Venous Thrombosis in Asia

Transcription

1 Venous Thrombosis in Asia Pantep Angchaisuksiri, M.D. Professor of Medicine, Mahidol University, Thailand Adjunct Associate Professor, University of North Carolina, Chapel Hill, USA

2 Venous Thromboembolism in Asia VTE is widely perceived to be less common in Asian populations than in Western populations Generally, thromboprophylaxis is not routinely prescribed However, the risk of VTE in Asia was challenged by recent studies

3 VTE Incidence in Asia Facts and Figures

4 International Journal of Angiology 13: (2004)

5 % of events Asymptomatic DVT Incidence Range after Surgery 100% 80% Asian studies Western studies 76.5% 84.0% 60% 40% 35.5% 64.3% 57.0% 45.0% 40.0% 53.1% 60.0% 36.0% 20% 19.1% 2.7% 6.0% 9.6% 11.3% 4.0% General surgery THR TKR Hip Fracture Leizorovicz A, et al. Intern J Angio. 2004;13:

6 VTE Incidence in Asia Autopsy Studies The incidence of fatal PE ranged from 0.2% to 6%. The 4.7% (Hong Kong) and 6.0% (Japan) incidences of fatal PE observed in the most recent studies match the lower range of the corresponding incidences observed in Western countries (4.0% to 13.0%). Leizorovicz A, et al. Intern J Angio. 2004;13:

7 The Incidence of Postoperative DVT Reported in Local Asian Studies Country Range in incidence of DVT (%) India Korea Singapore China Thailand Japan Malaysia 62.5 Indonesia 69.2 Cohen AT. Thromb Haemost. 2010;104:

8 Recent Multinational Prospective Epidemiological Studies SMART 1 Surgical Multinational Asian Registry in Thrombosis AIDA 2 Assessment of the Incidence of Deep-vein thrombosis in Asia 1.Leizorovicz A, et al. J Thromb Haemost. 2005;3: Piovella F, et al. J Thromb Haemost. 2005;3:

9 The SMART Study Surgical Multinational Asian Registry in Thrombosis A prospective observational study on the rate of symptomatic VTE 2,420 patients in 11 Asian countries (Bangladesh, China, India, Indonesia, Korea, Malaysia, Pakistan, Philippines, Singapore, Taiwan, Thailand) Major orthopedic surgery with no prophylaxis Leizorovicz A, et al. J Thromb Haemost. 2005;3:28-34.

10 Results of SMART Incidence of symptomatic VTE In-hospital 1-month follow-up Investigators 2.3% 2.8% CEC 1.2% 1.5% CEC = Critical Event Committee (adjudicate events) Leizorovicz A, et al. J Thromb Haemost. 2005;3:28-34.

11 SMART: Comparison of VTE Incidence with Other Studies SMART CEC 2005 (n=2,420, THR/TKR/HFS, no prophylaxis) SMART Investigators 2005 (n=2,420, THR/TKR/HFS, no prophylaxis) Samama 1997 (n=85, THR, no prophylaxis) VTE DVT PE Fatal PE 1.2% 0.9% 0.2% 0.2% 2.3% 1.8% 0.3% 0.4% 1.2% 1.2% 0 0 Douketis 2002 (n=6,089, THR/TKR, short-term prophylaxis) Turpie 2002 (n=7,211, THR/TKR/HFS, shortterm prophylaxis) 1.1% 0.04% 0.5% 0.3% 0.2% 0.1% Leizorovicz A, et al. J Thromb Haemost. 2005;3:28-34; Samama CM, et al. Br J Anaesth. 1997;78: ; Douketis JD, et al. Arch Intern Med. 2002;162: ; Turpie AG, et al. Arch Intern Med. 2002;162:

12 ; 2005 Conclusion: In Asian patients, the incidence of symptomatic VTE after major orthopedic surgery is not low (1.2%), consistent with the rates observed in Western countries.

13 The AIDA Study The Assessment of the Incidence of DVT in Asia International, multicenter, epidemiological study DVT rate after THR, TKR and HFS without thromboprophylaxis Post-operative screening with centrally adjudicated bilateral venography 6-10 days after surgery Piovella F, et al. J Thromb Haemost. 2005;3:

14 AIDA: 19 centers in 7 countries N = 407 S. Korea 5 centers China 3 centers Taiwan 4 centers Philippines 3 centers Thailand 1 center Malaysia 1 center Indonesia 2 centers

15 Results per Type of Surgery - The AIDA Study THR TKR HFS Total DVT 41.0% [ ; 95% Cl] Proximal DVT 10.2% [ ; 95% Cl] Piovella F, et al. J Thromb Haemost. 2005;3:

16 AIDA Study J Thromb Haemost 2005; 3: Conclusion: The rate of venographic thrombosis in the absence of thromboprophylaxis after major joint surgery in Asian patients (41%) is similar to that previously reported in Western countries.

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18 Incidence of VTE in the Whole Study Population (n = 173) Sakon M, et al. J Thromb Haemost. 2006:4:

19 VTE in Medical Patients

20 42 VTE from 7126 patients (0.6%) were found. (20 confirmed PE, 19 confirmed DVT, 3 sudden deaths) In patients with known risk factors, the rates of VTE were %. Immobilization (74%), active cancer (52%), rheumatologic diseases (12%) were common risk factors.

21 The incidence of DVT for medical patients was at least 10 per 1000 (19/1754).

22 Demographic Profiles of 19 Medical Patients who Developed DVT Males 9 Females 10 Median age, (range) 71 (28-95) Malignancy (n=94) 6 (6.3%) Cerebral vascular disease (n=97) 4 (4.1%) Cardiac failure (n=105) 4 (3.8%) Others (n=1458) 5 (0.34%) Median in-hospital days in medical 10 (3-52) ward prior to development of DVT Leung V, et al. Thromb Res. 2006;118:

23 Trend is of rapid increase over years Country VTE incidences in hospital (per 1000 pts) 1. Singapore Med J 1988;4: Ann Acad Med Singapore 1992;3: Ann Acad Med Singapore 1990;6: Ann Acad Med Singapore 2002;31: Thromb Haemost 2009;101: Eur J Vasc Endovasc Surg 2009;37: Yonsei Med J 2010;51: Blood Coagul Fibrinolysis 2010;21: Period Hong Kong Malaysia Singapore India Singapore Singapore Korea Thailand

24 Similar increase in PE over years has been noticed in other studies from Asia Country Metric Years compared PE rate Annual increase (%) Data source [reference] China Hospitalised adults (%) Yang, 2011 Hong Kong Autopsyconfirmed incidence (%) Chau, 1991 Japan New PE cases (annual) ,492 7, Sakuma, 2009 South Korea Incidence (100,000 person-years) Jang, 2011 Thrombosis Research 2015;136:

25 Population-based Annual Incidence of VTE Western Europe, North America, Australia, Argentina per 1,000 people 2 7 per 1,000 aged 70 years Korea and Taiwan (National Insurance Databases) Korea ( ): per 100,000 people (population 50 M) in men and in women per 100,000 aged years in men and in women per 100,00 aged 80 years Taiwan (2002): 16.5 per 100,000 people (population 23.3 M) 3 80 per 100,000 if age Almost 110 per 100,000 if age 80 years 1. ISTH Steering Committee for World Thrombosis Day. JTH 2014;12: MJ Jang et al, JTH 2011;9: CH Lee et al, Circulation Journal 2011;75:1998.

26 Age, Sex and the Population Incidence of VTE in Korea, Taiwan and Western France Korea A = Korea 1 B = Taiwan 2 C = Western France 3 B Taiwan C France 14 VTE Rate per 1000 people (by Age and by Sex) Whole of Population VTE Rate in Women VTE rate in Men 1. MJ Jang, JTH 2011;9: CH Lee, Circulation J 2011;75: E Oger, T & H 2000;83:657.

27 Recurrence of VTE in Taiwan : National Health Insurance Database , followed to 2004 The cumulative recurrence rate in a population-based Taiwan cohort was 9.4% at 1 year and 13.9% at 3 years Cumulative recurrence rate was higher in patients with prior VTE or cancer The risks of a recurrence after a transiently provoked or idiopathic VTE were similar CH Lee et al. J Thromb Haemost 2010;8:1515.

28 Thrombosis Research 2015;136:

29 Predispositions: Symptomatic VTE in Asia Country Taiwan 1 Japan 2 Singapore 3 Korea 4 China (HK) 5 Source National data ,347 VTE Tertiary hospital VTE Tertiary hospital DVT Tertiary hospital VTE Tertiary hospital medical wards DVT China Thailand 7 Thailand 8 (HK) 6 All HK hospitals ,830 VTE Tertiary hospital DVT Tertiary hospital 2007 Cancer 22% 16% 23% 25% 45% 40% 19% Postoperative 15% 21% 32% 14.0% 15.6% 3.5% Previous VTE 16% 8.5% 7.9%? 13.6% Autoimmune 10% Inherited 0.4% 13% 25.9% No cause found 27% 10% 12% 29% 105 VTE 1. CH Lee, et al. J Thromb Haemost M Kishimoto, et al. Thromb Haemost HJ Ng, et al. Thromb Haemost TM Kim, et al. Thromb Res C Cheng, et al. Thrombosis BLY Cheuk, Brit J Surg Mutirangura P, et al. Int J Angio Angchaisuksiri P, et al. Int J Hematol 2007.

30 Acquired Risk Factors for VTE in Asia Malignancy Prolonged duration of surgery Prolonged immobility Previous VTE Increased age Autoimmune/inflammatory disease Oral contraception Obesity

31 Circulation 2008;117: Obesity (BMI>30 kg/m 2 ) OR 2.33 (1.68, 3.24) Hypertension OR 1.51 (1.23, 1.85) Diabetes OR 1.41 (1.12, 1.77) Triglycerides levels WMD (9.64, 28.33) HDL cholesterol levels WMD 2.86 (-4.34, -1.38)

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33 Obesity

34 VTE Hazard Ratios for Various Food Types Factors significantly associated with VTE in multivariate analysis Factors significantly associated with VTE in multivariate analysis Low vegetable intake, hormonal use and high BMI are the risk factors for noncancer-related VTE in Thai population. Bhoopat L, et al Blood Coagul Fibrinolysis 2010;21:

35 Genetic Risk Factors Among Different Ethnic Groups in Patients with VTE Asian 1 African 2,3 European 3 Factor V Leiden 0 % % 20 % PT 20210A 0 % % 6 % PS deficiency % % 1-5 % PC deficiency 9-11 % % 3-5 % AT deficiency 5-8 % % 1-3 % 1 Angchaisuksiri P. Thromb Haemost 2011; 106: Heit JA et al. Am J Hematol 2010; 85: Roberts LN, et al. Br J Haematol 2009; 146:

36 ; Thrombophilia in Asians likely results from an abnormality in the APC anticoagulation system. - Many variants of protein C and of protein S, including PROC K150del, PROC R147W, and protein S Tokushima (K196E) were found at high frequencies in Chinese and Japanese and a significant number of Chinese and Japanese patients had low activity of the APC anticoagulation system.

37 Why is Prophylaxis Underused? Perceived low risk of VTE Heterogeneity of the (medical) conditions Difficulty with assessing risk level of patients Concern about bleeding Ownership of the patient Cost of prophylaxis

38 A Global Observational Study of Venous Thromboembolism Risk and Prophylaxis in the Acute Care Hospital Setting A multinational, cross-sectional survey assessing the prevalence of VTE risk in the acute hospital care settings, and the proportion of at-risk patients receiving prophylaxis Over 68,000 patients from 32 countries, including India; Pakistan; Bangladesh; Thailand VTE risk assessment was carried out based on ACCP guidelines Cohen AT, et al. Lancet. 2008;371:

39 Patients (%) Patients at Risk of VTE 52% at risk of VTE Overall (N = 68,183) 73% 36% Cohen AT, et al. Lancet. 2008;371:

40 Patients (%) Use of ACCP-Recommended Prophylaxis among Overall Population at Risk of VTE Mean = 50% N = 35,329 84% 1.6% Cohen AT, et al. Lancet. 2008;371:

41 ENDORSE: At-risk Surgical Patients Receiving Prophylaxis % Patients receiving prophylaxis UK USA India 19 Pakistan 14 Thailand Bangladesh Cohen AT, et al. Lancet. 2008;371:

42 Asian VTE Guidelines: Prevention of VTE Asian VTE Guidelines: Prevention of VTE International Journal of Angiology 2017 Feb;36(1):1-20 The Asian venous thromboembolism (VTE) prophylaxis guidelines was first published in Since its first edition, the Asian Venous Thrombosis Forum (AVTF) working group have updated the Asian VTE epidemiology and reviewed issues that were not addressed in the previous guidelines. The authors noted that the rising incidence of VTE across Asia may be attributable to aging population, dietary changes, and increasing incidence of obesity and diabetes. The new additions in the guideline include role of thrombophilia in VTE, bleeding risk in Asians, individual risk assessment, updates in the prevention of VTE in medically ill, bariatric surgery, cancer, orthopaedic and trauma patients. The influence of primary thrombophilia in perioperative VTE is still unclear. The secondary risk factors however, is similar between Asians and Caucasians. Liew NC. Int Angiol. 2012;31:

43 Recommendations 1. Asians at risk of VTE should be considered for VTE prophylaxis 2. Formal hospital VTE protocol for risk assessment and prophylaxis should be established 3. Balancing VTE risk versus bleeding complications 4. Appropriate methods of thromboprophylaxis Int Angiol. 2017

44 Thromboprophylaxis Bleeding Thrombosis Risk factors for bleeding Previous major bleeding Severe renal failure Concomitant antiplatelets Bleeding disorders Severe liver disease Thrombocytopenia Active ulcerative GI disease Uncontrolled hypertension Risk factors for VTE Previous VTE Malignancy Comorbidity Obesity Advanced age Varicose vein Immobilization Hormonal use

45 Conclusions The incidence of VTE in Asian populations has increased over time. Risk factors for thrombosis are not different in Asian patients from those of Western countries, with the exception of thrombophilic mutations. There is a very low rate of prophylaxis use in Asian patients, despite their high risk of VTE.

46 Thromb Haemost 2011; 106(Oct):

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