Are patients with high-normal platelet counts at increased risk of cancer?

Introduction

Thrombocytosis (clinically high platelet count) is a recently discovered risk marker for cancer. The incidence of cancer within one year of a high platelet count is 11.6% for men, and 6.2% for women; far exceeding the 3% threshold of cancer risk that the NICE clinical guidance (NG12) suggests should prompt a referral for further investigation. These findings suggest that patients with a platelet counts at the high end of the normal range may also be at increased risk of cancer, and this is what the NORMA study seeks to investigate.

NORMA is using a large dataset of electronic medical records from approximately 300,000 patients with recorded platelet counts in the Clinical Practice Research Datalink. These records are linked to cancer registration data to provide further information on cancer incidence and staging. The broad research questions for this study are:

• What is the one-year incidence of cancer in patients with a high-normal platelet count, compared to controls with counts in the remainder of the normal range?
• Which cancers are patients with high-normal platelet counts most at risk of?
• At which platelet count threshold are patients at a 3% risk of cancer?

Funding

Policy Research Unit for Cancer Screening, Awareness, and Early Detection

Aims & objectives

NORMA aims to estimate the one-year and two-year incidence of cancer for men and women of different ages and with various levels of high-normal platelet count, as well as controls with platelet counts in the remainder of the normal range. We will also explore which cancers are most common in these groups, and whether platelet count is associated with the stage of cancer at diagnosis.

NORMA will also investigate the platelet count at which men and women would meet the NICE criterion of 3% risk of cancer to prompt referral for further investigation for cancer.

Methodology

We have obtained electronic medical records (Clinical Practice Research Datalink) linked to national cancer registry data for 299,992 patients with platelet counts in the range of 150 to 400 x109/l. Patients with a platelet count >325 x109/l have been categorised as having a high-normal count, and further split into the following platelet count groups; 326-350 x109/l, 351-375 x109/l, 376-400 x109/l. Patients with a platelet count in the range of 150-325 x109/l are the control sample.

Additionally, patients have been grouped by 10-year age bands, from 40-49 years up to 80+, as well as by gender, for a total of 40 age-sex-platelet group strata. For each of these strata, we have investigated the one-year and two-year incidence of cancer, and determined which cancers are most common, and the proportions diagnosed at a late stage (stages 3-4).

Regression modelling and Receiver Operating Curve analyses will be used to explore the relationship between cancer incidence and platelet count as a continuous variable. This will enables us to explore at which platelet count patients meet the 3% risk threshold set by NICE for further cancer investigation.

Outputs & impact

Initial findings from NORMA will be presented at the 2019 international Ca-PRI conference in Toronto, Canada. The main findings will be written up for publication in a high-impact, peer reviewed journal, with additional papers under consideration.

The study that NORMA follows on from has been incorporated into NICE guidance on suspected cancer. The present study may help refine guidance for clinicians who may suspect cancer in a patient who has a high-normal platelet count. Additionally, there is currently a discussion as to whether the current clinical criterion for thrombocytosis is appropriate, and NORMA has the potential to inform that discussion.

Next steps

We are currently seeking funding to further develop this programme of work investigating cancer risk in patients with high platelets. This work would explore the early diagnostic potential of platelet count in lung cancer, as well as the molecular mechanisms of the association of platelets with cancer.

Resources

Clinical relevance of thrombocytosis in primary care: a prospective cohort study of cancer incidence using English electronic medical records and cancer registry data. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5442956/