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Thrombocytosis due to clozapine treatment: working towards an early marker for clozapine-induced agranulocytosis

Thames Gateway NHS Trust, Mental Health Directorate, Medway Maritime Hospital, Windmill Road, Gillingham, Kent ME7 5NY

EDITED BY MATTHEW HOTOPF

Recently, Hampson (2000) 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) (American 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 x 10⁹/l or neutrophil count below 1.5 x 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 (Provan, 1997), and is associated with clozapine response (Arranz 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.

REFERENCES

American Hospital Formulary Service (1997) Drugs Information (ed. G. K. McEvoy), pp. 1743-1744. Bethesda, MD: American Society of Health-System Pharmacists.

Arranz, M., Collier, D., Sodhi, M., et al (1995) Association between clozapine response and allelic variation in 5-HT2A receptor gene. Lancet, 346, 281-282.[CrossRef][Medline]

British Medical Association & Royal Pharmaceutical Society of Great Britain (2000) British National Formulary, no. 39 (March 2000). London: BMJ Books & Pharmaceutical Press.

Hampson, M. E. (2000) Clozapine-induced thrombocytosis (letter). British Journal of Psychiatry, 176, 400.[Free Full Text]

Provan, D. (1997) Myelodysplastic syndromes. Prescribers' Journal, 37, 17-23.

This Article Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Marlowe, K. Search for Related Content PubMed Articles by Marlowe, K.