| dc.description.abstract | Thrombocytosis (raised platelet count) has recently been identified as a prediagnostic
risk marker of cancer; however, the association has not been fully
investigated. This thesis aimed to explore the relationship between thrombocytosis
and a future diagnosis of cancer through three complementary
pieces of research.
Firstly, a systematic review was carried out which aimed to identify studies
that had investigated thrombocytosis as a diagnostic marker of cancer. Four
case-control studies were identified that had found thrombocytosis to be a
significant predictor of lung, oesophago-gastric, uterine, and renal cancer.
A further four studies found that thrombocytosis did not predict pancreatic,
breast, ovarian, or colorectal cancer. One further study had collected, but
not analysed, platelet count data. Data from all nine studies were included
in a meta-analysis. The findings of the review suggest that thrombocytosis
is a marker of some, but not all, types of cancer.
The second study used data from the Clinical Practice Research Datalink
(CPRD) and the English cancer registry. This cohort study examined the
relationship between thrombocytosis and cancer using two groups of patients.
The first included 40,000 patients with a raised platelet count (a
platelet count of > 400 x 109/L). The second cohort included 10,000 patients
with a normal platelet count (150 - 400 x 109/L) who were age, sex,
and practice matched to a random quarter of the first cohort. This study
found that the risk of cancer was greater in patients with thrombocytosis
compared to those with a normal platelet count. The one year cancer
incidence was 11.6% (95% CI 11.0 - 12.3) for male patients with thrombocytosis,
and 4.1% (95% CI 3.4 - 4.9) in males with a normal platelet count. In
female patients, the one year cancer incidence was 6.2% (95% CI 5.9 - 6.5)
for those with thrombocytosis and 2.2% (95% CI 1.8 - 2.6) for those with
a normal platelet count. Lung and colorectal cancer were more likely to be
diagnosed in patients with thrombocytosis than in patients with a normal
platelet count, and breast and prostate cancer less likely. In patients with
a sustained increase in platelet count over six months, the risk of cancer increased
to 18.1% in males (95% CI 15.9 - 20.5) and 10.1% in females (95%
CI 9.0 - 11.3). Around a third of patients with lung or colorectal cancer
and thrombocytosis had no other symptoms prior to diagnosis that would
have prompted investigation for cancer as per current NICE guidance.
The third study compared cancer recording in the CPRD and in the English
cancer registry. The aim of this study was to examine the validity of cancer
recording in the CPRD using cancer registry recording as the gold standard,
and to estimate predictors of concordance between the two data sources. A
sensitivity analysis repeated the primary analysis from the second study
to estimate the effect of including unverified CPRD cancer diagnoses. The
CPRD identified 5,924 of 7,785 cancers recorded in the cancer registry (sensitivity
76.1%, 95% CI 75.1 - 77.0). 36,255 patients with no record of cancer
in the CPRD also had no cancer record in the cancer registry (specificity
97.0%, 95% CI 96.1 - 97.2). 5,924 of 7,028 CPRD cancer diagnoses were
confirmed by the cancer registry data; the positive predictive value (PPV)
of a CPRD recorded diagnosis was 84.3% (95% CI 83.4 - 85.1). Male cancers,
those in younger patients, and those recorded from 2005 onwards were
more likely to be recorded in both sources. In a sensitivity analysis, the
exclusion of cancer diagnoses that were only recorded in the CPRD did not
significantly alter findings from the cohort study described above.
The findings from this thesis show that thrombocytosis is an important
predictor of undiagnosed cancer in adults aged 40 years and over. Patients
with thrombocytosis are more likely to be diagnosed with lung and colorectal
cancer than other types. These results suggest that cancer should be
considered as an underlying diagnosis in patients with unexpectedly raised
platelets, even if cancer was not suspected at the time that the blood test
was ordered. For at least a third of patients with thrombocytosis and cancer,
there will be no other clinical features of malignancy; for this proportion,
thrombocytosis has great potential to expedite diagnosis and improved survival. | en_GB |
