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1. Original Investigation | Oncology
Analysis of Platelet Count and New Cancer Diagnosis Over a 10-Year Period
Vasily Giannakeas, MPH; Joanne Kotsopoulos, PhD; Matthew C. Cheung, MD; Laura Rosella, PhD; Jennifer D. Brooks, PhD; Lorraine Lipscombe, MD;
Mohammad R. Akbari, MD, PhD; Peter C. Austin, PhD; Steven A. Narod, MD
Abstract
IMPORTANCE Individuals with cancer often have an elevated platelet count at the time of diagnosis.
The extent to which an elevated platelet count is an indicator of cancer is unclear.
OBJECTIVE To evaluate the association of an elevated platelet count with a cancer diagnosis.
DESIGN, SETTING, AND PARTICIPANTS This nested case-control study included Ontario residents
enrolled in the provincial health insurance plan who had 1 or more routine complete blood count
(CBC) tests performed between January 1, 2007, and December 31, 2017, with follow-up through
December 31, 2018. Case patients were individuals with a new cancer diagnosis during the
observation period. Eligible control individuals were cancer free before the date of diagnosis for a
case patient to whom they were matched. One case patient was matched to 3 controls based on sex,
age, and health care use patterns. Data were analyzed from September 24, 2020, to July 13, 2021.
EXPOSURES Case patients and controls were assigned to 1 of 5 exposure groups based on age- and
sex-specific platelet count distributions in the control population: very low (ⱕ10th percentile), low
(>10th to 25th percentile), medium (>25th to <75th percentile), high (75th to <90th percentile), and
very high (ⱖ90th percentile).
MAIN OUTCOMES AND MEASURES Odds ratios (ORs) were estimated for specific cancer sites for
each category of platelet count at intervals up to 10 years after a blood test.
RESULTS Of the 8 917 187 eligible Ontario residents with a routine CBC record available, 4 971 578
(55.8%) were women; the median age at the first CBC was 46.4 years (IQR, 32.5-59.5 years). Among
individuals with a routine CBC record available, 495 341 (5.6%) received a diagnosis of first primary
cancer during the 10-year observation period. The OR for a solid tumor 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. Odds ratios attenuated with increasing time from CBC test to
cancer diagnosis.
CONCLUSIONS AND RELEVANCE In this nested case-control study, an elevated platelet count was
associated with increased risk of cancer at several sites. Our findings suggest that an elevated platelet
count could potentially serve as a marker for the presence of some cancer types.
JAMA Network Open. 2022;5(1):e2141633. doi:10.1001/jamanetworkopen.2021.41633
Key Points
Question Is a high platelet count
associated with an increased risk
of cancer?
Findings In this nested case-control
study of 8 917 187 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. The magnitude of the
association varied by cancer type and
time elapsed since the blood test.
Meaning The findings suggest that a
high platelet count is associated with
increased cancer risk.
+ Supplemental content
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Open Access. This is an open access article distributed under the terms of the CC-BY License.
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2. Introduction
Patients with cancer often have an abnormally high platelet count at the time of diagnosis
(thrombocytosis), defined as a platelet count greater than 450 × 109
/L (to convert to ×103
per
microliter, divide by 1.0).1
A normal platelet count falls between 150 and 450 × 109
/L and varies with
the age and sex of the individual.1,2
Several conditions that commonly cause an elevated platelet
count include acute blood loss, infection, and inflammation.3
Solid tumor cancers can sometimes
lead to an elevated platelet count to the extent that an undiagnosed cancer is often considered in the
diagnostic workup of a patient with thrombocytosis.3
Cancer is believed to induce platelet formation
through the release of interleukin 6, a proinflammatory cytokine that stimulates the production of
thrombopoietin hormone.4
Elevated 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 leads to platelet formation.5
An elevated platelet count has been shown to be associated with short-term risk of cancer in the
general population.6-8
Prospective studies evaluating platelet count and survival among patients
with newly diagnosed cancer have also noted a high proportion of patients who presented with
thrombocytosis.9-12
The excess risk associated with an elevated platelet count varies by cancer site
but has been most studied for lung, colon, and gastric cancers. The full range of cancers associated
with a high platelet count and whether risks associated with platelet counts within the high-normal
range exist remain unclear. Furthermore, it is unclear whether the association between a high platelet
count and cancer is transient or prolonged. Based on results of previous studies,6-8
a high platelet
count may be a risk factor for developing cancer or, alternatively, a marker indicative of an
undetected cancer. It is also not clear whether an increasing platelet count is a better indicator of a
new cancer than is a high but steady platelet count.
We identified a cohort of adult residents in Ontario, Canada, who had 1 or more routine blood
tests performed for a complete blood count (CBC) including platelet counts and subsequently
received a diagnosis of cancer to assess the range of cancers associated with a high platelet count.
We also examined whether an increasing platelet count is associated with an increased cancer risk.
Methods
Study Design, Population, and Data
Ontario is the most populous province in Canada, with a population of 14.5 million. Ontario residents
are covered under the universal health insurance program, which includes coverage for primary care
services, emergency visits, hospitalizations, and (among older adults) medication. This nested case-
control study used data from ICES, a nonprofit organization that provides researchers with
deidentified data that can be used for research purposes. ICES is a prescribed entity under §45 of
Ontario’s Personal Health Information Protection Act, which allows for research conduct without a
research ethics board review and without the need for informed consent. This study followed the
Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) reporting
guideline for case-control studies.
ICES data include results of laboratory tests conducted in Ontario from January 2007 to
present. The Ontario Laboratory Information System data set includes more than 85 million CBC test
records, including those for 9.5 million (of the 14.5 million) Ontario residents. The CBC records
include the date of laboratory analysis, the platelet count, and other standard blood parameters.
Incident cancers in Ontario are recorded in the Ontario Cancer Registry, which was started in
January 1964. This study also used data on physician billing (Ontario Health Insurance Plan claims
database), emergency department visits (National Ambulatory Care and Reporting System
database), acute care hospitalizations (Discharge Abstract Database), and dispensed medications
among adults aged 65 years or older (Ontario Drug Benefit Claims database). These datasets were
linked using unique encoded identifiers and analyzed at ICES.
JAMA Network Open | Oncology Analysis of Platelet Count and New Cancer Diagnosis Over a 10-Year Period
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3. Construction of the Cohort
The nesting cohort consisted of 8 917 187 Ontario residents who had at least 1 routine CBC test
ordered by a practicing physician in a community health setting from January 1, 2007, through
December 31, 2017. Cohort entry date was the date of the first eligible CBC test. Patients with cancer
before the cohort entry date were excluded. Patients were observed from the date of their first
routine blood test to the first date of any cancer diagnosis, death from any cause, end of Ontario
Health Insurance Plan eligibility, or the end of the observation period (December 31, 2018) (eFigure 1
in the Supplement). Details on the inclusion criteria, exclusion criteria, and the study cohort are
available in eTables 1-3 in the Supplement.
Baseline Variables
Baseline information was obtained and updated at the time of each CBC test. We included
information on general demographic characteristics, health services use, comorbidities and chronic
conditions, medication use (among individuals aged ⱖ66 years), and additional CBC test results. The
Johns Hopkins ACG System software, version 10,13
was used to obtain aggregate diagnosis groups
and resource utilization bands.
Case Patients
Case patients were defined as individuals who received a cancer diagnosis after the date of cohort
entry. Data on first primary cancer diagnoses during the observation period were captured from the
Ontario Cancer Registry. The Ontario Cancer Registry is a validated cancer registry that provides
information on the date of diagnosis, cancer site, and tumor-specific data, such as morphologic
features, stage, grade, lymph node involvement, and for certain cancers, hormone receptor status.14
We restricted the interpretation of our findings to solid cancers other than liver cancer because both
liver and hematologic cancers may have a direct effect on platelet count; thrombopoietin production
occurs in the liver, and megakaryocyte production occurs in the bone marrow. For case patients, the
index date was defined as the date of diagnosis of cancer.
Matching
We hard-matched 3 control individuals to each case patient. Each matched control was alive and
cancer free on the date of diagnosis of the case patient (eFigure 1 in the Supplement). Case patients
and controls were matched based on sex, calendar date of CBC test (±30 days), age (±2 years), years
of coverage by the Ontario Health Insurance Plan (±2 years), and the patient’s resource utilization
band. Incidence density sampling was used such that case patients could serve as potential controls
at prior time points.
Exposure
We assigned a categorical value to each platelet count based on the percentile distribution for the
cancer-free controls. Five mutually exclusive categories were created: very low (ⱕ10th percentile),
low (>10th to 25th percentile), medium (>25th to <75th percentile), high (75th to <90th percentile),
and very high (ⱖ90th percentile). To account for variation in platelet count by sex and age, we
defined categories of platelet count using reference distributions that were standardized according
to age and sex from the pool of control patients (eFigure 2 in the Supplement).
Statistical Analysis
Primary Analysis
We performed a series of (nested) matched case-control analyses to measure the association of
platelet count with risk of cancer at various time intervals before the index date. Each matched
quadruplet of case patients and controls (3:1) was assessed at 7 time intervals before the index date:
0 to 6 months, 6 to 12 months, 12 to 18 months, 18 to 24 months, 2 to 3 years, 3 to 5 years, and 5 to
10 years. Each case patient could contribute to up to 7 observations (1 for each time interval). If
JAMA Network Open | Oncology Analysis of Platelet Count and New Cancer Diagnosis Over a 10-Year Period
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4. multiple routine CBC tests were performed within a given period, 1 was chosen at random. For each
cancer site and for each time point, an odds ratio (OR) was estimated using conditional logistic
regression. At each time point, the medium platelet count category was used as the reference group
and ORs were estimated for very high, high, low, and very low counts compared with the reference
group. Information on tumor stage was available for several sites. A subanalysis was conducted after
stratifying cancers by stage for these sites. In a thrombocytosis sensitivity analysis, we assigned
platelet levels using clinical cutoffs: thrombocytopenia (<150 ×109
platelets/L), normal level (150 to
450 ×109
platelets/L), and thrombocytosis (>450 ×109
platelets/L).
Secondary Analysis
As a secondary objective, we sought to assess whether a change in platelet count over time was
associated with a diagnosis of cancer. To study this, we selected individuals who had 2 routine CBC
tests recorded 9 to 15 months apart. If multiple CBC records were available in the 9- to 15-month
period, 1 was selected at random. A second iteration of matching (using the same matching criteria)
was done using this subset of individuals (n = 4 372 288 [49% of the primary cohort]). A difference in
platelet count was measured by subtracting the first platelet count from the second platelet count.
Sex- and age-standardized reference distributions for change in platelet count were created
(eFigure 3 in the Supplement). Five categories were created to classify the change in platelet count:
large decrease (ⱕ10th percentile), small decrease (>10th to 25th percentile), no substantial change
(>25 to <75th percentile [reference group]), small increase (75th to <90th percentile), and large
increase (ⱖ90th percentile). All statistical analyses were performed using SAS software, version 9.4
(SAS Institute Inc). Data were analyzed from September 24, 2020, to July 13, 2021.
Results
Of the 8 917 187 eligible individuals with 1 or more routine CBC tests identified in Ontario during the
accrual period, 4 971 578 (55.8%) were women; the median age at the first CBC was 46.4 years (IQR,
32.5-59.5 years) (Table 1). Of the entire cohort, 495 341 individuals (5.6%) received a cancer
diagnosis during the observation period. We successfully matched 491 779 case patients with cancer
(99.3%) to 3 controls in 1 or more predefined time intervals. Case patients were similar to controls
with respect to their demographic information, health services use, medication use, and comorbidity
variables (eTable 4 in the Supplement).
The mean platelet count at the most recent blood test was higher among case patients with
cancer than among matched controls (245.7 × 109
/L vs 237.0 × 109
/L). Case patients diagnosed with
a solid tumor were more likely to have a recent platelet count in the highest category compared with
cancer-free controls (44 344 [19.5%] vs 65 626 [9.6%]). For blood samples obtained during the 6
months before a cancer diagnosis, the OR for any solid cancer associated with a very high platelet
count (ⱖ90th percentile) vs a medium platelet count (reference, >25th to <75th percentile) was 2.32
(95% CI, 2.28-2.35) (Table 2). The OR for this association attenuated with increasing time from blood
test to cancer diagnosis (Table 2); the ORs for the very high platelet category were 1.41 (95% CI,
1.39-1.44) for 6 to less than 12 months before diagnosis, 1.20 (95% CI, 1.18-1.22) for 12 to less than 24
months before diagnosis, 1.15 (95% CI, 1.13-1.17) for 24 to less than 60 months before diagnosis, and
1.13 (95% CI, 1.10-1.15) for 60 to 120 months before diagnosis.
The ORs for the association of a high platelet count with a cancer diagnosis were greatest for
patients with cancers of the colon, lung, ovary, and stomach (Figure 1). During the 0- to 6-month
period before a cancer diagnosis, the ORs for the very high platelet count category were 4.38 (95%
CI, 4.22-4.54) for colon cancer, 4.37 (95% CI, 4.22-4.53) for lung cancer, 4.62 (95% CI, 4.19-5.09) for
ovarian cancer, and 4.27 (95% CI, 3.91-4.66) for stomach cancer (Figure 1 and eTable 5 in the
Supplement). Significant associations were also observed for esophageal cancer (OR, 3.18; 95% CI,
2.81-3.60), other gastrointestinal tract cancers (OR, 3.10; 95% CI, 2.75-3.49), and kidney cancer (OR,
JAMA Network Open | Oncology Analysis of Platelet Count and New Cancer Diagnosis Over a 10-Year Period
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5. Table 1. Characteristics of the Study Cohort at the First Eligible Routine
CBC Test
Description
Individuals
(N = 8 917 187)a
Sex
Female 4 971 578 (55.8)
Male 3 945 609 (44.2)
Age, y
Mean (SD) 47.0 (17.8)
Median (IQR) 46.4 (32.5-59.5)
Residence location
Urban 8 084 848 (90.7)
Rural 820 419 (9.2)
Missing 11 920 (0.1)
Core primary care visits to general practitioner or
family practitioner in previous 2 y, No.
Mean (SD) 2.8 (3.4)
Median (IQR) 2 (1-3)
Rostered to family physician 6 940 867 (77.8)
Comorbidities and chronic conditions
Asthma 796 810 (8.9)
Congestive heart failure 172 576 (1.9)
COPD 192 482 (2.2)
Hypertension 2 139 804 (24.0)
Diabetes 666 477 (7.5)
Kidney disease 88 520 (1.0)
Chronic coronary syndrome 321 278 (3.6)
Hemoglobin concentration, g/L
Mean (SD) 139.5 (14.9)
Median (IQR) 140 (130-150)
Platelet count, 109
/L
Mean (SD) 247.2 (64.5)
Median (IQR) 241 (205-282)
Observation time, yb
Mean (SD) 6.8 (3.0)
Median (IQR) 7.3 (4.4-9.3)
Routine CBC tests in observation period, No.
Mean (SD) 4.3 (6.3)
Median (IQR) 3 (1-6)
Cancer diagnosisb,c
Any 492 691 (5.5)
Solid tumor 429 222 (4.8)
Colon 51 521 (0.6)
Lung 56 724 (0.6)
Breastd
65 721 (1.3)
Ovaryd
7661 (0.2)
Cervicald
3494 (0.1)
Endometriald
17 101 (0.3)
Prostatee
62 946 (1.6)
Thyroid 21 478 (0.2)
Pancreas 12 021 (0.1)
Stomach 9195 (0.1)
Kidney 14 063 (0.2)
Bladder 23 344 (0.3)
Liver 7696 (0.1)
Esophagus 4712 (0.1)
Other gastrointestinal tract 5255 (0.1)
Brain 5724 (0.1)
Melanoma 20 192 (0.2)
(continued)
JAMA Network Open | Oncology Analysis of Platelet Count and New Cancer Diagnosis Over a 10-Year Period
JAMA Network Open. 2022;5(1):e2141633. doi:10.1001/jamanetworkopen.2021.41633 (Reprinted) January 11, 2022 5/13
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6. Table 1. Characteristics of the Study Cohort at the First Eligible Routine
CBC Test (continued)
Description
Individuals
(N = 8 917 187)a
Head and neck 13 363 (0.1)
Other 27 011 (0.3)
Hematologic tumor 63 469 (0.7)
Leukemia 5154 (0.1)
Lymphoma 33 827 (0.4)
Multiple myeloma 8274 (0.1)
Other 16 214 (0.2)
Abbreviations: CBC, complete blood count; COPD, chronic obstructive
pulmonary disease; OHIP, Ontario Health Insurance Plan.
SI conversion factors: To convert hemoglobin concentration to grams per
deciliter, divide by 10.0; platelet count to 103
per microliter, divide by 1.0.
a
Data are presented as number (percentage) of individuals unless otherwise
indicated.
b
Period of observation was from the first eligible CBC test to the earliest date of
death, end of OHIP eligibility, or end of the observation period (December
31, 2018).
c
Data are from the Ontario Cancer Registry.
d
Women only.
e
Men only.
Table 2. Odds Ratios of Any Solid Tumor Diagnosis by Platelet Count Category and Time From Complete Blood
Count Test to Cancer Diagnosisa
Platelet count percentile category
by time to cancer diagnosisb
No. (%)
Odds ratio (95% CI)c
Case patients Control individuals
<6 mo
Very low 19 161 (8.4) 74 891 (11.0) 0.87 (0.86-0.89)
Low 27 308 (12.0) 106 707 (15.6) 0.87 (0.86-0.89)
Medium 98 480 (43.3) 336 232 (49.2) 1 [Reference]
High 38 372 (16.9) 99 539 (14.6) 1.32 (1.30-1.34)
Very high 44 344 (19.5) 65 626 (9.6) 2.32 (2.28-2.35)
6 to <12 mo
Very low 14 870 (10.1) 48 700 (11.0) 0.95 (0.93-0.97)
Low 20 716 (14.0) 69 561 (15.7) 0.93 (0.91-0.95)
Medium 70 078 (47.4) 219 039 (49.4) 1 [Reference]
High 23 209 (15.7) 64 288 (14.5) 1.13 (1.11-1.15)
Very high 19 038 (12.9) 42 145 (9.5) 1.41 (1.39-1.44)
12 to <24 mo
Very low 22 086 (10.2) 70 743 (10.9) 0.95 (0.93-0.96)
Low 32 018 (14.7) 103 336 (15.9) 0.94 (0.93-0.95)
Medium 106 239 (48.9) 322 348 (49.5) 1 [Reference]
High 32 952 (15.2) 94 872 (14.6) 1.05 (1.04-1.07)
Very high 23 942 (11.0) 60 412 (9.3) 1.20 (1.18-1.22)
24 to <60 mo
Very low 27 116 (10.1) 87 869 (10.9) 0.93 (0.92-0.95)
Low 40 852 (15.2) 127 941 (15.9) 0.97 (0.95-0.98)
Medium 132 330 (49.4) 400 393 (49.8) 1 [Reference]
High 40 363 (15.1) 115 881 (14.4) 1.05 (1.04-1.07)
Very high 27 481 (10.2) 72 342 (9.0) 1.15 (1.13-1.17)
60-120 mo
Very low 15 744 (10.1) 49 761 (10.7) 0.96 (0.94-0.98)
Low 23 750 (15.3) 74 880 (16.1) 0.96 (0.94-0.97)
Medium 76 963 (49.5) 232 828 (49.9) 1 [Reference]
High 23 340 (15.0) 66 787 (14.3) 1.06 (1.04-1.08)
Very high 15 655 (10.1) 42 100 (9.0) 1.13 (1.10-1.15)
a
Liver cancer was excluded.
b
Platelet count percentile categories were defined as
follows: very low (ⱕ10th percentile), low (>10th to
25th percentile), medium (>25th to <75th
percentile), high (75th to <90th percentile), and very
high (ⱖ90th percentile).
c
P < .001 for all.
JAMA Network Open | Oncology Analysis of Platelet Count and New Cancer Diagnosis Over a 10-Year Period
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7. 2.55; 95% CI, 2.38-2.74) (eFigure 4 in the Supplement). The associations attenuated with increasing
time to diagnosis to varying degrees.
In addition, high platelet count was associated with risk of breast cancer (OR, 1.05; 95% CI, 1.01-
1.10) and prostate cancer (OR, 1.24; 95% CI, 1.19-1.29) but was not associated with risk of melanoma
(OR, 1.06; 95% CI, 0.97-1.15) or thyroid cancer (OR, 1.01; 95% CI, 0.94-1.09) (eFigure 4 in the
Supplement). A low platelet count and a very low platelet count were associated with a decreased
risk of breast and prostate cancer. In a sensitivity analysis, the ORs for the association of
thrombocytosis and increased cancer risk were greatest for colon cancer, lung cancer, ovarian cancer,
stomach cancer, esophageal cancer, and kidney cancer (eFigure 7 in the Supplement).
We also studied the associations between a high platelet count and risk of solid tumors by stage
at diagnosis (when data were available). There was a significant association across all stages of colon
cancer, but the OR for the association was greatest for metastatic disease (stage IV) (OR, 7.96; 95%
CI, 7.26-8.72) (Figure 2). Data for the other cancer sites by stage are presented in eFigure 6 in the
Supplement.
We also examined whether a substantial increase in platelet count (compared with a platelet
count measured in the previous 9 to 15 months) was associated with an risk of cancer. Case patients
diagnosed with a solid tumor were more likely to have a recent increase in platelet count (ⱖ90th
percentile) than were cancer-free controls (19 750[21.8%] vs 27 530 [10.2%]) (eTable 6 in the
Supplement). A recent increase in the platelet count was associated with risk of colon cancer (OR,
5.52; 95% CI, 5.21-5.86), lung cancer (OR, 4.77; 95% CI, 4.51-5.04), ovarian cancer (OR, 7.23; 95% CI,
6.12-8.53), and stomach cancer (OR, 5.51; 95% CI, 4.82-6.29) (Figure 3 and eTable 7 in the
Supplement). No associations were observed between a recent increase in the platelet count and
Figure 1. Odds Ratios of Cancer by Platelet Count Category and Time From Complete Blood Count Test to Cancer Diagnosis
Very low (≤10th percentile)
Low (>10th to 25th percentile)
Medium (>25th to <75th percentile)
High (75th to <90th percentile)
Very high (≥90th percentile)
10
1
0.5
Odds
ratio
Time to cancer diagnosis, mo
60-120 36-60 24-36 12-18
18-24 6-12 0-6
Colon cancer
A
10
1
0.5
Odds
ratio
Time to cancer diagnosis, mo
60-120 36-60 24-36 12-18
18-24 6-12 0-6
Lung cancer
B
10
1
0.5
Odds
ratio
Time to cancer diagnosis, mo
60-120 36-60 24-36 12-18
18-24 6-12 0-6
Ovarian cancer
C
10
1
0.5
Odds
ratio
Time to cancer diagnosis, mo
60-120 36-60 24-36 12-18
18-24 6-12 0-6
Stomach cancer
D
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8. breast cancer (OR, 1.01; 95% CI, 0.94-1.09), melanoma (OR, 1.01; 95% CI, 0.89-1.15), or thyroid cancer
(OR, 0.97; 95% CI, 0.86-1.09) (eFigure 5 in the Supplement).
Discussion
In this large, nested case-control study, we found that an elevated platelet count identified during a
routine blood examination was associated with an increased risk of developing a range of solid
tumors. The OR for the association was greatest for a diagnosis of cancer within 6 months of a blood
test. For several cancer sites (lung, colon, stomach, esophagus, and kidney), a high platelet count
was associated with a cancer diagnosis in the following 3 or more years. For lung cancer, a significant
association was present 10 years before diagnosis. Long-term associations were also seen for kidney
cancer and esophageal cancer. In contrast, for ovarian cancer, there was an association only in the 6
months before a diagnosis.
Overall, given the transient nature of the association with platelet count, our findings suggest
that an elevated platelet count detected through routine blood examination may be a consequence
of the presence of cancer rather than being a risk factor for the disease. The physiologic basis for the
association is not clear but may be multifactorial. Platelets are produced in the bone marrow in
response to thrombopoietin, which is upregulated by interleukin 6, primarily produced in the liver.15
It is possible that the increase in platelet count is a response to circulating factors produced by the
cancer cells or is a local response to inflammation induced by the cancer cell mass. Various
mechanisms have been proposed to explain the association between high platelet count and cancer,
Figure 2. Odds Ratios of Colon Cancer by Platelet Count Category and Time From Complete Blood Count Test to Cancer Diagnosis by Cancer Stage
10
1
0.5
Odds
ratio
Time to cancer diagnosis, mo
60-120 36-60 24-36 12-18
18-24 6-12 0-6
Stage I colon cancer
A
10
1
0.5
Odds
ratio
Time to cancer diagnosis, mo
60-120 36-60 24-36 12-18
18-24 6-12 0-6
Stage II colon cancer
B
10
1
0.5
Odds
ratio
Time to cancer diagnosis, mo
60-120 36-60 24-36 12-18
18-24 6-12 0-6
Stage III colon cancer
C
10
1
0.5
Odds
ratio
Time to cancer diagnosis, mo
60-120 36-60 24-36 12-18
18-24 6-12 0-6
Stage IV colon cancer
D
Very low (≤10th percentile)
Low (>10th to 25th percentile)
Medium (>25th to <75th percentile)
High (75th to <90th percentile)
Very high (≥90th percentile)
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9. including the aggregation of cancer cells by platelets, increased extravasation or enhanced
permeability of the basement membrane, and shielding cancer cells from immune attack in the
bloodstream.16-18
Other possible mechanisms include iron deficiency, bleeding (among patients with
colon cancer),19
abnormal platelet counts, and the infiltration of disseminated cancer cells in the
bone marrow.20
Several studies have demonstrated an association between an elevated platelet count
(thrombocytosis) and cancer risk. In general, these studies have either measured platelet counts at
the time of diagnosis or had a short follow-up period subsequent to a CBC test.6-8
Pharmacoepidemiologic studies have further shown a lower incidence of certain cancer types among
patients receiving platelet-inhibiting medications. For example, there is an established relationship
between aspirin use (an antiplatelet drug) and decreased incidence of colon cancer.21-23
A protective
effect of low-dose aspirin against ovarian cancer has also been suggested.24
Although antiplatelet
medications inhibit platelet function as opposed to lowering the platelet count, the decreased
incidence of cancer associated with aspirin use suggests the potential role functional platelets have
in cancer risk.
Our study findings suggest that individuals with a high platelet count might be candidates for
investigation for the presence of an occult cancer after other nonmalignant causes of an elevated
platelet count have been ruled out. Of individuals who had a cancer diagnosed within 6 months after
the blood test, 19.5% had a very high platelet count (top 10 percentile). In a sensitivity analysis, we
observed similar findings, with an association with some cancers among individuals with
thrombocytosis. Giannakeas and Narod25
recently reported an association between thrombocytosis
and incident cancers using the same data from the present study. The findings of the present study
Figure 3. Odds Ratios of Cancer by Change in Platelet Count Category and Time From Complete Blood Count Test to Diagnosis
10
1
0.5
Odds
ratio
Time to cancer diagnosis, mo
60-120 36-60 24-36 12-18
18-24 6-12 0-6
Colon cancer
A
10
1
0.5
Odds
ratio
Time to cancer diagnosis, mo
60-120 36-60 24-36 12-18
18-24 6-12 0-6
Lung cancer
B
10
1
0.5
Odds
ratio
Time to cancer diagnosis, mo
60-120 36-60 24-36 12-18
18-24 6-12 0-6
Ovarian cancer
C
10
1
0.5
Odds
ratio
Time to cancer diagnosis, mo
60-120 36-60 24-36 12-18
18-24 6-12 0-6
Stomach cancer
D
Large decrease (≤10th percentile)
Small decrease (>10th to 25th percentile)
No substantial change (>25th to <75th percentile)
Small increase (75th to <90th percentile)
Large increase (≥90th percentile)
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11. Ontario, Canada (Akbari, Narod); Institute of Health Policy Management and Evaluation, University of Toronto,
Toronto, Ontario, Canada (Austin).
Author Contributions: Mr Giannakeas had full access to all of the data in the study and takes responsibility for the
integrity of the data and the accuracy of the data analysis.
Concept and design: Giannakeas, Kotsopoulos, Rosella, Brooks, Akbari, Narod.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Giannakeas, Kotsopoulos, Brooks.
Critical revision of the manuscript for important intellectual content: All authors.
Statistical analysis: Giannakeas, Kotsopoulos, Rosella.
Obtained funding: Giannakeas, Kotsopoulos.
Administrative, technical, or material support: Giannakeas, Kotsopoulos, Akbari.
Supervision: Kotsopoulos, Cheung, Brooks, Lipscombe, Narod.
Conflict of Interest Disclosures: Mr Giannakeas reported receiving financial support through the Canadian
Institutes of Health Research Frederick Banting and Charles Best Doctoral Research Award during the conduct of
the study. Dr Lipscombe reported receiving grants from the Canadian Institutes of Health Research, personal fees
from Diabetes Canada, and salary support from the University of Toronto Novo Nordisk Network for Healthy
Populations outside the submitted work. Dr Austin reported receiving financial support through a Mid-Career
Investigator Award from the Heart and Stroke Foundation. Dr Narod reported being a recipient of the tier I Canada
Research Chair in Breast Cancer. Dr Kotsopoulos reported being a recipient of a tier II Canada Research Chair. No
other disclosures were reported.
Funding/Support: This work was supported by the Peter Gilgan Centre for Women’s Cancers at Women’s College
Hospital in partnership with the Canadian Cancer Society and by ICES, which is funded by an annual grant from
the Ontario Ministry of Health and Long-Term Care (MOHLTC).
Role of the Funder/Sponsor: The funders had no role in the design and conduct of the study; collection,
management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and
decision to submit the manuscript for publication.
Disclaimer: The analysis, results, conclusions, and opinions herein are solely those of the authors and do not
reflect those of the funding or data sources. No endorsement by ICES, the Ontario MOHLTC, the Canadian
Institutes of Health Research, or Cancer Care Ontario is intended or should be inferred.
Additional Information: Parts of the study data are based on data and/or information compiled and provided by
the MOHLTC; the Canadian Institute for Health Information; Immigration, Refugees and Citizenship Canada; and
Cancer Care Ontario. IQVIA Solutions Canada Inc allowed use of their Drug Information File.
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SUPPLEMENT.
eTable 1. Inclusion Table for CBC Tests
eTable 2. Exclusion Table for Study Cohort
eTable 3. Detailed Descriptive Table of Eligible Subjects, Measured at First Eligible Routine CBC Test (Cohort Entry
Date)
eTable 4. Descriptive Table of Matched Subjects (Primary Analysis), Variables Measured on Index CBC
eTable 5. Odds Ratio of Cancer by Platelet Count Category and Time From Diagnosis. Select Cancer Sites
JAMA Network Open | Oncology Analysis of Platelet Count and New Cancer Diagnosis Over a 10-Year Period
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13. eTable 6. Odds Ratio of Any Solid Tumour Diagnosis (Excluding Liver) by Change in Platelet Count Category and
Time From Cancer Diagnosis
eTable 7. Odds Ratio of Cancer by Change in Platelet Count Category and Time From Diagnosis. Select Cancer Sites
eFigure 1. Study Design Criteria Among Matched Individuals
eFigure 2. Age- and Sex-Specific Platelet Count Reference Distributions for Exposure Definition
eFigure 3. Age- and Sex-Specific Platelet Count Reference Distributions for Secondary Exposure Definition
eFigure 4. Odds Ratio of Cancer by Platelet Count Category and Time From Cancer Diagnosis. Additional Cancer
Sites
eFigure 5. Odds Ratio of Cancer by Change in Platelet Count Category and Time From Cancer Diagnosis. Additional
Cancer Sites
eFigure 6. Odds Ratio of Cancer by Platelet Count Category and Time From Diagnosis. Select Cancer Sites by
Cancer Stage
eFigure 7. Odds Ratio of Cancer by Platelet Count Category (Clinical Definition) and Time From Diagnosis
JAMA Network Open | Oncology Analysis of Platelet Count and New Cancer Diagnosis Over a 10-Year Period
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