cancer-associated thrombosis: what you need to know
DESCRIPTION
Cancer-Associated Thrombosis: What you need to know. Anne McLeod. Objectives. To discuss the risk of thrombosis in cancer patients To discuss signs and symptoms of thrombosis To discuss treatment of thrombosis in cancer pts. Why should you care about CAT?. - PowerPoint PPT PresentationTRANSCRIPT
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CANCER-ASSOCIATED THROMBOSIS: WHAT YOU NEED TO KNOW
Anne McLeod
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OBJECTIVES To discuss the risk of thrombosis in
cancer patients
To discuss signs and symptoms of thrombosis
To discuss treatment of thrombosis in cancer pts
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WHY SHOULD YOU CARE ABOUT CAT?
Cancer increases the risk of VTE ~4-7x
Diagnosis of venous thromboembolism (VTE) is associated with worsened mortality and morbidity in patients with cancer
Active cancer accounts for 20% of new VTEs
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VTE IN CANCER PATIENTS
VTE is a major complication of cancer affecting 5-20% of pts
Second leading cause of death
Autopsy rates of VTE in cancer patients~ 50%
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National Hospital Discharge Survey
Stein AJM 2006 119,60-68
827,000 of 40, 787,000 cancer pts also had a diagnostic code for VTE
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CONSEQUENCES OF VTE IN CANCER PTS
Hospitalized cancer pts with VTE have greater inpatient mortality and longer admissions
Risk of fatal PE in cancer surgery is 3X greater than similar noncancer surgery
Khorana JCO 24:484, 2006
Gallus Thromb Haemost 78:126, 1997
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CONSEQUENCES OF VTE IN CANCER PTS
Cancer patients with VTE have increased risk of recurrent VTE, bleeding complications, morbidity and utilization of health care resources
Newer anticancer drugs particularly antiangiogenic drugs more thrombogenic
Khorana JCO 27: 4919 2009
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Fatal PE, Deaths and Bleeding after Cancer Surgery
Haas – Thromb Haemost 2005;94:814
Non-cancer Cancer Outcome (N=16,954) (N=6,124) RR P Fatal PE* 0.09 % 0.33 % 3.7 0.0001 Death 0.7 % 3.1 % 4.5 0.0001 Abn bleeding 0.04 % 0.29% 7.3 0.0001
• double-blind RCT of LDH TID vs certoparin QD
* autopsy-proven
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0 5 10 15 20
100
80
60
40
20
Years after Diagnosis
Surv
ival
, % o
f pat
ient
s
VTE, CANCER AND SURVIVAL
Sorensen - NEJM 2000;343:1846
1- yr survivalCancer at time of VTE 12%Cancer without VTE 36% p< .001
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RISK FACTORS FOR VTE IN CANCER PTS
Patient-related factors• Older Age• Race (> African Americans)• Comorbid conditions (obesity, medical illness)• Prior VTE• Elevated prechemotherapy plt count• Inherited thrombophilia
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RISK FACTORS FOR VTE IN CANCER PTS
Cancer-related factors- tumours can produce procoagulants• Type of cancer
• Initial 3-6 mons after diagnosis
• Metastatic disease
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CANCER AND VTEMETASTATIC DISEASE AND VTEMetastatic Disease increases VTE risk 4-
13X
Incidence of VTE / 100 pt-yr
Pancreas 20.0Stomach 10.7Bladder 7.9Renal 6.0Lung 5.0
Chew et al. Arch Int Med. 2006;166: 458-64
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Levitan Medicine 1999 78:295
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RISK FACTORS FOR VTE IN CANCER PTS
Treatment-related factors• Current hospitalization- lines procedures
immobility
• Active chemotherapy
• Active hormonal therapy
• Antiangiogenic therapy (thalidomide, lenolidomide, becacizumab)
• Erythropoietin stimulating agents
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Volume 25 Number 34 December 1 2007
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ASCO RECOMMENDATIONS #1
Should hospitalized pts with cancer receive anticoagulation for VTE prophylaxis? YES
3 large RCTs in “acute medical pts” ~15% cancer pts
Bleeding complication rate was low
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ARE GUIDELINES BEING USED? ACCP guidelines recommend prophylaxis for
acutely ill hospitalized medical and surgical cancer pts
FRONTLINE Survey in Oncologist 2003 found >50% of oncology surgeons but only 5% of medical oncologists reported use of primary prophylaxis for high risk pts
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Kakkar, A. K. et al. Oncologist 2003;8:381-388
Medical Inpatients
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Service Total no. of patients
(2009) (2010)
No. of pts excluded1
(2009) (2010)
Prophylaxis indicated
(2009) (2010)
AppropriateProphylaxis
(2009)
AppropriateProphylaxis
(2010)
Cardiac Surgery 19 21 6 8 13 13 12 (92%) 12 (92%)Cardiology 37 17 28 10 9 7 3 (33%) 5 (71%)Endocrinology 0 2 NA 0 NA 2 NA 2 (100%)General Medicine 130 146 35 31 95 115 91 (96%) 90 (78%)General Surgery 40 39 7 7 33 32 33 (100%) 30 (94%)Gastroenterology 2 0 0 NA 2 NA 0 (0%) NAGynecology 31 12 17 6 14 6 9 (64%) 6 (100%)Gyne. Oncology 11 7 0 0 11 7 10 (91%) 7 (100%)Neurology 1 0 NA 0 1 NA 1 (100%) NANephrology 10 11 6 4 4 7 0 (0%) 3 (43%)Neurosurgery 19 20 7 7 12 13 10 (83%) 9 (69%)Med. Oncology 36 38 10 15 26 23 14 (54%) 12 (52%)Rad. Oncology 11 17 1 2 10 15 7 (70%) 8 (53%)Ophthalmology 1 0 NA 0 1 NA 0 (0%) NAOrthopedics 75 90 18 20 57 70 55 (96%) 69 (99%)Otolaryngology 4 11 1 7 3 4 3 (100%) 3 (75%)Plastics – Burn 8 10 1 0 7 10 7 (100%) 10 (100%)Plastic Surgery 4 2 1 1 3 1 3 (100%) 1 (100%)Respirology 2 0 1 NA 1 NA 0 (0%) NATrauma 25 21 6 1 19 20 17 (89%) 19 (95%)Urology 12 9 3 1 9 8 5 (56%) 5 (63%)Vascular Surgery 8 13 1 4 7 9 7 (100%) 9 (100%)Combined 486 486 149 124 337 362 287 (85%) 300 (83%)
Table 3: Appropriate Thromboprophylaxis by Clinical Service 1 = includes patients on therapeutic anticoagulants and those for whom thromboprophylaxis was not indicated
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WHERE IS THE LESION? Under recognition of risk factors?
Because many pts are elderly?
Because of the risk of bleeding?
Because of the risk of HIT?
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ASCO RECOMMENDATIONS #2 Should ambulatory pts with cancer receive
anticoagulation for VTE prophylaxis during systemic chemotherapy?
NO
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PREVENTION OF THROMBOEMBOLISM IN CANCERMEDICAL ONCOLOGY PTS
Levine 1994 Stage IV Breast – RRR 85% Hass 2005 TOPIC Breast/Lung -NS Perry 2007 PRODIGE – Gliomas - NS Agnelli 2008 PROTECHT Metastatic Ca- RRR
47%
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Prevention of Thromboembolism in Cancer
Stage IV breast cancer patients receiving CTX Double-blind RCT Very low-dose warfarin: 1 mg x 6 wks INR 1.3-1.9
Placebo WarfarinNo. 159 152Thromboembolism 4.4 % 0.6 % p = 0.03 Major bleeding 1.3 % 0.6 % NSAll bleeding 3.1 % 5.3 % NS
Levine - Lancet (1994)
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PREVENTION OF THROMBOEMBOLISM IN CANCERTOPIC STUDIESAdvanced Cancer on ChemoRxLMWH vs. placebo x 6 months Dopplers q 4
weeks
TOPIC 1- Breast Ca Placebo LMWH pVTE 3.9% 4%Bleeding 0% 1.7%TOPIC 2 - Lung Ca Overall VTE 8.3%
4.5% .07Stage IV VTE 10.1%
3.5% .03Bleeding 2.2% 3.7%
Haas et al J Throm Haemos 2005; 3 (suppl) OR 059
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PREVENTION OF THROMBOEMBOLISM IN CANCERPROTECHT STUDY 2009 OCT;10(10):943-9
Metastatic or locally advanced Ca (lung, gastrointestinal, pancreatic, breast, ovarian, or head and neck) on ChemoRx
RCT double-blind clinical outcome LMWH vs placebo 2:1 randomization while on
ChemoRx maximum 4 months 1,150 pts LMWH 769: Placebo
381 Primary Efficacy Endpoint: Composite of
Venous/Arterial Thromboembolic events- 2% treated vs 3.9% untreated
Safety: Major Bleeding –NS difference
Lancet Oncol. 2009 Oct;10(10):943-9
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ASCO RECOMMENDATIONS #2
Except pts receiving thalidomide or lenolidamide with chemo or dexamethasone should
Studies to identify better markers of increased risk ambulatory pts needed
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ASCO RECOMMENDATIONS #3 Should pts with cancer undergoing surgery
receive perioperative VTE prophylaxis? YES
1) All pts undergoing major surgical intervention for malignant disease should be considered for prophylaxis
2) Patients undergoing laporotomy, laparoscopy or thoracotomy lasting greater the 30 mins
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ASCO RECOMMENDATIONS #33) Prophylaxis should be commenced
preoperatively, or as early as possible in the postoperative period
4) Mechanical methods may be added to pharmacologic methods, but should not be used as monotherapy for VTE prevention unless contraindicated because of active bleeding
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ASCO RECOMMENDATIONS #35) A combined regimen of pharmacologic and
mechanical prophylaxis may improve efficacy
6) Prophylaxis should be continued for at least 7-10 days postop. Consider up to 4 wks in major abdo or pelvic surgery in pts with high-risk features such as residual disease, obese or previous VTE
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ASCO RECOMMENDATION # 4 What is the best treatment for patinets with
cancer and with established VTE to prevent recurrent VTE?
In general LMWH
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ASCO RECOMMENDATION #5
Should patients with cancer receive anticoagulants in the absence of established VTE to improve survival?
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COCHRANE DATABASE SYSTEMATIC REVIEW JULY 2007 Five RCTs (UFH or LMWH)
Heparin associated with a statistically and clinically significant survival benefit (HR=0.77 CI 0.65 to 0.91)
Subgroup analyses: limited small cell lung CA had a clear survival benefit (HR=0.56 CI 0.65 to 0.83)
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ASCO RECOMMENDATION #5 Should patients with cancer receive
anticoagulants in the absence of established VTE to improve survival?
Recommendations:1) NO2) Pts should be encouraged to
participate in trials
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WHY TREAT? To prevent fatal PE
To prevent recurrence
To prevent post-thrombotic syndrome
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TREATING PATIENTS WITH VTE
Does the patient need treatment? Small subsegmental PE? PICC line clots? Is it real? VOMIT Is patient symptomatic- then treat
Lovenox 1.5 mg/kg od or 1 mg/kg bid Check plt count and creatinine clearance may need
dose adjustment in renal dysfunction Weight based dosing even in obese pts
If can’t anticoagulate use TEDS stockings and TE service should assess role of IVC filter
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INCIDENCE OF CVC-RELATED DVT
Rate of thrombosis requiring PICC removal – 3.4% 1.1/1,000 catheter days - no prophylaxis (n=351)
Walshe – J Clin Onc 2002; 20:3276
Symptomatic thrombosis - 4%0.3 /1,000 device days PICCs, Porta- caths, Hickman
catheters – 444 ptsA. Lee - J Clin Onc 2006; 24:1404
Clinically Important CVC-related DVT 2 - 4%
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Preventing Central Venous Catheter Thrombosis in Cancer (RCTs)
Warfarin 1 mg/day
DVT sympt DVT Study Endpoint No. control warf control warfBern, 1990 venogram D90 82 38 % * 10 % 25 % 10 %
Couban, 2002 sympt. DVT 255 NR NR 4 % 5 %
Heaton, 2002 sympt. thromb 88 NR NR 12 % 18 %
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Preventing Central Venous Catheter Thrombosis in Cancer (RCTs)LMWH
DVT Study Endpoint No. control LMWH PMonreal, 1996 venogram Day 90 29 62 % * 6 % 0.002Reichardt, 2002 clinical 425 3.4 % 3.7 % 0.9
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CVC-related Thrombosis in Cancer Pts• Rate of clinically-important symptomatic DVT appears
to have decreased ~ 4%• Rate of thrombosis requiring PICC removal – 3.4%
• Primary prophylaxis with Minidose warfarin or LMWH
appear to NOT be effective nor necessary in general
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ApixabanIdraparinuxRivaroxaban
Dabigatran
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Questions?