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DVT & PE James Huffman & Dr. Trevor Langhan 11.12.2009

DVT & PE

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DVT & PE. James Huffman & Dr. Trevor Langhan 11.12.2009. DVT Diagnostic Algorithm Determining Pre-test Probability Useful Diagnostics Treatment Disposition Special Circumstances PE Similar topics, PLUS: Controversies. - PowerPoint PPT Presentation

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  • DVT & PEJames Huffman & Dr. Trevor Langhan

    11.12.2009

  • DVTDiagnostic AlgorithmDetermining Pre-test ProbabilityUseful DiagnosticsTreatmentDispositionSpecial CircumstancesPESimilar topics, PLUS:Controversies

  • 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

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

  • Diagnostic Approach: Pre-test ProbabilityScarvelis, D., and P. Wells. 2006. Diagnosis and Treatment of DVT. CMAJ: 175(9); 1087

  • DVT: History & PE are Risk Assessment

    Goals of H&P?Determine pre-test probabilityLook for other causes

  • Case 1: History & Physical Exam

  • History & Physical are 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 DVTUse them to decide pre-test probability

  • Pretest Probability

  • 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 Dimer!

  • D-Dimer TestingKline, et al. Ann Emerg Med (2003); 42(2): 266-275.

    Degradation product of fibrinNon-specificPPV bad+ve: surgery, trauma, hemorrhage, CA, pregnancy, sepsis, >80 yrs oldSensitivity variableNeed Pre-test probability to r/o DVT

    CLS uses

  • Clinical VariableScoreActive Cancer (treatment ongoing, within 6 months or palliative)1Paralysis, Paresis or recent casting of lower extremities1Recently bedridden 3 days or more, or Surgery A in past 3 months1Localized tenderness along distribution of deep venous system1Entire leg swollen1Calf swelling at least 3cm larger than asymptomatic leg1Pitting edema confined to the symptomatic leg1Collateral superficial veins (Non-varicose)1Previously documented DVT1Alternative Diagnosis at least as likely as DVT-2

  • D-Dimer Testing Wells, P., et al. 2003. NEJM: 349(13); pp1227-35RCT (N=1096)D-Dimer vs no D-DimerDVT unlikely (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 than ours) Conclusion:Wells

  • Level 1 Pretest Probability

  • 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)

    So she gets either 4 or 2 points = DVT likely

  • What next Einstein?

  • Level 2 D-dimer

    Her d-dimer was positive at 1.23

  • Level 3 Ultrasound (or not)

  • UltrasoundAmerican Journal of Respiratory Critical Care Medicine. 1999: 160; 1043-66

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

  • AnatomyDepth:DeepSuperficial*Proximity:Popliteal v. or higherDistal

    *Superficial femoral vein is a member of the deep groupEmerg Med Clin N Am. 26 (2008)

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

  • Bedside U/S?Jolly BT, et al. Acad Emerg Med 1997;4(2):12932.Frazee BW, et al. J Emerg Med 2001;20(2):10712.

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

    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): 10716

  • DVT: Bottom Line Thus Far?Hx/PE help decide pretest probability (Wells)Add a sensitive test (D-Dimer)Almost all cases, do a sensitive confirmatory test (U/S)

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

  • Level 4 - Treatment

  • Medical Management

    Rosens Emergency Medicine 7th EditionScarvelis, D., and P. Wells. 2006. Diagnosis and Treatment of DVT. CMAJ: 175(9); 1087

  • Treatment: Bottom Line

    IV UFH, LMWH, Fondaparinux are all acceptable

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

    In General, discharge home is safe. Admission may be required if:Renal failure, high bleeding riskExtensive DVT (painful blue leg)Necessity for parenteral narcoticsInability to have injections at home

  • Special Circumstances

  • Superficial Thrombophlebitis

    Rosens Emergency Medicine 7th EditionUncommonly evolves into a thromboemboic eventBUT, ~8% of patients have synchronous DVT

  • Isolated Calf or Saphenous V. ThrombosisCanadian Medical Association Journal. 2003; 168(2)Rarely cause significant PE25% of calf DVT extend to involve proximal veinsVast majority will extend within 7dDVT complications in 10-38% (untreated)

    Clinically this means you can Rx ASA (325mg/d) and arrange for re-U/S in 7d or just start on full DVT anticoagulation

  • Phlegmasia Cerulea Dolens (Painful Blue Leg)

  • Pulmonary Embolism

  • Case 2 61 presents to ED complaining of mild pleuritic chest pain

    Total knee arthroplasty 5/12 ago. Healthy otherwise

  • 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

  • Pretest Probability Emergency Medicine Reports. 2004;25(11)All decision rules start w/ scoreWells and Geneva validatedWells NPV: 99.5%Others more cumbersome

    Geneva (Wicki): adds ABG, CXRPISA-PED: Adds ECG

  • Bottom Line:Use history & physical exam risk stratify patients

    Wells 4 PE UnlikelyWells > 4 PE Likely

  • H&P are Risk AssessmentWells, PS. J Thromb Haemost. 2007; 5(Suppl 1):41-50Wells 4 UnlikelyWells > 4 Likely

  • 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 examsSimultaneous TWI in V1 and III are highly specificABG: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

  • Case 3 ContinuedHR: 104Nil else

    She gets 1.5 points

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

  • 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 inter-observer 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 Groups:Low risk (board certified EP believed D-dimer warranted but good enough to r/o PE) n = 1427, 114 (8%) had VTE diagnosed within 90d

    Very 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
  • PERC Rule Bottom LineCompliments clinical judgment 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 2 ContinuedAge > 50HR >100Does not meet PERC criteria. Wells 1.5 Send the D-dimerResult: 0.59 mg/L ()

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

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

  • PIOPED II CTA / CTV Stien, P. NEJM. 2006. 354; 22, pp 2317-2327CTA inconclusive: 6%CTA Sens: 83%, Spec: 96%CTA-CTV 90% and 95%

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

  • 8-bit vs 64-bit resolution

  • 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

  • Bottom LineMulti-detector row CTPA should be considered the gold standard

  • 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

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

  • Treatment Emergency Medicine Reports. 2004;25(12)Houman et al. J Thromb Thrombolysis. 2009. 28:270-7First decide primary therapySignificant clot burden immediate removalChemical - thrombolysisMechanical embolectomyLess Significant AnticoagulationUFH, LMWH, (Fondaparinux) Coumadin

    Next decide prevention against future emboliAnticoagulationIVC filters

  • Spectrum of PEKearon et al. 2008 Chest.Massive (PE + shock)Thrombolysis + ICU

    Submassive (PE + NBP + RV Dysfxn)Admission, anticoagulation, +/- thrombolysis

    Symptomaticprobable admission, anticoagulated, +/- echo

    AsymptomaticYou probably dont even know about it .

  • 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

  • GRS vs PESIGRSSn 34% (18-51)Sp 85% (82-88)PPV 11% (5-18)NPV 96% (94-98)

    PESISn 81% (68-95)Sp 37% (33-41)PPV 7% (4-9)NPV 97% (95-99)Jimenez. Chest 2007

  • 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 resultsAverage 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 guidelineCTPE is very powerfulIf neg safe to withhold treatmentFibrinolysis if hypotensive, hypoperfused or circling

  • 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]

  • 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

  • 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

  • *Welcome introductions ground rules parking lotOutlineWeve got a lot to cover today Ive done my best to pare this down to essential, important, relevent information.Expect that Ive made some assumptions about your knowledge level but if youre having problems at ANY time and need to review basics just ask. Algorithm is real-life [ask if anyone knows likely vs. not-likely approach as bridge-in/pre-assessment]Controversies include:Submassive PE and Firinolysis [reference EM:RAP]Outpatient treatment of PEsDiagnosis of PE in the pregnant patient*I want to make sure were always emphasizing the bottom line hereor in this case, the line of bottoms.*Slide to show you importance!

    VTE is a spectrum : Simple superficial thrombophlebitis to fatal PE [explain]Est incidence : 1 /10001/3 of cases are PEIncreases dramatically with age (sharp increase after the age of 45 100 times more in the oldies)

    Constantly have clot forming/breaking down. VTE is the end-product of imbalance btw these processes[R-2 Any ideas of what might contribute to this balance shifting to too much clot formation?] Virchows Triad!

    *Vascular injury initiates release of tissue factor that activates factor 10a and leads to increased fibrin formation and deposition.

    Venous stasis allow for increased fibrin cross-linking (conditions stasis = CHF, immobilization, pre-existing small clots)

    Hypercoagulable states should be obvious (but more than just factor 5 leiden, etc. Think smoking, BCP, CA, auto-immune disorders)

    One study I read: age as an independent risk factor but there regression model wasnt clear.

    All clinical states that involve the presence of Virchows triad result in more clot forming and thus a higher incidence of VTE*Nurse tells you it says please r/o DVT.

    [R1 or med student - Where do you want to start?]

    [Get them to talk about history and physicalGOOD! this introduces the concept of pre-test probability and clinical decision rules]*The goal of determining pre-test probability is to put people in groupshigh and low, or high, medium and low.

    Going to present you with the new algorithm right off the top. Its based on the Wells score and has dichotomized the risk groups into DVT likely and DVT Unlikely. [click]Two questions I know you have:Why are we using these clinical decision rules at all? Isnt my judgment as a physician just as good? And Why Wells? Is it the best? How do we know?

    Answers:Youre right, when you think about, oh say, the peds appendicitis scoreor most clinical decision rules for that matter. Theyre complex and basically just state the obvious leaving you in the middle ground. A limited number of studies have been performed evaluating empirical judgmentMeta-analysis of these found almost identical test characteristics [a +LR of 6.2 (compared to 5.2 for Wells DVT likely) and a LR of 0.18 (Wells = 0.25)]BUT: not validated, a lot of intra-observer discrepancy and results varied with physician experience

    Yes, there are several other rules out there. Some trying to simplify, some just trying to be famous.Wells is the most widely used and tested.Kappa is reasonable at 0.85 and is not impacted by experience of the physicianBUT, subjective component, not validated in all risk groups (preg. Or very old)Several others exist, but ROC curves rarely approach and never significantly surpass that of Wells (0.76) and none of those have been adequately validated.

    Bottom Line: We should be using a clinical decision rule to help us determine pre-test probability, and Wells is probably the one to choose.

    *History: my impression is that you need to work through Wells criteria, as well as look for elements of Virchows triad

    So youre going to look for Hypercoaguable states:CancerSyndromesSmokingMeds/BCPStasisImmobility: Not just surgery remember other conditions (oldies!)Heart Disease (AMI & CHF): independent of bedrestTravel ?Duration / proximity?HyperlipiedmiaPolycythemiaEndothelial InjuryStrokeVascular surgeryPVD

    Classic Physical exam:Leg tenderness , Homans SignSwellingPitting edemaDilated superficial veinsErythemaCalorWell talk more about the physical signs in just a few slides.**HistoryStarted 3 days 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

    [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?

    The problem with using clinical signs and symptoms for diagnosing DVT is that the classic findings 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.

    So this brings us to our bottom line on history and physical exam:

    *We need to remember that although making the diagnosis of DVT by history and physical examination alone is inadequate,BUT, at the same time, performing radiologic testing on all patients is unnecessary and inefficient.

    When clinical prediction rules are used to assess a patients pretest probability, the need for formal radiologic studies is reduced.*This is my segway into talking about the Wells Score*The Wells Score has gone through 3 versionsDont worry, Im only going to go through the final one. [click]The first Wells Criteria was based on a literature review and clinical experience of investigators. useful because they showed you could reduce the number of ultrasounds you do by using such a rule. [Click]

    Wells then revised his score through logistic regression.

    The new score was prospectively validated using same treatment algorithm as the first. (Basically put people into low, medium and high risk groups then ultrasounded everybody and looked at DVT rates in each group).

    They had 593 patients from two Canadian tertiary care centres and in the end they concluded that combining clinical probability and an ultrasound protocol was safe (0.6% miss rate).* The algorithm they used to develop and validate their ClinPredict Rule was good, and was re-published in the JAMA RCE series.

    Something was missing what test havent we spoken about yet [Ask R1 see if youre paying attention]

    Thats right! the use of D-dimers was evolving concurrently with the development of the rule. Lets look at them a little closer.

    *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.

    [Causes for a false-negative D-dimer test] include small amounts of thrombus, old thrombus, and impaired fibrinolysis.*Based on these new data, and an analysis of the data from their original validation studies, Wells and his group modified the score (added the circled element above), dichotomized the risk categories (=2 likely) and planned a new study using the simpliRED D-dimer.

    (This is the current, most validated version of the score Ill send it out to you guys if youre interested.)

    The study took 1096 outpts with presentations suspicious for DVT, assessed and put into one of the two categories. They were then either assigned to ultrasound alone, or d-dimer PLUS ultrasound (unless they were dvt unlikely and dimer was negative).

    In the DVT unlikely group, there wer 601 patients and their results played out like this [click]

    **In the end, they showed that a negative D-dimer test eliminated the need for ultrasound in patients who were DVT Unlikely!

    Take home points from this flowchart:If your pt is DVT unlikely (Wells