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The diagnosis and prognosis of venous thromboembolism : variations on a
theme
Gibson, N.S.
Publication date
2008
Link to publication
Citation for published version (APA):
Gibson, N. S. (2008). The diagnosis and prognosis of venous thromboembolism : variations
on a theme.
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In this thesis new variations on the themes diagnosis, prognosis and treatment of venousthromboembolismarediscussed.InpartIaspectsofthediagnosticprocessof venousthromboembolismareevaluated,andinpartIIsomeaspectsoftheprognosis, aswellasthetreatmentofpulmonaryembolismaredescribed.
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DIAGNOSISOFVENOUSTHROMBOEMBOLISM
Chapter2givesanoverviewoftheepidemiology,etiology,diagnosis,treatmentand prognosisofpulmonaryembolism. InChapter3avalidationoftheWellsclinicaldecisionruleindicates,thatalthoughthe odds ratios of the 7 items of the rule did decrease, the prevalence of pulmonary embolism in the three clinical probability groups are fully comparable to the prevalence distribution originally obtained. Therefore, seven years after the introduction of the Wells rule the diagnostic power of this simple tool remains adequate.However,duetotheregressionoftheoddsratiosoftheindividualitems,a simplificationoftheWellsclinicaldecisionrule,byassigningonepointtoeachitemof theruleseemedattractive.Ourfindingsshowthatbydoingso,usingacutoffvalue of 1 or less, the diagnostic power remains comparable to this slightly more complicatedcomputationoftheoriginalrule.AvalidationofthissimplifiedWellsruleispresentedinChapter4inanindependent large cohort of patients with suspected pulmonary embolism. It is shown that the proportion of patients categorized as pulmonary embolism unlikely is similar using the original Wells rule and the simplified version (78% and 70%, respectively). The prevalenceofpulmonaryembolismis13%and12%,respectively,inpatientswithan unlikelyclinicalprobability assessment.Therefore,thesimplifiedWellsrule appears tohavethesamepredictiveaccuracyastheoriginalruleandasimilarclinicalutility intermsoftheproportionofpatientsinwhomthediseasecanbesafelyexcluded. Chapter 5 evaluates by questionnaire based survey the implementation of clinical decision rules and Ddimer assays in clinical practice of internists and pulmonologists. Our findings indicate that although physicians are aware of the guidelinesforthesetestsforthediagnosisofpulmonaryembolism,theydonotuseit consistently. Furthermore, the knowledge of an abnormal Ddimer test result before seeingthepatient,leadstoahigherclinicaldecisionrulescore.Therefore,physicians
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should be cautious in requesting Ddimer assays, and they should first examine the patientbeforetakingnoticeoftheDdimertestresult.
ThisisfurthersupportedbythefindingsinChapter6thatshowthatinpatientswith anormalDdimerindependentoftheclinicalprobabilitythethreemonthVTEriskis 2.3% with an upper level of the 95% confidence interval of approximately 4%, whereas in patients with a likely clinical probability despite a normal Ddimer approximately 1 in 10 will still have pulmonary embolism. These patients with a likely clinical probability should undergo further testing, regardless the Ddimer outcome.
The findings of the measurement of the prothrombin fragment 1+2 (F1+2) concentration,reportedinChapter7revealalowerareaundertheROCcurveforthe fragment,relativetoDdimer(0.69and0.82,respectively;p<0.05).Furthermoreusing the information from F1+2 levels in patients with an abnormal Ddimer does not resultinaclinicallyusefulimprovementofexcludingthedisease.
In Chapter 8 the safety and efficiency of two diagnostic ultrasound strategies are compared in consecutive patients with suspected deep venous thrombosis (DVT). A total of 1002 patients were included and in 481 patients with an unlikely clinical probabilityandanormalDdimertestresultDVTwasconsideredexcluded(3month VTE rate 0.4%; 95% CI 0.051.5%). All others were randomized to undergo either a rapid CUS, repeated if necessary, or a single complete CUS examination. DVT was confirmedin59ofthe257patients(23%)thatunderwentrapidCUSandin99ofthe 264patients(38%)thatunderwentcomplete CUS.Venousthromboembolismduring followupoccurredinfourpatients(2.0%;95%CI0.65.1%)intherapidCUSarmand in2patients(1.2%;95%CI0.24.3%)inthecompleteCUSarm.Hence,itisconcluded that both the rapid and the complete ultrasound test are comparable and efficient strategieswithdifferingpro’sandcon’s.
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PROGNOSISANDTREATMENTOFPULMONARYEMBOLISM
InChapter9theprognosticvalueofrightventriculardysfunctionisevaluated.Seven studies that used echocardiography to diagnose right ventricular dysfunction were reviewed and they show that there is an association between right ventricular dysfunction and prognosis of pulmonary embolism in normotensive patients. Whether this is clinically useful in guiding more aggressive therapy, remains to be determined.Thusfar,theresultsofthestudiesthatusedspiralcomputedtomography
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to measure right ventricular dysfunction are too preliminary to enable definitive conclusionstobedrawnforthenormotensivepatientgroup.
Concerning chronic thromboembolic pulmonary hypertension (CTPH), our findings in chapter 10 do not support an active and systematic search for this disease in patients with a history of recent pulmonary embolism. Only one patient out of 110 patients (0.9%; 95% CI 0.024.96%) with pulmonary embolism was known to have CTPH, and this patient was diagnosed before our investigation. However, a low threshold approach in those patients with complaints of dyspnoea on exertion is warranted.
Chapter 11 is a survey of how patients with pulmonary embolism are treated inthe Netherlandsin2006.Intotal94%ofall140patientswithpulmonaryembolismwere admittedtohospital,withameanstayof8.2days(range152days).Itwasnotclear what the considerations were of physicians to treat patients in hospital for a certain period,butitcouldbeduetoaroutinesettingofadmittingpatientswithpulmonary embolism,ratherthanclinicalconsiderations.SecondaryprophylaxiswithvitaminK antagonists usually lasted 6 to 12 months and the treatment duration was guided mainly by well known risk factors, such as the presence of malignancy or previous venousthromboembolism.
