VTE Prevention In Action Interactive Case Scenarios

Dr Raj Patel King’s Thrombosis Centre Consultant Haematologist

Patient 1: Elective THR 78-year-old woman, osteoarthritis Elective THR BMI 31kg/m 2, weight 93kg DVT post-partum

Patient 1: VTE Risk Assessment

Patient 1: Who performs VTE risk assessment (elective patient)?

Patient 1: High Risk of VTE Major orthopaedic procedure Additional risk factors for VTE? –> 60 years old –Anticipated immobility 3 days –BMI above 30 kg/m 2 –Previous VTE

ACCP, 2008

Patient 1: Treatment Is mechanical or pharmacological thromboprophylaxis contraindicated?

Patient 1: Treatment choices- Mechanical Thromboprophylaxis

Patient 1: Treatment choices- Pharmacological Thromboprophylaxis

Patient 1: Other treatment choices?

ACCP 2008: THR guidance LMWH (12hrs preop, 12-24hrs postop, 4-6hrs postop 50%) Fondaparinux (2.5mg, 6-24hrs postop) VKA Mechanical device alone: only if bleeding risk high

Value of Mechanical Thromboprophylaxis? No bleeding (useful when bleeding risk high) May enhance effectiveness of pharmacological thromboprophylaxis Big variation in size/pressure/features - many brands not assessed in trials - fitting/compliance poor on wards Fewer/smaller studies - effect on reducing PE/death unknown - less effective in high risk groups - no study in medical inpatients

ACCP 2008: Mechanical Thromboprophylaxis Recommend primarily where bleeding risk high (1A) or as adjunct to pharmacological measure (2B) Careful attention to proper use and compliance ‘optimal use’

Regimen No. trials No. patients No. DVT patients Incidence % Risk reduction % Controls Aspirin Stockings Low-dose heparin LMWH IPC Prevention of DVT after general surgery (ACCP 2001)

ACCP 2008: Aspirin We recommend against the use of aspirin alone as thromboprophylaxis against VTE for any patient group (1A).

Patient 1: Treatment LMWH (preop) or oral agent (postop) once daily Plus Graduated compression stockings and/or SCD

Patient 1: Pharmacological Thromboprophylaxis –for how long?

ACCP: beyond 10 days, up to 35 days (1A) Patient 1: Pharmacological Thromboprophylaxis –for how long?

Epidurals ACCP: –insertion of spinal/epidural needle delayed 8-12 hrs following prophylactic heparin dose –removal scheduled just prior to next dose –following epidural removal, delay next dose by > 2 hrs Dabigatran: not recommended

Clinical presentation of HIT ThrombocytopeniaThrombocytopenia Timing of thrombocytopeniaTiming of thrombocytopenia Thrombosis / other sequelaeThrombosis / other sequelae oTher cause unlikelyoTher cause unlikely

Patient 2: Gynaecological surgery 63-year-old woman Uterine carcinoma Weight 135kg, BMI 38 kg/m 2 Abdominal hysterectomy

Patient 2: VTE risk assessment Major gynaecological procedure Additional risk factors for VTE? –> 60 years old –Anticipated immobility 3 days –BMI 38 kg/m 2 –Malignancy

Patient 1: Treatment Is mechanical or pharmacological thromboprophylaxis contraindicated?

Patient 2: Treatment choices- Mechanical Thromboprophylaxis

Patient 2: Treatment choices- Pharmacological Thromboprophylaxis

Patient 2: 135 kg - What dose of LMWH

Patient 2: Pharmacological Thromboprophylaxis – duration?

Gynaecologic surgery guidance (ACCP 2008) Minor procedures without ARFs: early ambulation only Laparosopic procedures - without ARFs: early ambulation -with ARFs: LMWH or LDUFH or IPC or GCS (1C) Major procedures: -Benign disease: LMWH (1A) or LDUFH (1A) or IPC (1B) -Malignancy: consider LMWH 28 days Bariatric surgery: higher doses LMWH or UFH suggested (2C)

Patient 3: Neurosurgery and Spinal Procedures 71-year-old woman Elective spinal procedure (disc prolapse) Smoker Varicose veins FV Leiden mutation heterozyous

ACCP, 2008

Patient 3: VTE Risk Assessment

Patient 3: Risk Assessment for VTE Major spinal procedure Additional risk factors for VTE? –> 60 years old –Anticipated immobility 3 days –FV Leiden

Patient 3: Treatment Is mechanical or pharmacological thromboprophylaxis contraindicated?

Patient 3: Treatment choices Mechanical Thromboprophylaxis

Patient 3: Treatment choices Pharmacological Thromboprophylaxis

Patient 3: Pharmacological Thromboprophylaxis – duration?

Elective spinal surgery guidance (ACCP 2008) No ARFs: early ambulation (2C) With ARFs: either Post op LMWH (1B) LDUFH (1B) Periop IPC (1B) or GCS (2b) With multiple ARFs: pharmacologic plus mechanical (2C)

Defining the Complex Medical Patient... A patient you would give LMWH to, but for some reason you feel uncomfortable A patient who would benefit from LMWH but may have a contraindication...

Patient 4 74-year-old woman, 15-year history of type 2 diabetes Peripheral neuropathy (feet), leg ulcers BMI 33 kg/m 2, 92kg Admitted with unilateral lower limb cellulitis, immobility, high BMs Treated with insulin, hydration and intravenous antibiotics

Patient 4: VTE Risk Assessment

Patient 4: Treatment Is mechanical or pharmacological thromboprophylaxis contraindicated?

Patient 4: Treatment choices Mechanical Thromboprophylaxis

Patient 4: Treatment choices Pharmacological Thromboprophylaxis

Patient 4: Risk Assessment for VTE > 40 years old with acute medical illness and reduced mobility? –Yes Additional risk factors –age > 70 years –infection –BMI 33 kg/m 2

KCH guidelines for medical thromboprophylaxis

Patient 4: Pharmacological Thromboprophylaxis –for how long?

Clear Benefits of Thromboprophylaxis over Placebo MEDENOX 1 63%Placebo Enoxaparin 40 mg PREVENT 2 49%Placebo Dalteparin ARTEMIS 3 47%Placebo Fondaparinux 14.9 * 5.5 Study RRRThromboprophylaxis Patients with VTE (%) 5.0* † 5.6 * VTE at day 14; † VTE at day 15. P<0.001 P= P=0.029 RRR 63% 45% 47%

Primary Efficacy Endpoints: Implications for Clinical Practice MEDENOX 1 Distal and proximal 63% venographic DVT + symptomatic VTE + fatal PE PREVENT 2 Compression 45% ultrasonographic DVT + symptomatic VTE + fatal PE ARTEMIS 3 Distal and proximal 47% venographic DVT + symptomatic VTE + fatal PE TrialVTERRR NNT Number needed to treat – justifies thromboprophylaxis

Patient 4 74-year-old woman, 15-year history of type 2 diabetes, diet controlled Peripheral neuropathy (feet), leg ulcers BMI 33kg/m 2 Admitted with unilateral lower limb cellulitis, immobility, and high BMs Treated with insulin, hydration and intravenous antibiotics

Patient 4: Platelet count 110x10 9 /L (Not bleeding)

Mild asymptomatic thrombocytopenia Seek haematology advice? No adjustment in prophylaxis

Patient 4: Platelet count 20x10 9 /L (Not bleeding)

Patient 4: Platelet count 20x10 9 /L (not bleeding) Significant unexplained thrombocytopenia Seek haematology advice Withhold LMWH

Patient 4 74-year-old woman, 15-year history of type 2 diabetes, diet controlled Peripheral neuropathy (feet), leg ulcers BMI 33kg/m 2 Admitted with unilateral lower limb cellulitis, immobility, and high BMs Treated with insulin, hydration and intravenous antibiotics

Patient 4: Creatinine 156 micromol/L (60–120) CC 40mls/min

Patient 4: Drug monitoring required?

Patient 4: Mild renal impairment ACCP: - consider renal function with LMWH - elderly, diabetics, high bleeding risk

Patient 4: Mild renal impairment ACCP options: -avoid drugs which bioaccumulate -lower dose -monitor drug level or anticoagulant effect 1.UFH 2.LMWH reduced dose 3.LMWH standard dose with anti-Xa monitoring if prolonged use

Patient 4 74-year-old woman, 15-year history of type 2 diabetes Peripheral neuropathy (feet), leg ulcers BMI 33kg/m 2 Admitted with unilateral lower limb cellulitis, immobility, and high BMs Treated with insulin, hydration and intravenous antibiotics

Patient 4: Creatinine 256 micromol/L (60–120) CC <20mls/min

Patient 4 : Drug monitoring required?

Patient 4: Severe renal impairment options: -avoid drugs which bioaccumulate -lower dose -monitor drug level or anticoagulant effect UFH

Patient 4: BMI=16 kg/m 2 74-year-old woman, 15-year history of type 2 diabetes, diet controlled Peripheral neuropathy (feet), leg ulcers BMI 16 kg/m 2 Admitted with unilateral lower limb cellulitis, immobility, and high BMs Treated with insulin, hydration and intravenous antibiotics

Patient 4: BMI=16 kg/m 2 Very low body weight patient Would you change LMWH prophylaxis?

Patient 4: BMI=16 kg/m 2

Patient 4 : very elderly 98-year-old woman, 15-year history of type 2 diabetes, diet controlled Peripheral neuropathy (feet), leg ulcers BMI 33kg/m 2 Admitted with unilateral lower limb cellulitis, immobility, and high BMs Treated with insulin, hydration and intravenous antibiotics

Patient 4 : very elderly Would you change LMWH prophylaxis?

Patient 4 : very elderly

Patient 5 66-year-old man admitted with acute exacerbation of COPD

KCH guidelines for medical thromboprophylaxis

Patient 5: Risk Assessment for VTE > 40 years old with acute medical illness and reduced mobility? –yes Additional risk factors –respiratory disease/acute infectious disease Is pharmacological thromboprophylaxis contraindicated? –no

Patient 5: Treatment LMWH: enoxaparin 40 mg s.c. daily AES

Patient 5: Very urgent arterial blood gas –would you change LMWH prophylaxis?

Patient 5 : Very Urgent Arterial Blood Gas

Patient 5: Needs non-urgent Central Venous Line –would you change LMWH treatment?

Patient 5: Non-Urgent Central Venous Line

Patient 5: Ultrasound guided liver biopsy –would you change LMWH prophylaxis?

Patient 5: Ultrasound guided liver biopsy

Patient 5: HIT? 6 days after admission his platelet count falls to 70x10 9 /L and the next day is 30x10 9 /L You are asked if this is ‘heparin- induced thrombocytopenia’

Patient 5: Falling platelets, HIT?