The video version of this podcast can be found here:

·      https://youtu.be/4NysH3aEPMM

This video refers to guidelines produced by a number of organisations (details below). Please note that the content on this channel reflects my professional interpretation/summary of the guidance and that I am in no way affiliated with, employed by or funded/sponsored by any of them.

My name is Fernando Florido and I am a General Practitioner in the United Kingdom. In this episode I neutropenia always focusing on what is relevant in Primary Care only. The information is based on Haematological guidance by Camden CCG, Manchester Foundation Trust and King’s Health Partners.

I am not giving medical advice; this video is intended for health care professionals, it is only my summary and my interpretation of the guidelines and you must use your clinical judgement.  

Disclaimer:

The Video Content on this channel is for educational purposes and not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read or seen on this YouTube channel. The statements made throughout this video are not to be used or relied on to diagnose, treat, cure or prevent health conditions.

In addition, transmission of this Content is not intended to create, and receipt by you does not constitute, a physician-patient relationship with Dr Fernando Florido, his employees, agents, independent contractors, or anyone acting on behalf of Dr Fernando Florido.

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There is a podcast version of this and other videos that you can access here:

Primary Care guidelines podcast:

·      Redcircle: https://redcircle.com/shows/primary-care-guidelines

·      Spotify: https://open.spotify.com/show/5BmqS0Ol16oQ7Kr1WYzupK

·      Apple podcasts: https://podcasts.apple.com/gb/podcast/primary-care-guidelines/id1608821148

There is a YouTube version of this and other videos that you can access here: 

• The Practical GP YouTube Channel: 

https://youtube.com/@practicalgp?si=ecJGF5QCuMLQ6hrk

My summary of the guidance consulted can be found here:

·      https://1drv.ms/b/s!AiVFJ_Uoigq0mQ4ZjYGRH1wkGBdc?e=Zuxx84

The resources consulted can be found here:

·      Camden CCG guidance: 1456246258-2f3891e610beaa6533f2c0ad7866e776.pdf(Review) - Adobe cloud storage

·      Manchester Adult anaemia guide: https://acrobat.adobe.com/id/urn:aaid:sc:EU:f96fe528-0a47-457c-b29a-a7efb87221e0

·      Manchester Haematology GP guide: https://mft.nhs.uk/app/uploads/2021/02/MFT-Haematology-GP-Pathway-Guide-v4-11.2.21.pdf

·      King’s Health Partners: https://www.kingshealthpartners.org/assets/000/002/294/KCH_-_king_s_health_partners_-_quick_guide_to_haematology_original.pdf

Transcript

If you are listening to this podcast on YouTube, for a better experience, switch to the video version. The link is in the top right corner of the video and in the episode description.

Hello and welcome, I’m Fernando, a GP in the UK. Today we are going to cover what to do when we encounter a high haematocrit, including initial assessment, follow up and management, always focusing on what is relevant in Primary Care only.

I have based this episode on Haematological guidance by Camden CCG, Manchester Foundation Trust and King’s Health Partners. The links to them are in the episode description.

Right, let’s jump into it.

And we will start by saying that haematocrit measures the proportion of blood volume taken up by red blood cells. It can be expressed either as a percentage—from 0 to 100 or as a decimal proportion, from 0 to 1. Because it reflects the relative volumes of red cells and plasma, the haematocrit is influenced not only by the absolute number of red blood cells but also by the amount of circulating plasma. Any change in either component will affect the final value.

A high haematocrit raises the possibility of polycythaemia. Polycythaemia can be diagnosed when the haematocrit is greater than 0.52 in men and greater than 0.48 in women. These thresholds help identify affected people, but they do not, by themselves, tell us the cause.

Polycythaemia is sometimes referred to as erythrocytosis, but this is not entirely accurate. Erythrocytosis specifically refers to an increased number of red blood cells in the circulation. Polycythaemia, on the other hand, is defined by a raised haematocrit, not by a direct count of red blood cells. As a result, it is possible to have a high haematocrit without true erythrocytosis.

This distinction matters because there are two types of polycythaemia. The first is absolute polycythaemia, where an increased red cell mass is genuinely present, that is, true erythrocytosis. The second is relative or apparent polycythaemia, where the haematocrit is high not because there are more red cells, but because the plasma volume is reduced. Dehydration, diuretics, or plasma loss can all create this picture, leading to a raised haematocrit despite a normal red cell mass. It is also common in obese men, and it is also associated with smoking, alcohol, hypertension and stress. Despite the potentially reversible causes of relative or apparent polycythaemia, these patients are also at risk of occlusive vascular episodes.

On the other hand, we have absolute polycythaemia, which reflects a true increase in red cell mass. This can be divided into primary and secondary causes.

The primary cause is Polycythaemia Vera (PV). Well over 90% of patients with PV have an acquired mutation in the JAK2 gene, which plays an important role in regulating erythropoiesis. Because of this mutation, the bone marrow becomes hypersensitive to growth signals and produces red blood cells even when erythropoietin levels are low. In other words, these patients do not need as much erythropoietin to drive red cell production.

The main features of Polycythaemia Vera are therefore:

• a positive JAK2 mutation test,

• a low serum erythropoietin level.

Polycythaemia Vera is also commonly associated with low ferritin, because the accelerated and unregulated production of red cells consumes large amounts of iron.

Being a myeloproliferative disorder, Polycythaemia Vera may also show raised white blood cells and/or platelets, reflecting the involvement of the bone marrow.

Secondary polycythaemia, on the other hand, results from a physiological increase in erythropoietin production. The kidneys release more erythropoietin in response to reduced oxygen levels, so secondary polycythaemia can be an appropriate response to chronic hypoxia, as seen in COPD, congenital or acquired heart disease, and in smokers.

It can also be an inappropriate response when erythropoietin is produced by tumours, such as certain renal or liver tumours, or even uterine fibroids, which can secrete erythropoietin autonomously.

Other possible causes of secondary polycythaemia include anabolic steroids and testosterone therapy, as androgens stimulate erythropoietin production through hormonal pathways.

In cases of secondary polycythaemia, the pattern is different:

• the JAK2 mutation is negative,

• erythropoietin levels are high, and

• ferritin, white blood cells and platelets are normal.

So what do we do when we receive a high haematocrit result? Well, Criteria for urgent referral are a haematocrit greater than 0.60 in men or greater than 0.56 in women. We should also refer urgently if the patient has had a recent thrombosis, shows any abnormal bleeding, or reports neurological or visual symptoms. These features raise concern for hyperviscosity or an underlying myeloproliferative disorder, both of which require immediate specialist assessment.

If the criteria for urgent referral are not met, the next step is to confirm the result by repeating the blood test. In order to differentiate between apparent and absolute polycythaemia, the blood sample should be taken without a tourniquet, and we should ensure that the patient has not been fasting, is well hydrated, and has been advised about alcohol intake and smoking, as these factors can artificially raise the haematocrit.

In this repeat blood test, we should request:

• A repeat full blood count, to confirm whether the raised haematocrit is persistent and to check for associated abnormalities in white cells or platelets.

• A blood film, which can reveal morphological clues to myeloproliferative disease or other haematological disorders.

• We should screen for diabetes, hyperlipidaemia and hypertension, as these cardiovascular risk factors often coexist with secondary causes of polycythaemia and may contribute to vascular complications.

• As mentioned earlier, we should also check Ferritin, to assess iron stores, which may be depleted in Polycythaemia Vera due to increased red cell production.

• and finally renal and liver function tests, since kidney or liver disease may contribute to secondary polycythaemia or influence erythropoietin production.

Additionally, if we suspect absolute polycythaemia, the following tests should be done:

• Genetic testing for the JAK2 mutation, which is positive in the great majority of patients with Polycythaemia Vera.

• And erythropoietin levels, which help distinguish primary from secondary causes, being low in PV and elevated in secondary polycythaemia.

However, in the UK, JAK2 mutation testing and serum erythropoietin levels are not routinely available in primary care. In most areas, these investigations are carried out by haematology teams, as they form part of the specialist work-up for myeloproliferative disorders. While some regions may allow primary-care access, this is not standard practice, and therefore, if absolute polycythaemia is suspected or the haematocrit remains persistently elevated, the appropriate course of action is to refer the patient to haematology, who will then arrange JAK2 and erythropoietin testing as part of their assessment.

So, let’s summarise these patients’ management again:

If we encounter someone with a high haematocrit, we will see if they meet the urgent referral criteria, that is, a haematocrit greater than 0.60 in men or greater than 0.56 in women. We should also refer urgently if the patient has had a recent thrombosis, shows any abnormal bleeding, or reports neurological or visual symptoms.

If the urgent criteria are not met, we will repeat the FBC and arrange routine screening investigations.

Criteria for routine referral are an unexplained, persistently elevated haematocrit above 0.52 in men or above 0.48 in women, taking into account that referral should be considered at lower thresholds if there is associated iron deficiency. “Persistently” means at least two readings above these levels taken four weeks apart.

Alternatively, routine referral is also justified if the haematocrit is above 0.52 in men or above 0.48 in women without waiting for a second test if there are associated symptoms of concern such as pruritus, raised white cell count and/or platelets, splenomegaly, or if there is a past, not recent history of arterial or venous thrombosis.

From a clinical perspective, we will suspect apparent polycythaemia if there is a history of factors such as dehydration, smoking, alcohol excess, diuretics, or other causes of haemoconcentration.

We will suspect absolute secondary polycythaemia if there is chronic hypoxia from conditions such as COPD, smoking, or cardiac disease, if the patient is taking anabolic steroids or testosterone therapy, or if there is a possibility of erythropoietin -producing tumours in the kidney or liver.

If none of these clues is present, we may be dealing with absolute primary polycythaemia, or Polycythaemia Vera. These patients should be referred to haematology, since confirming the diagnosis requires tests that are not routinely available in general practice, ike JAK2 mutation testing and serum EPO levels.

So that is it, a review of the initial assessment and management of neutropenia.

We have come to the end of this episode. Remember that this is not medical advice but only my summary and my interpretation of the guidelines. You must always use your clinical judgement.

Thank you for listening and goodbye.