Thrombocytosis and Cancer Risk: Management in Primary Care

This transcript has been edited for clarity.

In this podcast, I’m going to talk about unexplained high platelet counts, or thrombocytosis, and the risk for cancer in primary care. Let’s start with a typical case we all might see in primary care.

Louisa is 47 years old and is the chief financial officer for a tech startup company. She presents to us in primary care feeling tired all the time — a very common presentation in primary care — with associated reduced appetite. Past medical history includes irritable bowel syndrome, and she’s an ex-smoker.

Systemic inquiry is unremarkable. Specifically, there is no history of weight loss. Louisa has not been prescribed any medication and uses over-the-counter remedies for her irritable bowel syndrome. Examination is also unremarkable. Blood tests were checked, which were all reassuring, except for a platelet count of 612 × 10⁹ cells/L (usual normal range, about 150-450).

What do we do next? Do we refer for an urgent chest x-ray to exclude lung cancer? Do we check a quantitative immunohistochemical fecal occult blood test (qFIT) to identify any occult bleeding in her stool? Do we refer for a routine upper gastrointestinal endoscopy or pelvic ultrasound scan to exclude any upper gastrointestinal or endometrial malignancy?

Do we simply repeat the bloods? If so, do we repeat them routinely or urgently, and indeed, which ones should we recheck?

Louisa has an unexplained thrombocytosis. How do we manage this in primary care? Thrombocytosis is generally defined as a raised platelet count over 450. Importantly, thrombocytosis is a common incidental finding in around 2% of those over 40 years of age attending primary care. Reassuringly, 80%-90% of thrombocytosis is reactive, secondary to acute blood loss, infection, or inflammation, and the majority of cases resolve within 3 months.

Why the concern with Louisa then? Although most cases are reactive, clinical guidance (for example, NICE suspected cancer guidance in the UK and Scottish suspected cancer guidance in Scotland) reminds us that unexplained thrombocytosis is a risk marker for some solid-tumor malignancies.

Previous studies have demonstrated that unexplained thrombocytosis is associated with a 1-year cancer incidence of 11.6% in males and 6.2% in females, well exceeding the standard 3% threshold warranting investigation for underlying malignancy. However, thrombocytosis should not be used as a stand-alone diagnostic or screening test for cancer, or indeed to rule out cancer.

Instead, unexplained thrombocytosis should prompt us to think cancer. The Scottish suspected cancer referral guidelines include thrombocytosis in the investigation criteria for what they call the LEGO-C cancers — L for lung, E for endometrial, G for gastric, O for oesophageal, and C for colorectal, which is a useful reminder for us all.

What further history, examination, and investigations might we consider in primary care if we identify an unexplained high platelet count? As always, we should use our clinical judgment and trust our clinical acumen.

We should consider all the possible underlying causes, including infection, inflammation, and blood loss, including menstrual blood loss in women; myeloproliferative disorders such as polycythemia rubra vera, chronic myeloid leukemia, and essential thrombocythemia; and, of course, underlying malignancy. If a likely underlying reversible cause is present (for example, a recent lower respiratory tract infection), simply repeating the full blood count in 4-6 weeks is quite appropriate to see if the thrombocytosis has resolved.

Remember, 80%-90% of cases are reactive thrombocytosis, and most cases resolve within 3 months. If thrombocytosis is unexplained or not resolving, consider checking ferritin levels to exclude iron deficiency. Consider checking C-reactive protein (CRP) levels to exclude any inflammation, and also consider checking a blood film to exclude any hematologic disorders, in addition, of course, to more detailed history-taking and examination to elicit any red flags.

We can also consider a JAK2 gene mutation test, if it is available to you locally, or a hematology referral if we suspect a myeloproliferative disorder. JAK2 is a genetic mutation that may be present in people with essential thrombocythemia and can indicate a diagnosis of polycythemia rubra vera.

Subsequent to this, and again using our clinical judgment, we then need to exclude the LEGO-C cancers. Consider urgent chest x-ray to exclude lung cancer or pelvic ultrasound in women to exclude endometrial cancer. Also, we should consider an upper gastrointestinal endoscopy, particularly in those individuals who have associated upper gastrointestinal symptoms and/or weight loss.

Finally, consider a qFIT to identify any occult bleeding in the stool, again if it’s available to you, or certainly if not, urgent lower gastrointestinal investigations to exclude colorectal cancer.

Alongside these possible investigations, as always, we should safety-net appropriately within agreed timeframes and check for resolution of the thrombocytosis according to the condition being suspected. Remember, most cases resolve within 3 months.

Returning to Louisa, what did I do? After seeing a platelet count of 600, I subsequently telephoned her and reexplored her history, which yielded nil else of note. Specifically, there was no history of unexplained weight loss, no history of upper or lower gastrointestinal symptoms, and certainly nothing significantly different from her usual irritable bowel syndrome symptoms. There were also no respiratory or genitourinary symptoms of note.

I did arrange for Louisa to undergo a chest x-ray over the next few days, though, as she was an ex-smoker. This was subsequently reported as normal. I appreciate chest x-rays have poor sensitivity for detecting lung cancer, as highlighted in a number of recent papers, but it was mutually agreed with Louisa that we would simply repeat her blood test in around 6 weeks. As well as repeating the full blood count, I arranged to check her ferritin, CRP, and a blood film, and then I was planning to reassess her clinically in person.

These bloods and my subsequent clinical review were reassuring. In fact, her platelet count had normalized after that 6 weeks had elapsed. Her thrombocytosis had resolved.

I didn’t arrange any further follow-up for her, but I did give her the usual safety netting advice to re-present to me or one of my colleagues if she does develop any worrying symptoms or signs.

I appreciate these scenarios are not always this straightforward, but I wanted to outline what investigations and referrals we may need to consider in primary care if we encounter an unexplained high platelet count.

There are a couple of quality-improvement activities for us all to consider in primary care. Consider as a team how we would respond to an incidental finding of thrombocytosis on a full blood count. Also consider what are our safety-netting options for those found to have raised platelet counts but no other symptoms or risk factors for underlying malignancy.

Finally, I’ve produced a Medscape UK primary care hack or clinical aide-memoire on managing unexplained thrombocytosis and associated cancer risk in primary care for all healthcare professionals working in primary care. This can be found online. I hope you find this resource helpful.

Dr. Kevin Fernando, General practitioner partner with specialist interests in cardiovascular, renal, and metabolic medicine, North Berwick Group Practice in Scotland, has disclosed relevant financial relationships with Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Dexcom, Lilly, Menarini, Novartis, Novo Nordisk, Roche Diagnostics, Embecta, Roche Diabetes Care, Sanofi Menarini, and Daiichi Sankyo.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

In this podcast, I’m going to talk about unexplained high platelet counts, or thrombocytosis, and the risk for cancer in primary care. Let’s start with a typical case we all might see in primary care.

Louisa is 47 years old and is the chief financial officer for a tech startup company. She presents to us in primary care feeling tired all the time — a very common presentation in primary care — with associated reduced appetite. Past medical history includes irritable bowel syndrome, and she’s an ex-smoker.

Systemic inquiry is unremarkable. Specifically, there is no history of weight loss. Louisa has not been prescribed any medication and uses over-the-counter remedies for her irritable bowel syndrome. Examination is also unremarkable. Blood tests were checked, which were all reassuring, except for a platelet count of 612 × 10⁹ cells/L (usual normal range, about 150-450).

What do we do next? Do we refer for an urgent chest x-ray to exclude lung cancer? Do we check a quantitative immunohistochemical fecal occult blood test (qFIT) to identify any occult bleeding in her stool? Do we refer for a routine upper gastrointestinal endoscopy or pelvic ultrasound scan to exclude any upper gastrointestinal or endometrial malignancy?

Do we simply repeat the bloods? If so, do we repeat them routinely or urgently, and indeed, which ones should we recheck?

Louisa has an unexplained thrombocytosis. How do we manage this in primary care? Thrombocytosis is generally defined as a raised platelet count over 450. Importantly, thrombocytosis is a common incidental finding in around 2% of those over 40 years of age attending primary care. Reassuringly, 80%-90% of thrombocytosis is reactive, secondary to acute blood loss, infection, or inflammation, and the majority of cases resolve within 3 months.

Why the concern with Louisa then? Although most cases are reactive, clinical guidance (for example, NICE suspected cancer guidance in the UK and Scottish suspected cancer guidance in Scotland) reminds us that unexplained thrombocytosis is a risk marker for some solid-tumor malignancies.

Previous studies have demonstrated that unexplained thrombocytosis is associated with a 1-year cancer incidence of 11.6% in males and 6.2% in females, well exceeding the standard 3% threshold warranting investigation for underlying malignancy. However, thrombocytosis should not be used as a stand-alone diagnostic or screening test for cancer, or indeed to rule out cancer.

Instead, unexplained thrombocytosis should prompt us to think cancer. The Scottish suspected cancer referral guidelines include thrombocytosis in the investigation criteria for what they call the LEGO-C cancers — L for lung, E for endometrial, G for gastric, O for oesophageal, and C for colorectal, which is a useful reminder for us all.

What further history, examination, and investigations might we consider in primary care if we identify an unexplained high platelet count? As always, we should use our clinical judgment and trust our clinical acumen.

We should consider all the possible underlying causes, including infection, inflammation, and blood loss, including menstrual blood loss in women; myeloproliferative disorders such as polycythemia rubra vera, chronic myeloid leukemia, and essential thrombocythemia; and, of course, underlying malignancy. If a likely underlying reversible cause is present (for example, a recent lower respiratory tract infection), simply repeating the full blood count in 4-6 weeks is quite appropriate to see if the thrombocytosis has resolved.

Remember, 80%-90% of cases are reactive thrombocytosis, and most cases resolve within 3 months. If thrombocytosis is unexplained or not resolving, consider checking ferritin levels to exclude iron deficiency. Consider checking C-reactive protein (CRP) levels to exclude any inflammation, and also consider checking a blood film to exclude any hematologic disorders, in addition, of course, to more detailed history-taking and examination to elicit any red flags.

We can also consider a JAK2 gene mutation test, if it is available to you locally, or a hematology referral if we suspect a myeloproliferative disorder. JAK2 is a genetic mutation that may be present in people with essential thrombocythemia and can indicate a diagnosis of polycythemia rubra vera.

Subsequent to this, and again using our clinical judgment, we then need to exclude the LEGO-C cancers. Consider urgent chest x-ray to exclude lung cancer or pelvic ultrasound in women to exclude endometrial cancer. Also, we should consider an upper gastrointestinal endoscopy, particularly in those individuals who have associated upper gastrointestinal symptoms and/or weight loss.

Finally, consider a qFIT to identify any occult bleeding in the stool, again if it’s available to you, or certainly if not, urgent lower gastrointestinal investigations to exclude colorectal cancer.

Alongside these possible investigations, as always, we should safety-net appropriately within agreed timeframes and check for resolution of the thrombocytosis according to the condition being suspected. Remember, most cases resolve within 3 months.

Returning to Louisa, what did I do? After seeing a platelet count of 600, I subsequently telephoned her and reexplored her history, which yielded nil else of note. Specifically, there was no history of unexplained weight loss, no history of upper or lower gastrointestinal symptoms, and certainly nothing significantly different from her usual irritable bowel syndrome symptoms. There were also no respiratory or genitourinary symptoms of note.

I did arrange for Louisa to undergo a chest x-ray over the next few days, though, as she was an ex-smoker. This was subsequently reported as normal. I appreciate chest x-rays have poor sensitivity for detecting lung cancer, as highlighted in a number of recent papers, but it was mutually agreed with Louisa that we would simply repeat her blood test in around 6 weeks. As well as repeating the full blood count, I arranged to check her ferritin, CRP, and a blood film, and then I was planning to reassess her clinically in person.

These bloods and my subsequent clinical review were reassuring. In fact, her platelet count had normalized after that 6 weeks had elapsed. Her thrombocytosis had resolved.

I didn’t arrange any further follow-up for her, but I did give her the usual safety netting advice to re-present to me or one of my colleagues if she does develop any worrying symptoms or signs.

I appreciate these scenarios are not always this straightforward, but I wanted to outline what investigations and referrals we may need to consider in primary care if we encounter an unexplained high platelet count.

There are a couple of quality-improvement activities for us all to consider in primary care. Consider as a team how we would respond to an incidental finding of thrombocytosis on a full blood count. Also consider what are our safety-netting options for those found to have raised platelet counts but no other symptoms or risk factors for underlying malignancy.

Finally, I’ve produced a Medscape UK primary care hack or clinical aide-memoire on managing unexplained thrombocytosis and associated cancer risk in primary care for all healthcare professionals working in primary care. This can be found online. I hope you find this resource helpful.

Dr. Kevin Fernando, General practitioner partner with specialist interests in cardiovascular, renal, and metabolic medicine, North Berwick Group Practice in Scotland, has disclosed relevant financial relationships with Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Dexcom, Lilly, Menarini, Novartis, Novo Nordisk, Roche Diagnostics, Embecta, Roche Diabetes Care, Sanofi Menarini, and Daiichi Sankyo.

A version of this article first appeared on Medscape.com.

This transcript has been edited for clarity.

In this podcast, I’m going to talk about unexplained high platelet counts, or thrombocytosis, and the risk for cancer in primary care. Let’s start with a typical case we all might see in primary care.

Louisa is 47 years old and is the chief financial officer for a tech startup company. She presents to us in primary care feeling tired all the time — a very common presentation in primary care — with associated reduced appetite. Past medical history includes irritable bowel syndrome, and she’s an ex-smoker.

Systemic inquiry is unremarkable. Specifically, there is no history of weight loss. Louisa has not been prescribed any medication and uses over-the-counter remedies for her irritable bowel syndrome. Examination is also unremarkable. Blood tests were checked, which were all reassuring, except for a platelet count of 612 × 10⁹ cells/L (usual normal range, about 150-450).

What do we do next? Do we refer for an urgent chest x-ray to exclude lung cancer? Do we check a quantitative immunohistochemical fecal occult blood test (qFIT) to identify any occult bleeding in her stool? Do we refer for a routine upper gastrointestinal endoscopy or pelvic ultrasound scan to exclude any upper gastrointestinal or endometrial malignancy?

Do we simply repeat the bloods? If so, do we repeat them routinely or urgently, and indeed, which ones should we recheck?

Louisa has an unexplained thrombocytosis. How do we manage this in primary care? Thrombocytosis is generally defined as a raised platelet count over 450. Importantly, thrombocytosis is a common incidental finding in around 2% of those over 40 years of age attending primary care. Reassuringly, 80%-90% of thrombocytosis is reactive, secondary to acute blood loss, infection, or inflammation, and the majority of cases resolve within 3 months.

Why the concern with Louisa then? Although most cases are reactive, clinical guidance (for example, NICE suspected cancer guidance in the UK and Scottish suspected cancer guidance in Scotland) reminds us that unexplained thrombocytosis is a risk marker for some solid-tumor malignancies.

Previous studies have demonstrated that unexplained thrombocytosis is associated with a 1-year cancer incidence of 11.6% in males and 6.2% in females, well exceeding the standard 3% threshold warranting investigation for underlying malignancy. However, thrombocytosis should not be used as a stand-alone diagnostic or screening test for cancer, or indeed to rule out cancer.

Instead, unexplained thrombocytosis should prompt us to think cancer. The Scottish suspected cancer referral guidelines include thrombocytosis in the investigation criteria for what they call the LEGO-C cancers — L for lung, E for endometrial, G for gastric, O for oesophageal, and C for colorectal, which is a useful reminder for us all.

What further history, examination, and investigations might we consider in primary care if we identify an unexplained high platelet count? As always, we should use our clinical judgment and trust our clinical acumen.

We should consider all the possible underlying causes, including infection, inflammation, and blood loss, including menstrual blood loss in women; myeloproliferative disorders such as polycythemia rubra vera, chronic myeloid leukemia, and essential thrombocythemia; and, of course, underlying malignancy. If a likely underlying reversible cause is present (for example, a recent lower respiratory tract infection), simply repeating the full blood count in 4-6 weeks is quite appropriate to see if the thrombocytosis has resolved.

Remember, 80%-90% of cases are reactive thrombocytosis, and most cases resolve within 3 months. If thrombocytosis is unexplained or not resolving, consider checking ferritin levels to exclude iron deficiency. Consider checking C-reactive protein (CRP) levels to exclude any inflammation, and also consider checking a blood film to exclude any hematologic disorders, in addition, of course, to more detailed history-taking and examination to elicit any red flags.

We can also consider a JAK2 gene mutation test, if it is available to you locally, or a hematology referral if we suspect a myeloproliferative disorder. JAK2 is a genetic mutation that may be present in people with essential thrombocythemia and can indicate a diagnosis of polycythemia rubra vera.

Subsequent to this, and again using our clinical judgment, we then need to exclude the LEGO-C cancers. Consider urgent chest x-ray to exclude lung cancer or pelvic ultrasound in women to exclude endometrial cancer. Also, we should consider an upper gastrointestinal endoscopy, particularly in those individuals who have associated upper gastrointestinal symptoms and/or weight loss.

Finally, consider a qFIT to identify any occult bleeding in the stool, again if it’s available to you, or certainly if not, urgent lower gastrointestinal investigations to exclude colorectal cancer.

Alongside these possible investigations, as always, we should safety-net appropriately within agreed timeframes and check for resolution of the thrombocytosis according to the condition being suspected. Remember, most cases resolve within 3 months.

Returning to Louisa, what did I do? After seeing a platelet count of 600, I subsequently telephoned her and reexplored her history, which yielded nil else of note. Specifically, there was no history of unexplained weight loss, no history of upper or lower gastrointestinal symptoms, and certainly nothing significantly different from her usual irritable bowel syndrome symptoms. There were also no respiratory or genitourinary symptoms of note.

I did arrange for Louisa to undergo a chest x-ray over the next few days, though, as she was an ex-smoker. This was subsequently reported as normal. I appreciate chest x-rays have poor sensitivity for detecting lung cancer, as highlighted in a number of recent papers, but it was mutually agreed with Louisa that we would simply repeat her blood test in around 6 weeks. As well as repeating the full blood count, I arranged to check her ferritin, CRP, and a blood film, and then I was planning to reassess her clinically in person.

These bloods and my subsequent clinical review were reassuring. In fact, her platelet count had normalized after that 6 weeks had elapsed. Her thrombocytosis had resolved.

I didn’t arrange any further follow-up for her, but I did give her the usual safety netting advice to re-present to me or one of my colleagues if she does develop any worrying symptoms or signs.

I appreciate these scenarios are not always this straightforward, but I wanted to outline what investigations and referrals we may need to consider in primary care if we encounter an unexplained high platelet count.

There are a couple of quality-improvement activities for us all to consider in primary care. Consider as a team how we would respond to an incidental finding of thrombocytosis on a full blood count. Also consider what are our safety-netting options for those found to have raised platelet counts but no other symptoms or risk factors for underlying malignancy.

Finally, I’ve produced a Medscape UK primary care hack or clinical aide-memoire on managing unexplained thrombocytosis and associated cancer risk in primary care for all healthcare professionals working in primary care. This can be found online. I hope you find this resource helpful.

Dr. Kevin Fernando, General practitioner partner with specialist interests in cardiovascular, renal, and metabolic medicine, North Berwick Group Practice in Scotland, has disclosed relevant financial relationships with Amarin, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Dexcom, Lilly, Menarini, Novartis, Novo Nordisk, Roche Diagnostics, Embecta, Roche Diabetes Care, Sanofi Menarini, and Daiichi Sankyo.

A version of this article first appeared on Medscape.com.