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Venous Thromboembolism. Core Rounds April 10, 2003 A.F. Chad, MD, CCFP. DVT Objectives. Epidemiology Natural History Risk Factors Hx & PHx & Pre-test Probability Wells & Perrier Tests (D-dimer, Doppler, IPG, Venography) Upper Extremity DVT (Dx, RF, Rx, risk PE) Rx.
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Venous Thromboembolism Core Rounds April 10, 2003 A.F. Chad, MD, CCFP
DVT Objectives • Epidemiology • Natural History • Risk Factors • Hx & PHx & Pre-test Probability • Wells & Perrier • Tests (D-dimer, Doppler, IPG, Venography) • Upper Extremity DVT (Dx, RF, Rx, risk PE) • Rx
DVT: Submission move by Jake “The Snake” Roberts OR Badness in the Veins?
Epidemiology • Lifetime incidence VTE 2-5% • PE: 0.5/1,000/year • DVT: 1/1,100/year • Prospective studies of DVT: • 10-13% medical pts on bed rest 1 week • 29-33% pts in ICU • 20-26% pts pulmonary diseases given bed rest >3d • 27-33% CCU pts • 48% pts post CABG
History • 1550 BC: Ebers papyrus documented peripheral venous disease • 1644 Schenk observed venous thrombosis with occlusion in the IVC • 1846 Virchow -> association b/n venous thrombosis in legs & PE • 1937: Heparin comes into practice
Natural History • 19th C Virchow’s triad: venous stasis, injury to intima, hypercoagulability • Thrombosis: platelet nidus near venous valves->platelets and fibrin -> thrombus -> occlusion, embolism • Endogenous thrombolytic system -> partial dissolution-> organized into venous wall
Natural History • Most go away w/o Rx • 20% propagate proximally • Organize into vein by day 5-10 • Biggest risk of propagation, embolization is before this
Natural History • Debate whether isolated calf thrombi are important • Some said to have low risk PE • Others said just as bad
Risk Factors: General • Age • Immobilization longer than 3 days • Pregnancy and the postpartum period • Major surgery in previous 4 weeks • Long plane or car trips (>4-6 h) in previous 4 weeks • Wrestling Jake “The Snake” Roberts
Medical Cancer,Previous DVT, stroke, MI, CHF, sepsis, nephrotic, UC Trauma Multiple trauma, CHI, SCI, Burn, LE # Vasculitis SLE / LAC, Bechet, Homocystinuria Hematologic PRV, Thrombocytosis Clotting D/O Antithrombin III , Protein C, Protein S, Factor V Leiden, Dysfibrinogenemias and disorders of plasminogen activation Drugs/medications IV drug abuse Oral contraceptives Estrogens HIT Risk Factors: Specific
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
History • Many No Sx • Edema (unilateral) specific • Leg pain in 50% -> nonspecific • Tenderness in 75%, but also in 50% w/o DVT • 10% Sx PE • Amount pain / tenderness do not correlate to severity • Warmth, erythema
Physical • No ONE reliable history / physical finding • Sensitivity 60-96%, Specificity 20-72% • Need to look @ combination of factors • Anand SS, Wells PS, Hunt D, Brill-Edwards P, Cook D, Ginsberg JS. Does this patient have deep vein thrombosis? JAMA. 1998 Dec 2;280(21):1828-9.
Physical • Edema (unilateral) (> 3cm) • Homan’s (50% sens) • Superficial thrombophlebitis (up to 40% can have) • Fever (>39.5, something else) • Phlegmasia cerulea dolens • Swollen purple leg re venous engorgement • Cyanosis re massive venous obstruction • Phlegmasia alba dolens • Whitish inflammation associated with arterial spasm 2nd to massive venous obstruction • Worry about arterial occlusion
Clinical Presentation:DVT • Calf-popliteal • 80-90%, many asymptomatic • pain & swelling • 10-20% spreads proximally • Ileofemoral • pain in buttock, groin • thigh swelling • 10-20% cases • Do not adhere to vessel walls until 5-10d post formation -> high risk to propagate / embolize
Clinical Prediction Model for DVTWells et al. Ann Int Med, 1997
Tests • D-dimer • Doppler U/S • IPG • Venography
D-Dimer • Not “Clot specific” • recent surgery, trauma, MI, pregnancy, CA can all give false +
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%
IPG vs. Doppler • N=985 • PPV U/S=94% (CI 87-98%) • PPV IPG =83% (CI 75-90%) • P=0.02 • Harriet Heijboer, Harry R. Buller, Anthonie Lensing, Alexander Turpie, Louisa P. Colly, and Jan Wouter ten Cate. A Comparison of Real-Time Compression Ultrasonography with Impedance Plethysmography for the Diagnosis of Deep-Vein Thrombosis in Symptomatic Outpatients NEJM Volume 329:1365-1369November 4, 1993Number 19.
Venography • “?Gold Standard?” • Invasive • Contrast • Need experienced readers • Non-diagnostic up to 25%
Upper Extremity DVT • 8% of all DVT • 75% are related to hypercoag, CVC • 25% Paget-von Schroetter syndrome • Exertional DVT • Caused by underlying MSK deformities (Thoracic outlet, extra rib)
Upper Extremity DVT • Prandoni P, Polistena P, Bernardi E, Cogo A, Casara D, Verlato F, Angelini F, Simioni P, Signorini GP, Benedetti L, Girolami A. Upper-extremity deep vein thrombosis. Risk factors, diagnosis, and complications. Arch Intern Med. 1998 Sep 28;158(17):1950-2.
Upper Extremity DVT • N=58 Sx UEDVT • IPG, Doppler, venography • 27 (47%) + UEDVT • Test Sens & Spec: • compression ultrasonography (96% and 93.5%) • color flow Doppler imaging (100% and 93%)
Upper Extremity DVT • PE “Objectively” found in 36% • 2 yr F/U: 2 recurrent VTE • RF: • CVC • Thrombophilia • Previous VTE
U/S Upper Extremity DVT • The sensitivity of duplex ultrasonography ranged from 56% to 100%, and the specificity ranged from 94% to 100% • Unsure if Helpful • Bisher O. Mustafa, MD; Suman W. Rathbun, MD; Thomas L. Whitsett, MD; Gary E. Raskob, PhD Sensitivity and Specificity of Ultrasonography in the Diagnosis of Upper Extremity Deep Vein Thrombosis: A Systematic Review Arch Int Med Vol. 162 No. 4, February 25, 2002.
Upper Extremity DVT • 10-30% incidence PE associated • Therapy: • Usual Rx • Local thrombolytics appears to be Rx of choice with literature mainly case studies
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-reversible • indefinite if recurrent, CA, genetic • Anticoagulation Clinic
LMWH vs. UFH • N=432 • No difference in new VTE • Less died, complications in LMWH (SS) • RD Hull, GE Raskob, GF Pineo, D Green, AA Trowbridge, CG Elliott, RG Lerner, J Hall, T Sparling, HR Brettell, and et al Subcutaneous low-molecular-weight heparin compared with continuous intravenous heparin in the treatment of proximal-vein thrombosis NEJM Volume 326:975-982April 9, 1992Number 15
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
PE Objectives • Epidemiology & Natural History • Mortality & Pathophysiology • Hx & PHx • Pre-test Probability • Dx • Angio, Echo, CT, algorithms • Which tests / combo rules in / out • What to do if non-Dx results • Confounding Clinical Situations • Rx • Heparin, Thrombolysis (massive, submassive), embolectomy, IVC filter
Epidemiology • USA: 60-80% patients with DVT, >50% Sx free • 3rd in hospital mortality, 650,000 cases/yr • Autopsy studies: 60% pts who die in hospital had PE, diagnosis missed ~ 70%
Natural History • Most pulmonary emboli are multiple, and the lower lobes are involved • From deep veins of lower extremities • Also pelvic, renal, upper extremity, right heart chambers • Large thrombi lodge @ bifurcation of main PA or lobar branches -> hemodynamic compromise • Smaller thrombi occlude smaller vessels in periphery • More likely to cause pleuritic chest pain (inflammatory response adjacent to parietal pleura)
Mortality • Approximately 10% of patients who develop PE die within the first hour, • 30% die from recurrent embolism. Anticoagulant Rx decreases mortality < 5%
Pathophysiology Review • Normal RV has a narrow range over which it can compensate for acute increases in afterload. The pericardium has a limited ability to distend. • Increased RV afterload elevation in RV wall pressures dilation and hypokinesis of the RV wall shift of intraventricular septum towards left ventricle (tricuspid regurgitation) and decreased LV output.
Respiratory Consequences • Early • Increased alveolar dead space, Pneumoconstriction, hypoxemia, hyperventilation • Late: • regional loss surfactant, pulmonary infarction • Arterial hypoxemia frequent, not universal • V/Q mismatch, shunts, reduced CO, intracardiac shunt via PFO • Infarction uncommon re bronchial arterial collateral circulation
Hemodynamic Consequences • Reduces X-sectional area of pulmonary vascular bed -> incr pulmonary vascular resistance -> RV afterload -> RV failure • Reflex PA constriction • Prior poor cardiopulmonary status important factor re hemodynamic collapse