Curr Oncol, Vol. 21, pp. 163-164; doi: http://dx.doi.org/10.3747/co.21.2175
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Venous thromboembolism in cancer patients: a call for more awareness A. Delluc md PhD* and M. Carrier md msC
A s elegantly re p o rted by D rs. Shea—B udgell, D onnellan, and colleagues in the last issue o f C urrent O n cology, venous th rom boem bolism ( v t e ) is a frequent clinical problem in cancer patients1,2. T h ro m b o em b o lism is the 2nd leading cause o f death am ong cancer patients and dram atically w orsens cancer prognosis3,4. In can cer p atients ex periencing v t e , overall survival ju s t a q u a rte r o f th at experienced by cancer patients hav in g the sam e tu m o u r type and stage and receiving the sam e an tican cer treatm ent, but not experiencing v t e com plications. T he in creased overall m o rtality associated w ith v t e m ight be caused by postponed sur gical procedures, delayed chem otherapies, VTE-related m o rta lity (for ex am ple, fatal re c u rre n t p u lm o n a ry em bolism ), or m ajor bleeding caused by anticoagulant therapy. To prev en t v t e in h ig h -risk cancer patients, it is therefore im p o rtan t to increase clinical aw are ness am o n g oncology health care professionals and to provide tim ely, effective treatm en t to patients w ith acute cancer-associated throm bosis. To g u ide m ed ical oncologists in the v arious m an ag em en t op tio n s for the prevention an d tre a tm e n t o f v t e in ca n c e r p atien ts, clin ical p ra ctice g u id elin es have b ee n d ev elo p ed by the A m e ric a n S ociety o f C lin ical O ncology, th e U.S. N ational C om prehensive C an ce r N etw o rk , and th e E u ro p ean S ociety o f M ed i cal O n co lo g y 5-7. In th e ir n arrativ e review , Dr. D onn ellan an d co lleag u es su m m a riz e d the ra tio n ale and key re c o m m en d atio n s in th e u p d a te d version o f the A m e ric a n S o ciety o f C lin ica l O n c o lo g y ’s clin ical p ra ctice g u id elin e, en ab lin g clinical application o f th e g u id elin e in ev ery d ay p ra c tic e 1. A s em p h asized in th e review , cancer-specific d ata are available for som e clin ical in d ications (for exam ple, p h a rm a c o logic th ro m b o p ro p h y lax is a fte r cancer-related m ajor ab d o m in al su rg ery ), b u t no t for others (for exam ple, p h arm aco lo g ic th ro m b o p ro p h y lax is in h o sp italized m ed ica lly ill patients). In the latter cases, re co m m en d atio n s h ave to be b ase d on ex trap o latio n s th at u se th e re p o rte d h ig h rates o f efficacy an d low rates h em o rrh ag ic co m p licatio n s fro m clin ical tria ls th at in c lu d e d b o th c a n c e r a n d n o n -c a n c e r p a tie n ts 5,8.
G iven the k n o w n h eig h ten e d risk for bo th v t e and m ajor b leed in g in ca n cer patients, fu rth e r research is d e fin ite ly n e e d e d to a d d re s s th e s e im p o rta n t k n ow ledge gaps. T he ev id en c e-b a sed g u id an ce from Dr. S hea— B u d g e ll a n d c o lle a g u e s g o e s f u r th e r a n d a ls o ad d resses the challenges en c o u n tered in the m a n agem ent o f an tico a g u la tio n in ca n cer p atien ts2. A s h ig h lig h te d in th e ir review , p a tie n ts w ith cancerasso ciated th ro m b o sis are m ore likely to exp erien ce re c u rre n t v t e d espite an tico a g u la tio n or to develop m ajo r b leed in g ep iso d es d u rin g an tico a g u la n t th er apy. F u rth erm o re , ca n c e r p atien ts are m ore prone to un d erg o invasive p ro c ed u re s or to develop th ro m b o c y to p e n ia w h ile a n tic o a g u la te d , w h ic h m ig h t re q u ir e te m p o ra ry in te rru p tio n o f a n tic o a g u la n t th era p y an d u ltim a te ly in cre ase the risk o f b leed in g or re c u rre n t v t e . D esp ite the lack o f g o o d -q u a lity d a ta su p p o rtin g th e v a rio u s m an ag e m en t o p tio n s in th ese ch a lle n g in g clin ical situ atio n s, th e rev iew by Dr. S hea—B udgell an d co lleag u es p ro v id es m uch n ee d ed g u id a n c e to clin ician s. T he S cientific and S tandardization C om m ittee on H aem ostasis and M a lig n an cy o f th e In tern atio n al S ociety on T h ro m b o sis a n d H a em o sta sis also developed e x p e rt co n sen su s m an u scrip ts th at pro v id e g u id an ce ab o u t the v ario u s m an ag e m en t options in th ese d ifficu lt bu t freq u en t clin ical situ atio n s9. F or exam ple, it is su g g ested th at, in ca n c e r patien ts w ith sy m p to m atic re c u rre n t v t e d espite an tico a g u la tio n w ith low m o lecu lar w eight h ep a rin , the h ep a rin dose b e increased by 2 0% —25% . P atients should b e re assessed 5—7 days a fte r dose escalatio n to en su re im p ro v em en t o f sy m p to m s and good tolerance o f the in creased dose. A lthough these e x p e rt co n se n su s re c o m m e n d a tio n s are u sefu l in m an ag in g difficult cases, th e ir ra tio n ale is based on clinical ex p e rtise and sm all cohort stu d ies10,11. L arge pro sp ectiv e studies are d esp erately n eeded to help tailo r the recom m endations co n cern in g m anagem en t o f th ese freq u en t com plications. V e n o u s th ro m b o e m b o lism is a fre q u e n t a n d clinically im p o rtan t issue in cancer patients. C linical
C urrent O ncology— V olume 21 , N umber 4 , A ugust 2014 Copyright © 2014 Multimed Inc. Following publication in Current Oncology, the full text of each article is available immediately and archived in PubMed Central (PMC).
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p ractice g u id elin es and g u id an ce are im p o rta n t to ensure proper prevention and treatm ent o f vte and to help m anage anticoagulation challenges1,2. H ow ever, m ore research is required to optim ize prevention and to tailor m anagem ent strategies in cancer-associated throm bosis.
7.
CONFLICT OF INTEREST DISCLOSURES
8.
The authors have no relevant conflicts o f interest to declare. 9.
REFERENCES 1. Donnellan E, Kevane B, Healey Bird BR Ni Ainle, F. Can cer and venous thromboembolic disease: from molecular mechanisms to clinical management. Curr Oncol 2014;21: 134-143 . 2. Shea-Budgell MA, Wu CMJ, Easaw JC on behalf of the Al berta Venous Thromboembolism Cancer Guideline Working Group. Evidence-based guidance on venous thromboembo lism in patients with solid tumours. Curr Oncol 2014;21: e504-e514. 3. Khorana AA, Francis CW, Culakova E, KudererNM, Lyman GH. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost 2007;5:632-4. 4. Chew HK, Wun T, Harvey D, Zhou H, White RH. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med 2006;166:458-64. 5. Lyman GH, Khorana AA, Kuderer NM, et al. Venous throm boembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2013;31:2189-204. 6. National Comprehensive Cancer Network ( n c c n ). NCCN Clinical Practice Guidelines in Oncology: Venous Throm boembolic Disease. Ver. 1.2011. Fort Washington, PA: n c c n ;
164
10.
11.
2011. [Current version available online at: http://www.nccn. org/professionals/physician_gls/pdf/vte.pdf (free registration required); cited June 14, 2014] Mandala M, Falanga A, Roila F on behalf of the es m o Guidelines Working Group. Management of venous throm boembolism (v te ) in cancer patients: esm o Clinical Practice Guidelines. Ann Oncol 2011;22(suppl 6):vi85-92. Carrier M, Khorana AA, Moretto P, Le Gal G, Karp R, Zwicker JI. Lack of evidence to support thromboprophylaxis in hospitalized medical patients with cancer. Am J Med 2014;127:82-6.el. Carrier M, Khorana A, Zwicker J, Noble S, Lee A on behalf of the Subcommittee on Haemostasis and Malignancy for the ssc of the isth . Management of challenging cases of patients with cancer-associated thrombosis including recurrent thrombosis and bleeding: guidance from the ssc of the isth. J Thromb Haemost 2013;11:1760-5. Carrier M, Le Gal G, Cho R, Tierney S, Rodger M, Lee AY. Dose escalation of low molecular weight heparin to man age recurrent venous thromboembolic events despite sys temic anticoagulation in cancer patients. J Thromb Haemost 2009;7:760-5. Ihaddadene R, Le GG, Delluc A, Carrier M. Dose escalation of low molecular weight heparin in patients with recurrent cancer-associated thrombosis. Thromb Res 2014;:[Epub ahead of print].
C o rresp o n d en ce to: M arc C a rrie r, T he O ttaw a Hospital Research Institute and U niversity o f O t taw a, 501 Sm yth Road, Box 201A, O ttaw a, O ntario K1H 8L6. E -m ail: m carrier@ ottaw ahospital.on.ca * t
D epartem ent de M edecine Interne, U niversity of Brest, Brest, France. D epartm ent o f M edicine, The O ttaw a Hospital Research Institute, University o f Ottawa, Ottawa, ON.
C urrent O ncology— V olume 21 , N umber 4 , A ugust 2014_____________________________________________________ Copyright © 2014 Multimed Inc. Following publication in Current Oncology, the full text of each article is available immediately and archived in PubMed Central (PMC).
Copyright of Current Oncology is the property of Multimed Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
E
D
Venous thromboembolism in cancer patients: a call for more awareness A. Delluc md PhD* and M. Carrier md msC
A s elegantly re p o rted by D rs. Shea—B udgell, D onnellan, and colleagues in the last issue o f C urrent O n cology, venous th rom boem bolism ( v t e ) is a frequent clinical problem in cancer patients1,2. T h ro m b o em b o lism is the 2nd leading cause o f death am ong cancer patients and dram atically w orsens cancer prognosis3,4. In can cer p atients ex periencing v t e , overall survival ju s t a q u a rte r o f th at experienced by cancer patients hav in g the sam e tu m o u r type and stage and receiving the sam e an tican cer treatm ent, but not experiencing v t e com plications. T he in creased overall m o rtality associated w ith v t e m ight be caused by postponed sur gical procedures, delayed chem otherapies, VTE-related m o rta lity (for ex am ple, fatal re c u rre n t p u lm o n a ry em bolism ), or m ajor bleeding caused by anticoagulant therapy. To prev en t v t e in h ig h -risk cancer patients, it is therefore im p o rtan t to increase clinical aw are ness am o n g oncology health care professionals and to provide tim ely, effective treatm en t to patients w ith acute cancer-associated throm bosis. To g u ide m ed ical oncologists in the v arious m an ag em en t op tio n s for the prevention an d tre a tm e n t o f v t e in ca n c e r p atien ts, clin ical p ra ctice g u id elin es have b ee n d ev elo p ed by the A m e ric a n S ociety o f C lin ical O ncology, th e U.S. N ational C om prehensive C an ce r N etw o rk , and th e E u ro p ean S ociety o f M ed i cal O n co lo g y 5-7. In th e ir n arrativ e review , Dr. D onn ellan an d co lleag u es su m m a riz e d the ra tio n ale and key re c o m m en d atio n s in th e u p d a te d version o f the A m e ric a n S o ciety o f C lin ica l O n c o lo g y ’s clin ical p ra ctice g u id elin e, en ab lin g clinical application o f th e g u id elin e in ev ery d ay p ra c tic e 1. A s em p h asized in th e review , cancer-specific d ata are available for som e clin ical in d ications (for exam ple, p h a rm a c o logic th ro m b o p ro p h y lax is a fte r cancer-related m ajor ab d o m in al su rg ery ), b u t no t for others (for exam ple, p h arm aco lo g ic th ro m b o p ro p h y lax is in h o sp italized m ed ica lly ill patients). In the latter cases, re co m m en d atio n s h ave to be b ase d on ex trap o latio n s th at u se th e re p o rte d h ig h rates o f efficacy an d low rates h em o rrh ag ic co m p licatio n s fro m clin ical tria ls th at in c lu d e d b o th c a n c e r a n d n o n -c a n c e r p a tie n ts 5,8.
G iven the k n o w n h eig h ten e d risk for bo th v t e and m ajor b leed in g in ca n cer patients, fu rth e r research is d e fin ite ly n e e d e d to a d d re s s th e s e im p o rta n t k n ow ledge gaps. T he ev id en c e-b a sed g u id an ce from Dr. S hea— B u d g e ll a n d c o lle a g u e s g o e s f u r th e r a n d a ls o ad d resses the challenges en c o u n tered in the m a n agem ent o f an tico a g u la tio n in ca n cer p atien ts2. A s h ig h lig h te d in th e ir review , p a tie n ts w ith cancerasso ciated th ro m b o sis are m ore likely to exp erien ce re c u rre n t v t e d espite an tico a g u la tio n or to develop m ajo r b leed in g ep iso d es d u rin g an tico a g u la n t th er apy. F u rth erm o re , ca n c e r p atien ts are m ore prone to un d erg o invasive p ro c ed u re s or to develop th ro m b o c y to p e n ia w h ile a n tic o a g u la te d , w h ic h m ig h t re q u ir e te m p o ra ry in te rru p tio n o f a n tic o a g u la n t th era p y an d u ltim a te ly in cre ase the risk o f b leed in g or re c u rre n t v t e . D esp ite the lack o f g o o d -q u a lity d a ta su p p o rtin g th e v a rio u s m an ag e m en t o p tio n s in th ese ch a lle n g in g clin ical situ atio n s, th e rev iew by Dr. S hea—B udgell an d co lleag u es p ro v id es m uch n ee d ed g u id a n c e to clin ician s. T he S cientific and S tandardization C om m ittee on H aem ostasis and M a lig n an cy o f th e In tern atio n al S ociety on T h ro m b o sis a n d H a em o sta sis also developed e x p e rt co n sen su s m an u scrip ts th at pro v id e g u id an ce ab o u t the v ario u s m an ag e m en t options in th ese d ifficu lt bu t freq u en t clin ical situ atio n s9. F or exam ple, it is su g g ested th at, in ca n c e r patien ts w ith sy m p to m atic re c u rre n t v t e d espite an tico a g u la tio n w ith low m o lecu lar w eight h ep a rin , the h ep a rin dose b e increased by 2 0% —25% . P atients should b e re assessed 5—7 days a fte r dose escalatio n to en su re im p ro v em en t o f sy m p to m s and good tolerance o f the in creased dose. A lthough these e x p e rt co n se n su s re c o m m e n d a tio n s are u sefu l in m an ag in g difficult cases, th e ir ra tio n ale is based on clinical ex p e rtise and sm all cohort stu d ies10,11. L arge pro sp ectiv e studies are d esp erately n eeded to help tailo r the recom m endations co n cern in g m anagem en t o f th ese freq u en t com plications. V e n o u s th ro m b o e m b o lism is a fre q u e n t a n d clinically im p o rtan t issue in cancer patients. C linical
C urrent O ncology— V olume 21 , N umber 4 , A ugust 2014 Copyright © 2014 Multimed Inc. Following publication in Current Oncology, the full text of each article is available immediately and archived in PubMed Central (PMC).
163
DELLUC and CARRIER
p ractice g u id elin es and g u id an ce are im p o rta n t to ensure proper prevention and treatm ent o f vte and to help m anage anticoagulation challenges1,2. H ow ever, m ore research is required to optim ize prevention and to tailor m anagem ent strategies in cancer-associated throm bosis.
7.
CONFLICT OF INTEREST DISCLOSURES
8.
The authors have no relevant conflicts o f interest to declare. 9.
REFERENCES 1. Donnellan E, Kevane B, Healey Bird BR Ni Ainle, F. Can cer and venous thromboembolic disease: from molecular mechanisms to clinical management. Curr Oncol 2014;21: 134-143 . 2. Shea-Budgell MA, Wu CMJ, Easaw JC on behalf of the Al berta Venous Thromboembolism Cancer Guideline Working Group. Evidence-based guidance on venous thromboembo lism in patients with solid tumours. Curr Oncol 2014;21: e504-e514. 3. Khorana AA, Francis CW, Culakova E, KudererNM, Lyman GH. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost 2007;5:632-4. 4. Chew HK, Wun T, Harvey D, Zhou H, White RH. Incidence of venous thromboembolism and its effect on survival among patients with common cancers. Arch Intern Med 2006;166:458-64. 5. Lyman GH, Khorana AA, Kuderer NM, et al. Venous throm boembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update. J Clin Oncol 2013;31:2189-204. 6. National Comprehensive Cancer Network ( n c c n ). NCCN Clinical Practice Guidelines in Oncology: Venous Throm boembolic Disease. Ver. 1.2011. Fort Washington, PA: n c c n ;
164
10.
11.
2011. [Current version available online at: http://www.nccn. org/professionals/physician_gls/pdf/vte.pdf (free registration required); cited June 14, 2014] Mandala M, Falanga A, Roila F on behalf of the es m o Guidelines Working Group. Management of venous throm boembolism (v te ) in cancer patients: esm o Clinical Practice Guidelines. Ann Oncol 2011;22(suppl 6):vi85-92. Carrier M, Khorana AA, Moretto P, Le Gal G, Karp R, Zwicker JI. Lack of evidence to support thromboprophylaxis in hospitalized medical patients with cancer. Am J Med 2014;127:82-6.el. Carrier M, Khorana A, Zwicker J, Noble S, Lee A on behalf of the Subcommittee on Haemostasis and Malignancy for the ssc of the isth . Management of challenging cases of patients with cancer-associated thrombosis including recurrent thrombosis and bleeding: guidance from the ssc of the isth. J Thromb Haemost 2013;11:1760-5. Carrier M, Le Gal G, Cho R, Tierney S, Rodger M, Lee AY. Dose escalation of low molecular weight heparin to man age recurrent venous thromboembolic events despite sys temic anticoagulation in cancer patients. J Thromb Haemost 2009;7:760-5. Ihaddadene R, Le GG, Delluc A, Carrier M. Dose escalation of low molecular weight heparin in patients with recurrent cancer-associated thrombosis. Thromb Res 2014;:[Epub ahead of print].
C o rresp o n d en ce to: M arc C a rrie r, T he O ttaw a Hospital Research Institute and U niversity o f O t taw a, 501 Sm yth Road, Box 201A, O ttaw a, O ntario K1H 8L6. E -m ail: m carrier@ ottaw ahospital.on.ca * t
D epartem ent de M edecine Interne, U niversity of Brest, Brest, France. D epartm ent o f M edicine, The O ttaw a Hospital Research Institute, University o f Ottawa, Ottawa, ON.
C urrent O ncology— V olume 21 , N umber 4 , A ugust 2014_____________________________________________________ Copyright © 2014 Multimed Inc. Following publication in Current Oncology, the full text of each article is available immediately and archived in PubMed Central (PMC).
Copyright of Current Oncology is the property of Multimed Inc. and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use.
![[Introduction. Venous thromboembolism in cancer patients].](/assets/img/hold.png)
