Haematological ADRs

Haematological ADRs

INTRODUCTION

The scope of haematology for our purposes in this chapter is the consideration of effects on (a) the different cell types that circulate in the peripheral blood; (b) the bone marrow that generates and replenishes those cells, many of which have a short lifespan; and (c) the mechanisms involved in plasma coagulation that maintain haemostasis.

One of the adverse drug reactions (ADRs) most feared by both prescribers and manufacturers alike is the unpredictable, idiosyncratic and unexpected occurrence of peripheral blood cytopenias due to myelosuppression. These are type B reactions accord-ing to the classification of Rawlins and Thompson (1977). The demonstration of an association with this type of reaction has been responsible for the with-drawal of licensing of many drugs over the years by the relevant authorities.

It is salutary to reflect that, in the industri-alised world, serious life-threatening haematological ADRs are also a regular, deliberate and accepted part of everyday medical practice. Predictable dose-dependent, reversible, ‘type A’ cytopenias are the anticipated counterpart of effective cytotoxic ther-apy for malignant disease. Strategies and facilities for monitoring and detection followed by appropri-ate supportive intervention with antimicrobial agents, blood product and growth factor therapy are integral to the practice of physicians prescribing these drugs.

Whilst this chapter will concentrate on the rarer type B reactions, it is important to note that the advances in supportive care and expertise developed in relation to cytotoxic therapy that have led to improved outcomes and the safe intensification of many chemotherapy regimes are equally applicable to idiosyncratic reac-tions. It is critically important that affected patients are recognised early and referred to appropriate expertise and facilities.

Myelosuppression is the principal dose-limiting effect for most cytotoxic agents, but in the context of the treatment of malignant disease it is often appropriate to accept a narrow therapeutic index for effective agents. Although rare, there are examples where this can also be justified for type B reactions in non-malignant disease. Clozapine is an example of a uniquely effective drug in a difficult thera-peutic field (refractory schizophrenia). Despite an established association with the potentially danger-ous ADR of agranulocytosis, the drug is specially licensed for use under strictly specified monitoring conditions.

Genetic risk factors are being identified, which may predispose patients to reactions with particular drugs. As marker tests become available, previously appar-ently idiosyncratic reactions may be anticipated for certain individuals, allowing dose adjustment or alter-native treatment choices to prevent ADRs.

This chapter will review the types of reaction by which drugs may cause cytopenias or affect plasma coagulation. By considering examples of documented ADRs, strategies for predicting, detecting and preventing reactions, as well as managing those which do occur, are discussed.