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Neuro-Onc SIG Meeting
Venous Thromboembolic Events
Care Strategies for the Neuro-Oncology
Neuro-Onc SIG Meeting
Introduction & Welcome
CEU Presentation:
Venous Thromboembolic Events
Care Strategies for the Neuro-Oncology
III. SIG Meeting
Venous Thromboembolic Events
Care Strategies for the Neuro-Oncology
A Neu-Onc SIG CEU presentation
Mary Elizabeth Davis, RN, MSN, AOCNS
Clinical Nurse Specialist
[email protected]
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, (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
• 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 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
• DVT “classic” calf pain,
redness, tenderness,
• ** 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
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
• 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
• PRODIGE (Prophylaxis Using Dalteparin in
Glioblastoma Multiforme) Trial (Perry et al, 2010)
• Meta-analysis: Aikens, Rivey & Hansen, 2013
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
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
• 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%
• 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
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
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)
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)
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
• 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., (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.
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
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!
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Neuro-Onc SIG Meeting
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CEU Presentation: Venous Thromboembolic Events: Care
Strategies for the Neuro-Onc Patient
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