A large, population-based study published in 2017 in the British Journal of General Practice has led to the emergence of raised platelet levels as a risk marker of cancer. The study showed that 12% of men and 6% of women with thrombocytosis were diagnosed with cancer within the following year. If a second platelet count was taken within 6 months of the first and showed an increased or stable elevated platelet count, these figures rose to 18% in men and 10% in women.

Other causes of thrombocytosis

Thrombocytosis occurs when the platelet count exceeds 450 x 10⁹/l, although levels can rise above 1,000 x 10⁹/l without the patient experiencing symptoms. There are numerous causes of thrombocytosis, other than malignancy, and these include:

• Bleeding
• Infarction
• Infection
• Iron-deficiency
• Thrombosis
• Trauma

Malignancies associated with thrombocytosis

The BJGP study showed that thrombocytosis associated with malignancy is most commonly seen with colorectal and lung cancers and is often associated with a worse prognosis. In addition, one-third of the patients diagnosed with cancer in the study had no other symptoms that would have prompted an urgent cancer referral.

The exact mechanism of how these cancers lead to thrombocytosis is not fully understood, but one proposed theory is that pathogenic feedback loops exist between malignant cells and platelets, with a reciprocal interaction between tumour growth and metastasis and thrombocytosis and platelet activation. Another theory is that the thrombocytosis is occurring independently of the cancer but promoting the spread and development of it.

The results of the study demonstrate that substantial proportions of colorectal and lung cancer diagnoses could be expedited by at least 2 months if thrombocytosis were to be routinely investigated. This could yield around 5500 earlier cancer diagnoses per year in the UK.

Existing guidance by NICE

The 2015 NICE guidelines on the recognition and referral of suspected cancer already recommend that thrombocytosis is considered as a potential trigger for urgent cancer referral when encountered in certain clinical situations. These are summarised in the table below:

Implications of new findings

The positive predictive value of thrombocytosis in middle age for cancer (10%) is higher than that for a woman in her 50s presenting with a new breast lump (8.5%), so this is clearly a research paper of importance that should be used to adjust future clinical practice. The current NICE guidelines predate these new research findings, and we will have to wait to find out how cancer referral guidelines in the UK change as a result of them.

The range of possible associated cancers is extensive, so the treating clinician should obviously take a careful history and perform a thorough clinical examination if a patient is discovered to have thrombocytosis. This should help inform further investigation and the most appropriate referral route. It is important to note that the patients included the study had their blood tests performed for a clinical indication and not as a random screening test.

If there are no clearly relevant symptoms to help guide investigation and referral (one-third of the patients in the BJGP study had no other relevant symptoms), it should be borne in mind that the two commonest cancers encountered were colorectal and lung cancer, so a chest X-ray and faecal immunochemical test (FIT) for faecal blood may be reasonable initial investigations.

Further reading:

BJGP Paper: Clinical relevance of thrombocytosis in primary care

NICE guidelines on the recognition and referral of suspected cancer

Header image used on licence from Shutterstock

Thank you to the joint editorial team of MRCGP Exam Prep for this article.