fatal PE among hospitalised patients Death: (1991-2000) n=16 104 Autopsy: n=6833 (% 42.4) PE: n=265 (erişkinlerin %5.2) Medical patients n=212 (%80.8) Acute medical disease n=110 (%51.4) Acute infections n=26 (%24) R Alikhan.et al J Clin Pathol. 2004;57:1254-7

8. VTE:Mortality PE kills 3 times more medical patients than surgical patients. Sandler DA, et al. J R Soc Med. 1989;82:203-5.

9. VTE is a disease having long term complications and risk of recurrence. • % 30 VTE: • Recurrence within 10 years. • Venous stasis syndrome occurs within 20 years. Heit JA J Thromb Thorombolysis. 2006:21:23-9

10. Frequency of VTE • General population • Hospitalized patients (sugical, medical, ICU..) • Medical outpatients • In special group of patients • Women taking oral contraseption or HRT • Pregnent women ( pregnancy and the puerperium) • Patients with cancer • Patients with thrombophilia (congenital, acquired)

11. Epidemiology of VTE in the general population • Different countries • Gender and sex • In special groups • Recent studies (VITEA, IMPROVE, ENDORSE) • Risk factors and their relative weight

12. Epidemiology of VTE in the general population • Different countries • Gender and sex • In special groups • Recent studies (VITEA, IMPROVE, ENDORSE) • Risk factors and their relativeweight

13. Annual VTE incidence in the USA 60 0001 Death 30 0002 Pulmonery Hypertension 600 0001 Pulmonery Embolism 800 0003,4 Post-thrombotic syndrome Symptomatic DVT 2 million 1 Asymptomatic DVT 1.Hirsh J. Circulation,1996 2Pengo V. NEJM, 2004 3 Brandjes DP. Lancet 1997 4KahnSR. J Gen Intern Med 2000

14. Epidemiology of VTE in the USA • 250 000 incident VTE cases occur annually among US whites • incidence is similar or higher among African-Americans • and lower among Asian and native- Americans • VTE is one of the main cause of maternal death in the western wolrd.

15. Epidemiology of VTE in UK • Each year > 25 000 people die from VTE acquired in hospital. • Fatal PE is the cause of 10% of deaths duiring hospitalization • Mortality of VTE is higher than the mortality of AIDS, brest cancer and car accident www.parliament.uk (2005)

16. Epidemiology of VTE in France • EPI-GETBO Study: • in the Brest district • Annual incidence: 1.83/1,000 Oger E Thromb Haemost. 2000

17. Epidemiology of VTE in France EPI-GETBO Study: Charecteristics of patients with VTE (n=674) and clinical settings at the time of diagnosis DVT PE ±(DVT) Age (years) 66 ±17 77 ±15 % females % 57 % 61 • Clinical settings • Home % 68 %52 • Medical unit % 8 %34 • Surgical unit % 11 % 5 • Nursing home % 11 % 7 • Others % 2 % 2 Oger E Thromb Haemost. 2000 Geçirilmiş VTE % 27 % 23 Oger E Thromb Haemost. 2000

18. Epidemiology of VTE in the general population • Different countries • Gender and sex • In special groups • Recent studies (VITEA, IMPROVE, ENDORSE) • Risk factors and their relative weight

19. Gender, Age and VTE 1200 male female 1000 800 Annual incidence / 100 000 600 400 200 0 0-14 20-24 30-34 40-44 50-54 60-64 70-74 80-84 15-19 25-29 35-39 45-49 55-59 65-69 75-79 >85 age Arch Intern Med, 1998;158:585-93

20. Incidence of VTE, including patients diagnosed and managed outside the hospital EPI-GETBO Study Per 10000 • Total of all events: • 1.52 /1 000 / year in male • 2.03 / 1 000 / year in female Oger E Thromb Haemost. 2000; 83: 657-60.

21. Gender and age incidence of VTE per 1000 per annum years Oger E Thromb Haemost. 2000; 83: 657-60.

22. VTE in the elderly patients: findings from a prospective registry (RIETE) • 2 890 patients > 80 years old (out of 13 011 patients ) Age ≤ 80 years ≥ 80 years (n=10 121) (n=2 890) Fatal PE (%) 1.1 3.7 Fatal bleeding (%) 0.4 0.8 Major bleeding (%) 212 (2.1) 99 (3.4) Lopez-Jimetez. Haematologica. 2006; 91: 1046-51.

23. Epidemiology of VTE in the general population • Different countries • Gender and sex • In special groups • Recent studies (VITEA, IMPROVE, ENDORSE) • Risk factors and their relative weight

24. VITAE Study( VTEImpact AssessmentGroup in Europe) First large study to evaluate the burden of VTE in 25 European countries. • Total annual VTE events and mortality from 25 EU countries • DVT+ PE : 1.5 million • VTE mortality: 543.000 • DVT : 684.000 A T Cohen, et al, 2007 (in press)

25. VITAE Study( VTEImpact AssessmentGroup in Europe) • Results in France • General population: 60.424.000 • VTE-related deaths: 71.196 • Non-fatal VTE events: 140.000 • Cost (million Euros): 452 (316-621) A T Cohen, et al, 2006 (in press)

26. VITAE Study( VTEImpact AssessmentGroup in Europe) • Results: • VTE is a major public health problem in EU. • Given the availibilty of VTE prophlaxis, many of these events and deaths could be prevented A T Cohen, et al, 2007 (in press)

27. ENDORSE ( multinational, cross sectional, multicentric, observational survey) • Aim • To identify patients at risk of VTE among medical and surgical patients hospitalized in representative hospitals globally and locally throuhout the world. • To determine the propotion of at risk hospitalpatients who receive effective types of VTE prophylaxis based on consensus guidelines. ICTH Congress, 6-12 July 2007

28. 35 ENDORSE Ülkesi

29. Algeria Australia/NZ Bangladesh Brazil Bulgaria Colombia Czech Republic Egypt Greece Gulf States Saudi Arabia Slovakia Switzerland Thailand Tunisia Turkey Venezuela ENDORSE Countries • Hungary • India • Ireland • Israel • Mexico • Pakistan • Poland • Portugal • Romania • Russia

30. ENDORSE: Global data analysis flow • 35 countries • 165.831 beds in participating hospitals • 99.664 beds in eligible wards • 84.637 patients in eligible wards • 77.738 evaluable patients in eligible wards • 54.812 patients for VTE risk analysis

31. Study Population - TURKEY • 5161 beds in participating hospitals • 3119 beds in eligible wards • 2363 patients in eligible wards • 2066 evaluable patients in eligible wards • 1809 patients enrolled in eligiable wards 1503 patients for VTE risk analysis

32. Antakya-Hatay Istanbul (4) Kocaeli Gaziantep Izmir (2) Samsun Kayseri Turkey (11 sites)

33. ENDORSE: Selected centers • Anadolu Çınar Hospital(Ist) • Kocaeli University Hospital • Şişli Etfal Hospital (Ist) • Süreyyapaşa Hospital (İst) • Dr. Suat Seren Hospital (Izmir) • Hatay (Private) Hospital • Eşrefpaşa Hospital (Izmir) • Erciyes University, Oncology Hospital • Gaziantep University Hospital • Göztepe Education Hospital • Vezirköprü State Hospital (Samsun)

34. ENDORSE: Study population - TURKEY

35. History of DVT/PE * 15.6 (6.77-35.89) • Venous insufficiency 4.45 (3.10-6.38) • Chronic heart failure 2.93 (1.55-5.56) • Obesity ( BMI> 30 kg/m2 )2.49 (1.88-3.87) • > 3 months pregnancy • Prolonged standing ( > 6 hours /day) Intrinsic Factors • Pregnancy 11.41 (1.40-93.29) • Deterioration of general state 5.75 (2.20-15.01) • Immobilisation5.61 (2.30-13.67) • Long-duration travel (>5-6hr) 2.35 (1.45-3.80) • Infectious disease* 1.95 (1.31-2.92) Worsening Factors SIRIUSStudy: VTE risk factors in medical patients CI OD Risk Samama, Arch Inter Med. 2000; 160:3415-3420.

36. 70 % of medical patients with acute diseases do not receive any prophylaxis 50 %19 46%22 45%13 24%23 IMPROVE Study: International Medical Prevention Registryon Venous Thromboembolism Patients in prophylaxsis(%) cardiac n=254) Pulmonery ( n=348) Cancer ( n=104) Neurological ( n=208) Primary reason of admission J Thromb Haemost 2003;(suppl)

37. VTE:According to the wards Goldhaber SZ, et al. Chest. 2000;118:1680-4.

38. MAJOR MEDICAL RISK FACTORS?

39. Major VTE risk factors Inherited Acquired Inher./Acquir. age Immobiliztion Cancer Pregnancy/postpartum Oral contraception Hormone RT Antiphospholipid sendr. Myeloporoliferative sndr. • Hyperhomocysteinemia • Increased levels of: • Factor VII • Fibrinogen • Factor XI • Factor IX Deficiency in AT Deficiency in ProteinC Deficiency in Protein S Factor V Leiden Protrombin gene mut. Deficiency in Fibrinogen, Plasminojen Franco RT, Hum Genet. 2001;109:369-84.

40. The range of risk of VTE according to clinical situation Risk Factors Risk* Recent operation 3-21.7 Non-surgical hospitalization /immobilization 5.7-11.1 Congestive heart failure 1.4-9.6 Cancer and chemotherapy 6.5 Myocardial infarction 5.9 Venous insufficiency 0.9-4.2 Ischaemic stroke 2.0-3.0 Malignancy 2.4-5.6 Venous catheter 5.6-6.0 • *Risk includes odds ratio, relative risk, ralative hazard, and hazard ratio Samama MM,et al. Heamatologica,2003;88

41. Range of VTE Risk Risk Factors Risk* Age 1.8-14.8 Hyperhomocystenaemia 7.1 Oral contraception 1.7-4.7 Personel history of VTE 5.9 Obesity 1.0-4.5 Secondery antiphospholipid syndrome 4.3 *Risk, odd ratio, relatif risk, ralatif hazard, ve hazard ratio’yu kapsar Samama MM,et al. Heamatologica,2003;88

42. Range of VTE Risk Risk Factors Risk* Family history of VTE 3.3-3.4 Smoking 1.0-3.3 Hormone replacement therapy 2.1-2.7 Black ethnicity 1.4 Male 0.6-1.4 Samama MM,et al. Heamatologica,2003;88

43. Combination of Risk Factors • Combination of hereditary and/ or acquired risk factors • Multiplication effct of combination of risk factors • Mathematical models are very rare.

44. Risk assessment in medical patients?

45. Exposed risks(acute risks) • Ischaemic stroke • COPD, acute repr. Failu. + ventilation support • Myocardial infarction • Heart failure • COPD, acute repr. Failu. + no ventilation support • Sepsis • Infection/acute inflam.disease:confined to bed • Infection/acute inflam.disease:not confined to bed • Venous catheter • No risk 3 3 High Risk 2 2 1 Low Risk x 0 1 0 1 2 3 0 Predisposing risks No risk dehydratation> 60 ageThrombophliapolisitemia pregnancy history ofVTE varikosisnephrotic synd. Active cancerfamily his. VTE myoloprolipheratiph s. or obesitykateg.1 >2 risk Kateg. 1 > 3r Kateg. 2 >2r 0 1 2 3 Risk assessment in medical patients? Lutz L, et al. Med Welt, 2002

46. Stroke Congestive h. failure Acute respir. failure Infections Acute MI Risk assessment in medical patients Major Risks Minor Risks Additional Risks • Immobilization • Malignanacy • Chemoterapy • History of VTE • Advabced age > 65 • Obesity • Coagulation disorders At least 1+ 1 minor risk At least 1 At least2 Nicolaides AN et al. International Consensus Statement. Int Angiol 2006; 25: 101-61.