Thrombocytosis and abnormal liver enzymes: A trigger for investigation of underlying malignancy

Abstract

Background Thrombocytosis is often an incidental finding in primary care with a range of causes. Despite evidence of a strong association between thrombocytosis and malignancy, guidelines for investigating thrombocytosis in the absence of red flag symptoms remain unclear. A novel automated system of laboratory analysis, intelligent Liver Function Testing (iLFT), launched in Tayside in 2018 and has identified a patient group with thrombocytosis and abnormal liver test (LFT) results. This study analysed the outcome of these patients and investigated the use of thrombocytosis combined with LFTs in predicting risk of cancer. Methods and findings Between August 2018 and August 2020, 6792 patients underwent iLFT, with 246 found to have both thrombocytosis and at least one abnormal LFT. A random case-matched control group of 492 iLFT patients with normal platelet count and at least one abnormal LFT was created. 7.7% (95% CI 4.7–11.8%) of patients with thrombocytosis had cancer compared to 2.0% (1.0–3.7%) of controls. Patients <40 years or with pre-existing causes of thrombocytosis were then excluded. Subsequent analysis revealed a 10.8% (6.6–16.3%) incidence of cancer in thrombocytosis patients (n = 176) compared to 2.5% (1.2–4.6%, p = 0.00014) in patients with normal platelet count (PLT) (n = 398). When thrombocytosis is combined with elevated alkaline phosphatase (ALP), there is a positive predictive value (PPV) of 20% for cancer. These rules were subsequently applied to a validation cohort of 71,652 patients, of whom 458 had thrombocytosis and elevated ALP. There was a 30.6% cancer incidence, confirming the strong predictive value of the combined test of PLT and ALP. Conclusions These findings suggest a substantial increased risk of cancer in patients with thrombocytosis and raised ALP. This could be developed as an adjunct to current investigation algorithms, highlighting high-risk patients and prompting further investigation (such as computed tomography scans) where indicated.

Intelligent Liver Function Testing (iLFT): An Intelligent Laboratory Approach to Identifying Chronic Liver Disease

“…On further investigation, it was found that the specific combination of elevated alkaline phosphatase (>130 U/L) and platelets (>400 × 10 9 /L) in individuals over 40 years of age had a positive predictive value (PPV) of 20% for malignancy. When this was tested in a validation cohort of 71,652 patients, the PPV was 30.6%, vastly exceeding the 3% investigation threshold recommended by the National Institute for Health & Care Excellence for malignancy risk and warranting further (routine) investigation [39,40].…”