Venous Thromboembolism Denise Watt January 3, 2002

Outline l epidemiology l pathophysiology l risk factors l diagnosis clinical labs diagnostic imaging algorithms l treatment

Case 1 l Rural ED l 72 yo male l fever, SOB, pleuritic CP x 2 days l HR 110, bp 140/90, RR 22, sat 90% l CXR unremarkable l what test/Rx?

Case 2 l 55 yo man l sudden central CP, SOB, presyncope l HR 120, bp 90/70, RR 30, sats 88% l ECG: sinus tach l what tests/Rx?

Case 3 l 33 yo healthy woman, 34 wks GA l syncope at home l EMS called l asystolic arrest en route l CPR x 5 min l what do you do?

Epidemiology l Lifetime incidence VTE 2-5% PE: 0.5/1,000/year DVT: 1/1,100/year l PE mortality: 10% die in 1st hour 30% untreated 2-8% if anticoagulated l >50% PEs undiagnosed

Risk Factors l Primary Factor V leiden Antithrombin III deficiency Prot C deficiency Prot S deficiency hyperhomo- cysteinemia anticardiolipin Ab dysfibrinogenemia l Secondary age trauma / surgery malignancy immobilization stroke smoking obesity OCP/HRT lupus anticoagulant pregnancy hyperviscosity heart failure

Risk Factors l 50% without risk factors l OCP/HRT: 3x baseline risk 0.3/10,000/yr; 15/10,000/yr higher in 3rd gen progesterones l 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

Consequences of PE l Hemodynamic tachycardia hypotension RV overload and dilation  CVP  LV preload  myocardial flow pulmonary HTN pul A-V shunts l Respiratory hyperventilation PA HTN  compliance atelectasis broncho- constriction  airway resistance

Clinical Presentation: DVT l Calf-popliteal 80-90%, many asymptomatic pain & swelling spreads proximally l Ileofemoral pain in buttock, groin thigh swelling 10-20% cases

Clinical Prediction Model for DVT Wells et al. Ann Int Med, 1997

Clinical Model for DVT

Incidence of DVT by Clinical Probability

Clinical Presentation of PE: The great pretender l SOB, CP or tachypnea in 97% l individual s+s not sensitive/specific l peripheral (distal vessel) pleuritic CP, ± hemoptysis, ± SOBOE l central (lobar / segmental) SOBOE l massive (main pulmonary artery) syncope, hypotension, shock

Clinical Prediction Model for PE Wells. Ann Int Med, 1998

Incidence of PE by Clinical Probability

Ancillary tests for PE l CXR: r/o other diagnoses ‘classic’ signs non-specific l ABG: 20% have normal PaO % have normal Aa gradient l ECG: remember???

D-dimer l degradation product of fibrin l PPV poor; NPV excellent l non-specific: +ve: surgery, trauma, hemorrhage, CA 90% +ve >80 yrs old l most useful in ED patients l NOT to r/o PE in high PTP

D-dimer Assays Van der Graaf. Thromb Haemost, 2000.

Diagnostic Imaging for DVT l 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 l 2 protocols: Wells & Hull l may avoid angiography in ?PE l 2% +ve in 2 weeks (?PE) l if U/S -ve 2 weeks apart, <2% have VTE in next 6 mos

Diagnostic Imaging for DVT l IPG detects changes in flow before and after cuff inflated sensitivity 60%

Algorithm for Suspected first DVT: Perrier. Lancet, 1999

Diagnostic Imaging for PE: V/Q scan l PIOPED: ventilation component adds little info l PISAPED criteria: normal, non-diagnostic, high probability 25%, 50%, 25% respectively high prob: 85-90% PPV non-diagnostic: 25% PE l interpret in context of PTP

Diagnostic Imaging for PE: Pulmonary Angiography l Gold standard (imperfect) sens 98%, spec 95-98% l ED physicians reluctant to use: invasive, risks, requires expertise, not readily available, time consuming, $ l relative contraindications l indicated if non-invasive tests inconclusive

Diagnostic Imaging for PE: Spiral CT l IV contrast, direct visualization l subsegmental PE not well seen l more specific, underlying lung dx l sens depends on CT, experience l wide variation in studies Rathbun. Ann Intern Med, 2000 (review) sens %, spec % poor methodolgy of studies

Spiral CT l Perrier. Ann Intern Med, 2001 sens 70%, spec 91%, 4% inconclusive good interobserver agreement l CT venography: benefit over U/S not determined l role? no evidence to withold Rx if CT negative may replace angiography

Diagnostic Imaging in PE: Echocardiography l useful for patients in shock/arrest r/o DDx: tamponade, Ao dissection, AMI l indirect evidence of PE: RV overload, septal shift to L, TR,  PA pressure, RV wall motion abn sens 93%, spec 81% l ‘sub-massive’ PE: independent predictor of mortality (?significance)

Algorithm for suspected PE: Wells. Ann Int Med, 2001

Wells’ Algorithm: Criticism l Uses SimpliRED assay: lower sens. l sCT not included could replace angiography? l Low prevalence of PE (9%) l not validated by other RCTs

Treatment of VTE: Goals l reduce mortality l prevent extension/recurrence l restore pulmonary vascular resistance l prevent pulmonary hypertension

Treatment of VTE: Anticoagulation l Out-patient LMWH l LMWH superior to UFH? (Gould 1999) l out-pt Rx safe in PE ( Kovacs, 2000) l DVT: start Rx, definitive test in 24hr l baseline B/W

Anticoagulation l Enoxaparin 1mg/kg bid or 1.5 od l Tinzaparin 175 anti-Xa u/kg od l start warfarin 5mg on day 1 l d/c LMWH when INR >2.0 x 2 days l Rx 3 mos if 1st and reversible cause l 6 mos if non-reversbile l indefinite if recurrent, CA, genetic

Treatment of PE: Criteria for admission l Hemodynamic instability l O2 requirement l surgery < 48hr l risk of active bleeding l history of HIT l IV pain control

Treatment of massive PE l judicious fluids (500cc max) l NE, dopamine, dobutamine prn l O2, intubate if shock positive pressure worsens RV fn l anticoagulation if no contraindications UFH if hypotensive PTT x normal

Treatment of massive PE: Thrombolytics l no evidence of mortality benefit including in cardiac arrest (case series) l no benefit in hemodynamically stable l improves pul. perfusion (15% vs 2%), RV function (34% vs. 17%) cf. heparin l t-PA faster hemodynamic effect l IV same as intrapulmonary l 5-10% major bleed, 1-2% ICH

Thrombolytics l 2 week window of opportunity! effect  with time l no advantage of t-PA bolus l 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 l Indicated in acute, massive PE if: contraindication to thrombolytics unresponsive to medical mgt l moribund pt  poor results l no evidence cf. with thrombolytics l percutaneous vs. surgical ?role

IVC Filters l Indications: contraindication to anticoagulation recurrent VTE despite anticoagulation after surgical embolectomy l no long term adv vs. anticoagulation l anticoagulate if no contraindications DVT and IVC occlusion

Pregnancy l V/Q safe, no breastfeed x 15hr post l D-dimer  in pregnancy, wide Aa l angiography safer than empiric Rx l LMWH in DVT, not studied in PE l PE: UFH IV x 4-5 days, then s/c l treat x 3 months or 6 weeks postpartum l switch to oral postpartum