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PULMONARY EMBOLISM AND DEEP VENOUS THROMBOSIS James Huffman 11.13.2008 Thanks to Dr. Gil Curry, Dr. Nadim Lalani


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PULMONARY EMBOLISM AND DEEP VENOUS THROMBOSIS. James Huffman 11.13.2008 Thanks to Dr. Gil Curry, Dr. Nadim Lalani. Outline. Epidemiology / Pathophysiology DVT Anatomy Clinical Presentation Diagnostic Approach Pre-test probability Labs Imaging Real-Life Algorithm Treatment. Outline. - PowerPoint PPT Presentation


  • PULMONARY EMBOLISM AND DEEP VENOUS THROMBOSISJames Huffman11.13.2008Thanks to Dr. Gil Curry, Dr. Nadim Lalani

  • OutlineEpidemiology / PathophysiologyDVTAnatomyClinical PresentationDiagnostic ApproachPre-test probabilityLabsImagingReal-Life AlgorithmTreatment

  • OutlinePEClinical PresentationDiagnostic ApproachPre-test probabilityLabsEKGImagingX-ray, CT, MRReal-Life Algorithm

  • Focus: the bottom line

  • EpidemiologyVTE is a spectrum : Simple superficial thrombophlebitis to fatal PEEst incidence : 100 /100 0001/3 of cases are PEIncreases dramatically with age (sharp increase after the age of 45)DVT:Only 1/3 of pts investigated for DVT have itsilent PE present in 40-60% of pts with DVTIn asymptomatic pts w/ proven DVT, up to 1/3 will have undiagnosed PEWith treatment 50% have residual clot up to 1yWithout treatment 50% recurrence w/ in 3 mo

  • EpidemiologyPE:10% fatal w/ in 1st Hour75% pt w/ PE have DVT (2/3 proximal vein)Classic presentations are less common than atypicals and asymptomatic VTE is common20% have pleuritic CP in ED5-10% PE have shock as initial presentationDespite treatment, kills 1-8%

    Complications:postphlebitic syndrome [40%]pulmonary HTN [4%]

  • Pathophysiology of ThrombosisFibrinogen is converted to fibrin in response to vasc. Injury and inflammationFibrin is 1 structural framework of embolized clots and excessive fibrin deposition provides the nidus of VTE

    VTE is the end-product of imbalanced clot formation and breakdown

    What promotes this imbalance of fibrin deposition and removal?

  • Virchows TriadWhite, RH: The epidemiology of venous thromboembolism. Circulation 107(23 Suppl 1):I4, 2003.

    Injury to the vascular endotheliumAlterations in blood flowHypercoagulability

    Anything else associated with imbalanced clot formation?

    Age likely through a combination of the above mechanisms

  • Coagulation Cascade

  • Coagulation CascadePT/INRWarfarinPTTHeparin

  • AnatomyDepthDeepSuperficial*ProximalPopliteal v. or higherDistal

    *Superficial femoral vein is a member of the deep group

  • Case 155: Referred to ED for pain, redness and swelling of right calfWIC today: Sent to ED with note:

  • HistoryStarted 3/7 agoDenies previous DVTHas been on IV combo chemotherapy for ovarian Ca diagnosed six months ago (extensive pelvic lymph node involvement which has improved as per recent U/S)Fell day before this started and twisted her knee

    All this is good what are your main goals with history?Determine pre-test probability of DVTLook for other causes

  • DVT: History is Risk AssessmentHypercoagulability:Autoimmune Disease and Immune DeficiencyNot just SLE! Remember IBDCancerChemotherapy: especially breast CACoagulopathy: Factor V Leiden. Present in 7% pop = 50% Protein C, protein S & antithrombin III deficiency = 15% DVT. Resistance to aPC Lupus anticoagulant Prothrombin G20210A antiphospholipid antibodies others

  • DVT: History is Risk AssessmentStasis:Immobility: Not just surgery remember other conditions (oldies!)Heart Disease (AMI & CHF): independent of bedrestTravel ?Duration / proximity?HyperlipiedmiaPolycythemiaEndothelial Injury:StrokeVascular surgeryPVDOthers:Age, race, prior DVT, blood types, tissue antigens, homocysteine

  • Case 1 Continued When you examine her what do you expect to find?P/E:Generalised tenderness to her calfExquisite pain in popliteal fossa along veinEdema, erythema and warmthSwollen 3.5 cm Homans Sign +

    What do you think of this?

  • Physical is Risk AssessmentAnand, SS, Wells, PS, et al. 1998. Does this Patient have deep vein thrombosis? JAMA:279(14)Classically:Leg tenderness , Homans SignSwellingPitting edemaDilated superficial veinsErythemaCalorNeither sensitive nor specificORs between 2- 4

  • Physical is Risk AssessmentAnand, SS, Wells, PS, et al. 1998. Does this Patient have deep vein thrombosis? JAMA:279(14)

  • DVT: H&P Bottom LineNeither is sensitive or specifici.e. you cant rule-in or rule-out a DVT

    Use them to decide pre-test probability

  • Clinical Prediction Rule: EvolutionLandefeld et. Al 1990

    354 pts suspected of DVT that underwent venography5 clinical predictors identified:1 or more 95% Sens [92-100] 20% spec [15-25]Swelling above the kneeSwelling below the kneeRecent immobilityFeverCancerAbsence of all only 5% DVT

  • Pretest ProbabilityWells, P., et al. 1995. Accuracy of Clinical Assessment of Deep Vein Thrombosis. Lancet:345; 1326-30

    First Wells CriteriaBased on literature review and clinical experience of investigatorsStudy showed value in stratifying pretest probability with respect to eliminating need for repeat u/s

  • Pretest ProbabilityWells, P, et al. 1997. Lancet:350;1795.Revised Wells score through logistic regression analysisProspectively validated using same treatment algorithm (next slide)593 patients from two Canadian tertiary care centresScore 3 (high risk), 1 or 2 (moderate risk),
  • Pretest Probability Wells, P, et al. 1997. Lancet:350;1795.593 pts w/ suspect DVTStratified low, mod, high risk compression U/S /veno3% of Low risk, 17% of moderate risk, 75% of high risk pts had DVTConcluded that Clinical probability + U/S safe [0.6% missed]

  • Pretest ProbabilityThis algorithm re-presented in JAMA rational clinical examination seriesAnand 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.

    Whats missing?

    The NDimer!

  • D-Dimer TestingU/S not a perfect testDegradation product of fibrinNon-specificPPV bad+ve: surgery, trauma, hemorrhage, CA, pregnancy, sepsis, >80 yrs oldSensitivity variableNeed Pre-test probability to r/o DVT

    CHR uses

  • D-Dimer Testing Wells, P., et al. 2003. NEJM: 349(13); pp1227-35RCT (N=1096)D-Dimer vs no D-DimerDVT Likely = Wells 2# of U/S per pt decreased in D-dimer group (0.78 vs 1.34)

  • D-Dimer TestingWells, P., et al. 2003. NEJM: 349(13); pp1227-35

    Modified Wells CriteriaUsed SimpliRED and IL-Test assays (less sens) Conclusion:Clinical prediction rule + D-Dimer can safely r/o DVT

  • Case 1 continuedPretest probability?Active cancer (1)Localized tenderness (1)Calf swelling (1)Edema (1)Other Diagnosis? Compression by pelvic nodes? (Doesnt matter score would still be not low risk)What about the D-Dimer Would you order it?Doesnt matter it was sent already Level positive at 1.77C Both CMAJ and Wells protocols would have you order it anyway (well discuss)

    So she gets either 4 or 2 points = DVT likely

  • What next Einstein?

  • UltrasoundAmerican Journal of Respiratory Critical Care Medicine. 1999: 160; 1043-66Well studiedWidely availableProven accurate for Dx symptomatic prox DVTLike CT/PE provides other Dx: hematomas, bakers cysts, lymphad, aneurism, thrombophlebitis and abscessHas been advanced by the combination of compression and doppler

    Bottom line: U/S is the test of choice for DVT

  • Duplex UltrasoundStork, A. 2005. Calgarian J of PPT Slides. 1(1) pp1Two partsi) Compression - Tech applies pressure- clot not compressibleii) Doppler (B mode)Shows blood flow

  • Ultrasound Fields, JM, & Goyal, M. Venothromboembolism. Emerg Med Clin of N Am. 2008; 26: 649-83

  • EDEJolly BT, et al. Acad Emerg Med 1997;4(2):12932.Retrospective analysis 1994EPs trained to perform colour doppler US (20-30 studies each)100% sensitive, 75% specific for acute DVT2 false-positives were in chronic DVT

    Frazee BW, et al. J Emerg Med 2001;20(2):10712.Prospectively demonstrated 95.7% NPV for EP performed LCUS

  • Naughty by Nature - Feel me flow

  • EDE ED FlowBlaivas M, et al. Acad Emerg Med. 2000;7(2):1206.Median exam time of 3m 28s98% correlation with vascular lab-performed studies on same pts

    Theodoro D, et al. Am J Emerg Med. 2004;22(3):197200.125m reduction in time to pt disposition with EP-performed USKappa = 0.9, 99% agreement (154/156 cases)

    Jang T, et al. Acad Emerg Med. 2004;11(3):31922.8 emerg residents (4 PGY-1, 2 PGY-2, 2 PGY-3)1h focused training (didactic and practice on 2 healthy volunteers)SN = 100%, SP = 91.8%, avg scan time = 11.7min (self-reported)4 false-positives (chronic DVT), 0 false-negatives

  • Ultrasound: LimitationsObese, ++edema, immobilsation devices (x-fix)Doesnt see isolated thrombi in iliac or superficial femoral veins within abductor canal MRI betterPelvic masses may cause noncompressibility in absence of thrombus false +veMost importantly: U/S doesnt return to normal after acute DVTTherefore use impedance plethysmography for recurrent DVTU/S - 60-70% of studies return to normal at one yearIP 90% return to normal within a year

  • CT-VenographyGoodman LR, Stein PD, Matta F, et al. AJR Am J Roentgenol 2007;189(5): 10716PIOPED II Data711 pts with CT-V and sonographyResults:95.5% concordance for dx or exclusion of proximal DVTKappa = 0.809Simlar results across all subgroups (asymptomatic, symptomatic, previous DVT)

  • Bottom Line Thus Far?Hx/PE help us decide pretest probability (Wells)We add in a sensitive Test (D-Dimer)And a sensitive confirmatory test (U/S)

    Cause Stone Cold says so!

  • Real-Life ApproachScarvelis, D., and P. Wells. 2006. Diagnosis and Treatment of DVT. CMAJ: 175(9); 1087.

  • Orthe 1620h approachFields, JM, & Goyal, M. Venothromboembolism. Emerg Med Clin of N Am. 2008; 26: 649-83

  • CHR ApproachThe next 4 slides describe the current Calgary Health Region approachNot many people use this as it is a bit outdated but Ive kept the slides here for your interest

  • Wells Criteria for Probability of DVTLOW PROB< 0 pointsMOD PROB1 or 2 pointsHIGH PROB>3 points

    Clinical Hx/SignCriteriaPoints1.Malignancy receiving active treatment for cancerOR have received treatment for cancer in past 6 mo.OR are receiving palliative care for cancer1.02.Limb immobilization ParalysisOR ParesisOR Recent casting of lower extremity1.03.Patient immobilization bedrest (except access to BR) > 3 daysOR surgery in previous 4 weeks1.04.Localized tendernessAlong distribution of deep venous system1.05.Entire leg swollen1.06.Calf swelling>3cm when compared with asymptomatic legMeasured 10cm below the tibial tuberosity1.07.Pitting edemaGreater in the symptomatic leg1.08.Collateral superficial veins dilatedNon-varicose veins1.09.Alternative Dx as likely or more likely than that of DVTNo specific criteria use Hx, Physical, CXR, EKG, and labs to decide-2.0




  • Case 1 ContinuedOkay back to itU/S shows popliteal vein DVTManagement Doctor?

  • Treatment Scarvelis, D., and P. Wells. 2006. Diagnosis and Treatment of DVT. CMAJ: 175(9); 1087.Goals:Short Term:Prevent extension of thrombus and/or PELong Term:Prevent recurrent eventsPrevent complicationsChronic Venous InsufficiencyPainVericose VeinsUlcersPostphlebitc syndromePulmonary Hypertension

  • Medical ManagementRosens Emergency Medicine 6th EditionUsed to be admit start UFH and WarfarinNow know that LMWH equally efficacious and ?more safeMany centres now go for either tinzaparin (175 U/kg OD) or Enoxaparin (1mg/kg BID)UFH (80U/kg IV bolus then 18U/kg/h infusion)Unless contraindications, can start AC in ED[Warfarin (10mg) Required for at least 3 months] not all casesGoal INR is usually 2-3

  • Fixed dose subcutaneous low molecular weight heparins versus adjusted dose unfractionated heparin for venous thromboembolismVan Dongen C. Cochrane Review 200522 studies (n = 8867)

    Thrombotic complications (18 trials)LMWH = 151/4181 (3.6%)UFH 211/3941 (5.4%)OR 0.68; (0.55 to 0.84

    Thrombus size was reduced (12 trials)LMWH= 53%UFH 45%OR 0.69 (0.59 to 0.81)

    Major hemorrhages (19 trials)LMWH = 41/3500 (1.2%)UFH 73/3624 (2.0%)OR 0.57 (0.39 to 0.83)

    Mortality (18 trials)LMWH 187/4193 (4.5%)UFH 233/3861 (6.0%) OR 0.76 (0.62 to 0.92)

    BID dosing ? Better CI for OR crossed 0

    Aric 2005

  • Case 1 ContinuedPt started on Enoxaparin Arranged to see her oncologist and a hematologist as out-patient 2 days later

  • Discharge Scarvelis, D., and P. Wells. 2006. Diagnosis and Treatment of DVT. CMAJ: 175(9); 1087.Outpatient treatment is safe and effective in a wide variety of patientsAdmission may be required if:Co-morbidities:Renal failure, high bleeding riskExtensive DVT (painful blue leg)Necessity for parenteral narcoticsInability to have injections at home

  • Special Circumstances

  • Superficial ThrombophlebitisUncommonly evolves into a thromboemboic eventBUT, many patients have synchronous DVT (~8%)Consider treatment with ASA or LMWHThen symptomatic treatment with:NSAIDSHeatGraded compression stocking (30-40 mmHg)Ambulation

  • Case 244, painful swollen right calfHx/PE:3/7 days ago dull acheNo trauma/previous DVTCalf swollen 4cm, generally tenderNo other risk factorsU/S:Isolated calf DVT

    How do you want to manage this?

  • Isolated Calf or Saphenous DVTCanadian Medical Associan Journal. 2003; 168(2)Rarely causes leg symptoms (80% of symptomatic DVT involve proximal veins) Rarely cause clinical significant PE

    ~25% of untreated calf DVTs will extend to involve the proximal veinsVast majority of those that will progress do so within a week of presentationClinically this means that you can re-U/S them and hold the LMWH (+/- ASA)

  • Phlegmasia Cerulea Dolens (Painful Blue Leg)Massive iliofemoral occlusion results in swelling of the entire leg with extensive vascular congestion and associated venous ischemiaLeg is extremely painful and cyanoticVascular surgery consultIf timely consult not available, early thrombolytic therapy maybe limb-salvaging

  • Upper Limb Venous ThrombosesBernardi, E., et al. 2001. Semin Vasc Med. 1;105-10.Catheter related vs nonALL require treatmentHigh embolization rateIf present, central venous catheters should be removed

  • Whats new and exciting?

  • FondaparinuxMatisse Investigators. Ann Intern Med. 2004;140:867-73.Synthetic polysaccharideAnti Factor XaDBRCT Fondaparinux vs Enoxaparin in symptomatic DVT2205 pts with symptomatic DVT from 154 centres worldwideFondaparinux 7.5mg*sc od vs Enoxaparin 1mg/kg sc bidOutcomes:Symptomatic recurrent VTEBleedingDeath

  • Fondaparinux Matisse Investigators. Ann Intern Med. 2004;140:867-73.At least as safe and effective as LMHTo date: no reported heparin-induced thrombocytopeniaHowever, not available in Canada at this time

  • Other topics for you to think aboutSuperficial ThrombophlebitisThrombolysisIVC filters

  • Pulmonary Embolus (PE)

  • BackgroundRosens Emergency Medicine: 6th EditionPE results from a clot that formed hours, days, or weeks earlier in the deep veins which has traveled to the lungsPresentation is highly variableEPs probably correctly identify about half of pts with PE~10% of ED pts die within 30 days even with prompt diagnosisIf no cardiopulmonary disease, 30% obstruction can be tolerated with minor symptoms only

  • Case 361 presents to ED complaining of mild pleuritic chest pain

    Total knee arthroplasty 5/12 ago. Healthy otherwise

    Tell me about:HistoryPhysicalInvestigations

  • Risk AssessmentEmergency Medicine Reports. 2004;25(11)History and Physical do not confirm the diagnosis, they merely raise the suspicion of the diagnosis, triggering further investigation

    Hx:Have to consider PE: dyspnea, tachypnea Pleuritic CP, syncope, hypotension & hemoptysisNon-specific

    PE:Tachypnea and tachycardia are most common

  • Risk AssessmentEmergency Medicine Reports. 2004;25(11)CXR:Often AbN (Pleural effusion, atelectasis, elevated hemidiaphragm)N CXR with dyspnea & hypoxemia = PEKnow Hamptons and Westermark for examsEKG:Non-specific ST, Twave changes, Tachy Signs of R heart strain (Anterior/Inferior T-wave inversions)Know SIQIIITIII for examsABG:Hypoxemia common, but not always presentAAD02 >20 suggests PE (PIOPED) 25-35% of pts with PE have normal blood gasses, pulse ox, and A-A gradient

  • Bottom LineBy themselves, H&P can help to stratify patientsBut like w/ DVT, we now have standardized criteria

  • Pretest Probability Emergency Medicine Reports. 2004;25(11)All decision trees start hereSeveral existWells and Geneva validatedWells NPV: 99.5%Others more cumbersome to use

    Geneva (Wicki): add ABG, CXRPISA-PED: Add ECG

  • Case 3 ContinuedHR: 104Nil else

    She gets 1.5 points

    Now what?Do you even start to work her up for PE?

  • Pretest ProbabilityRosens Emergency Medicine. 6th Edition One approach is to compare pretest prob with the test thresholdTheoretical cutoff is pretest prob above which some workup should be initiated and below which the pt would be harmed by further testingTest Threshold for PE is ~1.8-2%Canadian (Wells) score
  • PE Rule-Out Criteria (PERC Rule)Kline, JA. et al. J Thromb Haemost. 2004; 2:1247-55Based on the premise that overuse of D-dimer to screen for PE can have negative consequencesDerivation phase:3148 patients evaluated for PE in 10 US EDsData collected on 21 variablesLogistic regression and interobserver agreement used to narrow to rule of 8.

  • PE Rule-Out Criteria (PERC Rule)Kline, JA. et al. J Thromb Haemost. 2004; 2:1247-55Age
  • PE Rule-Out Criteria (PERC Rule)Kline, JA. et al. J Thromb Haemost. 2004; 2:1247-55Validation Phase:2 GroupsLow risk (board certified EP believed D-dimer warranted but good enough to r/o PE) n = 1427, 114 (8%) had VTE diagnosed within 90dVery low risk (chief complain dyspnea PE not suspected) n = 382, 9 (2.4%) had VTE diagnosed within 90d

  • PE Rule-Out Criteria (PERC Rule)Kline, JA. et al. J Thromb Haemost. 2004; 2:1247-55Endpoint: VTE before 90 days. Good follow-upBoth Wells score and PERC rule functioned relatively wellWells better with very low risk population and included more patients in both groupsBoth had very wide confidence intervals

  • PERC Rule Bottom LineCompliments clinical judgement DOESNT REPLACE IT!

    Pause before ordering a D-dimer in a patient who does not have any of the eight criteria

    Then order it if you still think its indicated

  • Case 3 ContinuedAge > 50HR >100Does not meet PERC criteria. Wells 1.5 Send the D-dimerResult: 0.59 mg/L ()Does this mean anything? What if it was 1.9 mg/L?

  • D-dimer in PE

    Does D-dimer level correspond to clot burden in PE?What about mortality?

  • D-dimer in PEGrau, E. et al. Crit Care Med. 2007; 35:1937-41Observational study of 588 pts with symptomatic PEQuantitative D-dimer performed on admission (Automated Latex agglutination test) and clinical follow up for 90 days

  • D-dimer in PEGrau, E. et al. Crit Care Med. 2007; 35:1937-41Compared to pts with D-dimer 500-2499 ng/mL, OR of 90d mortality:1.91 (0.91 4.09) in pts with D-dimer 2500-49992.94 (1.42 6.45) in pts with D-dimer 5000

    Pts with D-Dimer 5000 ng/mL:Higher risk of death from fatal pulmonary embolism OR 4.4 (0.5-33) than from other causes OR 2.1 (0.7-6.0)95% CIs for odds ratios cross 1More of a point of interest= 0.5-2.49 mg/L= 5 mg/L= 2.5-4.999 mg/L

  • Confirmatory TestingEvaluation divided between screening and confirmatory testingScreening is H&P, D-dimerConfirmatory:Gold Standard ?still AngiographyLandmark Articles used: V/Q [Pioped I] CTPA [Pioped II] MRA [Pioped III]

  • PIOPED I V/Q ScanningPIOPED Investigators. JAMA. 1990;263:2753Multicentre study Sens/Spec of V/Q in setting of pre-test probReference standard was Angio/autopsy

  • PIOPED I V/Q ScanningPIOPED Investigators. JAMA. 1990;263:2753

  • PIOPED I V/Q ScanningPIOPED Investigators. JAMA. 1990;263:2753Most important finding was that PE often present in non-diagnostic scans w/ high clinical probabilityExcept in low probability pts, low probability scans require additional testingCT or repeated Dupplex U/S (Rosens)

  • PIOPED II CTA / CTV Stien, P. NEJM. 2006. 354; 22, pp 2317-2327Prospective multicentre study, N = 824Looking at the accuracy of CTA/CTV in setting of clinical prediction tool (Wells)Composite reference standard (incl V/Q, Angio neg U/S)

    CTA Report 51/824 inconclusive (6%)CTA Sens 83%, Spec 96%CTA-CTV inconclusive 87/824CTA-CTV 90% and 95%Mostly 4-slice CT (didnt have enough 8 & 16 slice to comment)

  • PIOPED II CTA / CTV Stien, P. NEJM. 2006. 354; 22, pp 2317-2327

  • PIOPED II Bottom LineLalani, N. Dont Feed Me BS and Call it Candy. 2006

    Didnt really give us the answers that we wantedDidnt enroll 2/3 of eligible ptsCT Scanners have evolved sinceCompared with V/Q, reports are far more binaryCT is probably better than this

  • Dutch study 510 pts all got spiral CT +/- U/SGold standard: 90d follow-upFalse Neg Rate 0.4%, Sens 99.6%8/510 scans indeterminate angio

  • Multi-detector Row CTStork, A. Knows Too Much for Own Good. 20054,8,16, 64 row scannersResolution
  • 8-bit vs 64-bit resolution

  • CT vs AngiographyWlner-Muram, HT. et al. Radiology. 2004; 233(3):806-15Prospective study of 93 pts (emerg and ward) in whom PE was suspected4-slice CT and pulmonary angiography within 48hSN: 100%SP: 89%

  • Meta-analysis of 23 studiesNegative CT PE who didnt receive AC4657 patients

    Results (3 month follow up)VTE: 1.4% (1.1-1.8%)Fatal PE: 0.51% (0.33-0.76%)

    ConclusionsCTPA has similar rates of recurrence as angiographyAppears safe to withhold anticoagulation based on negative CTPA

    Outcomes: Multi-detector Row CT Moores, L., et al. Ann Intern Med. 2004; 141:866-874

  • 15 Studies Reviewed, N=3500Studies excluded:D-Dimer used as initial triage toolInsufficient F/U (needed at least 3 months)Poor quality study (objective criteria)NPV: 99.1% (98.7 - 99.5)NLR: 0.07 (0.05 0.11)

    Outcomes: Multi-detector Row CT Quiroz, R., et al. JAMA. 2005; 293:2012-7

  • CTPEQuickWidely availableRelatively non-invasivePerforms similarly to angiographyProvides a binary outcome (interpreter dependent)Can offer alternative diagnosis when PE is absent

  • CTPE - WeaknessesPoor ability to detect small, peripheral PEs?Clinically relavence

    Protocol variability (slices, legs, venogram included)Interpretation variability (day/night, staff/resident)

    RadiationContrast (anaphylactoid reactions, nephropathy)Pts may have contraindications

  • CT Scanning: Bottom LineCTPA should be considered as good as the gold standard

    When used with DD and U/S, NPV of >95%

  • Magnetic Resonance AngiographyFields, JM, & Goyal, M. Venothromboembolism. Emerg Med Clin of N Am. 2008; 26: 649-83Advantages:Eliminates radiationProbably safer in pregnancyDecreased nephrotoxicity

    Disadvantages:CostAvailabilityFailure to demonstrate adequate SN in preliminary studies

  • PIOPED III MR-APurpose Determine accuracy of Gd-MRA of pulmonary arteries with MRV of the thigh veins in pts with clinically suspected PERationale: In PIOPED II, 25% had contraindications to CTPA/Angio such patients could benefit from safer MRExpect 1250 pts (lots of exclusions incl Pregnant)Calgary is one of the Centres

  • Real-Life AproachFields, JM, & Goyal, M. Venothromboembolism. Emerg Med Clin of N Am. 2008; 26: 649-83

  • CHR ApproachAgain, the next 4 slides describe the current Calgary Health Region approachEven fewer people use this than the DVT model:Released before PIOPED II (CTPE not included)V/Q results dont tend to be this straightforward

  • Wells Criteria for Probability of PETotal Points Probability LR6 HIGH 6.00

    Clinical Hx/SignCriteriaPoints1.S/S of DVT leg swelling objectively measuredAND pain with palpation in the deep vein region3.02.Pulse>100/min 1.53.Immobilization bedrest (except access to BR) > 3 daysOR surgery in previous 4 weeks1.54.Previous DVT or PEMust have been objectively diagnosed1.55.Hemoptysis1.06.Malignancy receiving active treatment for cancerOR have received treatment for cancer in past 6 mo.OR are receiving palliative care for cancer1.07.PE as likely or more likely than an alternative Dx.No specific criteria use Hx, Physical, CXR, EKG, and labs to decide3.0

  • LOW PROBABILITY PE:D-DimerNegPositiveSTOPVQ ScanNormalSTOPNon-highHighCUS legsNormalDVTPulm AngioNormalPositiveCUSIn 1 weekTREATSTOPTREAT

  • MODERATE PROBABILITY PE:D-DimerNegPositiveSTOPVQ ScanNormalNon-highHighCUS legsNormalDVTCUSIn 1 weekTREATTREATPulm AngioOR

  • HIGH PROBABILITY PE:VQ ScanNormalNon-highHighCUS legsNormalDVTCUSIn 1 weekTREATTREATPulm Angio ORPulm Angio OROR Pulm Angio

  • What does the expert say?Wells, PS. J Thromb Haemost. 2007; 5(Suppl 1):41-50Divide pts into PE likely (Wells >4) or unlikely (4)

  • Case 3 ContinuedRecallLow probability (Wells 1.5)D-Dimer: PositiveTherefore...CTPE Positive

  • Treatment Emergency Medicine Reports. 2004;25(12)First decide primary therapySignificant clot burden immediate removalChemical - thrombolysisMechanical embolectomyLess Significant AnticoagulationUFH, LMWH, Coumadin

    Next decide prevention against future emboliAnticoagulationIVC filters

  • Fibrinolysis Ramakrishnan, N. Thrombolsysis is not warranted in submassive pulmonary embolism: A systematic review and meta-analysis. Crit Care Resusc 2007; 9(4)Massive PE:PE with systemic arterial hypotension, cardiogenic shock, severe dyspnea or respiratory failureMultiple case reports/series of improved outcomes and ROSCKucher et al. 2006: no change in mortality or recurrence of PE

    Submassive PE:PE occurring in hemodynamically stable patients with evidence of right ventricular heart strain, as seen on ECG or echocardiographyNEJM 2002; 347(15) 100mg alteplase in addition to heparin improves clinical course (ARR = 13.6%, P=0.006)

  • Fibrinolysis in sub-massive PERamakrishnan, N. Thrombolsysis is not warranted in submassive pulmonary embolism: A systematic review and meta-analysis. Crit Care Resusc 2007; 9(4)Results of randomized trials comparing the addition of thrombolytic therapy to standard heparin therapy for treatment of submassive pulmonary embolism fail to show any significant differences in clinically important outcomes. [Ann Emerg Med. 2007;50:78-84.]

  • Fibrinolytics Bottom LineConsider in PE with hypotension or systemic hypoperfusion or in the rapidly deteriorating patient

  • Out-Patient Treatment of PEMerli, GC. et al. Treating Acute Pulmonary Embolism: Outpatient or Inpatient or Somewhere in between? Thromb Res. 2008; doi:10.1016

    Is it technically possible?Newer treatments allow out-pt treatment of VTELMWHSC UFHIs it safe?Pts at high risk of badness shouldnt go homeMassive & Submassive PE no brainersRisk stratify the rest:Geneva Risk ScorePulmonary Embolism Severity Index (PESI)

  • V. Low Risk = 1.1% 30d Mortality

  • Out-Patient Treatment of PEMerli, GC. et al. Treating Acute Pulmonary Embolism: Outpatient or Inpatient or Somewhere in between? Thromb Res. 2008; doi:10.1016

    Is outpatient treatment appropriate in THIS patient?

    Medical and Social Issues:

    Bleeding risk, underlying malignancy, renal status, obesity, heart failure, thrombophilia, and concomitant medications that interact with anticoagulants (aspirin, clopidogrel, NSAID etc)Medication compliance, availability of home-care, living situation, logistics of bloodwork

  • Out-Pt Treatment of PEBottom Line:

    There is no consensus on who can safely be treated at home

    If the patient is hemodynamically stable, with no signs of R heart strain and otherwise completely healthy, consideration of out-pt treatment is reasonable.

    Would make this decision in discussion with pulmonary or the patients FP.

  • Wait, is she just a little hefty or?Common VTE most frequent cause of death in pregnancy0.5-3.0 / 1000 pregnanciesMost trials exclude pregnant ptsD-Dimer is less specific!More false positives more work-upUS is greatif theres a DVT+ in 13-15% with suspected PEWhat about CTPE? V/Q?MRI/A not studied yet

  • PE in PregnancyWiner-Muram HT, et al. Pulmonary embolism in pregnant patients: fetal radiation dose with helical CT. Radiology 2002;224(2):48792.Historically, V/Q recommended less radiationNewer scanners supposed to be better?V/Q still gives indeterminate results Study used US to determine fetal geometryMonte Carlo method for measuring radiation dose of helical CT 2.5mm cuts to 4cm below xiphoidAverage fetal radiation dose with helical CT is less than that with V/Q lung scanning during all trimesters. Pregnancy should not preclude use of helical CT for the diagnosis of PE.

  • PE in PregnancyCook JV, Kyriou J. Radiation from CT and perfusion scanning in pregnancy. BMJ. 2005;331:350.Compared maternal and fetal-absorbed doses (16-slice)Maternal whole body effective dose:CTPE: 2 mSvV/Q: 0.6 mSvFetal absorbed doses:CTPE: 0.01mGy (1/1 000 000 risk of Ca by age 15)V/Q: 0.12 mGy (1/280 000)Breast absorbed doses:CTPE: 10 mGyV/Q: 0.28 mGy

    CTPE: less risk to fetus, more to moms breasts

  • PE in Pregnancy - TreatmentSame as other populations except WarfarinKnown Teratogen dont use.

  • Bottom LinesHistory and Physical are insensitive and non-specificUse them to determine pretest probabilityD-dimer is a sensitive screening testBut not benign use your headRemember PERC rule only a guidelineAll upper limb DVT require treatmentCTPE is very powerful when combined with DD, U/SIf neg safe to withhold treatment

  • ***Cases/100 000 in those younger than 15500 cases/100 000 in those older than 80SHARP increase after the age of 45

    *PE has an untreated mortality of 26-30% and one autopsy review found that 70% of PEs were not suspected clinically*Vascular injury initiates release of tissue factor that activates factor 10a and leads to increased fibrin formation and deposition.

    Venous stasis allow for increasd fibrin cross-linking

    Clinical states that involve the presence of Virchows triad result in a higher incidence of VTE**Superficial Femoral Vein is indeed a member of the deep group.

    Although thrombosis can occur anywhere in the venous system, it typically forms at locations of injury or stasis, particularly in the valve cusps in the venous sinuses of the calf veins.

    Only thrombus from deeper and more proximal vessels are believed to embolize to the lungs. For this reason, the venous system is divided by proximity and depth. Although distal DVTs are generally not thought to pose an immediate threat to embolization, there is a 20% to 30% incidence of propagation to the proximal venous system. Clinically significant thrombosis can also involve pelvic veins, upper extremity veins, and venous sinuses of the skull.Nurse tells you it says please r/o DVT.

    Where do you want to start?*The history and physical examination are helpful in suggesting the diagnosis, but no one sign or symptom in isolation maintains significant sensitivity or specificity for DVT**Although symptoms are less frequent with smaller and more distal clots, large proximal clots may also be asymptomatic in the presence of adequate collateral veins and patency of vessels.

    The clinical signs and symptoms of DVT are often found in many other conditions affecting the lower extremity including musculoskeletal injuries, cellulitis, ruptured Bakers cyst, vasculitis, congestive heart failure, lymphedema, and other nonthrombotic conditions. Laboratory and radiologic testing are fundamental in the diagnosis of DVT*We need to remember that although making the diagnosis of DVT by history and physical examination alone is inadequate, performing radiologic testing on all patients is unnecessary and inefficient.

    Implementation of clinical prediction rules to assess a patients pretest probability could reduce the need for formal radiologic studies to rule out DVT.**Relatively small study D-dimer - Use evolving concurrently with above studies

    *D-dimer is an end product of clot lysis. When its there, it signifies the existence of thrombus with an active deposition and degradation of cross-linked fibrin by plasmin somewhere in the body.

    Small amounts of D-dimer are normally present in the serum; however, elevated D-dimer levels correlate with increased thrombus volume.

    The problem with the test is that it doesnt discriminate between physiologic (eg, postoperative or post-trauma) and pathologic (eg, deep vein) thrombus.

    D-dimer levels may also be elevated in cancer, late pregnancy, recent trauma or surgery, sepsis, and many other medical conditions, limiting its use.For these reasons the D-dimer is a sensitive, but nonspecific test.

    QUESTION: Causes for a false-negative D-dimer test include small amounts of thrombus, old thrombus, and impaired fibrinolysis.**In 2003, Wells and colleagues showed that a negative whole-blood agglutination or immunoturbidimetric D-dimer test eliminated the need for ultrasound in low-risk patients. Although a negative D-dimer test does not eliminate the need for ultrasound in the intermediate and high-risk population.Nursing should not be ordering D-dimer not part of the protocol

    *possible discussion around what to do with the positive Dimer you didnt order (handover, nursing, etc)*Ultrasound is the test of choice for diagnosis of DVT. It is fast, accurate, and readily available in most EDs. Since the 1990s, ultrasound has replaced venography as the gold standard for DVT because it provides nearly equal diagnostic information while avoiding the risks of invasive venography, (which has a 2% chance of inducing DVT.)*The two methods of ultrasound commonly used when assessing DVT are compression and duplex.

    Compression ultrasound works by the principle that normal veins collapse when extrinsic pressure is applied by the sonographer. When a vein fails to collapse, it indicates the presence of an intravascular mass (thrombus by default).

    Duplex ultrasound is compression ultrasound with the addition of spectral and color flow Doppler to assess respiratory variation and augmentation.*In contrast to compression ultrasonography, duplex is relatively complicated, time consuming, and expensive. Despite these characteristics, it adds little to compression ultrasonography in the diagnosis of DVT.

    When performing compression ultrasonography, assessment of the entire proximal venous system is unnecessary to rule out proximal DVT.

    In a study of 562 venograms performed on patients with DVT, no cases of isolated superficial femoral or pelvic vein thrombosis were identified. All DVTs involved either the popliteal, common femoral, or both veins. This has led to the development of limited compression ultrasonography (LCUS). LCUS is compression ultrasonography focused on the common femoral and popliteal veins. Despite rare case reports of isolated superficial femoral DVTs, studies have demonstrated the safety of withholding anticoagulation after negative LCUS.

    BUT we dont do this here*Many clinicians, including emergency physicians (EPs), are performing bedside ultrasonography to evaluate for DVTs. Jolly and colleagues were the first to demonstrate the ability of EPs to perform color Doppler ultrasonography successfully in a retrospective observational analysis in 1994. Two EPs performed ultrasounds in the ED after training in a vascular laboratory (performing 2530 studies each). The sensitivity and specificity of their color Doppler ultrasounds for acute DVTs were 100% (seven of seven) and 75% (six of eight), respectively. The two false-positives were patients with old DVT.

    In 1999, Frazee prospectively demonstrated a 95.7% negative predictive value (NPV) of EP-performed LCUS.*So we know we can be accurate, but EPs can also maintain their goal of rapid throughput by performing LCUS. Blaivas demonstrated a median examination time of 3 minutes and 28 seconds of EP-performed LCUS, while maintaining a 98% correlation with vascular laboratoryperformed studies on the same patients.

    Another study by Theodoro observed a 125-minute reduction in time to patient disposition with EP-performed US compared with radiology-performed US while also maintaining good correlation.

    Jang and colleagues prospectively studied the ability of eight emergency medicine residents with minimal training in LCUS and found a sensitivity and specificity of 100% and 91.8%, respectively, with an average scan time of 11.7 minutes.**CT venography (CTV) is a diagnostic modality that evaluates the pelvis, thighs, and calves after injection of venous phase contrast material. It has near equal sensitivity and specificity to ultrasound for diagnosing proximal DVT. Because CT angiography (CTA) of the pulmonary vessels and CTV can be performed simultaneously, CTA-CTV is an attractive option for patients with concern for both DVT and PE. Furthermore, CTV can diagnose pelvic and calf DVTs. Cost, radiation exposure (particularly through the reproductive organs), intravenous contrast exposure, and needfor intravenous access are ongoing concerns about the use of CTV.*All patients in the DVT likely group should undergo ultrasonography.

    In patients with a negative LCUS and positive D-dimer test, repeat ultrasonography is recommended to exclude the possibility of distal DVT, which have a 20% to 30% incidence of propagation.

    Another approach is to administer one dose of LMWH and arrange an outpatient ultrasound within 24 hours.*This one gets the US first*The cornerstone of VTE treatment is pharmacologic anticoagulation.

    Anticoagulants work by inhibiting the clotting cascade and shifting the imbalance back in favor of endogenous fibrinolysis. No randomized controlled trial has ever been performed proving the usefulness of heparin, and it was accepted as standard therapy before the widespread use of current diagnostic modalities.

    Treatment with either fixed-dosing LMWH or adjusted-dosing unfractionated heparin (UH) is generally acceptable.

    Benefits of LMWH include easier dosing, no required serial laboratory studies, and easier transition to the outpatient setting potentially decreasing hospital length of stay.*A meta-analysis of LMWH versus UH found LMWH more efficacious with significantly less complications including major bleeding events and death, suggesting superiority of LMWH.

    One major limitation of LMWH is cost. Two studies have now demonstrated that subcutaneous UH can be used alone to treat VTE with similar efficacy and safety as LMWH. Furthermore, Kearon and colleagues validated a safe and effective method of fixed-dosing subcutaneous UH that does not require following activated partial thromboplastin times.

    Pending further studies, subcutaneous UH may provide a significantly cheaper and promising alternative to LMWH.*Superficial thrombophlebitis in the absence of proximal DVT is not known directly to lead to PE. Approximately 8% of superficial thrombophlebitis can extend into the deep venous system, however, usually at the site of the proximal greater saphenous vein, and potentially embolize to the lung.

    The main concern in the ED is to rule out superficial thrombophlebitis extension into the deep venous system by ultrasonography.

    Isolated superficial thrombophlebitis does not require admission, but treatment should be initiated to prevent propagation to deeper veins. Aspirin and LMWH both decrease superficial thrombophlebitis propagation and recurrence with similar efficacy and safety, and either is an acceptable option for superficial thrombophlebitis of the legs. Graded compression stockings, heat pads, and elevation of the affected extremity may help provide symptomatic relief.*Previously, it was believed that isolated calf DVTs did not pose a thromboembolic risk. Longitudinal studies have since shown a 20% to 30% incidence of clot propagation to the proximal venous system with a 20% incidence of embolization.

    In symptomatic patients, LCUS provides only 73% sensitivity for distal DVTs. High-risk patients with a negative LCUS and positive D-dimer test should undergo repeat ultrasound in 7 days to exclude propagation of a distal clot.

    In addition to clot propagation and PE, distal DVTs result in postthrombotic complications, such as pain, edema, and hyperpigmentation, in 10% to 38%of patients.

    Treatment of distal DVT is controversial and either aspirin or low-dose LMWH therapy is currently acceptable. Given the incidence of clot propagation and postthrombotic complications, many clinicians recommend treating distal DVTs the same as proximal DVTs with full anticoagulation therapy. When aspirin therapy is used alone, serial ultrasonography is recommended to ensure lack of propagation to proximal vessels.*Phlegmasia cerulea dolens is a severe form of DVT in which venous obstruction of the major deep veins and collateral veins leads to a sharp rise in venous pressure, massive interstitial fluid shifts, decreased arterial perfusion, compartment syndrome, and gangrene.

    Recognition of phlegmasia cerulea dolens is important in the ED for consideration of time sensitive interventions, including anticoagulation, catheter-directed thrombolysis, and vascular surgical consultation*Upper-extremity DVT includes thrombosis in the internal jugular, innominate, subclavian, or axillary veins. It occurs in approximately 16 per 100,000 persons in the United States. Central access devices represent the largest risk factor and are associated with 80% of all upper extremity DVTs.

    Peripherally inserted central catheters, frequently used for their lower incidence of infectious complications, have a 10% to 40% incidence of upper-extremity DVT.

    It is unclear why some patients form spontaneous (noncatheter associated) upper-extremity DVTs. An analysis of one large registry found younger age, lower body mass index, non-white race, and smoking to be factors more common in spontaneous upper-extremity DVTs, suggesting this entity has a differentpathophysiology from other forms of VTE*PE occurs when a thrombus breaks free from the endothelial wall, travels through the right side of the heart, and lodges into the narrowing pulmonary arteries. Depending on the size and shape of the clot, it may come to rest in the main pulmonary artery, in a tiny subsegmental artery, or anywhere in between. The shape may allow for normal blood flow or it may obstruct an entire vessel. Minute differences within the vasculature can lead to a myriad of pathophysiologic consequences resulting in a wide range ofclinical signs and symptoms.*Symptoms associated with PE depend on the degree of vascular obstruction, the magnitude of inflammatory response, and the patients physiologic reserve. V/Q mismatch manifests as dyspnea, hypoxemia, and increased A-a gradient.

    Extravasation of blood into alveoli can cause pleuritic pain, cough, or hemoptysis. Increased pulmonary vascular resistance can lead to strain patterns on EKG; pleural effusions; right ventricular dilatation or hypokinesis; or severe right heart outflow obstruction manifesting as hypotension, syncope, or pulseless electrical activity cardiac arrest. It may also manifest as hypoxia if previously closed atrial septal defects open and cause significant transcardiac shunting.

    The natural history of PE is to present atypically and can include any combination of these findings or none at all.*Similar to clinical signs and symptoms, most tests used in the ED have poor sensitivity and specificity for PE and are nondiagnostic. Nondiagnostic tests that may be abnormal in PE include electrocardiogram, chest radiograph, arterial blood gas, echocardiography, brain natriuretic peptide, and troponin-T.

    CXROften abN (one study says 76%, but the changes are often nonspecific

    EKGThe EKG occasionally reveals manifestations of right heart strain, usually in patients with massive PE. The most common finding in patients with non-massive PE is normal sinus rhythm. In patients with massive PE, anterior T-wave inversions were found more frequently (68%) than sinus tachycardia(28%) or S1Q3T3 (50%). In a population of patients with confirmed PE studied by Kosuge and colleagues, T-wave inversions in both leads V1 and III had 99% specificity. Some authors suggest that the finding of simultaneous T-wave inversions in the anterior and inferior leads should prompt consideration of PE even when it had not been previously suspected.*To avoid this problem, Kline and colleagues developed the pulmonary embolus rule out criteria rule to identify which low-risk patients do not need D-dimer or other testing, essentially a close to no-risk group. When all eight criteria are present there is less than 2% possibility of PE. *The PERC criteria have been validated in two separate patient populations.*Before single and MDR-CT, the V/Q scan was the first-line imaging modality for PE.

    It is a nuclear imaging test that assesses for areas of ventilation without perfusion as evidence of PE. Scan results include normal, low probability, intermediate probability, or high probability.

    *The appropriate interpretation of results depends on assessment of pretest probability. Here, a high probability scan was 96% accurate when the clinical probability was high, but only 56% accurate when clinical probability was low. Furthermore, 57% of patients with PE had low- or intermediate-probability V/Q scans.

    *Because of frequent indeterminate results, V/Q scans do not affect management 40% to 60% of the time, making it a less popular test in the ED.

    A normal chest radiograph increases the likelihood of a diagnostic V/Q scan, whereas patients with abnormal chest radiographs have diagnostic scintigraphy only 9% of the time in one report.

    Still, the V/Q scan is useful and needed in a subset of patients with a contraindication to CT. Data from PIOPED II are more promising for V/Q scan than PIOPED I, finding a determinate result of PE or no PE in 77.4% of patients.

    *Data from PIOPED II shows that CTA follows the rules of Bayes theorem similarly to other diagnostic tests in VTE. That is to say that the positive andnegative predictive values of CTA are affected by the pretest probability of disease. A negative CTA is more likely a true-negative in the low-risk group, and a positive CTA is most likely a true-positive in the high-risk group. In high-risk patients, the NPV is a disappointing 60%. In this group, the addition of CTV to CTA augments the NPV to 82% and is recommended by the PIOPED study group.

    *The weakness of CTA is its poor ability to detect small peripheral PEs. Further interpretation of this data as well as those from other studies go into this further, but in the interest of time, well move on.

    Many of these studies bring on the question of whether these additional subsegmental PEs found on MDR-CTA are clinically relevant. No study has demonstrated safety in withholding anticoagulation to patients with diagnosed isolated subsegmental PEs, but some authors liken them to distal DVTs that do not necessarily warrant full anticoagulation. Given the dynamic balance of fibrin formation and breakdown in the body, some believe that one of the natural functions of the lung vasculature is to filter the blood and prevent clots from traveling to other end-organs. Others believe, however, that diagnosis of subsegmental PE is evidence of a prothrombotic state and increased risk for further VTE.


    Not huge numbersHad 3 independent reviews of all studies*The weakness of CTA is its poor ability to detect small peripheral PEs. Further interpretation of this data as well as those from other studies go into this further, but in the interest of time, well move on.

    Many of these studies bring on the question of whether these additional subsegmental PEs found on MDR-CTA are clinically relevant. No study has demonstrated safety in withholding anticoagulation to patients with diagnosed isolated subsegmental PEs, but some authors liken them to distal DVTs that do not necessarily warrant full anticoagulation. Given the dynamic balance of fibrin formation and breakdown in the body, some believe that one of the natural functions of the lung vasculature is to filter the blood and prevent clots from traveling to other end-organs. Others believe, however, that diagnosis of subsegmental PE is evidence of a prothrombotic state and increased risk for further VTE.

    *MRA provides another diagnostic choice in PE diagnosis. Multiple MRA techniques exist with varying degrees of accuracy. The most common is gadolinium-enhanced MRA, which accurately identifies proximal clots,but poorly detects subsegmental emboli.

    One study found a sensitivity of 77% and specificity of 98% of gadolinium-enhanced MRA for PE.

    Recently, MR perfusion scanning was developed, which uses signals from gadolinium to estimate blood volume in regions of the lung. Identification of decreased blood volume represents indirect evidence of PE. Although studies are few, one study found a sensitivity and specificity of 100% and 91%, respectively, when perfusion MRI was compared with MDR-CTA.

    Role still needs to be defined my take: dont hold your breath! (Sorry, bad joke)*There is some debate to the use of D-dimer in the intermediate probability group. Although some studies have demonstrated that a single D-dimer may safely be used in the intermediate-risk group, the clinician must be aware that the posttest probability from a negative D-dimer in this group was still 5% (assuming a pretest probability of 30% and a NLR of 0.1)

    *Prevalence rates of PE for each pretest probability group based on multiple clinical prediction rules*On diagnosis or high suspicion of PE, rapid initiation of therapy can be lifesaving. Treatment with either UH or LMWH is acceptable and the principles are similar to treatment of DVT.

    When PE is strongly suspected (ie, high probability), initiation of heparin therapy before radiologic confirmation likely provides more benefit than risk. Clots can enlarge at an exponential rate. Furthermore, normotensive patients who die from PE do so within the first 24 hours, underscoring the importance of rapid assessment and treatment.

    In patients with PE and an absolute contraindication to anticoagulation or patients already on full anticoagulation, an emergent inferior vena cava filter should be considered.*Fibrinolytics rapidly dissolve clot by active breakdown of fibrin, but they are nonselective and can cause severe bleeding.

    Fibrinolysis involves the administration of recombinant or bacterial tissue plasminogen activators that increase circulating plasmin and accelerate fibrin breakdown.

    Their use is generally recommended for massive PE with hemodynamic instability where the risk of bleeding is overshadowed by the potential benefits, but the benefit is unclear.

    Multiple case reports and small case series suggest potential improved outcomes and return of spontaneous circulation following fibrinolytic administration

    In a study by Kucher and colleagues fibrinolytic therapy did not decrease 90-day mortality or recurrence of PE in patients with massive PE. The data are equally as unimpressive in patients with submassive PE.

    Still, fibrinolysis should be considered in patients who show signs of clinical deterioration with worsening respiratory distress or hypotension because PE-related cardiac arrest has a dismal prognosis.

    *In the NEJM paper, the primary end point was in-hospital death or clinical deterioration requiring an escalation of treatment, which was defined as catecholamine infusion, secondary thrombolysis, endotracheal intubation, cardiopulmonary resuscitation, or emergency surgical embolectomy or thrombus fragmentation by catheter.

    When you separate out the important clinical outcomes.this is what you see obviously not as impressive!*Im not going to present any data specifically on massive PE, but basically, if theyre going down the tubes, consider lytics.

    With respect to embolectomy, in patients with massive PE refractory to fibrinolysis, surgical embolectomy performs better than repeat fibrinolysis. Embolectomy provides a reasonable and potentially lifesaving final therapeutic pathway in massive PE. When successful, patients have excellent long-term results. *The Geneva Risk Score (Table 4) is a clinical scoring system that has undergone both internal and external validation.

    The Geneva Risk Score was developed using multi-variate analysis of clinical factors present at the time of admission in 296 consecutive patients with pulmonary embolism.

    During the 3 month follow-up, 2.2% (4 of 180) of low risk patients (a score 3).

    Aujesky et al developed and validated the pulmonary embolism severity index to classify patients with acute pulmonary embolism into categories of increasing risk of mortality and other adverse medical outcomes. In this study of 15,531 inpatients discharged with pulmonary embolism from 186 Pennsylvania hospitals, 11 factors were found to be independently associated with 30 day mortality.

    The risk class specific mortality varied from 1.1% in Risk Class I to 24.5% in Risk Class V.*So, Is it technically possible to treat somebody at home? Yes

    Can it be safe? In the right, low-risk patients probably

    Now you need to look at your patient and decide if its appropriate to treat them out of hospital. That requires consideration of their other medical conditions and their unique social factors*VTE is the most frequent cause of death in pregnancy with the highest risk in the postpartum period.

    As with non-pregnant patients, symptoms and signs of VTE can be highly variable. Because many trials exclude pregnant patients, questions arise as to the correct usage of diagnostic testing in this population.

    Use of D-dimer testing in pregnancy is controversial. As in non-pregnant patients, D-dimer tests provide good sensitivity, but specificity decreases asgestational age increases. Lower specificity means more false positives and more patients needing imaging. When signs of DVT are present, ultrasound is the recommended diagnostic strategy because it poses no known risk to the fetus. When PE is suspected, presence of DVT clinches the diagnosis, but when symptoms of DVT are absent, ultrasound is rarely positive.

    What about CTPE or V/Q?*Previously, V/Q scan was recommended over CTA as the initial diagnostic study for PE in pregnant patients because of decreased radiation exposure.Newer-age CT scanners have significantly less radiation delivered to the fetus to near equal or even lower doses of radiation from V/Q scanning.

    Fetal radiation dose from lung scanning is approximately 100370 Gy, which is apparently a relatively low exposure.

    For helical CT, estimated mean fetal doses in micrograys at varying gestational ages were as follows: 3.320.2 Gy, first trimester; 7.976.7 Gy,second trimester; and 51.3130.8 Gy, third trimester*Less risk to fetus, more to mom (particularly breast Ca)

    Pregnant women with a family history of breast cancer or who have had previous computed tomography for pulmonary angiography may wish to elect for lung perfusion scans, despite the slightly higher risk to the fetus.*