Primary VTE Prophylaxis Ponlapat Rojnuckarin, MD PhD Chulalongkorn University Bangkok, Thailand
A 70-yr-old female before THA BMI 31 kg/m 2 with varicose vein What do you recommend for VTE prevention? A. None B. IPC C. ASA D. ASA+ IPC E. DOAC x 5 d then ASA 30 days F. LMWH x 5 d then ASA 30 days
VTE prophylaxis in Thailand Patients at risk for VTE Prophylaxis given Thailand Lancet 2008; 371: 387
Rationale of VTE prophylaxis Incidence of VTE? Clinically-relevant VTE? Asymptomatic vs. Symptomatic Proximal vs. Distal Fatal PE Efficacy vs. Safety of prophylaxis? Cost-effectiveness?
Incidence of VTE in hip/knee surgery in Asia (N = 2454) Publication from 1979 to 2009 Total DVT (Venography) 30-40% Proximal VTE 5-10% Symptomatic DVT* 2.8-4.5% Symptomatic PE 0.6% Fatal PE None reported *The limbs with surgery are frequently swollen without thrombosis. Meta-analysis Br J Surg 2011; 98: 1356 JTH 2005; 3: 2664-70, JTH 2005; 3: 28.
Increasing Incidences of VTE in Thailand Settings Year Total Number Incidence Notes HIP/KNEE SURGERY Hip Surgery 1 1984-1986 50 4% Angiography Knee Surgery 2 2004 67 24% Radionuclide Scan Hip Fracture 3 2005 96 48% Angiography GYNECOLOGICAL CANCER SURGERY Gynecologic cancer surgery 4 1975 52 3.8% Radionuclide Scan (No symptom) Ovarian cancer 5 2004-2013 305 5.9% Symptomatic DVT by US Gynecologic cancer 6 2014 100 7.0% Proximal DVT by US 1. Atichartakarn et al. Arch Intern Med 1988; 148: 1349 4. Chumnijarakit et al. Lancet 1975; 1: 1357-8 2. Pookarnjanamorakot et al. J Med Assoc Thai 2004; 87: 869 5. Oranratanaphan et al. Asian Pac J Cancer Prev 2015; 16: 6705 3. Chotanaphuti et al J Med Assoc Thai 2005; 88 (S3): S159 6. Sermsathanasawadi et al. J Med Assoc Thai. 2014; 97: 153-8
VTE in Hip/knee Arthroplasty Siriraj Hospital (N = 896) TKA (714) Supervised calf muscle exercise Early ambulation (Mean: 2 days post -op) Follow-up by phone and imaging for symptoms Symptomatic DVT 2/896 (0.22%): Both of them had no risk factor Leg swelling is common after surgery. Diagnosis by symptoms is difficult. Some might have been missed? Wongprasert C et al. JTH 2015; 13 (Suppl 1): 984.
Non-orthopedic surgery Chulalongkorn Hospital, Thailand 2009 General and gynecologic surgery Age > 40 yr and Major surgery (GA or > 1 hr) (Moderate risk, ACCP recommends heparin) N=1432 Symptomatic VTE 11 (0.77%) Most of VTE had cancer. Yongkasem Vorasettakarnkij et al.
VTE in Thai surgical ICU Doppler Ultrasonography in all cases Ramathibodi Hospital (Surgical ICU) 2005-2006 10.5% (20/190) DVT KCMH (Surgical ICU) 2011-2012 3.6% (11/305) DVT (2 with PE) Risk factors: Previous VTE (OR 34.3), Orthopedics group (OR 27.2) and female sex (OR 14.3) Wilasrusmee et al. Asian J Surg 2009;32:85 Prichayudh et al. J Med Assoc Thai. 2015; 98: 472
Medical patients Chulalongkorn Hospital, 2007-2008 (N = 7126) Admit > 3 d, No active VTE on admission 42/7126 (0.59%) symptomatic VTE Arthritis (7.7%), Cancer (1.8%), Ventilator (1.5%) 23/42 (55%) symptomatic PE 10 (0.14%) fatal PE (41.7% of PE) 2 deaths from anticoagulants Aniwan & Rojnuckarin. Blood Coagul Fibrinolysis 2010; 21: 334
High-risk medical patients Chulalongkorn Hospital, 2007-2008 7.7% (2/26) of arthritis of lower limbs 4.7% (3/64) of SLE 1.8% (22/1211) of active cancer 1.5% (5/543) of mechanical ventilation 0.5 % (1/204) of congestive heart failure 0.4% (1/240) of acute stroke
High-risk medical patients (N = 1290) (Western risk scores: Not working) 6 11 1 1 1 Total VTE = 27 (2.1%) Rojnuckarin et al. Thromb Haemost 2011; 106: 1103
VTE in Thailand The incidence of Symptomatic VTE in High-risk patients is NOT LOW. Major Hip and Knee Surgery: 0.22-4.5% Active cancer patients: 2-3% Over 50% of all VTE are attributed to hospitalization or cancer. The prevention will be helpful for public health.
Hospitalization and cancer attributed to over half of VTE in population Admission within 3 months Arch Intern Med 2002; 162: 1245
Perioperative heparin reduced Mortality Heparin Control Non Fatal PE 1.3% 2.0% p<.0005 Fatal PE 0.26% 0.81% p<.0005 Mortality 3.3% 4.2% p<0.02 N Engl J Med 1988; 318: 1162
DVT prophylaxis in high-risk medical patients No Anticoagulant Anticoagulant Any PE 0.49% 0.20% NNT=400 Fatal PE 0.39% 0.14% DVT 0.81% 0.38% Mortality 4.5% 4.3% Significant reduction in PE/fatal PE/DVT Meta-analysis, N=19 958 Symptomatic only Ann Intern Med. 2007;146:278-88.
Anticoagulant Prophylaxis increased risk of major bleeding. Are there other choices of prophylaxis? J Thromb Haemost 2008; 6: 405 14
Pathogenesis of VTE Anesth Analg 2017; 125: 403.
Intermittent Pneumatic Compression
Intermittent Pneumatic Compression (IPC) for VTE prophylaxis Meta-analysis of 70 trials (N =16 164) Surgical or Medical Hospitalized patients DVT :RR 0.43 (p<0.01) PE :RR 0.48 (p<0.01) Less bleeding compared with anticoagulant RR 0.41 (p < 0.01) Add medication to IPC : RR 0.54 (p 0.02) Side effects: Skin breaks 2%, discomfort Circulation 2013; 128: 1003
IPC in Orthopedic and Neurological surgery DVT Ann Surg 2016; 263: 888
IPC in Critically-ill patients Network meta-analysis J Korean Med Sci 2016; 31: 1828
Pathogenesis of VTE: Platelets Anesth Analg 2017; 125: 403.
Hip/Knee Surgery DVT rate: ASA vs. Anticoagulant J Hosp Med 2014; 9: 579
Hip/Knee Surgery PE rate: ASA vs. Anticoagulant J Hosp Med 2014; 9: 579
Bleeding ASA vs. Anticoagulant J Hosp Med 2014; 9: 579
THA or TKA Rx Rivaroxaban 5 days Rivaroxaban vs. ASA for total of 30 or 14 d N Engl J Med 2018; 378: 699
Meta-analysis: ASA in THA and TKA Retro-/Prospective/RCT: Symptomatic events Year 1976-2014 (39 studies) DVT 1.2% (N = 59,273) PE 0.6% (N = 61,315) Major bleeding 0.3% (N = 54,255) Year 2014-2017 (7 studies) DVT 0.66% (N = 43,012)
Thai Society of Hematology Guideline: Hip/Knee surgery THA/TKA: LMWH, fondaparinux, LDUH, DOACs, warfarin, or aspirin (ค ณภาพหล กฐาน ก๑ น าหน กค าแนะน า +) or IPC (ค ณภาพหล กฐาน ข๑ น าหน กค าแนะน า +) Hip fracture: LMWH, fondaparinux, LDUH, warfarin or aspirin (ค ณภาพหล กฐาน ก๑ น าหน กค าแนะน า +) or IPC (ค ณภาพหล กฐาน ข๑ น าหน กค าแนะน า +) High risk for bleeding: IPC (ค ณภาพหล กฐาน ง๑ น าหน ก ค าแนะน า +) Thai Society of Hematology Guideline 2017
Caprini score for surgical patients Calculator is available online. ACCP guideline, Chest 2012; 141: e227s
Abdominal or pelvic surgery Risk Caprini VTE risk Methods score Very low 0 <0.5% Early ambulation Low 1-2 1.5% IPC (+/-) Moderate 3-4 3% LMWH or LDUH or IPC (+/-) High 5 6% LMWH or LDUH or IPC (+) Hip/Knee arthroplasty or Hip fracture = +5 Cancer (+2) Major surgery (+2) = +4 Thai Guideline 2017
Risk Factors in Cancer patients Breast and prostate CA have low-risk. Thromb Res 2015; Suppl 1: S8
Thai Society of Hematology Guideline: Medical inpatients All require VTE risk assessment (ค ณภาพหล กฐาน ง๑ น าหน กค าแนะน า +) Select appropriate VTE prevention for each patient (ค ณภาพหล กฐาน ง๑ น าหน กค าแนะน า +) High risk VTE (Padua score 4): LMWH, LDUH or fondaparinux (ค ณภาพหล กฐาน ก๑ น าหน กค าแนะน า +/-) High risk for bleeding: IPC (ค ณภาพหล กฐาน ค๑ น าหน ก ค าแนะน า +) Thai Society of Hematology Guideline 2017
How to improve VTE prevention Multidisciplinary action Surgeon concerns Gynecological Oncologists Orthopedists, Surgeons, Anesthesiologists Professional societies Open guidelines with choices Raise the concern Early ambulation Mechanical prophylaxis Pharmacological prophylaxis (LMWH or SH)
Rationale of VTE prophylaxis Incidence of VTE Clinically relevant VTE Asymptomatic vs. Symptomatic Distal vs. Proximal Fatal PE Efficacy vs. Safety of prophylaxis (Mechanical or ASA prophylaxis) Cost-effectiveness analysis (ASA in Hip/knee surgery)
A 70-yr-old female before THA BMI 31 kg/m 2 with varicose vein What do you recommend for VTE prevention? A. None B. IPC C. ASA D. ASA+ IPC E. DOAC x 5 d then ASA 30 days F. LMWH x 5 d then ASA 30 days
Summary All doctors need to be aware of and assess the VTE risks of patients. Consider prophylaxis in very high risk Caucasian patients History of previous VTE Hip and knee surgery (Consider ASA) High-risk Cancer undergoing Major Surgery Non-pharmacological or Pharmacological prophylaxis, e.g. IPC in ICU patients