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Venous Thromboembolism. Denise Watt January 3, 2002. Outline. epidemiology pathophysiology risk factors diagnosis clinical labs diagnostic imaging algorithms treatment. Case 1. Rural ED 72 yo male fever, SOB, pleuritic CP x 2 days HR 110, bp 140/90, RR 22, sat 90%
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Venous Thromboembolism Denise Watt January 3, 2002
Outline • epidemiology • pathophysiology • risk factors • diagnosis • clinical • labs • diagnostic imaging • algorithms • treatment
Case 1 • Rural ED • 72 yo male • fever, SOB, pleuritic CP x 2 days • HR 110, bp 140/90, RR 22, sat 90% • CXR unremarkable • what test/Rx?
Case 2 • 55 yo man • sudden central CP, SOB, presyncope • HR 120, bp 90/70, RR 30, sats 88% • ECG: sinus tach • what tests/Rx?
Case 3 • 33 yo healthy woman, 34 wks GA • syncope at home • EMS called • asystolic arrest en route • CPR x 5 min • what do you do?
Epidemiology • Lifetime incidence VTE 2-5% • PE: 0.5/1,000/year • DVT: 1/1,100/year • PE mortality: • 10% die in 1st hour • 30% untreated • 2-8% if anticoagulated • >50% PEs undiagnosed
Primary Factor V leiden Antithrombin III deficiency Prot C deficiency Prot S deficiency hyperhomo-cysteinemia anticardiolipin Ab dysfibrinogenemia Secondary age trauma / surgery malignancy immobilization stroke smoking obesity OCP/HRT lupus anticoagulant pregnancy hyperviscosity heart failure Risk Factors
Risk Factors • 50% without risk factors • OCP/HRT: 3x baseline risk • 0.3/10,000/yr; 15/10,000/yr • higher in 3rd gen progesterones • pregnancy: 5x baseline risk • 75% DVT antepartum, 66% PE postpartum
Pathophysiology:Source of VTE • most start in calf, extend proximally • 70% PE have DVT evidence at autopsy • 70-90% known source: IVC, ileofemoral or pelvic veins, 10-20% SVC • incidence of PE from DVT • calf: 46% • thigh: 67% • pelvic: 77% • other: UE, jugular, mesenteric, cerebral
Hemodynamic tachycardia hypotension RV overload and dilation CVP LV preload myocardial flow pulmonary HTN pul A-V shunts Respiratory hyperventilation PA HTN compliance atelectasis broncho-constriction airway resistance Consequences of PE
Clinical Presentation:DVT • Calf-popliteal • 80-90%, many asymptomatic • pain & swelling • spreads proximally • Ileofemoral • pain in buttock, groin • thigh swelling • 10-20% cases
Clinical Prediction Model for DVTWells et al. Ann Int Med, 1997
Clinical Presentation of PE:The great pretender • SOB, CP or tachypnea in 97% • individual s+s not sensitive/specific • peripheral (distal vessel) • pleuritic CP, ± hemoptysis, ± SOBOE • central (lobar / segmental) • SOBOE • massive (main pulmonary artery) • syncope, hypotension, shock
Ancillary tests for PE • CXR: • r/o other diagnoses • ‘classic’ signs non-specific • ABG: • 20% have normal PaO2 • 15-20% have normal Aa gradient • ECG: • remember???
D-dimer • degradation product of fibrin • PPV poor; NPV excellent • non-specific: • +ve: surgery, trauma, hemorrhage, CA • 90% +ve >80 yrs old • most useful in ED patients • NOT to r/o PE in high PTP
Diagnostic Imaging for DVT • Duplex / compression U/S • non-invasive, portable • direct visualization of veins and flow • loss of compression = DVT • 97% sensitive & specific for symptomatic proximal/popliteal DVT • 62% sensitive for asymptomatic DVT • +ve in 30-50% PE; 5% non-dx V/Q scans
Serial Venous U/S • 2 protocols: Wells & Hull • may avoid angiography in ?PE • 2% +ve in 2 weeks (?PE) • if U/S -ve 2 weeks apart, <2% have VTE in next 6 mos
Diagnostic Imaging for DVT • IPG • detects changes in flow before and after cuff inflated • sensitivity 60%
Diagnostic Imaging for PE:V/Q scan • PIOPED: ventilation component adds little info • PISAPED criteria: • normal, non-diagnostic, high probability • 25%, 50%, 25% respectively • high prob: 85-90% PPV • non-diagnostic: 25% PE • interpret in context of PTP
Diagnostic Imaging for PE:Pulmonary Angiography • Gold standard (imperfect) • sens 98%, spec 95-98% • ED physicians reluctant to use: • invasive, risks, requires expertise, not readily available, time consuming, $ • relative contraindications • indicated if non-invasive tests inconclusive
Diagnostic Imaging for PE:Spiral CT • IV contrast, direct visualization • subsegmental PE not well seen • more specific, underlying lung dx • sens depends on CT, experience • wide variation in studies • Rathbun. Ann Intern Med, 2000 (review) • sens 53-100%, spec 81-100% • poor methodolgy of studies
Spiral CT • Perrier. Ann Intern Med, 2001 • sens 70%, spec 91% , 4% inconclusive • good interobserver agreement • CT venography: • benefit over U/S not determined • role? • no evidence to withold Rx if CT negative • may replace angiography
Diagnostic Imaging in PE:Echocardiography • useful for patients in shock/arrest • r/o DDx: tamponade, Ao dissection, AMI • indirect evidence of PE: • RV overload, septal shift to L, TR, PA pressure, RV wall motion abn • sens 93%, spec 81% • ‘sub-massive’ PE: independent predictor of mortality (?significance)
Wells’ Algorithm:Criticism • Uses SimpliRED assay: lower sens. • sCT not included • could replace angiography? • Low prevalence of PE (9%) • not validated by other RCTs
Treatment of VTE:Goals • reduce mortality • prevent extension/recurrence • restore pulmonary vascular resistance • prevent pulmonary hypertension
Treatment of VTE:Anticoagulation • Out-patient LMWH • LMWH superior to UFH? (Gould 1999) • out-pt Rx safe in PE (Kovacs, 2000) • DVT: start Rx, definitive test in 24hr • baseline B/W
Anticoagulation • Enoxaparin 1mg/kg bid or 1.5 od • Tinzaparin 175 anti-Xa u/kg od • start warfarin 5mg on day 1 • d/c LMWH when INR >2.0 x 2 days • Rx 3 mos if 1st and reversible cause • 6 mos if non-reversbile • indefinite if recurrent, CA, genetic
Treatment of PE:Criteria for admission • Hemodynamic instability • O2 requirement • surgery < 48hr • risk of active bleeding • history of HIT • IV pain control
Treatment of massive PE • judicious fluids (500cc max) • NE, dopamine, dobutamine prn • O2, intubate if shock • positive pressure worsens RV fn • anticoagulation • if no contraindications • UFH if hypotensive • PTT 1.5-2.5 x normal
Treatment of massive PE:Thrombolytics • no evidence of mortality benefit • including in cardiac arrest (case series) • no benefit in hemodynamically stable • improves pul. perfusion (15% vs 2%), RV function (34% vs. 17%) cf. heparin • t-PA faster hemodynamic effect • IV same as intrapulmonary • 5-10% major bleed, 1-2% ICH
Thrombolytics • 2 week window of opportunity! • effect with time • no advantage of t-PA bolus • protocols: • t-PA: 100mg over 2 hr • UK: 4400U/kg over 10min; rpt x 12-24hr • SK: 250,000U over 30min; 100,000 x 24h • arrest: t-PA 10mg/kg bolus x 2 q 30 min
Embolectomy • Indicated in acute, massive PE if: • contraindication to thrombolytics • unresponsive to medical mgt • moribund pt poor results • no evidence cf. with thrombolytics • percutaneous vs. surgical • ?role
IVC Filters • Indications: • contraindication to anticoagulation • recurrent VTE despite anticoagulation • after surgical embolectomy • no long term adv vs. anticoagulation • anticoagulate if no contraindications • DVT and IVC occlusion
Pregnancy • V/Q safe, no breastfeed x 15hr post • D-dimer in pregnancy, wide Aa • angiography safer than empiric Rx • LMWH in DVT, not studied in PE • PE: UFH IV x 4-5 days, then s/c • treat x 3 months or 6 weeks postpartum • switch to oral postpartum