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DA’s Despicable DVT / PE Prophylaxis November 4, 2009 Surgery Rotation Sandra Katalinic Pharmacy Resident

DA’s Despicable DVT / PE Prophylaxis

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DA’s Despicable DVT / PE Prophylaxis. November 4, 2009 Surgery Rotation Sandra Katalinic Pharmacy Resident. Outline. Objectives Patient Profile Presentation Medications Review of Systems Lab Values Disease States Signs and Symptoms Risk Factors Pathophysiology - PowerPoint PPT Presentation

Text of DA’s Despicable DVT / PE Prophylaxis

  • DAs Despicable DVT / PE ProphylaxisNovember 4, 2009Surgery RotationSandra KatalinicPharmacy Resident

  • OutlineObjectivesPatient Profile Presentation Medications Review of Systems Lab Values Disease StatesSigns and SymptomsRisk FactorsPathophysiologyTreatment Options

  • OutlinePharmacy Assessment Drug Related Problems Goals of Therapy Clinical Question Literature ReviewChest Guidelines 1 articleTherapeutic OptionsOutcomeMonitoring

  • Objectives

    Explain the procedure of a hemicolectomy with re-anastomosis List the risk factors for VTEList the symptoms of DVT/PE and diagnostic optionsState the Chest Guidelines DVT / PE prophylaxis recommendation for cancer patients undergoing surgery for their cancer

  • Our PatientDA 57 y/o manAdmitted for right hemicolectomy w/ re-anastomosisThe story:Originally scheduled for knee replacementFound to be anemicColonoscopy revealed GI bleed tumor on splenic flexureSurgery = tumor on hepatic flexureExtended right hemicolectomy w/ lymph nodes

  • Our PatientAllergyNKAPMHHypertension, anemia, hypokalemiaFHFather = HTNSHNon-smoker, well balanced diet, non-coffee drinker, rarely drinks ETOH

  • Home MedsRamipril 10mg PO dailyAtenolol 50mg PO dailyHCTZ 12.5mg PO dailyKCl 600mg PO dailyASA 81mg PO dailyB12 injection once monthly

  • Hospital MedsCefazolin 1g IV on call to ORMetronidazole 500mg IV on call to ORHeparin 5000 units SC BIDAPAP 1000mg PO q6h (ATC)Ibuprofen 60mg PO q6h (ATC)Morphine PCA 2mg/ml Morphine 20 mg PO QID (Post PCA)Morphine 5-10mg SQ q4h prnMorphine 1-5mg IV q4h prnDimenhydrinate IV/IM/PO 25-50mg q4h prnOndansetron 4mg IV q8h prnNaloxone 0.1mg IV prnDiphenhydramine 25-50mg IV/IM/PO q4h prnD5 NS + 20mEq K+/L @ 125cc/hrZopiclone 3.75-7.5mg PO qhs+ Home meds (ramipril, atenolol, HCTZ, ASA)

  • Review of Systems

  • Vitals

  • Labs

  • The Surgery

  • Risk FactorsIncreased agePrevious VTEMajor illness (CHF)Major surgery (general anesthesia >30min)ParalysisObesityTraumaOrthopedic surgeryIndwelling venous catheterGenetic hypercoagulabilitiesEstrogen replacementSERMsHIT

  • Venous ThromboembolismA blood clot which typically forms in lower extremitiesStays there = DVTDislodges to lungs = PECan occur anywhere, typically presents in the lungs or lower extremitiesPresentation differs depending on where the clot is

  • Deep Vein ThrombosisOccurs in the deep veins of the legsSymptoms occur below the clot typically occur in the calfSymptoms: calf pain, swelling, redness, heat10-20% of general surgery patients get DVTDiagnosis: ultrasound, D-dimer, venography

  • Pulmonary EmbolismClot in the pulmonary artery of the lungs or one of its branchesSymptoms: dyspnea, tachypnea, and tachycardia, chest pain, coughHemoptysis < 1/3 of patientsCardiovascular collapse (cyanosis, shock, and oliguria)

  • ComplicationsThe post-thrombotic syndrome: a long-term complication of DVT from damage to the venous valvesSymptoms are similar to an acute thrombotic event: chronic lower-extremity swelling, pain, tenderness, skin discoloration, ulceration.

  • Cancer patientsCancer surgery seems to have at least 2x the risk of postoperative DVT and >3x the risk of fatal PE than similar procedures in non-cancer patientsTumor cells secrete pro-coagulants activate coagulation cascade and suppress levels of protein C, S and antithrombin

  • PreventionPost operatively:Low molecular weight heparinUnfractionated heparinFondaparinux

    All considered equally efficacious by the Chest Guidelines

  • DRPs

  • DRPs

  • DRPs

  • Goals of TherapyPrevent development of PE / DVTSOB, chest pain, cough, calf pain, swelling, feverPrevent long term complications Recurrent VTE, post-thrombotic disorderMaintain mobility (as before surgery)Minimize / prevent side effectsBleeding, bruising, HIT

  • PICO questionsP = 57 year old male with newly discovered colon cancer who has undergone a right hemicolectomy for cancer treatmentI = unfractionated heparin (UFH) regimen C = Low molecular weight heparin (LMWH) regimenO = post-operative DVT/PE prophylaxis?

    In a 57 y/o male with newly discovered colon cancer who has undergone a right hemicolectomy for cancer treatment, what is the recommended regimen for DVT/PE prophylaxis with either LMWH or UFH?

  • 2008 Chest Guidelines2.1.3. For higher-risk general surgery patients who are undergoing a major procedure for cancer, we recommend thromboprophylaxis with LMWH, LDUH three times daily, or fondaparinux (each Grade 1A)

    What is the evidence behind this?

  • Study #1Low molecular weight heparin for the prevention of venous thromboembolism after abdominal surgery.

    Bergqvist D. British Journal of Surgery 2004; 91: 965974.

  • Study #116 comparative studies published between 1980-2003Search: heparin, surgery, abdominal or rectal or colorectal or rectum or colon, clinical trialsEvaluated general abdominal surgery, surgery in patients with abdominal surgery, colorectal surgery

  • Study #1Surgery in patients with abdominal cancer:Multiple studies demonstrating therapeutic equivalence of UFH and LMWHTID dosing of UFH = LMWH daily or BID enoxaparin & nadroparin studiedHigher dose LMWH is >effective than low dose (5000 units vs. 2500 units dalteparin) w/ no increased bleeding complicationsHypercoagulable state in cancer?

  • Study #1Additionally, this study claimsColorectal surgeries carry ++ VTE risk (30%) and 4x risk for PE (compared to?)

  • Study #2A Randomized Study Comparing the Efficacy and Safety of Nadroparin 2850 IU (0.3 mL) vs. Enoxaparin 4000 IU (40 mg) in the Prevention of Venous Thromboembolism after Colorectal Surgery for Cancer

    Simonneau G. et al. Journal of Thrombosis and Haemostasis. 2006; Vol 4: p. 16931700.

  • Study #2950 patients randomized to receive Nadroparin 2850 units SC once daily + enoxaparin placeboEnoxaparin 4000 units SC once daily + nadroparin placeboResultsNon-inferiority was not established (power?)Nadroparin asymptomatic distal DVT symptomatic DVT or PE, anemia, profuse peri-operative bleed, post-operative transfusions, total transfusions Study concluded: nadroparin = attractive option for colorectal cancer surgery

  • Therapeutic OptionsUnfractionated heparinEqually as efficacious as LMWHCheaper than other alternativesCurrently in hospital = can be monitored as required

    Low molecular weight heparin


  • Risk Vs. BenefitClotting RiskCancerColorectal surgery / surgery in generalImmobility post-opAdvanced age (>40)

    Bleed riskCancer surgeryIbuprofen + ASA (no hx of ulcer / GI bleed)

  • MonitoringLow molecular weight heparinSx of DVT leg pain, swelling, rednessSx of PE chest pain, SOB, cough, feverBleeding / bruisingHemoglobin, plateletsHIT (drop in platelets >50% or count
  • OutcomeRecommended heparin 5000 units SC TIDSuggest consider d/c ibuprofen if concerned about bleed riskResident took my recommendationPatient completed hospital stay (10 days) without symptoms of DVT/PE or bleedDVT/PE usually occur in first 2 weeks post-op risk continues up to 3 months

  • Duration of therapyFor selected high-risk general surgery patients, including some of those who have undergone major cancer surgery or have previously had VTE, we suggest that continuing thromboprophylaxis after hospital discharge with LMWH for up to 28 days be considered (Grade 2A).

  • ReferencesFirst Consult - http://www.mdconsult.com/das/pdxmd/lookup/168950262-2?type=medDiPiro JT. Et al. Pharmacotherapy: A Pathophysiologic Approach 7th Ed. McGraw Hill. New York. 2008; p. 331.370Chest Guidelines The Perioperative Management of Antithrombotic Therapy. Chest. 2008; 133: p.299S-339S.Bergqvist D. Low molecular weight heparin for the prevention of venous thromboembolism after abdominal surgery. British Journal of Surgery 2004; 91: 965974.A Randomized Study Comparing the Efficacy and Safety of Nadroparin 2850 IU (0.3 mL) vs. Enoxaparin 4000 IU (40 mg) in the Prevention of Venous Thromboembolism after Colorectal Surgery for Cancer. Simonneau G. et al. Journal of Thrombosis and Haemostasis. 2006; Vol 4: p. 16931700.Comparison of a Low Molecular Weight Heparin and Unfractionated Heparin for the Prevention of Deep Vein Thrombosis in Patients Undergoing Abdominal Surgery. The European Fraxiparin Study (EFS) Group. British Journal of Surgery. 1988; Vol 75(11): 1058-1063.

    WBC 4-10 x 109/LHgb 140-180g/LMCV 82-100 fLPlatelet 230-380x106Na 135-148mmol/LK 3.5-5.0 mmol/LCl 98 107mmol/LCrCl Previous VTE is strongest risk factor because of possible valve damage and obstruction of blood flow from previous eventRapid blood flow has an inhibitory effect on thrombus formation, but a slow rate of flow reduces the clearance and dilution of activated clotting factors in the zone of injury and slows the influx of regulatory substances.Activated protein C degrades factor Va and VIIIa which promote thrombin activation via Factor XaFactor V Leiden a genetic variant of factor V which is cofactor for X to activate thrombin degraded by protein CProtein S cofactor to protein Cexcessively high concentrations of factors VIII, IX, and XI also increase the risk of VTE.Tumor cells secrete pro-coagulants activate coagulation cascade and suppressed levels of protein C, S and antithrombinestrogens increase serum clotting factor concentrations and induce activated protein C resistance

    Deep veins = femoral, popliteal, tibial, peroneal veins of the legD-dimer is a degradation product of a fibrin blood clot and levels of D-dimer are significantly elevated in patients with acute thrombosis. Although the D-dimer test is a very sensitive marker of clot formation, it is not sufficiently specific. A variety of conditions can cause elevations of serum D-dimer, including recent surgery or trauma, pregnancy, and cancer. Therefore, a negative test can help to rule out a DVT or PE but a positive test should not be used to rule in the diagnosis

    Common causes: DVT, which may be symptomatic or clinically 'silent'; >95% arise from proximal deep veins of the lower extremities Immobilization/paralysis (bedridden, stroke, or intensive care patients) Major surgery/trauma Presence of malignant disease or cancer chemotherapy Oral contraceptives (particularly in smokers over 35 years of age), pregnancy (particularly if on bed rest), postpartum Obesity Indwelling central venous catheters

    Wells Clinical Prediction Rule Scores for pulmonary embolism:Clinical symptoms of DVT: 3 Other diagnosis less likely than pulmonary embolism: 3 Heart rate greater than 100 beats per minute: 1.5 Immobilization or surgery within past 4 weeks: 1.5 Previous DVT or pulmonary embolism: 1.5 Hemoptysis: 1 Malignancy: 1

    antithrombin degrades VIIa, IXa, Xa, XIa, XIIa and thrombin (IIa)Prospective, randomized, double blind, double dummy parallel group multicenter trialsMonitoring: bleeding, aPTT, HITSurgical andother invasive procedures associated with a high bleedingrisk include: coronary artery bypass or heart valvereplacement surgery25,26; intracranial or spinal surgery27;aortic aneurysm repair, peripheral artery bypass,and other major vascular surgery; major orthopedicsurgery, such as hip or knee replacement28; reconstructiveplastic surgery29; major cancer surgery; and prostateand bladder surger65,54,63,64,72