DVT Prophylaxis in Orthopaedic Surgery - Healthcare Professionals

Robert Probe MDProfessor and ChairmanDepartment of OrthopaedicsScott & White Memorial Hospital

Disclosures• Consulting• Stryker Orthopaedics• Speaking• AO• OTA• AAOS• Boards• Orthopaedic Trauma Association• Scott & White Board of Trustees• Scott & White Memorial Hospital

Danish Knee RegistryYear of surgery1997-1999 40 (0.82%) 1.0 (reference) 1.0 (reference)2000-2003 131 (1.10%) 1.34 (0.89-2.00) 1.35 (0.90-2.02)2004-2007 270 (1.32%) 1.27 (1.05-1.55) 1.28 (1.05-1.57)Age (yr)10-49 15 (0.86%) 1.0 (reference) 1.0 (reference)50-59 66 (1.09%) 1.26 (0.78-2.05) 1.26 (0.76-2.11)60-69 139 (1.15%) 1.33 (0.88-2.01) 1.29 (0.83-2.01)70-79 153 (1.23%) 1.44 (0.93-2.22) 1.40 (0.85-2.33)≥80 68 (1.41%) 1.65 (1.11-2.43) 1.58 (1.01-2.47)Pederson et al, JBJS-A 2011

Post-op?

6 weeks post-op

Your questions:• Why does this happen in trauma?• What is the quantitated risk?• What prophylaxis does this risk justify?• Should we screen?• How long to treat?• What Guidelines are available to direct us?• What do the regulators require?

Virchow’s Triad• Venous stasis• Vascular Injury• Hypercoagulable

FIRST HITTISSUE INJURY

Risk

Low Risk-Age > 40-ISS> 9-transfusion-Lower Extremity Fx-Estrogen therapy-Pregnant-History of DVT-Malignancy-Hypercoaguable-CHFHigh Risk-Age > 50-ISS > 16-Femoral line-AIS >2 (any region)-Pelvis Fx-Femur or Tibia FxVery High Risk-Spinal Cord Injury-Head AIS > 2 and long bone

Risk StratificationCalf Clot Prox Clot Clinical PE Fatal PE ScoreLow 2 .5 .2 .002 1Moderate 15 3 .5 .3 2High 30 6 3 .7 3-4Highest 60 15 7 2.5 >41 pt 2 pt 3 pt5 pt* Minor surgery* Age 41-60* Pregnancy* Varicose veins* Swelling of legs* Obesity (BMI >25)* Oral contraceptives,* Age over 60 years* Major surgery (>45 minutes)* Confined to bed more than 72 hours* Immobilizing cast* Central venous access* Tourniquet time over 45 minutes* History of DVT* Family history* Age over 75 years* CHF, MI, COPD* thrombophilia* Hip, pelvis or leg fracture* Stroke* Multiple trauma* Spinal Cord InjuryChest Guidelines 2004

Other Risk Factors• Obesity• Immobilization• Central Venous Access• Polytrauma• Head Injury• Spinal Cord Injury• Oral Contraceptives• Comorbidities• MI, COPD, CHF• Family History

Oral contraceptive (OCP) use 4Factor V Leiden, heterozygous 6Factor V Leiden, heterozygous + OCP 32Factor V Leiden, homozygous 80Prothrombin Gene Mutation, heterozygous 3Prothrombin Gene Mutation, heterozygous + OCP 16Protein C deficiency, heterozygous 7Protein S deficiency, heterozygous 6Antithrombin deficiency, heterozygous 5Hyperhomocysteinemia 3Hyperhomocysteinemia +Factor V Leiden 20http://www.med.illinois.edu/hematology/PtProtS.htm

Composite Risk• Patient predisposition• Risk of procedure or condition• Risk of bleeding

Prophylaxis

Risk Stratification

Meta Analysis in Pelvic Trauma• Eleven studies• 1760 subjects• Types of interventions:• mechanical compression devices• inferior vena cava filters• low-molecular weight heparins• ultrasound screening• magnetic resonance venography screening.• Most studies were observational designs with minimalcontrol data for comparison.Slobogean, J Ortho Trauma 2009

In the matter of the Matthew Flinders Taverner66. There was one aspect of the evidence of Mr Sherlock upon which theCommission did have some reservations. Mr Sherlock stated that legaladvice had been obtained as to the possibility that the egms at the sub-branchcould be transferred to other RSL venues within the City of Monash, and thatsuch possibilities had been explored but had ultimately come to nothingbecause of problems associated with those sub-branches. The Commissionhas been aware of earlier matters in which a particular sub-branch has ceasedto operate gaming machines and those gaming machines have been removedto another RSL sub-branch which has, thereby, been strengthened as a resultof this exercise. In turn the stronger sub-branch which has received theadditional egms has been able to make a continuing contribution to the subbranchfrom which the egms have been removed.67. Both in the evidence which he gave on his first occasion in the witness boxand when he returned to the witness box subsequently, Mr Sherlock wasquestioned about this. Ultimately we are satisfied that appropriate steps havebeen taken to investigate the possibility that the egms could be transferredwithin the RSL network and that for various reasons this cannot be achieved.One other important aspect of his evidence was the fact that in this instance(unlike approximately 90 per cent of the sub-branches) the RSL does notown the freehold upon which the sub-branch is erected. That freehold isowned by the local council.68. Mr Sherlock was followed by Mr John Poland whose current role is that ofActing General Manager and Secretary of the Oakleigh RSL. He listed anumber of the activities which take place at the sub-branch where the mostattractive old buildings are also used for external purposes such asneighbourhood watch and a mother’s club. The main commercial activity is27

Dalteparin in all high risk traumapatients• Demographics:• 743 were considered at high risk for DVT• mean age of 38.7 years (range 15–89 years)• Mean injury severity score (ISS) of 19.5• Results:• DVT was detected in 3.9%• PE in 0.8%• Wound complications rate was 2.7• There were no exacerbations of head injury followingdalteparin initiation due to bleedingCothren, World Journal of Surgery, 2006

Trauma Studies

Management GuidelineUniversity of Pennsylvania Department of Orthopaedic Surgery

Patients• 4076 blunt eligible blunt trauma patients identified• 233 (5.7%) had Thromboembolic Event• 213 DVT• 31 PE• 20 diagnosed with PE only• 202 diagnosed with DVT only• 11 diagnosed with both DVT & PE• Power of 0.80 and a two sided alpha of 0.05 to detect adifference of 20% in any given parameter between groups• 226 controls selected by picking every 20th blunt traumapatient in the database, then eliminating duplicates with thecase groupUniversity of Pennsylvania Department of Orthopaedic Surgery

Results• Refractory Risk Factors• Pelvic fractures (3.62x)• Major lower extremityinjury (1.83x)• > 3 days mechanicalventilation (8.15x)• Increasing injury severityscore (1.04x)• Spinal cord injury (4.3x)University of Pennsylvania Department of Orthopaedic Surgery

Revised Management GuidelineSCDSCDorornonoDVTDVTprophylaxisprophylaxisNOLMWHRiskRiskfactorsfactors??(A) LMWH++(A) YES SCDSCDHighHighRiskRiskLMWHLMWH++FactorsFactors(B)(B) YESSCDSCDAA..ModerateModerateriskriskfactorsfactors• AgeAge>40*>40*••ISSISS>9*>9*••SurgicalSurgicalprocedureprocedure7272hrs*hrs*••Immobilization*Immobilization*••Pregnancy*Pregnancy*••EstrogenEstrogentherapy*therapy*••HistoryHistoryofofDVTDVTororPE*PE*••Malignancy*Malignancy*••Hypercoagulability*Hypercoagulability*••ExtensiveExtensivesoftsofttissuetissuetrauma*trauma*••CHFCHF**NO+DuplexDuplexofofLELEwithinwithin72 hr then q5-7 days72 hr then q5-7 daysAfterAfterthatthatB.B.HighHighriskriskfactorsfactors••AgeAge>50*>50*••ISS>16*ISS>16*••FemoralFemorallinelineplacedplacedininbay*bay*••GCSGCS/=3) + long bone fracture• Multiple >/= 3 long bone fractures*• Multiple >/= 3 long bone fractures*• Severe pelvic fracture†• Severe pelvic fracture†• Mechanical ventilation longer than 3 days†• Mechanical ventilation longer than 3 days†• Severe LE fracture + ISS >16†• Severe LE fracture + ISS >16†University of Pennsylvania Department of Orthopaedic Surgery

Future Directions• The more effectively a chemoprophylactic reduces DVTincidence, the higher the risk of major bleeds.(Levine et al, 7th ACCP conference, Chest 2004;12:287S)• EAST guidelines recommend LMWH for patients with certaintypes of “severe” orthopaedic trauma. Their recommendations,however, are based on DVT rates.1. Is LMWH really necessary?Recent guidelines by the AAOS suggest that, for lower risk patients, aspirin can be used forDVT prophylaxis.2. Would the incorporation of Aspirin for low risk patients resultin similar VTE rates?University of Pennsylvania Department of Orthopaedic Surgery

Hip Fracture Trial:enoxaparin vs fondaparinux• 1,711 Randomised hip fracture patients• enoxaparin at 40 mg SC qd starting 12h postoperatively,• fondaparinux at 2.5 mg SC qd starting 4h after surgery.• VTE by postoperative day 11• 19.1% enoxaparin• 8.3% fondaparinux• respectively (p 0.001).• Proximal DVT was also• 4.3% enoxaparin• 0.9% fondaparinux• p 0.001).• The improved efficacy with fondaparinux was notaccompanied by more bleeding.Bauer, N Engl J Med 2001

DVT Incidence in Head InjuryPatients• 939 eligible patients 200-2006• Mechanical prophylaxis only• Weekly duplex screening• DVT rates• Overall 32%• Isolated HI 26%• Associated Injury 35%• Independent Risk Factors• Male gender (p = 0.04)• Age >or=55 (p < 0.001)• ISS >or=15 (p = 0.014)• Subarachnoid hemorrhage (p = 0.006)• Lower extremity injury (p = 0.001)Ekeh, J of Trauma 2010

Incidence of DVT with closedtreatment of ankle fractures• 100 patients in the absence of anythromboprophylaxis• Doppler duplex ultrasound scan was doneat the time of the removal of the cast.• Results:• Five patients did develop DVT• None had clinical signs suggestive of it• 2 Proximal lesions• “As the incidence of DVT after anklefractures is low, we do not recommendroutine thromboprophylaxis.Patil, JBJS-B 2007

Prolonged Dalteparin followingankle fracture• double-blind, placebo-controlled study, 272 consecutivepatients were randomized to receive either thromboprophylaxiswith Dalteparin (n = 136) or placebo (n = 136) for 5 weeks afterankle fracture surgery.• All patients received 1 week of initial treatment with Dalteparinbefore randomization.• incidence of DVT was• 21% Dalteparin group• 28% in the placebo• proximal DVTs was• 4% in the Dalteparin group• 3% in the placebo group• “We found no significant difference in the incidence of DVTbetween the 2 treatment groups”Lapidus, Acta Orthop 2007

Operatively treated Achillesrupture: Dalteparin vs placebo• Design:• 105 randomized patients• 5000 u Dalteparin for 6 weeks• Duplex sonography at 3 wk, 6 wk• Outcome• Dalteparin group• 16/47 (34%)• Placebo group• 16/44 (36%)Lapidus et al, J Ortho Trauma 2006

Upper Extremity DVT• 25 year old following cyclingaccident• Tx with figure of 8 dressing• Returns at one week with aswollen armPeivandi, Orthopedics 2011

Venous thromboembolic eventsfollowing shoulder surgery:analysis of a national databasePatients without withReplacement 4,061 0.1 0.2Arthroscopy 63,302 0.01 0.02Fracture 4,696 0.30 3.02Jmeson et al, J Shoulder Elbow Surg 2011

Rivaroxaban for total kneeprophylaxisLassen et al, NEJM 2008

Rivaroxaban vs EnoxaparinThromboembolismOutcome Rivaroaban Enoxaparin RiskreductionP valueTotal VTE 9.7% 18.8% 48 0.01Major VTE 1.0% 2.5% 60 0.024BleedingRivaroxabanEnoxaparinMajor Bleeding 0.6% 0.5%Clinically relevant 2.7% 2.4%Wound Complications 2.1% 2.0%Lassen et al, NEJM 2008

Heparin InducedThrombocytopenia• Incidence• LMWH 0.6%• Unfractionated 4.6%

Heparin InducedThrombocytopenia• Immune mediated aggregation of platelets• IgG antibody• Binds to heparin platelet binding site 4• Creates “white thrombus”• Typically presents between days 4 and 14 of treatment• Diagnosis• Antibody testing has poor specificity• Stress thrombocytosis may mask• Pragmatic: unexplained decrease of platelets by 50%

Cost• 5 mg Coumadin brand~ $1.50 per pill• 5 mg warfarin (generic)~$40 cents/pill• 40 mg q day of Lovenox~$90/day• 30 mg BID of Lovenox~ $135• 5000 units heparin• 10 mg Rivaroxaban4 cents/pill6 cents/pill$17.50/day$13 ea= $26/day$1.70 each; = $5.10/day$6.80/ day

Contraindications for ChemicalProphylaxis• Active bleeding or risk of bleeding• Intracranial bleed• Spine Injury• Abdominal organ injury• Coagulophathy• INR > 1.5• aPTT > 40 seconds• < 50,000 platelets• History of heparin inducedthrombocytopenia• (may use fondaparinux)

Thromboprophylaxis with SpinalInjury• Metaanalysis thru 4/2008• twenty-one studies med inclusion criteria• Patients with SCI had relative risk increase of 6.0• Patients managed with VKA had fewer events thancontrols• Treatment initiated within two weeks more effective• LMWH out performed UFHPloumis, JBJS-Am 2009

Indications for Vena Cava Filter• Failure of Prophylaxis• Contraindications to prophylaxis in high risk patients• High risk of Pulmonary Embolism• Large Cava thrombus

IVC Filter Retrival?• 125 retrievable filters placed over 4 years• Indications (66%)• Head injury• Spinal Cord Injury• 70% of removal candidates did not have their filtersremovedHelling, J of Trauma 2009

Filters in DVT Treatment• 102 patients with DVT followingpelvic fracture• No DVT recurrences• 7% with new swelling• 1% with PTSToro, J Trauma 2008

Screening

Screening and PulmonaryEmbolism• From November 1, 1997 though November 31, 1999, ascreening protocol for deep vein thrombosis wasemployed using ultrasound and magnetic resonancevenography.• From January 1, 2000 through December 1, 2001, noscreening was used• 486 patients with fractures of the pelvis or acetabulumscreened• 487 without screening• PE rates• 2% with screening• 1.4% without screeningBorer, J Orthop Trauma, 2005

Contrast enhanced CT vs MRV forpelvic thrombosis• 30 patients with pelvic or acetabular fractures andwho met the study criteria were prospectivelyscreened with magnetic resonance venography andcomputed tomography venography• Detection rate:• computed tomography venography in two patients(7%)• magnetic resonance venography in four patients (13%)• Confirmatory venography• CT false posistive 50%• MRV false positives 100% Stover, J Orthop Trauma 2002

Chest Guidelines• we recommend that every hospitaldevelop a formal strategy thataddresses the prevention of VTE(Grade 1A).• We recommend against the use ofaspirin alone as thromboprophylaxisfor any patient group (Grade 1A)• We recommend that mechanicalmethods of thromboprophylaxis beused primarily for patients at highbleeding risk (Grade 1A)• Possibly as an adjunct to anticoagulantthromboprophylaxis (Grade 2A).

Chest Guidelines• Hip fracture surgery (HFS), we recommend theroutine use of fondaparinux (Grade 1A), LMWH(Grade 1B), a VKA (target INR, 2.5; range, 2.0 to3.0) [Grade 1B], or LDUH (Grade 1B).• For patients undergoing HFS, we recommendagainst the use of aspirin alone• For patients undergoing HFS in whom surgery islikely to be delayed, we recommend thatthromboprophylaxis with LMWH or LDUH beinitiated during the time between hospitaladmission and surgery (Grade 1C).

Chest Guidelines• We recommend that all major trauma and allspinal cord injury (SCI) patients receivethromboprophylaxis (Grade 1A).• For asymptomatic patients following majororthopedic surgery, we recommend against theroutine use of DUS screening before hospitaldischarge (Grade 1A).

Chest Guidelines• For patients undergoing HFS, we recommendthat thromboprophylaxis be extended beyond 10days and up to 35 days after surgery (Grade 1A).• The recommended options for extendedthromboprophylaxis in HFS includefondaparinux (Grade 1A), LMWH (Grade 1C), or aVKA (Grade 1C).

Chest Guidelines• For patients with isolated lower-extremityinjuries distal to the knee, we suggest thatclinicians not routinely use thromboprophylaxis(Grade 2A).• For major trauma patients, in the absence of amajor contraindication, we recommend thatclinicians use LMWH thromboprophylaxisstarting as soon as it is considered safe to do so(Grade 1A).

Chest Guidelines• No randomized trials have studied the prophylacticuse of IVC filters in any patient population, and weare not aware of evidence that their use is of anybenefit when added to the most effectivethromboprophylaxis modality appropriate for theclinical status.

The counter claim…..• "At this point, on the basis of an extensive review ofthe literature, we believe that the inexpensiveprotocol involving the administration of aspirincombined with intraoperative and postoperativeexercises is as effective as the expensive protocolinvolving the administration of warfarin or lowmolecular-weightheparin, and the former isassociated with fewer complications. There are alsostrong data suggesting that chemical prophylaxisfollowing total hip surgery may not be necessary."Sarmiento, JBJS-A 2002

Mortality Risk from PulmonaryEmbolism• 1/3 of thromboembolicdisease identified withsymptoms ofpulmonary embolism• 10% mortality• 10% of hospital deathsLankeit, Clin Chest Med. 2010

AAOS Rationale:PE rather than DVT

• The AAOS panel ignored the randomized data demonstratingthat thromboprophylaxis reduces both DVT and PE, and many oftheir recommendations are based on expert opinion and lack ascientific basis. We recommend the ACCP guidelines becausethe methodology is explicit and rigorous and the treatmentrecommendations reflect all of the evidence from therandomized trials.Eikelboom, Chest 2009

NQF Measure• Percentage of patients >18 in whom prophylaxis isindicated• Order for:• Low Molecular Weight Heparin (LMWH)• Low-Dose Unfractionated Heparin (LDUH)• adjusted-dose warfarin• Fondaparinux• mechanical prophylaxis• Given within 24 hours of the time of surgery.

• —SCIP VTE 1: Surgery patients withrecommended venousthromboembolism prophylaxis ordered• —SCIP VTE 2: Surgery patients whoreceived appropriate venousthromboembolism prophylaxis within 24hours prior to surgery to 24 hours aftersurgery

Scott & White HealthcareDVT Prophylaxis

Scott & White HealthCareDVT Order Set

My Practice• Fractures• Pelvis – mid Tibia• Isolated upper extremity• Hip fractures• Spine• AnkleBID enoxaparinNothingFondaparinuxIndividualizedASA if additional riskfactors are present• Filters restricted to those with anticoagulantcontraindications

Thrombolysis• 56 patients prospectively evaluated after lowerextremity thrombolysis for DVT• Demographics• Ave age 48• Symptoms less than two weeks• Results• Venographic success 79%• Preserved femoral vein valves 83%• Post thrombotic syndrome 9%Manninen et al, Eur J Radiol 2011

At risk for intraoperative bleeding?Risk Factors• Personal or family history ofabnormal bleeding• Liver disease• Significant alcohol use• Malabsorption• Anticoagulant therapyOK to proceed• INR 1.5 or below• PTT within 10 seconds ofcontrol• Platelets > 70,000

Thrombolytics, anticoagulants &antiplatlet drugsWikipedia

Perioperative Management ofantithrombotic therapies• Antiplatelet therapies (ASA & clopidogrel)• Stop 5- 7 days before elective surgery• Exceptions• Drug eluting coronary artery stentsDouketis et al, Chest Guidelines 2008

High Risk Anticoagulated PatientsHigh risk for thrombosis• Mitral mechanical valve• High risk a-fibrillation• Stroke, TIA• Recent VTE (