Objectives At the end of this talk you will be able to: - PowerPoint Presentation

Slide1

Slide2

ObjectivesAt the end of this talk you will be able to:

Describe the rationale for extended duration (30 days)

thromboprophylaxis

in abdominopelvic surgical cancer patients

Assess the thrombotic risk and bleeding risk abdominopelvic surgical cancer patients

Describe the evidence and guidelines supporting the use of extended duration

thromboprophylaxis

in abdominopelvic surgical patients

Assess the thrombotic risk and bleeding risk in urology patients

Explain the rationale for the order set developed by Thrombosis Canada for cancer patients having undergone abdominopelvic surgery

Slide3

Talk OverviewIntroduction

Rationale for Extended Duration

Thromboprophylaxis

in abdominopelvic Surgical Cancer Patients

Assessing the Bleeding Risk and Thrombotic Risk

Review key evidence-based clinical data and guidelines related to VTE prophylaxis in abdominopelvic surgical cancer patients

Considerations for urology, renal failure and obesity

Review the Thrombosis Canada protocol/Order Set for

thromboprophylaxis

of abdominopelvic surgical cancer patients

Slide4

Introduction:

Virchow

’

s Triad

Vascular Injury

Direct invasion

Central catheters

Endothelial damage

Surgery

Chemotherapy

Hypercoagulability

Tumor procoagulantsCytokinesImpaired endothelial cell defenseCellular interactions

Rudolph Virchow

Adapted from Joist JH.

Semin Thromb Hemost

. 1990;16:151-157.

Venous Stasis

Vascular compression

by tumor

Prolonged bed rest

Hypotension

Slide5

Introduction:Rationale for Post Surgical Thromboprophylaxis

Pulmonary embolism (PE) is the most common preventable cause of hospital death and the number-one strategy to improve patient safety in hospitals

Approximately one third of the 150,000 to 200,000 VTE-related deaths per year in the United States are post-surgical

A vast number of randomized clinical trials over the past 30 years have confirmed benefit, safety and cost effectiveness

Thromboprophylaxis

effectively reduces: DVT/PE, Fatal PE, Death from any cause and Health care management costs

Geerts

WH et al. Chest. 2008 Jun;133(6

Suppl

):381S-453S

Gould et al. Chest. 2012;141 e227S-77S.Horlander KT, Mannino DM, Leeper KV. Arch Intern Med. 2003 28;163(14):1711-7.

Slide6

Introduction:9th ACCP Guideline Recommendations for Standard Surgical Thromboprophylaxis

Patients undergoing general and abdominal pelvic surgery should receive a risk assessment before their procedure to predict their risk of VTE

For patients at moderate risk for VTE (

Caprini

Score of 3-4) who are not at high risk for major bleeding complications, guidelines suggest LMWH, LDUH (Grade 2B) for 7-10 days or mechanical prophylaxis (Grade 2C)

For patients at high risk for VTE (

Caprini

Score of 5 or more) who are not at high risk for major bleeding complications, guidelines recommend pharmacologic prophylaxis with LMWH or LDUH (Grade 1B) for 7-10 days

Gould MK, et al.

Chest

2012;141;e227S-e277S

Slide7

What is the rationale for Extended Duration (30 days) Thromboprophylaxis in Surgical Cancer Patients?

Slide8

VTE Post Surgery is Common in Cancer Patients

20,762 pts undergoing major cancer surgery

Followed for 30 days

Overall VTE rate 3.5%

(95% CI, 3.2–3.7%) with a range 1.8%-13.2%

Hammond J, et al. Ann

Surg

Oncol

(2011) 18:3240-3247

0 5 10 15 20

PercentEsophageal resectionCysectomy, radicalPancreatectomyPancreaticduodenectomyGastrectomyOther surgeriesNephrectomy, radicalAbdominoperineal resectionColectomyPulmonary resectionNephrectomy, partialLow anterior resectionProstatectomy, allOverall

Slide9

Risk of VTE Post Surgery is Higher in Cancer Patients than Non-Cancer Patients

Risk

Level

Calf DVT

Proximal

DVT

Clinical PE

Fatal PE

Low risk

Minor surgery in patients aged ˂ 40 y with no additional risk factors2%0.4%0.2%˂0.01%Moderate riskMinor surgery in patients with additional risk factorsSurgery in patients aged 40–60 y with no additional risk factors10-20%2-4%1-2%0.1-0.4%

High riskSurgery in patients ˃ 60 y or with additional risk factors (eg, prior VTE, CANCER)20-40%4-8%2-4%0.4-1%Highest riskSurgery in patients with multiple risk factors(age ˃ 40 y, CANCER, prior VTE)Hip or knee arthroplasty

, hip fracture surgery

40-80%10-20%4-10%

0.2-5%VTE Risk in Surgical Patients Without Prophylaxis

Agnelli G.. Circulation 2004;110(suppl 4):4-12

Slide10

All patients

(LDUH or LMWH)

Cancer

(n = 6,124)

No cancer

(n = 16,954)

p value

Death (%)

192 (3.1)

120 (0.7)

0.0001Fatal PE (%)20 (0.33)15 (0.09)0.0001Non-fatal PE (%)5 (0.08)4 (0.02)

Kakkar AK, et al. Thromb Haemost 2005;94:867-71.Trinh VQ, et al. JAMA Surg

. 2014;149(1):43-49.

VTE is associated with Worse Survival in Cancer patients than Non-Cancer Surgical Patients

LDUH: Low dose unfractionated heparin; LMWH: Low molecular weight heparin; PE: pulmonary embolism

Cancer patients with VTE have a 5.3-fold greater odds of mortality post surgery than patients without cancer

Slide11

VTE is associated with Worse Survival in Cancer patients than Non-Cancer Surgical Patients

23,541 patients having cancer surgery

474 (2%) VTEs

5

yr

OS 43.8%

vs

61.2%

Auer, RAC. Annals of Surgery.

255.5 (2012): 963-970.

Overall survivalTime to death or last follow-up (mo)

0 10 20 30 40 50 601.00.80.60.40.20.0no VTE (n=23,067)VTE (n=474)P<0.0001

Slide12

Abdominal and Pelvic Cancer Surgical Patients Continue to have a Significant Proportion of Late VTE Events

Agnelli

G et al.

Ann Surg.

2006;243(1):89-95.

Prospective study, 2373 patients undergoing general, urologic, or gynecologic surgery - @RISTOS Registry

40% of VTE events occurred >21 days after surgery

N=2373, @RISTOS Registry: Prospective cohort study

Slide13

Abdominal and Pelvic Cancer Surgical Patients Continue to have a Significant Proportion of Late VTE Events

NSQIP 2006-2008

211 hospitals, 44,656

pts

30-37% of VTE events

occurred post-discharge

Merkow

RP et al. Annals of Surgery.

2011; 254.1 131-137

33.4%

66.6%30.6%69.4%37.8%62.2%Post-dischargePre-discharge

Slide14

Assessing the Thromboticand Bleeding Risks

Slide15

Assessing the Thrombotic RiskRisk Factors for Cancer-Associated VTE

Cancer Related

Treatment Related

Patient related

Biomarkers

Primary site

Chemotherapy

Older Age

Platelet count

(≤ 350,000/µL)

Stage(higher for advanced stage)Antiangiogenic agents(eg, thalidomide, lenalidomide)Race (higher in African Americans; lower in Asians/Pacific Islanders)Leukocyte count(> 11,000/µL)Cancer histology(higher for adenocarcinoma than squamous cell)Hormonal therapyMedical comorbidities (infection, renal disease, pulmonary disease, arterial thromboembolism)Hemoglobin (< 10 g/dL)Time after initial diagnosis (highest in first 3 to 6 months)Erythropoiesis-stimulating agentsTransfusionsIndwelling venous access devicesRadiation therapySurgery > 60 minObesityHistory of VTEDiminished performance statusInherited prothrombotic mutations

VTE = venous thromboembolismAdapted from Lyman GH, et al. ASCO Update. J Clin Oncol. 2013;31:2189-204.

Slide16

Assessing the Thrombotic RiskWho is high risk?

High risk patients require

thromboprophylaxis

, but who is

high risk?

Based on the randomized controlled trials in this setting,

the indications for extended duration

thromboprophylaxis

in patients undergoing open abdominal or pelvic surgery for cancer (i.e. high risk patients) would include:Patients over 40 years of age or older requiring admission orPatients over the age of 40 whose surgery lasts longer than an 30 minutes to an hourPatients with alternate risk factors for example between ages of 18-40 with additional risk factors shown in previous slide.

Bergqvist

D, et al. N Engl J Med 2002;346:975-80Rasumssuen MS, et al. J

Thromb Haemost 2006;4:2384-90Kakkar VV, et al. J Thromb Haemost 2010;8:1223-9Gould, MK, et al.. Chest 2012;141(2_suppl):e227S-e277S

Slide17

Assessing the Bleeding Risk:Risk Factors for Major Bleeding Complications Post Surgery

General Risk Factors

Procedure-specific risk factors

Procedures*

Active bleeding

Previous major bleeding

Known, untreated bleeding disorder

Severe renal or hepatic failure

Thrombocytopenia

Acute stroke

Uncontrolled systemic hypertensionLumbar puncture, epidural, or spinal anesthesia within previous 4 h or next 12 hConcomitant use of anticoagulants, antiplatelet therapy, or thrombolytic drugs

Abdominal surgery: Male sex, preoperative hemoglobin level ˂13 g/dL, malignancy, and complex surgery defined as two or more procedures, difficult dissection, or more than one anastamosis Pancreaticoduodenectomy: Sepsis, pancreatic leak, sentinel bleed Hepatic resection: Number of segments, concomitant extrahepatic organ resection, primary liver malignancy, lower preoperative hemoglobin level, and platelet countsCardiac surgery: Use of aspirinUse of clopidogrel within 3 d before surgeryBMI >25 kg/m2

, nonelective

surgery, placement of≥ 5 grafts, older age

Older age, renal insufficiency, operation other than CABG, longer bypass time Thoracic surgery: Pneumonectomy or extended resectionCraniotomySpinal surgerySpinal traumaReconstructive procedures involving free flap

Gould, MK, et al.. Chest 2012;141 (2_suppl):e227S-e277S

*Procedures in which bleeding complications may have specially severe consequences

Bleeding risk tends to be transient and is highest immediate post-surgery

Slide18

What is the evidence to support extended-duration (30-days) anticoagulant prophylaxis after Abdominal & Pelvic cancer surgery?

Slide19

Bergqvist

D, et al. ENOXACAN II investigators.

N

Engl

J Med.

2002;346(13):975-980.

NNT: Number needed to treat

RRR: Relative risk reduction

P

=0.02

3-month follow-up

VTE rate difference persisted (13.8% placebo

vs

. 5.5% enoxaparin)

Extended Prophylaxis with Enoxaparin

Post Abdominal & Pelvic Cancer Surgery: ENOXACAN II TrialP=NS

P=NS

RRR=60%

Slide20

Extended Prophylaxis with Dalteparin Post Abdominal & Pelvic Cancer Surgery: FAME Trial

p=0.012

p=0.027

p=0.28

p=0.009

Rasmussen MS, et al. Journal of Thrombosis and Haemostasis.2006..

4: 2384-2390

Slide21

Extended Prophylaxis with Bemiparin Post Abdominal & Pelvic Cancer Surgery: CANBESURE Trial

p=0.26

p=0.10

p=0.54

p=0.02

p=0.01

*

* Proximal DVT, non-fatal PE, VTE-related death

Kakkar

, VV, et al. J

Thromb

and Haemost. 2010., 8: 1223-1229

Slide22

Cancer

ENOXACAN II

1

FAME

2

CANBESURE

3

patients (n) 332 199 625

Extended Prophylaxis with Low-Molecular Weight Heparins Post Abdominal & Pelvic Cancer Surgery: Summary of Trials

Bergqvist

D, et al.

N Engl J Med 2002;346:975-80Rasumssuen MS, et al. J Thromb Haemost 2006;4:2384-90Kakkar VV, et al. J Thromb Haemost 2010;8:1223-9p = 0.02

p = 0.01

p = 0.06

NSNSNS

NS = Not significant

Slide23

Study or subgroup

Treatment

n/N

Control

n/N

Peto

Odds Ratio

Peto, Fixed, 95% CI

Weight

Peto

Odds RatioPeto, Fixed, 95% CIBergqvist 2002J rgensen 2002Lausen 1998Rasmussen 20068/1654/583/5812/16520/16710/506/6029/178

31.2%14.8%10.2%43.8%0.40 [0.18, 0.86]0.32 [0.10, 0.97]0.51 [0.13, 1.96]0.43 [0.22, 0.82]Total (95% CI)Total events: 27 (Treatment), 65 (Control)Heterogenicity: Chi2 = 0.32, df = 3 (P = 0.96); I2 = 0.0%Test for overall effect: Z = 4.09 (P = 0.000043)Test for subgroup differences: Not applicable446

455

100.0%

0.41 [0.26, 0.63]Extended Prophylaxis with Low-Molecular Weight Heparins Post Abdominal & Pelvic Cancer Surgery: Cochrane ReviewProlonged thromboprophylaxis with LMWH (4 weeks compared to usual 5-7 days) for abdominal or pelvic surgery: Comparison LMWH vs placebo for all VTERasmussen MS, et al. Cochrane Database Syst Rev

. 2009;(1):CD004318.

0.1 0.2 0.5 2 5 10

Favours

treatment

Favours

control

Slide24

Extended Prophylaxis with Low-Molecular Weight Heparins Post Abdominal & Pelvic Cancer Surgery: Cochrane ReviewProlonged

thromboprophylaxis

with LMWH (

4 weeks compared to usual 5-7 days)

for abdominal or pelvic surgery: Comparison LMWH vs placebo for

Proximal DVT

Rasmussen MS,

et al.

Cochrane Database Syst Rev

. 2009;(1):CD004318.

Study or subgroupTreatmentn/NControln/NPetoOdds RatioPeto, Fixed, 95% CIWeightPetoOdds RatioPeto, Fixed, 95% CIBergqvist 2002J rgensen 2002Lausen 1998Rasmussen 20061/1651/580/58

3/16531/1674/502/60141/17814.7%17.8%7.4%60.1%0.37 [0.05, 2.64]0.24 [0.04, 1.47]0.14 [0.01, 2.23]0.28 [0.10, 0.74]

Total

(95% CI)Total events: 5 (Treatment), 23 (Control)Heterogenicity: Chi2 = 0.34, df = 3 (P = 0.95); I2

= 0.0%Test for overall effect: Z = 3.41 (P = 0.00066)Test for subgroup differences: Not applicable446455100.0%0.27 [0.13, 0.57]

0.1 0.2 0.5 2 5 10

Favours

treatment

Favours

control

Slide25

Study or subgroup

Treatment

n/N

Control

n/N

Peto

Odds Ratio

Peto, Fixed, 95% CI

Weight

Peto

Odds RatioPeto, Fixed, 95% CIBergqvist 2002J rgensen 2002Lausen 1998Rasmussen 200613/2536/932/754/1939/2485/943/846/202

45.7%22.6%10.5%21.2%1.43 [0.61, 3.36]1.23 [0.36, 4.13]0.74 [0.13, 4.41]0.70 [0.20, 2.44]Total (95% CI)Total events: 25 (Treatment), 23 (Control)Heterogenicity: Chi2 = 1.09, df = 3 (P = 0.78); I2 = 0.0%Test for overall effect: Z = 0.35 (P = 0.73)Test for subgroup differences: Not applicable614

628

100.0%

1.11 [0.62, 1.97]Extended Prophylaxis with Low-Molecular Weight Heparins Post Abdominal & Pelvic Cancer Surgery: Cochrane ReviewComparison: LMWH vs. placebo, Outcome Bleeding complicationsRasmussen MS, et al. Cochrane Database Syst Rev. 2009;(1):CD004318.Prolonged thromboprophylaxis with LMWH (4 weeks compared to 5-7 days) significantly reduces the risk of VTE compared to thromboprophylaxis during hospital admittance only, without increasing bleeding complications after major abdominal or pelvic surgery.

0.1 0.2 0.5 2 5 10Favourstreatment

Favours

control

Slide26

What do the Guidelines say about extended-duration (30-days) anticoagulant prophylaxis after cancer surgery?

Slide27

No good quality studies have been done using unfractionated heparin for extended duration thromboprophylaxis

Guideline Recommendations for

SURGICAL VTE Prophylaxis

ASCO 2013

Pharmacological

thromboprophylaxis

to all patients with malignant disease undergoing

major surgical interventions

Prophylaxis should be commenced preoperatively,

should be continued for at least 7 to 10 days.

Extended prophylaxis with LMWH for up to 4 weeks postoperatively should be considered for patients undergoing major abdominal or pelvic surgery for cancer who have high-risk features such as restricted mobility, obesity, history of VTE, or with additional risk factorsNCCN

Out-of-hospital primary VTE prophylaxis is recommended for up to 4 weeks postoperatively (particularly for high-risk abdominal or pelvic cancer surgery patients )ESMO 2011Pharmacological thromboprophylaxis to all cancer patients undergoing major cancer surgerypatients having a laparotomy, laparoscopy, thoracotomy or thoracoscopy lasting >than 30

min,consider

s.c. LMWH for at least 10 days postoperatively.Cancer patients undergoing elective major abdominal or pelvic surgery

should receive in hospital and post-discharge prophylaxis with s.c. LMWH for up to 1 month after surgeryACCP 2012General and abdominal-pelvic surgery patients for cancerHigh risk for VTE/not at high bleeding risk → extended duration, 4 weeks, prophylaxis with LMWH

LDUH, LMWH or mechanical prophylaxisLyman GH, et al. J Clin Oncol. 2013;31:2189-204Streiff MB, et al. JNCCN 2011;9:714–777Madnala M, et al. Annals Oncology 2011;22 (Supplement 6): vi85–vi92Gould, MK, et al. 9th

Chest.

2012;141(2_suppl):e227S-e277S

Slide28

What anticoagulant regimens and doses are approved in Canada for DVT prophylaxis after surgery?

Slide29

Fragmin

(

dalteprain

) Product Monograph; Jan.6, 2014.

Lovenox

(enoxaparin) Product Monograph; Dec. 20, 2013.

Innohep (

tinzaparin

) Product Monograph; Feb. 3, 2011.

Dosing Regimens for Extended Duration

Thromboprophylaxis VTE in Abdomino-Pelvic Cancer Surgical Patients – Canadian Labeling DrugRegimen

Dalteparin 2500 U 2-4 hours preoperatively and 5000 U once daily thereafter or 5000 U 10-12 hours preoperatively and 5000 U once daily thereafter Enoxaparin 20 mg 2-4 hours preoperatively and 40 mg once daily thereafter or 40 mg 10-12 hours preoperatively and 40 mg once daily thereafterTinzaparin3500 IU SC 2 hours before surgery followed by 4500 IU once daily

Slide30

Considerations in Urology Patients

Slide31

VTE in Patients Undergoing Urological Procedures

VTE is

Among the most common causes of non-surgical death in patients undergoing urologic surgery

Preventable

DVT prophylaxis

has been identified by a number of organizations as a marker of good quality of patient care

Quek

ML, et al.

J

Urol

2006;175:886-90Forrest JB, et al. J Urol 2009;181:1170-7

DVT = Deep vein thrombosis

Slide32

Risk of VTE With Radical Prostatectomy in the SEER Database: 1994–200935,104 patients with nonmetastatic prostate cancer who underwent

radical prostatectomy

30 days after

radical prostatectomy

:

931 (2.7%) VTEs

87 (0.25%) deaths

90 days after radical prostatectomy

:1,112 (3.2%) VTEs 121 (0.3%) deaths

Slide33

Risk of Major Bleeding FollowingUrologic SurgeryThe risk of major bleeding in urologic surgery is derived from the RCTs where urologic surgery was included as part of all abdominal-pelvic surgeries where the bleeding risk was shown to be low as in the previous slides.

Tikkinen KA, et al. Syst Rev 2014;3:150

SAME AS SLIDE 22

Bergqvist

D, et al.

N Engl J Med

2002;346:975-80

Rasumssuen

MS, et al.

J

Thromb Haemost 2006;4:2384-90Kakkar VV, et al. J Thromb Haemost 2010;8:1223-9

Slide34

Timing of Major Bleeding and VTE Following All Urologic Surgeries

All urologic surgeries were assessed

The risk of bleeding in urology surgery is transient, within the first few days, however the risk of VTE is progressive over a

3 month period

see following 2 slides

Tikkinen KA, et al. Syst Rev 2014;3:150

Tikkinen

KA, et al.

Syst

Rev

2014;3:150

Slide35

Timing of Major Bleeding Following

All Urologic Surgeries

~75% of the bleeding events occur in the first 2 days and 90% percent of the bleeding events happen during the first week after surgery

Tikkinen

KA, et al.

Syst

Rev

2014;3:150

0

1

2

3

4

0

2040

6080100Post-operative weeksProportion (%) of cumulative riskVTEBleeding

~75%

~90%

2 Days

Slide36

Tikkinen

KA, et al.

Syst

Rev

2014;3:150

Timing of VTE Following All Urologic Surgeries

~70% of VTE events occur in the first month after surgery

0

1

2

3

4

5

6

7

89101112

Weeks since surgery

0

20

40

60

80

100

Proportion (%) of cumulative risk of

VTE at 12 weeks

Slide37

European Association of Urology (EAU) Thromboprophylaxis Guideline Recommendations

The EAU compiled some

thromboprophylaxis

guidelines published in 2017

The panel was made up of urologists, internists, hematologists and clinical epidemiologists

They reviewed the risks of bleeding and venous thromboembolism after a urologic surgery and came up with recommendations

The recommendations for open cancer urologic surgery are outlined here

Tikkinen

KAO, et al.

uroweb.org/guideline/thromboprophylaxis.

March 2017

Slide38

EAU Guidelines: First Step - Risk Stratification

Risk

Likelihood of VTE

Low risk

No risk factors

1×

Medium risk

Any one of the

following:

Age ≥ 75 years

BMI ≥ 35

VTE in 1st degree relative

2×

High

riskPrior VTEAny combination of ≥ 2 risk factors

4×Tikkinen KAO, et al. uroweb.org/guideline/thromboprophylaxis. March 2017

Slide39

Procedure

Risk

Recommendation for pharmacological

prophylaxis*

Strength of Recommendation

Nephrectomy,

open partial

Low - High



Weak

Nephrectomy, o

pen radical

Low - High



WeakRadical nephrectomy with thrombectomy

Low - HighWeak

Open

nephro-ureterectomy

Low - High



Weak

*Based on starting time of the morning after surgery, with optimal duration of

prophylaxis of ~4 weeks post-surgery

Tikkinen

KAO, et al.

uroweb.org/guideline/thromboprophylaxis.

March 2017

EAU Guideline Recommendations– Open Nephrectomy & Other Kidney Procedures for Cancer

Slide40

Procedure

Risk

Recommendation for pharmacological

prophylaxis*

Strength of Recommendation

Open Radical Cystectomy

Low - High



Strong

*Based on starting time of the morning after surgery, with optimal duration of

prophylaxis of ~4 weeks post-surgery

Tikkinen KAO, et al.

uroweb.org/guideline/thromboprophylaxis.

March 2017EAU Guideline Recommendations – Open Radical Cystectomy

Slide41

EAU Guideline Recommendations – Open Radical Prostatectomies

Procedure

Risk

Recommendation for pharmacological

prophylaxis*

Strength of Recommendation

Open without PLND

Low

Mod - High





Weak

Strong

Open with standard PLND

LowMod - High

WeakStrongOpen with extended PLNDLow - High



Strong

*Based on starting time of the morning after surgery, with optimal duration of

prophylaxis of ~4 weeks post-surgery

PLND = Pelvic lymph node dissection

Tikkinen

KAO, et al.

uroweb.org/guideline/thromboprophylaxis.

March 2017

Slide42

Procedure

Risk

Recommendation for pharmacological

prophylaxis*

Strength of Recommendation

Primary Nerve-sparing Retroperitoneal Lymph Node Dissection

Low - High



Weak

*Based on starting time of the morning after surgery, with optimal duration of

prophylaxis of ~4 weeks post-surgery

Tikkinen

KAO, et al.

uroweb.org/guideline/thromboprophylaxis.

March 2017EAU Guideline Recommendations – Open Primary Nerve-sparing Retroperitoneal Lymph Node Dissection

Slide43

EAU Guideline RecommendationsFor open urologic cancer surgery there were no deviations from the ACCP guidelines or any other major guidelines that

thromboprophylaxis

for four weeks with low-molecular-weight heparin is required after surgery

Thromboprophylaxis

for other urologic procedures was also addressed this guideline, but would be empiric

Tikkinen

KAO, et al.

uroweb.org/guideline/thromboprophylaxis.

March 2017

Slide44

Additional Considerations Reflected on the EXTEND Order Set: Renal Impairment, Obesity & Concomitant Medications

Slide45

Renal Impairment:Product Monographs

Fragmin

(Dalteparin)

1

Lovenox

(Enoxaparin)

2

Innohep

(Tinzaparin)4Use in CautionFRAGMIN should be used with caution in patients with renal insufficiency.LOVENOX should be used with caution in patients with renal insufficiency.INNOHEP should be used with caution in patients with moderate to severe renal impairment.Dosing for ThromboprophylaxisConsideration of dosage adjustment of Fragmin in patients with severe renal impairment should be undertakenLovenox dosage should be reduced in patients with severely impaired renal function.Dosage adjustment was not recommended for prophylaxis

Fragmin® (Dalteparin Sodium Injection) Product Monograph. March 2016.Lovenox® (Enoxaparin sodium) Product Monograph. July 2014..Innohep® (tinzaparin sodium) Product Monograph. March 2016.

Slide46

Obesity: Altered Drug Distribution and Metabolism in Obese PatientsObesity is an independent risk factor for VTE

Bariatric surgery is an effective weight loss strategy in the morbidly obese (BMI > 40 kg/m

2

) and can significantly improve

health outcomes

Data on dosing for

thromboprophylaxis

in obesity is not of

high qualityObesity has been associated with increased clearance and altered volume of distribution of low-molecular-weight heparinsFunctional and structural renal changes and glomerular hyperfiltration

in obesity  increases glomerular filtration by up to 51% and renal plasma flow by up to 31%

Patel JP, et al. Br J Haematol. 2011;155:137-49

Slide47

Obesity: Altered Dosing May be Requiredin Obese Patients

Pharmacokinetic study

28 morbidly obese (BMI ≥ 35 kg/m

2

), medically ill patients

Enoxaparin 0.5 mg/kg sc once daily

Peak anti-

Xa

levels measured ~4–6 hours after each doseAverage daily dose 67 mgAverage peak anti-Xa level 0.25 units/mLPeak anti-

Xa levels did not significantly correlate with weight or BMINo bleeding events, symptomatic VTE, or significant thrombocytopeniaIncreased dosing in the obese was associated with no increase in bleeding events and no symptomatic VTE, suggested that their weight-based regimen is safe and effective

Rondina MT, et al. Thromb Res 2010;125:220-3.

Slide48

Concomitant MedicationsThere is no good data to show that antiplatelet therapy provides thromboprophylaxis for this group of patients

post surgery

The use of aspirin,

clopidogrel

or other non-steroidal anti-inflammatory drugs post-surgery

is not a contraindication

to the use of standard thromboprophylaxis

Gould, MK, et al..

Chest

2012;141(2_suppl):e227S-e277S

Slide49

Practical Considerations

Slide50

Practicalities of Implementing Extended Duration Thromboprophylaxis

Discharge Pathway:

How does the patient get coverage of the drug?

Private Insurance or

Government coverage (by a Government Drug Card) or

Compassionate coverage or

If a patient does not qualify for any of the above then they

pay out of pocket

Slide51

Practicalities of Implementing Extended Duration Thromboprophylaxis Discharge Pathway:

How does the patient administer the drug?

The patient is taught to inject

If the patient is unwilling/unable to inject, then a family member is taught

If patient and family are unable to, then a referral is sent to the community nurse

Slide52

Extended Thromboprophylaxis after Abdomino-Pelvic Surgery Patient Order set

This order set was designed for the point of discharge, but may also be used immediately post-op

Slide53

Extended Thromboprophylaxis after Abdomino-Pelvic Surgery Patient Order set

Slide54

Extended Thromboprophylaxis after Abdomino-Pelvic Surgery Patient Order set

Slide55

EntryPoint View

Slide56

Patient Handout

Slide57

Clinical CaseA 65

yr

old obese man has stage 1 adenocarcinoma of

the colon

His weight is 125kg

He has a WCC of 15, Hemoglobin of 95, MCV of 76 and platelets of 490

He undergoes a 1hr 20 min laparotomy surgery and the surgeon and pathologist are confident that the entire mass was resected

He is admitted to the floor and is expected to remain admitted for 5 days

He has a low risk of bleedingHe is on metformin and aspirin 81 mg orally daily

for diabetes mellitus type II

Slide58

Clinical CaseWould he be a candidate for

thromboprophylaxis

with low-molecular weight heparin?

Yes

No

Don’t know

Slide59

Clinical CaseWould he be a candidate for

thromboprophylaxis

with low-molecular weight heparin?

Yes

No

Don’t know

A.

Yes. Because he is admitted, he would require

thromboprophylaxis

. His other indication would be a patient over the age of 40 yrs with surgery lasting > 1 hour

Slide60

Clinical CaseYou decide that he will receive

thromboprophylaxis

with enoxaparin. What dose should he receive?

30 mg s.c. daily

40 mg s.c. daily

60 mg s.c. daily

40 mg

s.c.

2x daily

120 mg s.c. daily

Slide61

Clinical Case

You decide that he will receive

thromboprophylaxis

with enoxaparin. What dose should he receive?

30 mg s.c. daily

40 mg s.c. daily

60 mg s.c. daily

40 mg

s.c. 2x daily120 mg s.c. daily

Because of his weight of 125kg, his enoxaparin dose could be increased to:C. 60 mg (or up to 80 mg)

sc once daily ORD. up to 40 mg twice daily

Slide62

Clinical CaseFor how long should he receive thromboprophylaxis

?

5 days

7 days

10 days

Till discharge

28 days

Slide63

Clinical CaseFor how long should he receive

thromboprophylaxis

?

5 days

7 days

10 days

Till discharge

28 days

E.

28 days. Because he has had open abdominal surgery for cancer, he requires 28 days of thromboprophylaxis with a low-molecular-weight heparin despite being on aspirin.

Slide64

A Canadian Resource…

Slide65

Concise Clinical Guides

Slide66

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Slide67

Summary: Extended Duration Thromboprophylaxis VTE in Abdomino-Pelvic Cancer Surgical Patients

VTE Post Surgery is More Common in Cancer Patients than Non-Cancer Patients

VTE is associated with Worse Survival in Cancer patients than Non-Cancer Surgical Patients

Cancer Surgical Patients Continue to have a Significant Proportion of Late VTE Events

When present the bleeding risk is usually transient over days but the thrombotic risk persists up to 3 months

Slide68

Summary: Extended Duration Thromboprophylaxis VTE in Abdomino-Pelvic Cancer Surgical Patients

Extended-duration (30-days) anticoagulant prophylaxis with a low-molecular-weight heparin after Abdominal & Pelvic cancer surgery in high risk patients at low bleeding risk has been shown to be effective and safe

Extended-duration (30-days) anticoagulant prophylaxis with a low-molecular-weight heparin after Abdominal & Pelvic cancer surgery in high risk patients at low bleeding risk has been recommended by the leading guideline bodies on

thromboprophylaxis

Slide69

Summary: Extended Duration Thromboprophylaxis VTE in Abdomino-Pelvic Cancer Surgical Patients

Urologic Surgery cancer patients are also at increased risk of venous thromboembolism extended-duration

thromboprophylaxis

with a low-molecular-weight heparin has been shown to be safe

Reduced dosing is generally recommended for patients with renal failure

Increased dosing may be necessary for obese patients

Order sets/protocols ensure that a large number of patients receive an intervention that is appropriate to that patient