1. Venous Thromboembolism & Cancer Dr. Rasna Gupta

2. Disclosures: None related to this presentation.

3. Question Which of the following statements is true?
Rate of VTE is 4-13 times higher in metastatic disease compared to those with localized disease.
Cancer patients on chemotherapy has 9 fold risk of developing VTE compared to non cancer patient.
The probability of readmission for recurrent VTE within 6 months is 22% for cancer patients compared to 6.5% for those without malignancy.
Both 1 and 2
All the above.

4. Objectives Understanding Risks.
Thrombo-prophylaxis in cancer patients:
Ambulatory cancer patients, Medical and
surgical patients.
Direct Oral Anticoagulants in Cancer patients.
Management of VTE in cancer patients. .

5. The Risks: VTE occurred significantly more commonly in the cancer patients than in the non-cancer patients
*P < .0001
Incidence of all VTE over 12 months after the initiation of chemotherapy (12.6% vs 1.4%; P <.0001)
Khorana AA, et al. Cancer. 2013;119:

6. Risk Factors for Cancer-Associated VTE
Patient-related
Increased age
Ethnicity
Co-morbidities
Obesity
Performance status
Treatment-related
Chemotherapy, antiangiogenesis agents, hormonal therapy
Radiation therapy
Surgery ≥60 mins
ESAs, transfusions
Indwelling venous access
Bio-markers
Platelet count ≥ 350 x 109/L
Leukocyte count >11 x 109/L
Hemoglobin < 100g/L
Cancer-related
Primary site of cancer
Stage
Histology
Time since diagnosis
Adapted from Lyman GH, et al. ASCO Update. J Clin Oncol. 2013;31:

7. Prognosis
Cancer diagnosed at the same time or within 1 year of an episode of VTE, is associated with an advanced stage and a 3-fold lower survival at 1 year.

8. Thromboprophylaxis in Cancer Patients

9. Ambulatory Oncology Patients on Chemotherapy

10. Patient Characteristic
Risk Assessment
Patient Characteristic
Score
Site of Cancer
Very high risk (stomach, pancreas)
High risk (lung, lymphoma, gynecologic, GU excluding prostate) 2 1
Platelet count > 350 x 109/L
Hb < 100 g/L or use of ESA
Leukocyte count > 11 x 109/L
BMI > 35 kg/m2
Low risk: score=0; Intermediate risk: score=1-2; High risk:score ≥3
Adapted from Khorana AA, et al. Blood. 2008;111(10):

11. Progression-Free Survival and Overall Survival by VTE Risk Category
Outcomes
(at 4 months)
Low Risk
N=1,206
Intermediate Risk
N=2,709
High Risk
N=543
All Patients
N=4,458
Mortality
Risk (%)
1.2%
5.9%
12.7%
5.6%
HR [+/- CI]
1.0
3.56 [ ]
6.89 [ ] -
PFS
93%
82%
72%
84%
2.77 [ ]
4.27 [ ]
Adapted from Kuderer NM, et al. ASH 2008; abstract 172

12. Randomized Trials on VTE Prevention in Out-Patients Receiving Chemotherapy
Study
Duration
VTE (%)
CT+LMWH vs CT
Major Bleeding
QT+LMWH vs QT
Minor Bleeding
NNT
PROTECHT
Lancet Oncology 2009
4 months
2.0% vs 3.9%
*(VTE+ATE)
p=0.02
0.7% vs 0%
p=0.18
7.4% vs 7.9% 53
FRAGEM UK
EJC 2011
12 weeks
3.4% vs 23.0%
RR p=0.002
3.4% vs 3.2%
9.0% vs 3.0% -
CONKO 004
ASCO 2010
6 months
5.0% vs 14.5%
p<0.05
No difference
p=NS NR
12(sVTE)
SAVE ONCO
NEJM 12
Until a change of CT regimen
1.2% vs 3.4%
HR 0.36, p<0.001
1.2% vs 1.2%
1.5% vs 0.9% 46
Heparin vs. no treatment
0.57 ( )
1.06 ( )
1.18 ( )
sVTE:symptomatic VTE
Adapted from Agnelli G. ICHTHIC PL-23, data adapted from Akl EA, Schunemann HJ. N Engl J Med. 2012;366(7):661-2.

13. Illustrative comparative risk (95% CI) No. of participants (studies)
Primary thromboprophylaxis with LMWH significantly reduced the incidence of symptomatic VTE in ambulatory cancer patients treated with chemotherapy
Outcomes
Illustrative comparative risk (95% CI)
Relative effect (95% CI)
No. of participants (studies)
Assumed risk
Corresponding risk
Placebo or no AC
LMWH
Symptomatic VTE
44 per 1000
27 per 1000
RR 0.62 [0.41, 0.93]
2464 (6)
Major bleeding
11 per 1000
18 per 1000
RR 1.57 [0.69, 3.60]
2394 (5)
Symptomatic PE
8 per 1000
5 per 1000
RR 0.63 [0.21, 1.91]
1710 (3)
1-year mortality
503 per 1000
523 per 1000
RR 1.04 [0.92, 1.16]
1848 (4)
This Cochrane review compared the efficacy and safety of LMWHs, vitamin K antagonists (VKAs), and direct thrombin inhibitors with no intervention or placebo in ambulatory patients with cancer.
Conclusion: Primary thromboprophylaxis with LMWH significantly reduced the incidence of symptomatic VTE in ambulatory cancer patients treated with chemotherapy
The risk of overall VTE was reduced by 45% (RR 0.55, 95% CI 0.34 to 0.88; I2 = 0%) whereas there was no statistically significant benefit or harm for asymptomatic VTE, minor bleeding, one-year mortality, symptomatic arterial thromboembolism, superficial thrombophlebitis or serious adverse events (Data and analyses).
Fewer symptomatic VTEs occurred with LMWH thromboprophylaxis in the pooled analysis of 2,400 patients (RR, 0.62;95% CI, 0.41 to 0.99). Rates of major and minor bleeding were not consistently increased with anticoagulation compared with placebo.
None of the studies considered quality of life, heparin-induced thrombocytopenia or the incidence of osteoporosis as study outcomes.
Reference:
Di Nisio M, et al. Primary prophylaxis for venous thromboembolism in ambulatory cancer patients receiving chemotherapy. Cochrane Database Syst Rev Feb 15;2:CD
Based on pooled estimates from six RCTs, LMWH when compared with placebo was associated with a significant reduction in symptomatic VTE (RR 0.62, 95% CI 0.41 to 0.93) which corresponded to a NNT of 60.
Adapted from Di Nisio M, et al. Cochrane Database Syst Rev. 2012;2:CD

14. Guideline Recommendations for Ambulatory Cancer Patients
ASCO
NCCN
ESMO
All cancer outpatients
Routine prophylaxis not recommended
Multiple myeloma patients receiving imid-based regimens
Aspirin or LMWH for low-risk and LMWH for high-risk patients is recommended
Aspirin for low-risk and LMWH or warfarin for high-risk patients is recommended
Consider LWMH, aspirin or adjusted dose warfarin (INR ~2.5)
“High-risk” Outpatients
Consider LMWH prophylaxis on a case-by-case basis in highly select outpatients with solid tumours on chemotherapy
Consider patient conversations about risks and benefits of prophylaxis in Khorana score ≥ 3 population
Consider in high-risk ambulatory cancer patients. Predictive model may be used to identify patients clinically at risk for VTE.
Lyman GH, et al. ASCO Update. J Clin Oncol. 2013;31: ;
Streiff MB, et al. NCCN Clinical Practice Guidelines in Oncology for Venous Thromboembolic Disease. JNCCN 2011;9:714–777;
Madnala M, et al. ESMO Clinical Practice Guidelines. Annals Oncology 2011;22 (Supplement 6): vi85–vi92.

15. Ambulatory Patients at High Risk of VTE
Duration of Therapy
Prolonging anticoagulation reduces VTE event rates, risk of bleeding increases
Reassess as appropriate, and at a minimum of 3 months after initiation of prophylactic treatment
Lyman GH, et al. ASCO Update. J Clin Oncol. 2013;31:

16. Thromboprophylaxis in Oncology Surgical Patients

17. Thromboprophylaxis in Oncology Surgical Patients
No risk assessment needed
Prolonged thromboprophylaxis with LMWH (4 weeks compared to usual 5-7 days) for abdominal or pelvic surgery: Comparison LMWH vs placebo for all VTE
Rasmussen MS, et al. Cochrane Database Syst Rev. 2009;(1):CD

18. Thromboprophylaxis in Oncology Surgical Patients
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.
Comparison: LMWH vs. placebo, Outcome Bleeding complications
Rasmussen MS, et al. Cochrane Database Syst Rev. 2009;(1):CD

19. Thromboprophylaxis in Oncology Surgical Patients
Prophylaxis should be commenced preoperatively and be continued for at least 7-10 days.1
Pre‡-/Peri-operatively
Duration
UFH
5 000 U 2-4 hours preoperatively and once every 8 hours thereafter or 5,000 U hours preoperatively and U once daily thereafter
5-7 days or longer
Dalteparin
2 500 U 2-4 hours preoperatively and U once daily thereafter or 5,000 U hours preoperatively and
5 000 U once daily thereafter
Enoxaparin
20 mg 2-4 hours preoperatively and 40 mg once daily thereafter or 40 mg hours preoperatively and mg once daily thereafter
7-14 days
Tinzaparin
3 500 IU 2-4 hours preoperatively and IU/kg once daily thereafter or IU hours preoperatively and IU once daily thereafter
7-10 days
‡Preoperative prophylaxis is uncommon in Canada.
Adapted from: 1. Lyman GH, et al. ASCO Update. J Clin Oncol. 2013;31: ; 2. VTE Shared Care Guidelines May 2014, accessed from www. vtesimplified.ca.

20. Thromboprophylaxis in Oncology Surgical Patients
Consider LMWH for minimum of 7-10 days . For patients having a laparotomy, laparoscopy, thoracotomy or thoracoscopy lasting >than 30 min.
Data supports prolonged thromboprophylaxis (4 weeks compared with 5-7 days) with LMWH to significantly reduce the risk of VTE in patients undergoing major abdominal or pelvic surgery.
Lyman GH, et al. ASCO Update. J Clin Oncol. 2013;31: ;
Rasmussen MS, et al. Cochrane Database Syst Rev. 2009;(1):CD

21. Thromboprophylaxis in Oncology Medical Patients

22. Prophylaxis in Hospitalized Medical Patients: Risk Reduction
MEDENOX1
14.9
5.5
5.0
2.8
10.5
5.6
P < 0.001
P =
Placebo
Enoxaparin 40 mg
Dalteparin 5,000 units
Fondaparinux 2.5 mg
ARTEMIS3
PREVENT2
RRR
63%
45%
47%
Study Thromboprophylaxis Patients with VTE (%)
Clinical studies show that relative risk (RR) is reduced with thromboprophylaxis.
RR: Relative Risk Reduction
Reference:
Francis CW. Clinical practice. Prophylaxis for thromboembolism in hospitalized medical patients. N Engl J Med. 2007:356;
Adapted from 1. Samama MM, et al. N Engl J Med. 1999;341: ; 2. Leizorovicz A, et al. Circulation. 2004;110:874-9; Cohen AT, et al. BMJ. 2006; 332: ; Francis CW. N Engl J Med. 2007:356; .

23. Guideline Recommendations for MEDICAL VTE Prophylaxis
Guidelines differ, not clear which ones to follow
Guideline Recommendations for MEDICAL VTE Prophylaxis
ASCO 2013
Give pharmacologic thromboprophylaxis to hospitalized patients who have:
active malignancy and acute medical illness or reduced mobility, in the absence of bleeding or other contraindications
Consider pharmacologic thromboprophylaxis in:
hospitalized patients without additional risk factors, in the absence of bleeding or other contraindications.
Not recommended in:
patients admitted for minor procedures or short chemotherapy infusion or in patients undergoing stem-cell/bone marrow transplantation.
NCCN
Recommend VTE prophylaxis in high risk settings
Consider VTE prophylaxis in other outpatients at risk
ESMO 2011
Prophylaxis with UFH, LMWH or Fondaparinux in hospitalized cancer patients confined to bed with an acute medical complication is recommended
Extensive, routine prophylaxis for advanced cancer patients receiving chemotherapy is not recommended, but may be considered in high-risk ambulatory cancer patients
Prophylaxis in cancer patients receiving adjuvant chemotherapy and/or hormone therapy is not recommended
ACCP 2012
Patients at increased risk of thrombosis,
LMWH, LDUH) bid, LDUH tid, or fondaparinux
suggest against extending the duration of thromboprophylaxis beyond the period of patient immobilization or acute hospital stay
Patients at low risk of thrombosis
No pharmacologic or mechanical prophylaxis
ACCP vs. ASCO vs. NCCN guidelines differ, not clear which ones to follow
Lyman GH, et al. ASCO Update. J Clin Oncol. 2013;31: ; Streiff MB, et al. NCCN Clinical Practice Guidelines in Oncology for Venous Thromboembolic Disease. JNCCN 2011;9:714–777; Madnala M, et al. ESMO Clinical Practice Guidelines. Annals Oncology 2011;22 (Supplement 6): vi85–vi92.; Kahn SR, et al. 9th ACCP Guidelines. Chest. 2012;141(2_suppl):e195S-e226S.

24. Guideline Recommendations for Central Venous Catheters Prophylaxis
Guidelines differ, not clear which ones to follow
Guideline Recommendations for Central Venous Catheters Prophylaxis
Incidence of symptomatic CVC-related VTE is 3–4%.
There is no difference between prophylaxis and no prophylaxis.
ASCO 2013
No specific recommendation
NCCN
ESMO 2011
Extensive, routine prophylaxis to prevent CVC-related VTE
is not recommended
Lyman GH, et al. ASCO Update. J Clin Oncol. 2013;31: ;
Streiff MB, et al. NCCN Clinical Practice Guidelines in Oncology for Venous Thromboembolic Disease. JNCCN 2011;9:714–777;
Madnala M, et al. ESMO Clinical Practice Guidelines. Annals Oncology 2011;22 (Supplement 6): vi85–vi92.

25. Medical Patients Thromboprophylaxis options
Lyman GH, et al. ASCO Update. J Clin Oncol. 2013;31:
VTE Shared Care Guidelines May 2014 accessed from

26. Direct Oral Anticoagulants

27. DOACs in VTE Treatment in Cancer Patients: Recurrent Events
Number of patients with active cancer in 5 trials included in analysis was 5.1% of the total patients.
Cancer/Total
Recurrent VTE, %
Major and CRB,%
NOAC
n/N (%)
VKA
Dabigatran1
335/4772
(4.8%)
5.8
7.4
14.5
13.2
Rivaroxaban2
207/3449
(6.0%)
3.4
5.6
14.4
15.9
Rivaroxaban3
223/4832
(4.6%)
1.8
2.8
12.3
9.3
Apixaban4
143/5395
(2.7%) NA
Edoxaban5
771/8240
(9.4%)
3.7
7.1
12.4
18.8
DOAC: direct oral anticoagulant
NOAC: new oral anticoagulant
van der Hulle T, et al. J Thromb Haemost May 12.

28. NOACs in Treatment of CAT
4/28/2017
NOACs in Treatment of CAT
Recurrent VTE:
non-significant difference between NOAC and warfarin
RR 0.67 (0.38 – 1.18)
Major Bleeding:
non-significant difference between NOAC and warfarin
RR 0.85 (0.44 – 1.63)
Dr. Marc Carrier has pooled all this data in a meta-analysis, you can see that there is a non-significant difference between NOAC and warfarin in the risk of recurrent VTE.
For major bleeding, not surprisingly we also find no significant difference between NOACs and warfarin.
Courtesy of M. Carrier.

29. Limitations of DOACS in treatment of CAT
Clinical equipoise compared with warfarin
Not compared to long-term LMWH for treatment
Drug interactions with chemotherapy
Hepatic metastases and renal dysfunction limitations
Unreliable administration and absorption in GI toxicities
Lack of experience
Lee AYY. ICTHIC PL-31.

30. Comments on Use of Direct Oral Anticoagulants in Cancer
Direct oral inhibitors for thromboprophylaxis – reserve for clinical trials until data supports broader clinical use
ASCO 2014 Guidelines don’t recommend use of direct orals in cancer patients at this time in absence of supporting efficacy and safety data

31. Treatment of Thrombosis in Cancer Patients

32. Considerations when Selecting a LMWH for Cancer-Associated Thrombosis: Efficacy
Study
Published
Compara-tor
Efficacy
Safety
CLOT (dalteparin)
Lee AYY et al.
N Engl J Med 2003;
349: 146–153
Warfarin
RR 52%
p=.0017
Any bleed
14% (dalt) vs. 19% (warfarin)
(ns)
LITE (tinzaparin)
Hull RE, et al.
Am J Med 2006; 119(12):
Heparin/
warfarin
RR 66%
P=.044
27% (tinz) vs. 24% (usual care)
Enoxaparin
Merli G, et al.
Ann Intern Med. 2001; 134:
UFH No
Major Bleed
CATCH
(Tinzaprin)
Lee et al, 2015 JAMA
VKA
Risk Reduction 35 %
Clinical relevant bleed. HR-0.58 (Tinzaprarin vs VKA)
CANTHANOX
(enoxaparin)
Meyer G, et al. Arch Intern Med. 2002; 162(15):
No†
7% (enox) vs. 16% (warfarin)
ns: not significant; †no efficacy due to lack of completed phase III study.

33. CLOT Trial: reduction in recurrent VTE Dalteparin vs. Warfarin25
Recurrent VTE (%)
Risk reduction=52%
p=.0017 20 15
Warfarin
OAC
Probability of Recurrent VTE (%) 10 5
Dalteparin 30 60 90
120
150
180
210
Days Post Randomization
LMWH
N=338
Warfarin
N=335 P
Major Bleed
19 (6%)
12 (4%)
0.27
Any Bleed
46 (14%)
62 (19%)
0.093
*P Fishers exact test
Adapted from Lee AYY, et al. N Engl J Med. 2003:349:146–153.

34. LITE Trial: reduction in recurrent VTE Tinzaparin vs. Warfarin20
IV Heparin/Warfarin 15
Cumulative incidence % 10
Tinzaparin 5
100
200
300
Multi-centre randomized, open-label clinical trial using objective outcome measures comparing long-term therapeutic tinzaparin (100 patients) subcutaneously once daily with usual-care long-term vitamin-K-antagonist (100 patients) therapy for 3 months.
Subjects were patients with cancer and acute symptomatic proximal-vein thrombosis. Outcomes were assessed at 3 and 12 months.
At 12 months, the usual-care group had an excess of recurrent venous thromboembolism; 16 of 100 (16%) versus 7 of 100 (7%) receiving tinzaparin (P=.044; risk ratio=.44; absolute difference -9.0; 95% CI, to -0.7).
Bleeding, largely minor, occurred in 27 patients (27%) receiving tinzaparin and 24 patients (24%) receiving usual care (absolute difference -3.0; 95% CI, -9.1 to 15.1).
In patients without additional risk factors for bleeding at the time of randomization, major bleeding occurred in 0 of 51 patients (0%) receiving tinzaparin and 1 of 48 patients (2.1%) receiving usual care. Mortality at 1 year was high, reflecting the severity of the cancers; 47% in each group died.
Hull RD, Pineo GF, Brant RF, Mah AF, Burke N, Dear R, et al. Long-term low-molecular-weight heparin versus usual care in proximal-vein thrombosis patients with cancer. Am J Med. 2006;119(12):
# at risk
IV Hep/War
Cumulative incidence of recurrent venous thromboembolism in the cancer groups
At 12 months: 7 of 100 patients (7%) in the tinzaparin group and 16 of 100 patients (16%) in the heparin-warfarin group had new episodes of symptomatic venous thromboembolism (p=0.044; RR=0.44; absolute difference, -9.0, 95% CI:-2.17 to -0.7%).
Adapted from Hull RE, et al. Am J Med. 2006;119(12):

35. CANTHANOX Trial: Reduction in Recurrent VTE Enoxaparin vs. Warfarin
Recurrent VTE or major hemorrhage during the 3-month treatment period
Randomized, open-label multicenter trial in cancer patients – study closed prematurely
Warfarin associated with a high bleeding rate in patients with VTE and cancer
Prolonged treatment with enoxaparin may be as effective as warfarin and may be safer in these cancer patients
P = .04
Meyer G, et al. Comparison of Low-Molecular-Weight Heparin and Warfarin for the Secondary Prevention of Venous Thromboembolism in Patients With Cancer. A Randomized Controlled Study. Arch Intern Med. 2002;162(15):
During treatment, 21 patients (29.6%) receiving warfarin (95% CI, 19.3%-41.6%) experienced major hemorrhage or recurrent thromboembolism or died compared with 13 patients (19.4%) receiving once-daily enoxaparin (95% CI, 10.8%-30.9%; P = .17).
Adapted from Meyer G, et al. Arch Intern Med. 2002;162(15):

36. CATCH Trial. Tinzaparin vs Warfarin for Treatment of Acute Venous Thromboembolism in Patients With Active Cancer:  A Randomized Clinical Trial

37. For initial treatment of VTE, LMWH is superior to UFH in reducing mortality
Significant 29% mortality reduction in cancer patients receiving LMWH for acute* treatment of VTE versus those receiving UFH
Forest plot for death in patients with cancer. LMWH indicates low molecular weight heparin; UFH, unfractionated heparin; M-H, Mantel-Haenszel;
95% CI, 95% confidence interval; df, degrees of freedom.
Note: the CLOT and LITE trials assessed long-term LMWH vs. warfarin/UFH
Akl E, et al. Anticoagulation for the initial treatment of venous thromboembolism in patients with cancer. Cochrane Database Syst Rev. 2008;1: CD *
*5-7 days
Akl E, et al. Cochrane Database Syst Rev. 2008;1:CD006649

38. Guideline Recommendations for Treatment of VTE
ASCO
NCCN
ESMO
ACCP
Initial/acute treatment
LMWH is preferred for initial 5-10 d of
treatment in patients with a CrCl >30 mL/min.
LMWH
Dalteparin 200 U/kg OD
Enoxaparin 1 mg/kg BID
Tinzaparin 175 U/kg OD
Fondaparinux OD
APTT-adjusted UFH infusion
LMWH or UFH
In patients with CrCl <25–30 ml), UFH i.v. or LMWH with anti-Xa activity monitoring is recommended
Fondaparinux
Rivaroxaban
Long-term treatment
LMWH is preferred for long-term therapy.
VKAs (target INR, 2-3) are acceptable for long-term therapy if LMWH is not available.
LMWH is preferred for first 6 mo as monotherapy without warfarin in patients with proximal DVT
or PE and metastatic or advanced cancer.
Warfarin mg every day initially with subsequent dosing based on INR value targeted at 2-3.
VKA administered for 3–6 months, at
therapeutic INR 2-3.
Start VKA within
24 h from initiating heparin (UFH or LMWH) administration, continue heparin until INR >2 for 2 consecutive days.
LMWH is preferred for 3 months and extended therapy (cancer patients)
LMWH is preferred over VKA
LMWH or VKA preferred over direct oral anticoagulants
Lyman GH, et al. ASCO Update. J Clin Oncol. 2013;31: ; Streiff MB, et al. NCCN Clinical Practice Guidelines in Oncology for Venous Thromboembolic Disease. JNCCN 2011;9:714–777; Madnala M, et al. ESMO Clinical Practice Guidelines. Annals Oncology 2011;22 (Supplement 6): vi85–vi92; Kearon C, et al. 9th ACCP Guidelines. Chest. 2012;141(2_suppl):e419S-e494S.

39. Guideline Recommendations for Duration of Treatment of VTE
ASCO
NCCN
ESMO
Duration
At least 6 mo duration.
Indefinite anticoagulant if active cancer or persistent risk factors.
Extended anticoagulation with LMWH or VKA may
be considered beyond
6 mo for patients with
metastatic disease or patients who are
receiving chemotherapy.
Minimum 3 mo.
For cancer patients receiving chemotherapy in the
adjuvant setting, a long-term treatment for 6 months with
75–80% (i.e. 150 U/kg once daily) of the initial dose of LMWH
should be adopted [
Lyman GH, et al. ASCO Update. J Clin Oncol. 2013;31: ;
Streiff MB, et al. NCCN Clinical Practice Guidelines in Oncology for Venous Thromboembolic Disease. JNCCN 2011;9:714–777;
Madnala M, et al. ESMO Clinical Practice Guidelines. Annals Oncology 2011;22 (Supplement 6): vi85–vi92.

40. Considerations when Selecting a LMWH for Cancer-Associated Thrombosis: Kidney Function
Dose Adjustments for LMWH
eGFR (mL/min)
Tinzaparin
(innohep®)
Dalteparin
(Fragmin®)
Enoxaparin
(Lovenox®)
>30 NO
20 – 29
NO2
YES‡*
Yes§ -150 IU/kg
once daily
<20
YES*
Studies ongoing
Dialysis
Yes§
Speaker Notes:
It is important that patients with kidney dysfunction receive anticoagulation if needed to prevent or treat VTE.
Choice of anticoagulant should be based on level of kidney function, which will guide choice and dosing, as well as other patient considerations including dosing frequency, administration (sc, IV, oral), monitoring, efficacy, and safety.
More frequent monitoring and management of warfarin may be required in patients with lower kidney function.
Dose Adjustments for LMWH (from Product Monographs):
innohep with renal impairment: consider dose adjustment
Fragmin in cancer patients: 200 IU/kg once sc once daily for first 30 days, then 150 IU/kg sc once daily Fragmin with renal impairment: Consider dose adjustment
Lovenox with renal impairment: dose adjust if CrCl <30 mL/min for DVT ± PE to 1 mg/kg once daily
References:
INNOHEP Product Monograph. LEO Pharma Inc. February 3, 2011.
FRAGMIN Product Monograph. Pfizer Canada Inc. December 15, 2011.
LOVENOX Product Monograph. Sanofi-aventis Canada Inc. September 28, 2010.
*Bioaccumulation possible; Consider dose adjustment
§ Dose adjustment required
Note: LMWHs cannot be used interchangeably, unit for unit with UFH, or with other LMWHs.
ACCP Guidelines; 2. Siguret V, et al. J Thromb Haemost. 2011;9: 966–1972.

41. Thank you.