Recently, Hampson (Reference Hampson2000) reported thrombocytosis with clozapine, and serious consideration must be given to reports that identify potential markers for the development of agranulocytosis. Haematological side-effects include leucopenia, neutropenia and thrombocytopenia (1-3% of patients); and anaemia, leucocytosis and thrombocytosis (<1% of patients) (Reference McEvoyAmerican Hospital Formulary Service, 1997). Thrombocytosis reported with clozapine treatment may give evidence of the mechanism of agranulocytosis in some patients.
In some cases clozapine is discontinued if the differential white blood cell count shows an initial drop with starting clozapine treatment. If a re-challenge on clozapine results in either thrombocytosis or thrombocytopenia, this may be a result of an immune reaction, as both these platelet abnormalities are recognised features of such a reaction. (Note that it is now recommended that permanent withdrawal of clozapine should occur for leucopenia below 3 × 109/l or neutrophil count below 1.5 × 109/l (British Medical Association & Royal Pharmaceutical Society of Great Britain, 2000)).
Clozapine has a direct action on the haematopoietic stem cells of the bone marrow and can therefore trigger a reaction similar to an acute myeloid leukaemia or myeloproliferative disorder. It is hypothesised that an abnormal haematocrit and platelet abnormality could be seen if clozapine caused these side-effects via an immune reaction on the haemopoietic tissue. Karyotype analysis provides useful prognostic information in myelodysplastic syndrome (Reference ProvanProvan, 1997), and is associated with clozapine response (Reference Arranz, Collier and SodhiArranz et al, 1995). A high index of suspicion when reviewing the full blood count or karyotype analysis could lead to a marker before fatal agranulocytosis occurs as a result of clozapine.
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