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Factors that may affect Risk for Cancer-Associated VTE
Venous thromboembolism (VTE), which includes pulmonary embolism (PE) and deep vein thrombosis (DVT), represents one of the most important causes of morbidity and mortality in cancer patients. Thromboembolism is the 2nd most common cause of death in ambulatory cancer patients (tied with infections).
The following factors can impact a patient’s risk for cancer-associated VTE.9,10,13
Cancer patients are at a significantly greater risk for developing a blood clot (PE or DVT)compared with patients without cancer.Key Facts in Cancer Patients:1-7
with localized disease•Clinicalratesmayunderrepresentburden;atautopsy,VTEratesareashighas50%
Theunderlyingmechanismsarenotcompletelyunderstood.However,weknow thatcanceris a prothrombotic state, with the activation of the coagulation cascade integrally linked to the processes of tumor growth, metastasis and angiogenesis. Further, chemotherapy can result in activation of coagulation within a few hours of administration through the induction of tissue factor (TF) in tumour cells and monocytes, the downregulation of anticoagulant proteins, damagetovascularendothelium,andplateletactivation.Anti-angiogenicagentsalsocontributeto thrombosis, perhaps through endothelial cell and platelet activation.8
The pathophysiology of cancer-associated thrombosis is likely multifactorial with different factors assuming lesser or greater degrees of importance depending on the patient, the type of cancer and the clinical setting.8
Background
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All cancer patients have an increased risk of VTE. However, routine pharmacologicalthromboprophylaxis is not indicated in cancer outpatients. Evidence suggests that certainpatientshaveahigherriskthanothers.Withthisknowledge,Dr.AlokKhoranaandcolleaguesdeveloped a risk assessment tool to assist with identifying cancer patients at the greatest risk of VTE. This tool was developed from a database of neutropenic patients and has been validated inalmost10,000patients*includingapost-hocanalysiswithintheSAVE-ONCOstudy.11,12
Symptoms of Possible DVT• Recentswellingofonelegorarm• Unexplainedpainortendernessofonelegorarm• Skinmaybewarmtothetouchorisdiscoloured(red,purpleorblue)
Symptoms of Possible PE • Recentorsuddenshortnessofbreathorbreathlessness• Sharpchestpainorupperbackpain,especiallywheninhaling• Light-headednessorcoughingupblood
CurrentInternationalGuidelinesdoprovidesomerecommendationsforthromboprophylaxisinoncologypatientssomeusingtheKhoranaRiskscore.However,whilethereissomeconsensusonthromboprophylaxisofinpatients,thereisnoconsensusonthromboprophylaxisinoncologyoutpatients despite the fact that the risk of VTE remains increased in some cancer patients, even when ambulatory.
AllcancerpatientsshouldbeassesedforVTEriskatthetimeofchemotherapyinitiationandperiodically thereafter. In the outpatient setting, risk is best assessed using a validated riskassessmenttool liketheKhoranatool.ConsiderationshouldalsobegiventootherpotentialVTE risk factors.
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Consider other VTE Risk Factors•Previousvenousthrombosis•Immobilization•Angiogenesisinhibitors(e.g.
thalidomide, lenalidomide)
Step 1: Calculate Risk Score Step 2
Canadian Prophylaxis Recommendations
Contraindications to Anticoagulation
Initiating Anticoagulation
If patient is High Risk (score ≥3 &/or other risk factors)•ConsiderprophylaxiswithaLMWHatprophylacticdose^•Decisionshouldbeguidedbycontraindicationsaswellasrisk:benefitratio
Patients should be reassessed periodically, at least every 3 months, after initiation of prophylactic treatment.If patient is Non-High Risk (score <3)
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Prior to initiating any anticoagulant, the following assessments should be done:•Assessforadditionalmedicalconditions•Determinerenalfunction,bodyweight,knowcoagulopathy•Baselinebloodworkperformed,includingserumcreatinineandCBC•Identificationofcurrentantiplateletoranticoagulantuse(e.g.ASA,Warfarin)
Choosing the Appropriate Anticoagulant
Dosage and Administration
Monitoring / Follow-Up
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Always weigh the benefits vs. risks of anticoagulation. Risk for bleeding is increased in patients with:
in this patient group and may increase risk of bleeding.•Tinzaparin:nodoseadjustmentoftinzaparinatprophylaxisdosesisneededinpatientswith
impaired renal function19, renal failure20,21, or on hemodialysis20,21
LMWH:Weight Dalteparin Dose Enoxaparin Dose Tinzaparin Dose<40kg 2,500USConcedaily 30USConcedaily 3,500USConcedaily40-100 kg 5,000 U SC once daily 40 mg SC once daily 4,500 U SC once daily101-150kg 5,000USCBID 40mgSCBID 10,000USConcedaily151-200kg 40U/kgSCBID 0.40mg/kgSCBID 14,000USConcedaily
Note: There is insufficient clinical data to support the efficacyand safetyof theneworal anticogulant agents(apixaban,dabigatran,rivaroxaban)asprimarythromboprophylacticagentsinoncologypatients.
Anticoagulation monitoring is not needed with LMWHs. However follow-up at specific stages isrecommended to reassess the balance of thrombosis, bleeding and anticoagulation, as well as reassessing anticoagulant dose and duration. Patient weight and kidney function should also be reassessed at follow-up.Follow-up recommendations:
•Bringpatientback,ifpossible,inthefirstweektoensureself-injectionsareproperlyadministered,and to assess for bleeding complications
Patients should be reassessed as appropriate, and at a minimum of 3 months after initiation of prophylactic treatment.
Patient Education
Information to the patient
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Patients/carers need to be educated about VTE risk and the available options to lower the risk. Ifthromoboprophylaxisisinitiatedtheneducationaboutthisnewtherapymustalsobedone.Reviewbenefits/requirementsforthromboprophylaxisaswellasrestrictions/risks.Havepatientorcarerdothefirstinjectionintheclinicwiththeassistanceofclinicnurseorphysician.
Items that should be reviewed with the patient/carer:•Patient’sVTEriskandoptionstolowertheirrisk
•Explainwhyinjectionvs.oralmedication(notecurrentlynoindicationordataforneworal agents in oncology). Patients should be reassessed as appropriate, and at a minimum of 3 months after initiation of prophylactic treatment
4. Prandoni P, et al. Recurrent venous thromboembolism and bleeding complications during anticoagulanttreatment in patients with cancer and venous thrombosis. Blood.2002;100:3484-8.
11. KhoranaAA,et al. Development and validation of a predictive model for chemotherapy-associated thrombosis. Blood.2008;111:4902-7.
12. Agnelli G, SAVE-ONCO Investigators, et al. Semuloparin for thromboprophylaxis in patients receivingchemotherapy for cancer. N Engl J Med.2012;366:601-9.
20. PROTECT Investigators for the Canadian Critical Care Trials Group and the Australian andNew ZealandIntensive Care Society Clinical Trials Group, et al. Dalteparin versus unfractionated heparin in critically ill patients. N Engl J Med.2011;364:1305-14.
21. NutescuEA,et al. Low-molecular-weight heparins in renal impairment and obesity: available evidence and clinical practice recommendations across medical and surgical settings. Ann Pharmacother.2009;43:1064-83.
VTE Simplified Oncology Outpatient Prophylaxis Protocol May 2013 Page 9 of 10HCPName(print):____________________________Signature:____________________________________
Absolute Contraindications to LMWHs•Heparininducedthrombocytopenia•Activebleeding•StopLMWHatleast12hoursbeforespinalinvasion;Nextdoseshouldbeheldatleast2hoursafterspinalinvasion
Relative Contraindications to LMWHs•Severethrombocytopenia•Severecoagulopathy•Highbleedingrisk