The majority of hospitalized patients exhibiting extreme thrombocytosis, defined as a platelet count of greater than 1000 × 109/L, do not have an underlying hematologic malignancy, according to results of a study published in the Mayo Clinic Proceedings.

Two retrospective studies conducted several decades ago showed that extreme thrombocytosis can be due to inflammation occurring secondary to another disorder or condition (ie, reactive thrombocytosis) or occur as a primary manifestation of an underlying hematologic malignancy (ie, a clonal thrombocytosis). However, neither of these studies accounted for whether or not the patient with extreme thrombocytosis was hospitalized, and both attributed the condition to a single cause.

In this retrospective chart review study, 305 adult patients seen at the Mayo Clinic in Rochester, Minnesota, between 2011 and 2016 were classified as having extreme thrombocytosis according to 2 separate platelet count readings within 30 days, and also underwent bone marrow biopsy when recommended.

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Interestingly, of the more than 44,000 patients examined at the Mayo Clinic during this period who were classified as having thrombocytosis, 1.4% exhibited extreme thrombocytosis. Hence, extreme thrombocytosis was shown to be “a rare occurrence in unselected patients who had thrombocytosis.”

In the overall group of patients with extreme thrombocytosis, 68.9% were determined to have reactive thrombocytosis alone resulting from trauma, surgery, asplenia, infection, inflammatory disorder, nonhematologic malignancy, medications, hemorrhage, iron deficiency, and/or electroconvulsive therapy and 10.8% had a clonal hematologic malignancy without reactive causes of extreme thrombocytosis. In the remaining 20.3% of patients, the etiology of essential thrombocytosis was determined to be due to both reactive causes as well as an underlying hematologic malignancy.

“Most cases of extreme thrombocytosis were multifactorial, and likely the results of cumulative ‘hits’ from various conditions known to cause thrombocytosis,” the researchers noted. Furthermore, essential thrombocytosis resolved within 30 days for most patients in the study group.

Of the 38 patients (12.5%) with a newly diagnosed malignancy, 33 were determined to have hematologic cancers and 5 were non-hematologic cancers. Almost all patients (91%) in the subgroup with newly diagnosed hematologic malignancies were determined to have myeloproliferative neoplasms, with essential thrombocytosis most common (44.7%), followed by chronic myeloid leukemia (15.8%), polycythemia vera (7.9%), and primary myelofibrosis (5.3%).

Notably, when the patient care setting was taken into account, surgery and an underlying hematologic malignancy were found to be the most likely causes of extreme thrombocytosis in inpatients and outpatients, respectively.  A hematologic malignancy was more than 3-fold more likely to be a factor contributing to the manifestation of extreme thrombocytosis when the patient was evaluated outside of the hospital compared with a hospital setting. Furthermore, a patient with essential thrombocytosis in an outpatient setting was nearly twice as likely to have a new hematologic malignancy compared with a patient in an inpatient setting.

Based on their findings, the study authors recommend a bone marrow evaluation “only if none of the major causes — recent surgery, active infection, history of splenectomy, and myeloproliferative neoplasms — are present at the time of extreme thrombocytosis evaluation.”


Hsieh RW, Ravindran A, Hook CC, et al. Etiologies of extreme thrombocytosis: a contemporary series. Mayo Clin Proc. 2019;94:1542-1550.