Esami ematochimici e
biomarcatori nel paziente con
Perdita Transitoria di Coscienza
(T-LOC): PRO e CONTRO
Gianfranco Cervellin
UO Pronto Soccorso e Medicina d’Urgenza
Azienda Ospedaliero-Universitaria di Parma
www.gimsi.it
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Due punti fermi:
•  80% delle decisioni terapeutiche (anche
quelle sbagliate!), in ambito
ospedaliero, sono fondate su risultati di
esami di laboratorio
•  Responsabilità del clinico nella fase
pre-analitica! SINCOPE
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Jones BA, Arch Pathol Lab Med, 2009
Brain-to-brain loop
Responsabilità clinica Responsabilità clinica Responsabilità clinica Responsabilità del laboratorio Responsabilità clinica Responsabilità clinica Responsabilità organizza3va Il sogno del laboratorista ! Quesito fondato sulla diagnosi “pancrea3te? " lipasi” SINCOPE
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“Lex parsimoniae.
Pluralitas non est ponenda sine necessitate.” William of Ockham, 1287-1347
Il sogno del medico d’urgenza ! Quesito fondato sul sospe>o sincope " neuromediata? ipovolemica? gravidanza ectopica? TEP? aritmia? dissecazione aor3ca? aneurisma aorta addominale? etc. etc. Test specifico??? SINCOPE
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“Lex vasti.
Pluralitas est ponenda ex necessitate.” Medico di origini veneziane, 1955-vivente
È evidente che le due visioni difficilmente si conciliano SINCOPE
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Quindi: i profili! SINCOPE
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I profili di laboratorio in emergenza-­‐urgenza. Dubbi: • 
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Per diagnosi? Per quadro sindromico? Sono clinicamente efficien3 ed efficaci? Sono economicamente sostenibili? Sono Evidence Based? Sono Pa3ent Based? I profili di laboratorio in emergenza-­‐urgenza • 
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Dolore toracico Dolore addominale Dispnea Stroke Aritmie Sincope Alterazioni stato di coscienza Gastroenterite/Diarrea Trauma maggiore Us3oni ……… I profili di laboratorio in emergenza-­‐urgenza • 
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Dolore toracico Dolore addominale Dispnea Stroke Aritmie Sincope Alterazioni stato di coscienza Diarrea Trauma maggiore Us3oni Profilo sincope??? SINCOPE
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Profilo sincope??? SINCOPE
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Emerg Med Clin N Am 2010
Emerg Med Clin N Am 2010
Piccola parentesi: la gravidanza in PS SINCOPE
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Una diagnosi di gravidanza Inaspe>ata ogni 3.8 giorni! Amer J Med 2015;128: 161-170
SINCOPE
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Amer J Med 2015;128: 161-170
SINCOPE
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Amer J Med 2015;128: 161-170
SINCOPE
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Amer J Med 2015;128: 161-170
SINCOPE
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Amer J Med 2015;128: 161-170
Increased cTnThs levels indicate adverse prognosis
in patients with noncardiac causes of syncope, but not
in patients with cardiac syncope, being a risk factor
for adverse outcome by itself.
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Emerg Med Clin N Am 2010
Di tuV i test diagnos3ci per la sincope, l’approfondita valutazione della storia clinica e l’ esame fisico hanno la più alta “resa” diagnos3ca Cosa cresce invecchiando? SINCOPE
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D-dimer is an old test:
•  Early 60s: fibrin(ogen) degradation products (FDP)
•  Early 80s: first monoclonal antibody-based assay for
D-dimer, a specific fibrin(ogen) degradation products
Topics •  S3ll valid the “posi3ve/nega3ve” rule? Do age, gender, plasma levels ma>er? •  Only useful in ruling out venous thromboembolism? •  How to use it in the Emergency Department? SINCOPE
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Topics •  S3ll valid the “posi3ve/nega3ve” rule? Do age, gender, plasma levels ma>er? •  Only useful in ruling out venous thromboembolism? •  How to use it in the Emergency Department? SINCOPE
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2014;25:45-48
•  Retrospec3ve inves3ga3on. Year 2012, ED of Academic Hospital of Parma (88958 visits) •  All the pa3ents for whom a D-­‐dimer test was requested by an EP in order to exclude or reinforce a diagnos3c suspicion of VTE according to clinical signs and symptoms (clinical Gestalt and/or predic3on rule based on Revised Geneva score or on Wells score). •  All the cases displaying a value above the 243 ng/mL diagnos3c cut-­‐off for VTE of the local immunoassay, regardless of their pre-­‐test clinical probability for VTE, were selected. •  Final cohort: 1647 pts. (mean age: 77±15 yrs.; 756♂ and 891♀) 2014;25:45-48
•  Highly significant correla3on between age and D-­‐dimer levels in the en3re cohort of pts. (R=0.08; p=0.010) •  Highly significant correla3on between age and D-­‐dimer levels in the VTE pts. (n=200; R=0.23; p=0.001) •  Highly significant correla3on between age and D-­‐dimer levels in the non-­‐VTE pts. (n=1447; R=0.08; p=0.005) 2014;25:45-48
Infection: ~2/3 pneumonia
VTE: 88 PE, 112 DVT
Using the conventional cut-off of 0.5 mg/dl,
PE/DVT could be excluded in 68%
of patients, whereas the age-adjusted cut-off
[(age ×0.016) mg/l] ruled out 77% of patients.
Particularly in patients >70 years, the negative
prediction accuracy of excluding a PE/DVT
increased explicitly. The failure rate of the
age-adjusted cut-off value was 0.8%
(95% confidence interval 0.3–1.6%).
These data suggest that method specific cut-off values calculated
according to patient age and gender can be more accurate in
identifying patients at a higher risk for VTE recurrence.
These method-specific cutoff values are being evaluated in the
ongoing prospective management multicenter DULCIS study.
Topics •  S3ll valid the “posi3ve/nega3ve” rule? Do age, gender, plasma levels ma>er? •  Only useful in ruling out venous thromboembolism? •  How to use it in the Emergency Department? SINCOPE
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1990
2014, epub ahead of print
•  An inverse and highly significant correlation was found between
serum potassium and D-dimer (r = −0.21; p < 0.001), even after
adjustments for age and sex.
•  The relative risk for a positive D-dimer value attributed to
hypokalemia was 1.64 (95% CI, 1.02 to 2.63; p = 0.040).
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Medicine 2015;94(4):e471)
34 studies.
The pooled sensitivity of D-dimer levels in AAD patients was 94.5% (95%
confidence interval [CI] 78.1%–98.8%,P<0.001)
The specificity was 69.1% (95% CI 43.7%–86.5%,P¼0.136).
The pooled area under the receiver-operating characteristic curve for D-dimer
levels in AAD patients was 0.916 (95% CI 0.863–0.970, P<0.001).
D-dimer levels are best used for ruling out AAD in patients with low likelihood
of the disease.
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Topics •  S3ll valid the “posi3ve/nega3ve” rule? Do age, gender, plasma levels ma>er? •  Only useful in ruling out venous thromboembolism? •  How to use it in the Emergency Department? SINCOPE
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Preanalytical issues:
remember Rev. Thomas Bayes!
Rev. Thomas Bayes 1702 – 1761
2009;16:256-60
•  Of 237 patients enrolled, 205 patients had a suitable plasma sample
and complete follow-up.
•  Nearly a half of all patients (n=94; 46%) had a plasma D-dimer
concentration above the upper limit of normal.
•  An elevated plasma D-dimer concentration was found in all patients
with a pulmonary embolus.
•  Plasma D-dimer is frequently raised in patients presenting with
syncope to the ED and does not predict 1-month serious outcome
or death.
•  We conclude that there is no role for the routine measurement
of D-dimer in themanagement of patients presenting to the ED
with syncope.
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Napoleone Bon
“La tecnologia è considerata – erroneamente -­‐ un sos3tuto efficace del tempo.” Bernard Lown, Lituania 1921(inventore del defibrillatore;
S. di Lown-Ganong-Levine….)
Take your 3me and observe the pa3ent! SINCOPE
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Documento di consenso GIMSI-­‐AcEMC (*) Ges3one della sincope di natura inspiegata dopo la valutazione iniziale in Pronto Soccorso I.Casagranda (chairman), M.Brignole, S.CenceV, G. Cervellin, G.Costan3no, R.Furlan, G. Mossini, F. Numeroso, M.Pesen3 Campagnoni , P. Pinna Parpaglia, A Ungar. SINCOPE
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Keywords:
1. OBI
2. Syncope Unit
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Messaggio (scien3fico) finale: Per gli esami di laboratorio u3lizzare un unico percorso clinico… SINCOPE
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Il percorso vena (del paziente)
" cervello (del medico)
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