Are patients with high-normal platelet counts at increased risk of cancer? The NORMA study.
Problem
Thrombocytosis – a platelet count greater than 400 x109/l – is a newly discovered risk marker of cancer, with a one-year cancer incidence of 11.6% for men and 6.2% for women. This exceeds the 3% risk threshold set by the UK National Institute of Health and Care Excellence for rapid investigation of suspected cancer. These findings suggest that patients with a platelet count at the upper end of the normal range may be at increased risk of an undiagnosed malignancy. The present study investigated the one-year cancer incidence in patients with a peri-normal platelet count.
Approach
We conducted a primary care-based cohort study using electronic medical records from 2005-2015 within the Clinical Practice Research Datalink. The study cohort consisted of 295,316 patients stratified by platelet count; 150-325 x109/l (control sample), 326-350 x109/l, 351-375 x109/l, and 376-400 x109/l. Patients’ primary care records were linked to National Cancer Registration and Analysis Service (NCRAS) data to obtain one-year cancer incidence, and stage at diagnosis. Patients were aged 40 years or older and had no malignancies prior to their platelet count date.
Findings
One-year incidence of all cancers (excluding non-melanoma skin cancer) increased greatly with age, male gender, and higher platelet count. The highest incidence was found in males aged 80+ years in the 376-400 x109/l group at 7.6% (95% CI 6.1%-9.4%), whereas the incidence for males in this age group in the control sample was 4.6% (95% CI 4.1%-5.1%). The 3% risk threshold was reached for all males aged 70+, and for all men aged 60-69 with a high-normal count. No female grouping reached this threshold. Stage at diagnosis for incident cancers was more likely to be late (stages 3-4) in patients with a high-normal platelet count. Colorectal cancer was the most common incident cancer.
Consequences
These results suggest that clinicians should consider the possibility of cancer in males aged 60 or over with a platelet count greater than 325 x109/l. A high-normal count may also reflect a more advanced malignancy. These results support previous work suggesting that the upper threshold for a normal platelet count in men aged 60 years could perhaps be reduced.