Primary VTE Prophylaxis

Ponlapat Rojnuckarin, MD PhDChulalongkorn UniversityBangkok, Thailand

A 70-yr-old female before THABMI 31 kg/m2 with varicose veinWhat do you recommend for VTE prevention?A. NoneB. IPCC. ASAD. ASA+ IPCE. DOAC x 5 d then ASA 30 daysF. LMWH x 5 d then ASA 30 days

VTE prophylaxis in Thailand

Lancet 2008; 371: 387

Thailand

Patients at risk for VTE

Prophylaxis given

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 2009Total 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: 1356JTH 2005; 3: 2664-70, JTH 2005; 3: 28.

Increasing Incidences of VTE in ThailandSettings Year Total

NumberIncidence Notes

HIP/KNEE SURGERYHip Surgery1 1984-1986 50 4% Angiography

Knee Surgery2 2004 67 24% Radionuclide ScanHip Fracture3 2005 96 48% Angiography

GYNECOLOGICAL CANCER SURGERYGynecologic cancer surgery4 1975 52 3.8% Radionuclide Scan

(No symptom) Ovarian cancer5 2004-2013 305 5.9% Symptomatic DVT by USGynecologic cancer6 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: 1357-82. Pookarnjanamorakot et al. J Med Assoc Thai 2004; 87: 869 5. Oranratanaphan et al. Asian Pac J Cancer Prev 2015; 16: 67053. 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 2009General and gynecologic surgeryAge > 40 yr and Major surgery (GA or > 1 hr)(Moderate risk, ACCP recommends heparin)N=1432Symptomatic VTE 11 (0.77%)Most of VTE had cancer.

Yongkasem Vorasettakarnkij et al.

VTE in Thai surgical ICUDoppler Ultrasonography in all casesRamathibodi 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;32:85Prichayudh et al. J Med Assoc Thai. 2015; 98: 472

Medical patientsChulalongkorn 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 patientsChulalongkorn 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)

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11

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1

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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

Arch Intern Med 2002; 162: 1245Admission within 3 months

Perioperative heparin reduced Mortality

Heparin Control

Non Fatal PE 1.3% 2.0% p<.0005Fatal PE 0.26% 0.81% p<.0005

Mortality 3.3% 4.2% p<0.02

N Engl J Med 1988; 318: 1162

No Anticoagulant Anticoagulant

Any PE 0.49% 0.20%Fatal PE 0.39% 0.14%DVT 0.81% 0.38%Mortality 4.5% 4.3%

Significant reduction in PE/fatal PE/DVT

DVT prophylaxis in high-risk medical patients

Ann Intern Med. 2007;146:278-88. Meta-analysis, N=19 958Symptomatic only

NNT=400

Anticoagulant Prophylaxis increased risk of major bleeding.

J Thromb Haemost 2008; 6: 405–14Are there other choices of prophylaxis?

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 patientsDVT :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 surgeryDVT

Ann Surg 2016; 263: 888

IPC in Critically-ill patientsNetwork meta-analysis

J Korean Med Sci 2016; 31: 1828

Pathogenesis of VTE: Platelets

Anesth Analg 2017; 125: 403.

Hip/Knee SurgeryDVT rate: ASA vs. Anticoagulant

J Hosp Med 2014; 9: 579

Hip/Knee SurgeryPE 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 daysRivaroxaban 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 eventsYear 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 HematologyGuideline: Hip/Knee surgery THA/TKA: LMWH, fondaparinux, LDUH, DOACs,

warfarin, or aspirin (คุณภาพหลกัฐาน ก๑ นํ้าหนกัคาํแนะนาํ

+) or IPC (คุณภาพหลกัฐาน ข๑ นํ้าหนกัคาํแนะนาํ +)

Hip fracture: LMWH, fondaparinux, LDUH, warfarin or aspirin (คุณภาพหลกัฐาน ก๑ นํ้าหนกัคาํแนะนาํ

+) or IPC (คุณภาพหลกัฐาน ข๑ นํ้าหนกัคาํแนะนาํ +)

High risk for bleeding: IPC (คุณภาพหลกัฐาน ง๑ นํ้าหนกั

คาํแนะนาํ +)

Thai Society of Hematology Guideline 2017

Caprini score for surgical patients

ACCP guideline, Chest 2012; 141: e227SCalculator is available online.

Abdominal or pelvic surgeryRisk Caprini

scoreVTE risk Methods

Very low 0 <0.5% Early ambulationLow 1-2 1.5% IPC (+/-)Moderate 3-4 3% LMWH or LDUH or

IPC (+/-)High ≥ 5 6% LMWH or LDUH

or IPC (+)

Thai Guideline 2017

Hip/Knee arthroplasty or Hip fracture = +5Cancer (+2) Major surgery (+2) = +4

Risk Factors in Cancer patients

Thromb Res 2015; Suppl 1: S8 Breast and prostate CA have low-risk.

Thai Society of HematologyGuideline: Medical inpatients All require VTE risk assessment (คุณภาพหลกัฐาน ง๑

นํ้าหนกัคาํแนะนาํ +)

Select appropriate VTE prevention for each patient (คุณภาพหลกัฐาน ง๑ นํ้าหนกัคาํแนะนาํ +)

High risk VTE (Padua score ≥4): LMWH, LDUH or fondaparinux (คุณภาพหลกัฐาน ก๑ นํ้าหนกัคาํแนะนาํ +/-)

High risk for bleeding: IPC (คุณภาพหลกัฐาน ค๑ นํ้าหนกั

คาํแนะนาํ +)

Thai Society of Hematology Guideline 2017

How to improve VTE preventionMultidisciplinary action

Surgeon concernsGynecological OncologistsOrthopedists, Surgeons, AnesthesiologistsProfessional societiesOpen guidelines with choices

Raise the concernEarly ambulationMechanical prophylaxisPharmacological 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 THABMI 31 kg/m2 with varicose veinWhat do you recommend for VTE prevention?A. NoneB. IPCC. ASAD. ASA+ IPCE. DOAC x 5 d then ASA 30 daysF. 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