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DISCRASIE EMATICHE DA TICLOPIDINA
(Achille P. Caputi, Dipartimento Clinico e Sperimentale di Medicina e Farmacologia, Sezione di Farmacologia, Facoltà di Medicina, Università di Messina)

La ticlopidina è un farmaco antiaggregante piastrinico, efficace nel trattamento delle vasculopatie cerebrali, coronariche, periferiche e, associato all'aspirina, dopo l'inserimento di stents coronarici.
Sebbene la neutropenia, la più frequente forma di discrasia ematica, da ticlopidina sia stata individuata per la prima volta nei trials clinici pre-marketing di fase III , solo gli studi di farmacovigilanza hanno permesso di osservare che il farmaco produce altre rare e gravi forme di discrasia ematica.
In letteratura esistono numerose segnalazioni che documentano che il farmaco può provocare:

• Agranulocitosi^(1-11);
• Anemia aplastica^{(8, 12-30)};
• Neutropenia^{(1, 31-38)};
• Pancitopenia^(39-42):
• Trombocitopenia^(43-45):
• Porpora trombotica trombocitopenica^{(38, 46-57)}.

Conseguentemente alla morbidità sopra riportata (ed alla mortalità conseguente), la ticlopidina deve essere considerato come farmaco di seconda scelta in pazienti che risultano intolleranti nei riguardi dell'aspirina, hanno controindicazioni o non rispondono.

Il rischio relativo di patologie ematologiche, a seguito di terapia con ticlopidina, è riportato in tabella I, anche in confronto ad altri farmaci.

Recentemente, Paradiso-Hardy e coll⁽⁷⁰⁾ hanno condotto una analisi in letteratura (dal gennaio 1966 al dicembre 1999 su MEDLINE) analizzando tutte le segnalazioni di discrasie ematiche da ticlopidina, riportate in lingua inglese e francese. Hanno così identificato 211 casi di cui 91 sono stati analizzati attentamente per valutarne il rapporto di causalità con il BARDI (Bayesian Adverse Reaction Diagnostic Instrument)^(71-73).
Tali rapporti erano relativi a:

• Agranulocitosi : 15 casi
• Anemia aplastica: 29 casi;
• Neutropenia: 14 casi
• Pancitopenia: 4 casi
• Trombocitopenia: 3 casi:
• Porpora trombotica trombocitopenica: 26 casi.

In 22 di questi casi le reazione avversa è risultata fatale (24% dei casi).
Il tempo di latenza della reazione avversa, la sua durata ed il suo esito per i 91 casi sono riportati nella tabella II.

L'analisi condotta da Paradiso-Hardy e coll⁽⁷⁰⁾ dimostra che nel 90% dei rapporti pubblicati (82 su 91) la ticlopidina era sicuramente la causa della patologia ematologica.

Circa i meccanismi che possono essere implicati nel causare discrasie ematiche da ticlopidina, sono state avanzate le seguenti ipotesi:

• Effetto citotossico diretto, in pazienti geneticamente predisposti, sui precursori mieloidi a livello del midollo osseo^{(7, 12, 74)};
• Formazione, come per i sulfamidici e gli anticonvulsivanti, di un metabolita attivo che potrebbe risultare tossico a livello ematologico in pazienti incapaci a metabolizzarlo⁽¹⁹⁾.
• Meccanismi immunologici diversi^{(5, 31, 74)}.

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