Thrombocytosis (raised platelet count) and subsequent cancer risk

A prospective cohort study has been undertaken investigating the association between thrombocytosis and subsequent development of cancer (1).

• the cohort was a random sample of 50000 patients who had had a primary care full blood count taken. Within this there were two sub-cohorts: patients with thrombocytosis and patients with a normal platelet count
  • the thrombocytosis sub-cohort included 40000 patients selected using four criteria:
    • a platelet count of >400 x 10^9/L, henceforth labelled 'thrombocytosis'; no previous thrombocytosis;
    • aged >=40 years at the time of thrombocytosis;
    • and the thrombocytosis event was recorded from 2000 to 2013 inclusive
      
      
  • a 1-year cancer incidence of 11.6% (95% CI = 11.0 to 12.3) for males and 6.2% (95% CI = 5.9 to 6.5) for females; this is equivalent to the PPV of a raised platelet count
    • in patients with a normal platelet count there were 106 cancers diagnosed in males and 119 in females; a 1-year cancer incidence of 4.1% in males (95% CI = 3.4 to 4.9) and 2.2% in females (95% CI = 1.8 to 2.6)
      
      
  • the risk of cancer increased with increasing platelet count - risk of cancer increased to 18.1% (95% CI = 15.9 to 20.5) for males and 10.1% (95% CI = 9.0 to 11.3) for females, when a second raised platelet count was recorded within 6 months
    
    
  • patients with thrombocytosis were at consistently greater risk than those with normal platelet counts across all ages; the difference in risk between those with and without thrombocytosis increased from age 70 years
    
    
  • specific cancers:
    • lung and colorectal cancers were the most commonly diagnosed cancers in the thrombocytosis cohort
      • lung cancer - of the 31 261 patients with thrombocytosis, 573 were diagnosed with lung cancer; 195 (35.7%) had no symptoms warranting urgent investigation as per NICE guidance, other than thrombocytosis
      • colorectal cancer - 627 of the 31 261 patients with thrombocytosis were diagnosed with colorectal cancer; 206 (32.9%) had no symptoms in the year before diagnosis warranting urgent investigation for cancer
      • at least one-third of patients with lung and colorectal cancer with pre-diagnosis thrombocytosis had no other symptoms indicative of malignancy
        
        
  • positive predictive value of thrombocytosis is 11.6% (95% confidence interval [CI] = 11.0 to 12.3) for males and 6.2% (95% CI = 5.9 to 6.5) for females

Notes:

• the acronym LEGO is used to define the cancers possibly suggested by thrombocytosis by NICE cancer guidance (2):
  • Lung cancer
  • Endometrial cancer
  • Gastric cancer
  • Oesophageal cancer
• the association between thrombocytosis and colorectal cancer has been noted by SIGN (3)
  • there is emerging evidence that thrombocytosis is a risk marker for underlying cancer, including colorectal
• the acronym has therefore been updated to LEGO-C
  • Lung cancer
  • Endometrial cancer
  • Gastric cancer
  • Oesophageal cancer
  • Colorectal cancer
    
    
• thrombocytosis and cancer (4):
  • activated platelets can participate in tumour progression via multiple mechanisms
    • platelets themselves can promote primary cancer growth by releasing different types of growth factors, chemokines, proangiogenic regulatory proteins, and proteolytic enzymes that promote tumour cell growth and invasion; platelets can also enhance the dissemination and implantation of cancer by assisting in the formation of platelet-tumour cell hetero-aggregates
    • cancer is believed to induce platelet formation through the release of interleukin 6, a proinflammatory cytokine that stimulates the production of thrombopoietin hormone (7)
      • raised levels of thrombopoietin have a direct effect on increased platelet production
        • excess levels of thrombopoietin in the blood stimulate megakaryocyte cell division in the bone marrow, which in turn results in platelet formation
          
          
• high-normal platelet count and cancer risk: (5)
  • there is study evidence that platelet counts at the high-normal range in males aged >=60 years may be indicative of an underlying malignancy
  • however this addition to the knowledge base concerning platelet count and cancer risk may be impractical operationally if asking GPs to be aware of "normal" platelet counts in case of possible malignancy. This seems to indicate the need to have more specific platelet count ranges (based on age and gender) which would alleviate the need to assess a "normal" test result as potentially "abnormal" (6)
    
    
• raised platelet count and subsequent risk of cancer - 10 year study
  • nested case-control study of 8,917187 Ontario residents who had 1 or more routine complete blood count tests performed, an elevated platelet count was associated with a diagnosis of cancer within 10 years after the blood test
  • magnitude of the association varied by cancer type and time elapsed since the blood test
  • each platelet count based on the percentile distribution for the cancer-free controls
    • five mutually exclusive categories were created: very low (<=10th percentile), low (>10th to 25th percentile), medium (>25th to <75th percentile), high (75th to <90th percentile), and very high (>=90th percentile)
  • OR (odds ratio) for a solid tumour diagnosis associated with a very high platelet count vs a medium platelet count in the 6-month period before the diagnosis was 2.32 (95% CI, 2.28-2.35)
    • a very high platelet count was associated with colon (OR, 4.38; 95% CI, 4.22-4.54), lung (OR, 4.37; 95% CI, 4.22-4.53), ovarian (OR, 4.62; 95% CI, 4.19-5.09), and stomach (OR, 4.27; 95% CI, 3.91-4.66) cancers
    • of individuals who had a cancer diagnosed within 6 months after the blood test, 19.5% had a very high platelet count
    • findings of the present study suggest that platelet counts might be useful as a cancer screening tool alone or in combination with other cancer screening modalities, in particular spiral computed tomography for lung cancer, colonoscopy for colon cancer, and a cancer antigen 125 test or transvaginal ultrasonography for ovarian cancer

References:

1. Bailey SER et al. Clinical relevance of thrombocytosis in primary care: a prospective cohort study of cancer incidence using English electronic medical records and cancer registry data. Br J Gen Pract 2017; 67 (659): e405-e413
2. Suspected cancer: recognition and referral. NICE guideline [NG12]. Published: 23 June 2015 Last updated: 02 October 2023
3. Scottish Referral Guidelines for Suspected Cancer (January 2019).
4. Chen S et al. Pre-treatment platelet count as a prognostic factor in patients with pancreatic cancer: a systematic review and meta-analysis.Onco Targets Ther. 2018; 11: 59-65.
5. Mount LTA et al.Cancer incidence following a high-normal platelet count: cohort study using electronic healthcare records from English primary care. British Journal of General Practice 27 July 2020
6. Personal Comment, Dr Jim McMorran, Editor in Chief GPnotebook (July 29th 2020).
7. Giannakeas V, Kotsopoulos J, Cheung MC, et al. Analysis of Platelet Count and New Cancer Diagnosis Over a 10-Year Period. JAMA Netw Open. 2022;5(1):e2141633. doi:10.1001/jamanetworkopen.2021.41633