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VTE PROPHYLAXIS IN ONCOLOGY OUTPATIENTS
Steering CommitteeMarc Carrier, MD, M.Sc., FRCP(C) • Jay Easaw, MD, PhD, FRCP(C)
• Sudeep Shivakumar, MD, M.Sc., FRCP(C)
OncologistsScott Berry, B.Sc., MD, MHSc., FRCP(C) Norman Blais, MD, M.Sc., FRCP(C)Neil Chua, MD, FRCP(C) Christine Cripps, MD, FRCP(C) Robert El-Maraghi, MD, FRCP(C) Petr Kavan, MD, FRCP(C)Philip Kuruvilla, MD, FRCP(C) Dorothy Lo, MD, FRCP(C)Matilda Ng, MD, FRCP(C)Yasmin Rahim, MD, FACP, FRCP(C) Sandeep Sehdev, MD, FRCP(C), BC(ABIM)Denis Soulieres, MD, FRCP(C)Catherine Sperlich, MD, FRCP(C)Srikala Sridhar, MD, FRCP(C) Elizabeth Strevel, MD, FRCP(C)Sunil Verma, MD, MSEd, FRCP(C)Jonathan Wilson, MD, FRCP(C)Pawal Zalewski, MD, FRCP(C)
HematologistsPeter Gross, MD , M.Sc., FRCP(C)Jeannine Kassis, MD, FRCP(C)Alejandro Lazo-Langner, MD, M.Sc., FRCP(C)Anne McLeod MD, M.Sc., FRCP(C)Vicky Tagalakis, MD, M.Sc., FRCP(C)Axel Tosikyan, MD, FRCP(C)
Oncology NursesKristine Frandsen, RN Krista Neubauer, RN, BSNKelly Savage RN, CNS, LNS, CONC
Oncology PharmacistsDarryl Boehm, B.Sc. (Pharm)Amine Bouziane, B. Pharm, M.Sc.Carlo De Angelis, PharmD Dominique Duquette, B. PharmKimberly Kuik, B.Sc. (Pharm)Josee Martineau, B.Pharm, M.Sc. BCPSSharon Meeke, B.Sc. (Pharm) Colleen Olson, B.Sc. (Pharm)Jack Seki, RPh, B.Sc. (Pharm), PharmDLaura Wilcock, RPh, B.Sc. (Pharm)
SHARED CARE GUIDELINES
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
Patient-related factors• Increasedage• Ethnicity(riskincreasedinAfrican
Americans)• Co-morbidities(infection,renal
and pulmonary disease, arterial thromboembolism, VTE history, inherited prothrombotic mutations
• Obesity• Performancestatus
Cancer-related factors• Primarysiteofcancer• Stage(riskincreaseswithhigherstage)• Comorbidconditions• Histology• Timesincediagnosis(riskincreasesduring
first3-6months)
Treatment-related factors• Chemotherapy,antiangiogenesisagents,
hormonal therapy• Radiationtherapy• Surgery≥60mins• Erythropoiesis-stimulatingagents(ESAs),
transfusions• Indwellingvenousaccess
Biomarkers• Platelets≥350x109/L• Leukocytecount>11x109/L• Hemoglobin<100g/L
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
•IncidenceofVTErangesfrom4-20%•4-to6-foldincreasedriskforVTEvs.non-cancerpatients•3-foldincreasedriskforrecurrenceofVTEvs.non-cancerpatients•4to13timeshigherrateofVTEinthosewithmetastaticdiseaseascomparedwiththose
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
VTE Simplified Oncology Outpatient Prophylaxis Protocol May 2013 Page 2 of 10
➠➠CANCER VTE
Symptoms of VTE
Assessing Risk for VTE
Symptomsarethesameforcancerpatientsastheyareforpeoplewithoutcancer.
Beyondtherisk factors identified intheKhoranariskassessmentmodel,otherpotential riskfactorsthatshouldbeconsideredinclude:(fromACCPGuidelines2008)
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
• Previousvenousthrombosis• Immobilization• Hormonaltherapy• Angiogenesisinhibitors(i.e.Avastin,thalidomide,lenalidomide)
* Patient groups included in the risk analysis had cancers of: lung, stomach, pancreas, lymphoma, gynecological,andGUexcludingprostate
VTE Simplified Oncology Outpatient Prophylaxis Protocol May 2013 Page 3 of 10
Patient Characteristic Score RISK OF VTE based on score
Site of Cancer•Veryhighrisk(stomach,pancreas)•Highrisk(lung,lymphoma,gynecologic,GUexcludingprostate)
•PlateletCount≥350x109/L •Hb<100g/LoruseofESA•Leukocytecount>11x109/L •BMI≥35kg/m2
Total
2
11111
RISK OF VTE based on score:
•Score0 =0.5%
•Score1–2=2%
•Score≥3 =7%
Patient Characteristic Score
Site of Cancer•Veryhighrisk(stomach,pancreas)•Highrisk(lung,lymphoma,gynecologic,GUexcludingprostate)
•PlateletCount≥350x109/L •Hb<100g/LoruseofESA•Leukocytecount>11x109/L•BMI≥35kg/m2
Total
2
11111
Determine Risk•HighRisk:score≥3&/orother
VTE risk factors•Non-HighRisk:riskscore<3
Indication for VTE Prophylaxis within Guidelines
Canadian Prophylaxis Recommendations
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.
ASCO 201313/ESMO 201114
– Routinepharmacologicthromboprophylaxisisnotrecommendedincanceroutpatients– CliniciansmayconsiderLMWHprophylaxisonacase-by-casebasisinhighlyselected
outpatients with solid tumours receiving chemotherapy– Patientswithmultiplemyelomareceivinglenalidomide-orthalidomide-basedregimens
with chemotherapy and/or dexamethasone should receive thromboprophylaxis witheitheraspirinorLMWHforlower-riskpatientsandLMWHforhigher-riskpatients
ACCP 201215
− NoroutineanticoagulationUNLESS• Solidtumor• Presenceofriskfactorsincluding:previousVTE,hormonetherapy,immobilization,
angiogenesis inhibitors, lenalidomide, thalidomide –Ifabovepresent,thenconsiderLMWHorunfractionatedheparin
NCCN 201316
− Thalidomide/lenalidomidepatients,otherwisenoroutinethromboprophylaxis− UtilizingKhoranapredictiveriskmodel:patientswithhighrisk(≥3)COULDBEconsidered
forprophylaxisonanindividualbasisevaluatingrisk/benefitratio
VTE Simplified Oncology Outpatient Prophylaxis Protocol May 2013 Page 4 of 10
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)
•ReassessasappropriateOR•ConsiderthromboprophylaxisifotherVTEriskfactorsexist
^enoxaparindoseadjustmentrecommendedinpatientswithimpairedrenalfunction17
Note:Thereisnoclinicaldatatosupporttheefficacyorsafetyoftheneworalanticoagulantagents(apixaban,dabigatran,rivaroxaban)inoncologypatients.
It is important to review and understand the patient`s risks and possible contraindications to anticoagulation.
• Currentanticoagulationtherapy• Recentbleedingevents–increasesriskforfurtherbleeds• HIT• Bleedingdisorder
VTE Simplified Oncology Outpatient Prophylaxis Protocol May 2013 Page 5 of 10
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
VTE Simplified Oncology Outpatient Prophylaxis Protocol May 2013 Page 6 of 10
Always weigh the benefits vs. risks of anticoagulation. Risk for bleeding is increased in patients with:
•Thrombocytopenia•Moderate-severekidneydysfunction
−almost1/3ofcancerpatientshaverenalinsufficiency,with1in5havingnormalserumcreatininebutloweGFR18
•CurrentantiplatelettherapyChoice of anticoagulant should be guided by best practices with consideration to the following criteria:
•Kidneyfunction•eGFR<30mL/mindoseadjustmentforenoxaparinrecommended nodoseadjustmentneededfortinzaparinordalteparin
•eGFR20-30mL/min:tinzaparin*•Provincialreimbursement/cost^
^OutpatientchoicemayhavefewerrestrictionsasallLMWHshavesimilarcoverageonthemajorityofprovincialformularies.*tinzaparinclearancewasnotshowntobecorrelatedwithCrCl,evenwhentheCrClwasaslowas20 mL/min15.
LMWH isthetherapyofchoiceexceptinthecaseofseverekidneyfailureforVTEpreventionforinpatientsandoutpatients.Thromboprophylaxisshouldcontinueforaminimumof3months,itmaybeextendedif clinically warranted.
Inpatientswithimpairedrenalfunction(<30mL/min):•Dalteparin:nodoseadjustmentisrequired•Enoxaparin:adosageadjustmentisrecommendedsinceenoxaparinappearstoaccumulate
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
•Monitoraspartofstandardchemotherapyprotocol•Reviewinjectiontechniqueateachvisit.Providepatientswithtipstomaximizeinjectionsuccess
Patients should be reassessed as appropriate, and at a minimum of 3 months after initiation of prophylactic treatment.
Patient Education
Information to the patient
VTE Simplified Oncology Outpatient Prophylaxis Protocol May 2013 Page 7 of 10
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
•Symptomsofabloodclot,particularlyDVTorPE•Whattodoifsymptomsaresuspected
•Seekmedicalattention➝ provide clear direction including phone numbers etc.•Purposeofanticoagulationmedication
•Anticoagulantsreducetheamountofclottingtakingplaceinthebloodallowingthebloodtoflowmorefreely.Theyalsopreventtheformationofbloodclotsorpreventexistingbloodclotsfromgrowing
•Therapywillneedtocontinueforseveralmonthstoreducetheriskofdevelopingaclot
•Restrictionswhenonanticoagulationmedication•NodietaryrestrictionswithLMWHs•Alcoholinmoderationonly
•Risksofusing/takinganticoagulationmedication•Increasedriskofbleeding–exercisecautionwithsharpobjects,avoidcontactandhigh-riskphysicalactivities,andavoidusingASA&NSAIDswithoutyourdoctor’spermission
•InformotherHealthcareProfessionals/providersincludingdentiststhattheyareusinganticoagulation.Theremaybeaconcernwithdentalextractions,butreallyonlyifthereare4ormoreextractions
• Bleeding on an anticoagulant/blood thinner is a medical emergency•Bloodclotprevention
•Stayactive•Don’tsmokeorstopsmoking•Maintainanormalbodyweight,ifpossible•Drinkplentyofliquids•Whentravellingwearcompressionstockingsand/orgetupandwalkfrequently
Provide the patient with information about VTE in oncology and their treatment.
References
VTE Simplified Oncology Outpatient Prophylaxis Protocol Mayt 2013 Page 8 of 10
1. AgnelliG,VersoM.Managementofvenousthromboembolisminpatientswithcancer.J Thromb Haemost. 2011;9Suppl1:316-24.
2. Heit JA,et al.Risk factors fordeepvein thrombosisandpulmonaryembolism:apopulation-basedcase-control study. Arch Intern Med.2000;160:809-15.
3. HeitJA,et al. Relativeimpactofriskfactorsfordeepveinthrombosisandpulmonaryembolism:apopulation-based study. Arch Intern Med.2002;162:1245-8.
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.
5. WhiteRH,et al.Incidenceofsymptomaticvenousthromboembolismafterdifferentelectiveorurgentsurgicalprocedures. Thromb Haemost. 2003;90:446-55.
6. Sørensen HT, et al. Prognosis of cancers associated with venous thromboembolism. N Engl J Med. 2000;343:1846-50.
7. LevitanN,et al.Ratesofinitialandrecurrentthromboembolicdiseaseamongpatientswithmalignancyversusthosewithoutmalignancy.RiskanalysisusingMedicareclaimsdata.Medicine(Baltimore).1999;78:285-91.
8. KhoranaAA,et al. Thromboembolism is a leading cause of death in cancer patients receiving outpatient chemotherapy. J Thromb Haemost.2007;5:632-4.
9. Sousou T, Khorana AA. New insights into cancer-associated thrombosis. Arterioscler Thromb Vasc Biol. 2009;29:316-20.
10. KhoranaAA,RaoMV.Approachestorisk-stratifyingcancerpatientsforvenousthromboembolism.Thromb Res.2007;120Suppl2:S41-50.
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.
13. LymanGH,et al.Venousthromboembolism(VTE)prophylaxisandtreatmentinpatientswithcancer:AmericanSocietyofClinicalOncologyClinicalPracticeGuidelineUpdate.J Clin Oncol.2013;accessedonlineaheadofPrint.
14. MandalàM,et al. Managementofvenousthromboembolism(VTE)incancerpatients:ESMOClinicalPracticeGuidelines.Annals of Oncology 2011;22(Supplement6):vi85–vi92.
15. KearonC,et al.AntithrombotictherapyforVTEdisease:AntithromboticTherapyandPreventionofThrombosis,9thed:AmericanCollegeofChestPhysiciansEvidence-BasedClinicalPracticeGuidelines.Chest.2012;141(2Suppl):e419S-94S.
16. Streiff MB, et al.NCCNClinicalPracticeGuidelinesinOncology,VenousThromboembolicDisease.JNCCN 2011;9:714-777;Version2.2013.Updatesaccessedonlineatwww.nccn.org.
17. Lovenox®ProductMonograph.Sanofi-aventisCanadaInc.September28,2010.18. Launay-Vacher V, et al.PrevalenceofRenalInsufficiencyincancerpatientsandimplicationsforanticancerdrug
management:therenalinsufficiencyandanticancermedications(IRMA)study.Med Sci Monit 2004;10:CR209-CR212.
19. MahéO,et al.Tinzaparinandenoxaparingivenatprophylacticdoseforeightdaysinmedicalelderlypatientswith impaired renal function: a comparative pharmacokinetic study. Thromb Haemost.2007;97:581-6.
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:____________________________________
Date:
Time:
VTEOutpatientAssessmentFormandProphylaxisRecommendations
PatientWeight:(kg)____________SiteofCancer____________________________________________
oBaselineCBCoSerumcreatinineeGFR_____mL/min
CurrentCancerTherapyoAngiogenesisinhibitors(e.g.Avastin,thalidomide,lenalidomide)oBiologicalresponsemodifiers(e.g.interferon,Rituxan,Herceptin)oNonspecificimmunomodulatingagents(e.g.5-fluorouracil)
CurrentAnticoagulantTherapy•AnticoagulanttherapyoYesTypeanddose:__________________________________oNo•OralAnticoagulanttherapy(e.g.warfarin,dabigatran,rivaroxaban,apixaban): oYesTypeanddose:__________________________________oNo
eGFR>30mL/min:
Inpatientswithimpairedrenalfunction(<30mL/min):•Dalteparin:nodoseadjustmentisrequired•Enoxaparin:adosageadjustmentisrecommendedsinceenoxaparinappearstoaccumulateinthispatient
group and may increase risk of bleeding.•Tinzaparin:nodoseadjustmentoftinzaparinatprophylaxisdosesisneededinpatientswithimpairedrenal
function19, renal failure20,21, or on hemodialysis20,21
Step 2: Other Risk Factorso Previous venous thrombosisoImmobilizationoHormonaltherapyoAngiogenesisinhibitors(e.g.
thalidomide, lenalidomide)
Investigations:
Thromboprophylaxis Recommendedo Yes oNo–StateReason
VTE RISK
Considerations
Thromboprophylaxis - Low Molecular Weight Heparin
RISK SCOREoHighRisk(score≥3&/orotherVTEriskfactors)oNon-HighRisk(riskscore<3)
Patient Characteristic ScoreSite of Cancer•Veryhighrisk(stomach,pancreas)•Highrisk(lung,lymphoma, gynecologic,GUexcludingprostate)
•PlateletCount≥350x109/L •Hb<100g/LoruseofESA•Leukocytecount>11x109/L•BMI≥35kg/m2
Total
2
11111
➠
Weight Dalteparin Dose Enoxaparin Dose Tinzaparin Dose<40kg 2,500USConcedaily 30USConcedaily 3,500USConcedaily40-100 Tkg 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
VTE Simplified Oncology Outpatient Prophylaxis Protocol May 2013 Page 10 of 10
Contraindications to LMWHs
•Intheprophylaxissetting,mechanicalthromboprophylaxisshouldbeprovidedtoallpatientswithacontraindicationtoLMWHs*Useclinicaljudgmenttoweightheriskofvenousthromboembolismversustheriskofbleeding^enoxaparindoseadjustmentrecommendedinpatientswithimpairedrenalfunction.1,2
1.MahéI,et al. Thromb Haemost.2007;97:581-6;2.Lovenox®ProductMonograph.Sanofi-aventisCanadaInc.September28,2010
Patient Characteristic ScoreSite of Cancer•Veryhighrisk(stomach,pancreas)•Highrisk(lung,lymphoma,gynecologic,GUexcludingprostate)
•PlateletCount≥350x109/L •Hb<100g/LoruseofESA•Leukocytecount>11x109/L•BMI≥35kg/m2
Total
2
11111
•Previousvenousthrombosis•Immobilization•HormonalTherapy•Angiogenesisinhibitors(e.g.
thalidomide, lenalidomide)
Risk •HighRisk:score≥3&/orother
VTE risk factors•Non-HighRisk:riskscore<3
Step 1 Calculate Risk Score
Step 2Consider other VTE Risk Factors
Assess patient for VTE risk using Khorana tool plus considerations of other potential VTE risk factors
Educate patient about VTE risk and prevention options
➠ ➠
ConsiderPharmacologicProphylaxisAnyLMWHatprophylacticdose^
Decision should be guided by contraindicationsAssessrisk:benefitratio*:
thrombocytopenia, mod-severe renal dysfunction, antiplatelet therapy
^enoxaparindoseadjustmentisrecommended in patients with impaired renal function1,2
ReassessasappropriateOr
Considerthromboprophylaxis ifotherVTEriskfactorsexist
Reassessasappropriate,andataminimumof 3 months after initiation of prophylactic
treatment
➠ ➠High RiskIf risk score ≥3 &/or other VTE risk factors
➠ ➠
➠
Absolute Contraindications to LMWHs•Heparininducedthrombocytopenia•Activebleeding•StopLMWHatleast12hoursbeforespinalinvasion;Nextdoseshouldbeheldatleast2hoursafterspinalinvasion
Relative Contraindications to LMWHs•Severethrombocytopenia•Severecoagulopathy•Highbleedingrisk
Non-High RiskIf risk score <3
Recommended