Proximal versus Calf Vein Thrombosis: Differences in ...

1 Proximal versus calf Vein thrombosis : Differences in ManagementMarc A. Passman, Professor of SurgeryUniversity of Alabama at BirminghamDisclosureMarc Passman, have no financial relationship(s) to Objectives Review currently available anticoagulation options and role in VTE treatment. Implement current evidence based guideline recommendations for VTE treatment Understand difference between Proximal and calf DVT and controversies in treatment VTE Treatment Modalities Untreated DVT PE approximately 50% of patients Death in 20% Initial Treatment = ANTICOAGULATION Anticoagulation reduces risk of PE to 1-2% in adequately dosed patients5 Acute VTET reatment ModalitiesThe mainstay of therapy Full-dose anticoagulation CompressionOptional interventions Thrombolytic therapy (catheter-directed or systemic) Thrombectomy (percutaneous or surgical) Angioplasty and stenting Inferior vena cava interruption6 Treatment of VTEC urrent Anticoagulants Glycosaminoglycans (act mostly by stimulating AT III) Unfractionated heparin (UFH) Low-molecular weight heparin (LMWH) Fondaparinux (pentasaccharide) Synthetic anticoagulants (for patients with heparin-induced thrombocytopenia)

2 Direct (ie, ATIII-independent) antithrombins (argatroban, lepirudin, bivalirudin) Vitamin K antagonists WarfarinGlycosaminoglycansUFHLMWHF ondaparinuxSourcePorcine/bovineAltered UFHS yntheticMean no. of 36135saccharidesActionATIII, IIa>XaATIII, Xa>IIaATIII, XaPlasma protein binding+++++BioavailabilityVariable90%10 0%Half-life, hVariable (SQ)~6 (SQ)~17 (SQ)<1-3 (IV)PF4 binding++++++GAG/PF4 antibodies++++++HIT1%-5% neverEffect of renal dysfunction++++++MonitoringPTTAnti-XaAnt i-XaProtamine as antidote+++ Pregnancy categoryCBBW arfarin Advantages: Oral Effective Antidotes exist(vitamin K, fresh frozen plasma, 4-factor concentrates) Long half-life Disadvantages: Long half-life Not immediately active Very low therapeutic index Very significant drug / dietary interactions Very significant effect of hepatobiliary and gastrointestinal function Requires close monitoring Protein C / S deficiency -paradoxically hypercoagulable Vitamin K IV, FFP, and 4-factor concentrates have risks Pregnancy category X ( warfarin embryopathy, midface hypoplasia and skeletal defects, especially weeks 6-9).

3 Fetal hemorrhaging (3rd trimester)9 Direct Thrombin InhibitorsArgatrobanLepirudinBivalirudin Standard loading mg/kgStandard infusion dose2 g/ mg/ mg/kg/hHow monitoredPTTbPTTPTTT arget PTT xAntidoteNoneNoneNonePregnancy categoryBBBHalf-life45 min75 min25 minEffect of renal dysfunction ++++a++aEffect of liver dysfunction++a AntibodiesNoOccasionalbRare10 The New AnticoagulantsNew Anticoagulants Rivaroxaban: oral anti-Xa Apixaban: oral anti-Xa Dabigatran: oral antithrombinPrincipal areas of study VTE prophylaxis Treatment of acute VTE and extended prophylaxis Stroke prevention in chronic atrial fibrillation Acute coronary syndromeDabigatranFDA ApprovalFDA NEWS RELEASE For Immediate Release: Oct. 19, 2010 Consumer Inquiries: 888-INFO-FDAFDA approves Pradaxa to prevent stroke in people with atrial fibrillation The Food and Drug Administration today approved Pradaxa capsules (dabigatran etexilate) for the prevention of stroke and blood clots in patients with abnormal heart rhythm (atrial fibrillation).

4 11 Acute DVT/PE: Initial Anticoagulant Therapy Short-term treatment with SC LMWH, IV UFH, or SC fondaparinux (Grade 1A) LMWH SC once or twice daily over UFH as an outpatient if possible (Grade 1C) and as an inpatient if necessary (Grade 1A), unless renal failure (Grade 2C) IV UFH: continuous infusion with aPTT monitoring (Grade 1C) If clinical suspicion of DVT is high, treatment should be initiated while awaiting results of diagnostic tests (Grade 1C) Treat for at least 5 d with LMWH, UFH, or fondaparinux until the INR for 24 h (Grade 1C) Start warfarin on first treatment day together with LMWH, UFH, or fondaparinux (Grade 1A)13 Acute DVT / PE: Duration & Intensity For transient, reversible risk factor, anticoagulation for at least 3 months (Grade 1A), then evaluate risk-benefit equation for longer treatment (Grade 1C) For an unprovoked proximalDVT or PE, long-term anticoagulation (Grade 1A) For a second episode of VTE, long-term anticoagulation (Grade 1A) For an unprovoked distal DVT, anticoagulation for at least 3 months (Grade 2B) Warfarin INR target , not (both Grade 1A) For cancer-related VTE, anticoagulation with a LMWH (rather than warfarin) for 3-6 months (Grade 1A), then reassessAdditional factors that may prompt longer treatment Residual significant venous obstruction Hypercoagulable state(s) Ongoing estrogenic drugs, thalidomide or lenalidomide Immobile status Significantly elevated or rising D-dimers when anticoagulation is stopped Patient preferenceAcute DVT / PE.

5 Duration & IntensityGoals of these procedures To reduce acute symptoms To reduce risk of postthrombotic syndromeEligibility Extensive femoral or iliofemoral DVT Duration <14 days Good performance status Low bleeding risk (for thrombolytic therapy) Life expectancy >1 yearAcute DVT / PE: Lysis, Thrombectomy, StentsAcute DVT / PE: IVC Interruption Routine use of an IVC filter as an adjunct to anticoagulation is not advised (Grade 1A) For Proximal DVT, IVC filter indicated if a bleeding risk precludes use of anticoagulation (Grade 1C) If an IVC filter is placed, the bleeding risk subsides, and anticoagulation is no longer precluded, then anticoagulation is advisable (Grade 1C) calf Vein DVT Evidence? Definition? Infrapopliteal Intramuscular Plantar Incidence? Asymptomatic 12%-40% Symptomatic 8-49% PE? Propagation? 4%-15% Postthrombotic Syndrome 8% -57% C2-C3 3%-5% C4 C6 calf Vein DVT Evidence? Definition?

6 Nicos Incidence? Nicos PE? Nicos Passman Propagation Nicos Postthrombotic Syndrome Nicos PassmanCalf Vein DVTE vidence Based OutcomesStudyDVT LocationNTreatmentF/UDVT RecurrencePEGalanaud et al. Thromb Haemost, 2009 Infrapopliteal78781% oral anticoagulation3% None3 et al. J Vasc Surg 2010 Intramuscular 109 Group 1:LMWH 10 days + compressionGroup 2:compression3 monthsGroup 1 2 1:0%Group 1:0%Baglin et al. J Thormb Haemost 2010 Distal DVT171 Heparin 5-10 days then oral anticoagulation 3 months5 et al. J Vasc Surg 2007 Intramuscular131 Oral anticoagulation 1-3 months + compression3 et al. Circulation 2001 Infrapopliteal197 Group 1:LMWH or UFH 12 weeksGroup 2:6 weeks LMWH or UFH15 monthsGroup 1 2 1 2:0%20 calf Vein DVT Duration & Intensity For transient, reversible risk factor, anticoagulation for at least 3 months (Grade 1A), then evaluate risk-benefit equation for longer treatment (Grade 1C) For an unprovoked proximalDVT or PE, long-term anticoagulation (Grade 1A) For a second episode of VTE, long-term anticoagulation (Grade 1A) For an unprovoked distal DVT, anticoagulation for at least 3 months (Grade 2B) Warfarin INR target , not (both Grade 1A) For cancer-related VTE, anticoagulation with a LMWH (rather than warfarin) for 3-6 months (Grade 1A), then reassessCalf Vein DVT Treatment AlgorithmCalf DVTI nfrapoplitealUnprovokedAnticoagulation 12 weeks 3 months then re-evaluate-Leg sxs-Respiratory sxs-PEAnticoagulation 3 months then re-evaluate-Propagation-RecurrenceAntico agulation 3 months then re-evaluate-Asymptomatic-Transient, Reversible Risk FactorBleeding Risk Low.

7 Consider anticoagulation vssurveillanceBleeding Risk High:Surveillance IntramuscularSurveillanceProximal vs calf DVTC onclusion Iliofemoral DVT: anticoagulation consider catheter clot removal options compression Femoral Popliteal DVT: anticoagulation transient reversible risk factor: 3 months then re-evaluate unprovoked or recurrent: long-term compression calf DVT: more evidence needed anticoagulation unprovoked: 12 weeks to 3 months PE, leg symptoms, recurrence or propagation: 3 months then re-evaluate surveillance transient reversible risk factor asymptomatic intramuscular compressio