Article

Tempo di protrombina: quale denominatore per il PT Ratio e quali possibilità di utilizzo dell’INR al di fuori della terapia anticoagulante orale

Rivista Italiana della Medicina di Laboratorio 8(1). DOI: 10.1007/s13631-012-0039-y

ABSTRACT Premesse
Nella pratica di laboratorio, il tempo di protrombina (PT) viene utilizzato per la diagnostica dei difetti congeniti o acquisiti della coagulazione o per il monitoraggio della terapia con i farmaci anticoagulanti orali. L’espressione del risultato in termini di INR è raccomandata solo nell’ultimo caso, ma in molti laboratori si utilizza lo INR anche per i pazienti non anticoagulati. Inoltre, come denominatore per l’espressione dei risultati del PT viene raccomandato il “mean normal PT” (MNPT), ma questo è spesso sostituito da un plasma “normale” liofilo, con la conseguenza di intervalli di normalità potenzialmente diversi con la stessa combinazione reagente-coagulometro.

Metodi
L’imprecisione di due tromboplastine del commercio (Neoplastin Plus, cervello di coniglio, Roche, e Innovin®, fattore tissutale umano ricombinante, Siemens) è stata testata sul medesimo coagulometro (STA-R, Roche) con plasmi liofili normali e patologici (Roche, control plasma 1 and 2; Siemens, normal and abnormal plasma and INR calibrator L1). L’intervallo di normalità dei rapporti del PT (PT Ratio) con i due reagenti è stato ottenuto per 40 volontari adulti apparentemente sani utilizzando il MNPT (calcolato in precedenza su 20 altri volontari sani) o i plasmi “normali” liofili come denominatore. Il paragone delle diverse modalità di espressione del PT Ratio con i due reagenti è stato condotto su 200 plasmi da pazienti esterni (n=90) od ospedalizzati (n=110) non anticoagulati. I risultati sono stati anche paragonati utilizzando lo INR.

Risultati
L’imprecisione totale (CV%) dei due reagenti, valutata con i plasmi normali e patologici ricostituiti, era simile e variava da 1,1% a 2,5%. Nei controlli, i PT Ratio ottenuti con i due reagenti erano simili e la media non differiva da 1,0 (p ≥0,17) utilizzando il MNPT come denominatore, ma le medie risultavano significativamente diverse da 1,0 con i plasmi normali liofili (da 0,90±0,07 a 1,05±0,08, p ≤0,03). Nei pazienti, i valori di PT Ratio erano simili solo quando si utilizzava il MNPT a denominatore. Utilizzando una procedura WHO semplificata e assumendo Neoplastin Plus (ISI coagulometro-specifico =1,31), come tromboplastina di riferimento, l’indice di sensibilità coagulometro-specifico di Innovin® risultava pari a 0,77 (0,73–0,80, LC al 95%), con correzione di Tomenson (10−d) pari a 1,09. La trasformazione dei PT Ratio in INR dava luogo, indipendentemente dal termine a denominatore, a significative differenze tra le due tromboplastine, e la percentuale dei pazienti con valori anormali di PT con Innovin® saliva da 38,5 a 62,5.

Conclusioni
I plasmi liofili commerciali “normali” non sono un valido sostituto del MNPT nel determinare gli intervalli di normalità del PT, e dovrebbero essere utilizzati solo per il controllo di qualità. L’espressione dei risultati del PT come INR nei pazienti non anticoagulati dà luogo a falsi valori anormali e andrebbe evitata nella pratica di laboratorio.

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