INTRODUCTION

A platelet count of >400 × 109/L far exceeds the 95th percentile range for both women and men and is therefore considered to represent the threshold platelet count for “thrombocytosis.” Recent evidence implicates thrombopoietin (TPO) receptor (i.e., MPL) polymorphisms as being partially responsible for the marked variation in normal platelet counts. In fact, some MPL polymorphisms – for example, G1238T, which results in lysine-to-asparagine change at amino acid 39, has been shown to be associated with abnormally increased platelet counts in approximately 7% of African Americans. Therefore it is important to appreciate the possibility that some cases of “thrombocytosis” might not represent disease.

Causes of thrombocytosis include nonneoplastic conditions as well as hematologic and solid malignancies (Table 11.1). Because thrombocytosis associated with a myeloid disorder is integral to the underlying clonal process, it is usually referred to as “primary” or clonal thrombocytosis (CT). CT is distinguished from all other thrombocythemic states including reactive (RT) and congenital thrombocytosis. The latter condition is very rare and should be distinguished from “familial ET,” which is equally rare. Some cases of congenital thrombocytosis have recently been associated with mutations of either TPO or MPL. In the former instance, transmission is usually autosomal dominant and the mutation involves the 5′-untranslated regions of the TPO mRNA (a donor splice site), resulting in efficient ligand production.