Neuro-Onc SIG Meeting
Venous Thromboembolic Events
Care Strategies for the Neuro-Oncology
Patient
Neuro-Onc SIG Meeting
I.
II.
Agenda
Introduction & Welcome
CEU Presentation:
Venous Thromboembolic Events
Care Strategies for the Neuro-Oncology
Patient
III. SIG Meeting
Venous Thromboembolic Events
Care Strategies for the Neuro-Oncology
Patient
A Neu-Onc SIG CEU presentation
Mary Elizabeth Davis, RN, MSN, AOCNS
Clinical Nurse Specialist
MSKCC
davism@mskcc.org
Venous Thromboembolic Events
VTE stats:
• Includes PE and DVT
• 3rd most common cardiovascular illness
• Approx 1 million/year in US
• 2/3 result from hospitalization: approx 300K die
• PE - most common preventable cause of hospital
related death
• 2nd leading cause of death in patients with active
cancer (possibly 1st)
Stats Specific for Glioma :
• Semrad, et.al. (2007) -9489 malignant glioma pts
- 7.5% had VTE within first 6mos dx (55% within 2
months post-op)
- Associated with poorer prognosis
-+ VTE = 30% ↑ risk death within 2yrs
• Risk-3-60% first 6 wks after sx then 24% over life (Batchelor &
Byrne, 2006, Jenkins, et. al, 2010, Marras, Geerts & Perry, 2000)
Specific for Glioma Proposed pathophysiology:
• Higher plasma levels of thrombosis associated
biomarkers (D-dimer, lipoprotein A, VEGF, tissue
plasminogen factor(tPA), PAI-1)
• Pathologic specimens: intra-lumen thrombosis
common (distorted vasculature, increased interstitial
pressure)
• Surgical resection make cause release of procoagulant
microparticles into circulation & post-op immobility/
paresis may further contribute
Jenkins, et al., 2010, Sartori, et al,2011)
Consequences of VTE
• Inpatient hospitalization
• Interruption of cancer treatment
• Need for pharmacologic management- chronic anticoagulation
- financial burden
- ↑ risk of bleeding
• ↑ risk of recurrent DVT (PTS)
• ↓ QOL
• ↓ survival
- likelihood of death 2-6x > for patients with
cancer who have VTE
Risk of VTE
• Active cancer Dx
• 4-7x > risk VTE than no Ca
(Aikens, Rivey & Hansen, 2013)
• Hi risk Cas: Pancreatic, gastric,
brain, myeloproliferative
• √ Malignant Gliomas
• Histology: Adeno > SCC
• N/A, but …GBM 5x> other
brain histology (such as AA,
AO) (Brandes et al 1997)
• Metastatic Dx 2x >
local disease
• N/A PBTs- rarely
metastasize outside CNS
• Previous h/o DVT
• ? Patient specific
Risk of VTE
• Cancer treatment
• Surgical procedures
• Chemotherapy
Risk AnalysisChemotherapy Predictive model
(Khorana et.al 2008)
• Glucocorticoids
(Johannesdottir, et al, 2013)
• √ brain tumors
• ↑ risk surgery> 4 hours
• Subtotal resection > total
• Larger tumor size (5cm)
• √ high grade Gliomas
• esp bevacizumab NCCN
5 clinical lab parameters
- site of cancer
- pre chemo plt ct > 350x109 /L
- hgb < 10g/dL (or use ESA)
- leukocyte ct > 11 x 109/L
- BMI > 35kg/m2
• √ brain tumors
Risk of VTE
• Immobility
• √ Gliomas –especially leg
paresis; DVT more likely in
paretic limb (Brandes, et al, 1997)
• ↑ incidence with ↑ age
• √ GBM : peak incidence at 4570 years
• CVC line
• ESA (erythropoiesis
• Not usu applicable for Gliomas
stimulating agent)
• Obesity
• ? Patient specific
Other patient specific risks:
• Cardiovascular risk factors: htn, DM, cigarette smoking, high cholesterol levels
• Genetic risk factors: factor V Leiden, prothrombin gene mutation G20210A, protein C
and S deficiency, and anti-thrombin deficiency
Assessment/ Diagnosis
S/S:
• DVT “classic” calf pain,
redness, tenderness,
swelling
• ** steroids may mask
• Acute PE: dyspnea,
tachypnea, and pleuritic
chest pain- also
apprehension, cough,
syncope, and tachycardia.
Dx: US, VQ scan, CXR, CT
Photo by Dr. James Heilman, used with permission
©2000 by Radiological Society of North America teaching slide
Schoepf U J et al. Radiology 2000;217:693-700
Peri-Op Prophylaxis
Mechanical
compression
Photo by ME Davis, used by permission
• Ruff & Posner 1983; retrospective chart review-postop glioma pts: elastic bandages verses external pneumatic
compression; Incidence clots 25% vs 3%
• Frim et al, 1992: Neurosurgery regimen: compression
boots and low dose heparin: adding heparin sig ↓ VTE
Peri-Op Prophylaxis
• MacDonald, et al 2003: Unfractionated Heparin
vs LMWH with pneumatic compression boots in
craniotomy patients
- No difference in intra-op blood loss, transfusion requirements or
post-op plts counts
- No difference in post-op VTE events, hemorrhage or
thrombocytopenia
• Pan, Tsa & Mitchell, 2009 : retrospective review
of 294 GBM pts with VTE
– 2 % rate ICH: “the benefits of anticoagulation therapy may
outweigh the risk of ICH”
Ambulatory Prophylaxis
• Vena Cava Filters
• prevention of PE for hi risk pts
• Contraindication to anticoag
• Filter does NOT prevent DVT
• Anticoagulation
• PROTECHT (Prophylaxis of thromboembolism during
chemotherapy) Trial (Agnelli et al, 2009)
• SAVE-ONCO (Agnelli, et al 2011), FRAGEM (Marraveyas, et al
2012)
• PRODIGE (Prophylaxis Using Dalteparin in
Glioblastoma Multiforme) Trial (Perry et al, 2010)
• Meta-analysis: Aikens, Rivey & Hansen, 2013
Prophylaxis
ASCO, 2007
• All hospitalized cancer patients should be
considered for prophylaxis in the absence of
bleeding or other comps.
• Routine prophylaxis of ambulatory cancer
pts is NOT recommended except pts on
lenalidomide or thalidomide
• Pts undergoing major surgery for malignant
disease should be considered for
pharmacologic prophylaxis
Prophylaxis
NCCN Guidelines, 2013
• All surgical oncology pts receive
pharmacologic VTE prophylaxis with or
without mechanical prophylaxis for duration
of hospitalization
• if contraindications to anticoag- mechanical
prophylaxis should be used;
• High risk post op patients- extended
duration of prophylaxis up to 4 weeks
Anticoagulation
• Unfractionated heparin (UFH)converting to warfarin
• Low Molecular weight Heparin
(LMWH) :
– Dalteparin - Fragmin®
– Enoxaparain - Lovenox®
– Tinzaparin - Innohep®
• Factor Xa inhibitor:
Fondaparinux- Arixtra®
Clot Trial
Treatment VTE
Lee, et al, 2003
676 pts pt with active Ca and acute VTE randomized
to either
• LMWH (Dalteparin) 200 IU/kg/day x 1mo then ↓ 150
IU x 5months
• LMWH (Dalteparin) 200 IU/kg x 5 days with transition
to oral warfarin
Results: LMWH only arm: 50% reduction in
recurrent VTE (9 vs 17% p= .002) with no
difference in rate of major bleeding (6% vs 4%
p=.27)
• Results repeated and confirmed (Cochrane Review)
• NCCN guidelines recommend LMWH FIRST line for
Ca pts
Treatment VTE
MSK Guidelines: Tx ADULT Acute DVT/PE:
• Enoxaparin (Lovenox®) 1mg/kg SCq 12
(alternatively 1.5mg/kg SC QD)
Patient Weight (kg)
Enoxaparin Dose (mg)
= Syringe Size Used
40-50.9
40
51-70.9
60
71-90.9
80
91-110.9
100
111-140.9
120
141-165
150
>165
Requires hematology consult
Nsg Considerations- VTE
• Pt/family education:
–
–
–
–
–
Pt risk factors, s/s VTE
Promotion of activity as tolerated/ indicated
Medication indication, dose, schedule, SE, self care
Subcutaneous injection technique, needle disposal
When to call & S/S to report
• Monitor for SE, bleeding;
– Special caution LMWH: renal insufficiency, obesity,
LBW/elderly <50kg
– Antiangiogenic therapies
Anti-angiogenic therapy and
Anticoagulation
Limited data- mainly retrospective reviews
• Nghiemphu, Green, Pope, Lai & Cloughesy, 2007
• Norden, Bartolomeo at al, 2011
“Data raises concern about the risks of full anticoagulation
in bevacizumab treated pts, however both VTE and
bleeding are a known risk… (from gliomas) and whether or
not anticoagulation increases this risk to a clinically
significant degree has yet to be shown” (Perry, 2010, pg 595)
References
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•
•
Agnelli, G., George, D.J., Kakkar, A.K. et al (1012) Semuloparin for thromboprophylaxis in
patients receiving chemotherapy for cancer NEJM 366, 601-9.
Agnelli, G., Gussoni, G., Bianchi, C et al, (2009) Nadroparin for the prevention of
thromboembolic events in ambulatory patients with metastatic or locally advanced solid
cancer receiving chemotherapy: a randomised placebo-controlled double blind study.
Lancet Oncology 10 ,943-949.
Aikens, G.B., Rivey, M.P. & Hansen C.J. (2013) Primary Venous Thromboembolism
Prophylaxis in ambulatory cancer patients The Annals of Pharmocology 47, 198-209
Batchelor T.T. & Byrne, T.N. (2006) Supportive care of brain tumor patients. Hematol Oncol
Clin N Am 20 , 1337-1361.
Brandes, A.A., Scelzi, E., Salmistraro, G. et al (1997) Incidence of risk of thromboembolism
during treatment high-grade gliomas: a prospective study. EurJ cancer33, (10) 1592-96.
Frim, D.M., Barker, F.G., Poletti, C.E & Hamilton A. (1992) Postoperative low-dose heparin
decreases thromboembolic complications in neurosurgical patients Neurosurgery 30 (6)
830-833.
Jenkins , E.O., Schiff, D., Mackmanm N. & Key, N.S. (2010) Venous thromboembolism in
malignant gliomas J Thromb Haemost 8 (2) 221-227.
Khorana, A.A., Kuderer, NM., Culakova, E., Lyman, G.H.& Francis, C.W. (2007) Development
and validation of a predictive model for chemotherapy associated thrombosis
References
• Lee, A.Y., Levine, M.N., Baker, R.I. et al (2003) Low-molecular-weight heparin versus a
coumarin for the prevention of recurrent venous thromboembolism in patients with cancer.
NEJM 10;349(2):146-53.
• Lyman, G.H.,et.al (2007) American Society of Clinical Oncology Guideline:
recommendations for Venous Thromboembolism Prophylaxis and treatment in patients
with Cancer. JOC 25( 34) 5490-5505.
• Maraveyas, A., Walters, J., Roy, R. et al (2012) Gemcitabine verses gemcitabine plus
dalteparin thromboprophylaxis in pancreatic cancer Eur J Canc 48, 1283-92.
• Marras, L.C Geerts, W.H, & Perry, J.R (2000) The risk of venous thromboembolism is
increased throughout the course of malignant glioma: an evidence based review Cancer 89
(3) 640-6.
• Nghiemphu, P.L., Green, R.M., Pope, W.B., Lai, A.,& Cloughesy, T.F (2008) Safety of
anticoagulation use and bevacizumab in patients with glioma Neuro-oncology 10: 355-360.
• Norden, A.D., Bartolomeo, J., Tanaka, S….& Wen, P.Y (2011) Safety of concurrent
bevacizumab and anticoagulation in glioma patients J Neuroonc106; 121-125
• Perry, J.R. (2010) Anticoagulation of malignant glioma patients in the era of novel
antiangiogenic agents Current Opinions in Neurology 23: 592-596.
References
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Perry, J.R., Julian, J.A., Laperriere, N.J et al.,(2010)PRODIGE: a randomized placebocontrolled trial of dalteparin low molecular weight heparan thromboprophylaxis in
patients with newly diagnosed malignant glioma J Thomb Haemost 8, 1959-65.
Ruff, R. L. & Posner, J.B. (1983) Incidence and treatment of peripheral venous thrombosis
in patients with glioma Annals of Neurology 13 (3) 334-336.
Sartori, M.T. et al (2010) Prothrombotic state in glioblastoma multiforme: an evaluation
of the procoagulant activity of circulating microparticles J Neuroncol doi
10.1007/z11060-010-0462-8
Semrad , T.J., O’Donnell, R., Wun, T., Chew, H., Harvey, D., Zhou, H & White, R. (2007)
Epidemiology of venous thromboembolism in 9489 patients with malignant glioma J
Neurosurg 106:601–608,
Streiff, M.B (2011) Anticoagulation in the management of venous thromboembolism in
the cancer patient J Thromb Thrombolysis 31; 282-294.
Thank you!
Any Questions?
Neuro-Onc SIG Meeting
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VIX.
Agenda
Introduction & Welcome
CEU Presentation: Venous Thromboembolic Events: Care
Strategies for the Neuro-Onc Patient
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