The video version of this podcast can be found here:

·      https://youtu.be/goK_Q4P2qpk

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 neutropenia, 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.

Neutrophils are the most numerous subtype of white blood cell and they are the body’s first responders to bacterial infections.

Neutropenia is when the neutrophil count is low. A normal neutrophil count in adults ranges from 2.0 to 7.5. However, an isolated low neutrophil count is extremely common in clinical practice. A result between 1.5 and 2.0 × 10⁹/l, while technically below the normal reference range, is rarely clinically significant. Many healthy people fluctuate in this borderline range due to factors such as minor viral infections, recent exercise, or simply natural day-to-day variation in blood counts.

We also have to remember that normal ranges differ across populations. People of Afro-Caribbean or Middle Eastern heritage often have a normal baseline neutrophil count between 1.0 and 1.8 × 10⁹/l. This is known as constitutional or ethnic neutropenia, which is of no clinical consequence. It is a benign, lifelong finding and does not increase susceptibility to infection. For these patients, referral is usually only needed if the neutrophil count falls below 1.0 × 10⁹/l on repeat testing.

For everybody else and for the purpose of this episode, we will define neutropenia as a neutrophil count below 1.5.

Possible causes of neutropenia are as follows:

• first we have drugs: such as phenytoin, carbimazole, antipsychotics, and co-trimoxazole, which can suppress neutrophil production in the bone marrow or trigger immune-mediated neutrophil destruction. Some drugs are directly toxic to the bone marrow, while others induce antibody formation against neutrophils.

• then we have Malignancy: including conditions like myeloma or any cancer that infiltrates the bone marrow. This reduces the marrow’s ability to produce neutrophils. Additionally, chemotherapy and radiotherapy further compound this by damaging rapidly dividing cells, leading to predictable and sometimes profound neutropenia.

• Also Vitamin B12 and folate deficiency: which impair DNA synthesis. Because neutrophils and their precursors divide rapidly, they are particularly sensitive to this.

• then we have Iron deficiency: which reduces the efficiency of haematopoiesis in general. Although iron deficiency is normally associated with anaemia, iron is also required for normal development of all blood cell lines, including neutrophils. Severe or prolonged deficiency can therefore lead to mild neutropenia.

•Another cause ca be Autoimmune diseases: which can cause neutropenia through immune-mediated destruction by autoantibodies that target neutrophils or their precursors.

• then we have viral infections: including EBV, HIV, and hepatitis B and C, which can directly suppress bone marrow activity or cause redistribution of neutrophils from the bloodstream into tissues. Many other viruses also transiently inhibit neutrophil production during acute illness, making mild neutropenia very common.

• Also, another possible cause is excess alcohol: which is toxic to the bone marrow and can impair the proliferation and differentiation of myeloid precursors. Chronic alcohol use is also associated with nutritional deficiencies, particularly folate, compounding the effect on marrow function.

• then we have Liver disease and cirrhosis: which can lead to neutropenia through hypersplenism causing increased sequestration and destruction of blood cells in the spleen. Another mechanism is metabolic effect of cirrhosis on overall bone marrow function. And finally, as we have already explained there is:

• Ethnic variation: like constitutional or ethnic neutropenia in people of Afro-Caribbean and Middle Eastern descent. Again, this is a benign inherited pattern without any impairment in immune function.

How should we manage these patients? We should send the patient to hospital as an emergency if:

• There is any evidence of sepsis, because neutropenic patients are at high risk of overwhelming infection. This means they can deteriorate rapidly, often without the typical signs of infection.

• Additionally, we should also send the patient to hospital as an emergency if the neutrophil count is below 1.0 × 10⁹/l and any of the following factors are present:

– First, if the patient is on chemotherapy.

This is because chemotherapy-induced neutropenia can progress quickly, and these patients are at particularly high risk. In this setting, infection can become severe within hours leading to sepsis.

– Also, if there is lymphadenopathy because enlarged lymph nodes raise concern for an underlying haematological malignancy, such as lymphoma or leukaemia, or for a significant viral infection causing significant bone marrow involvement.

– Also if there is splenomegaly because an enlarged spleen suggests increased sequestration and destruction of blood cells, or infiltration by malignancy or infection. Splenomegaly with neutropenia can be suggestive of serious conditions such as myeloproliferative disorders, autoimmune cytopenias, or advanced liver disease with hypersplenism.

– And finally, we should also send the patient to hospital as an emergency if the neutrophil count is below 1.0 × 10⁹/l if there are other cytopenias.

For example, if anaemia or thrombocytopenia is also present, this points toward a significant bone marrow problem which increases the risk of complications.

We should make an urgent haematological referral on a cancer pathway if:

• The neutrophil count is below 0.5 × 10⁹/l and the patient is otherwise well.

This is because a neutrophil count this low is concerning even in the absence of symptoms. Counts below 0.5 significantly increase the risk of serious infection, and they also raise the possibility of an underlying bone marrow disorder. Conditions such as acute leukaemia, myelodysplastic syndromes, or bone marrow infiltration can initially present with isolated severe neutropenia before other clinical signs appear.

If the neutrophil count is above 0.5 × 10⁹/l and the patient is clinically well, we can safely take a stepwise approach. The first action is to repeat the blood test within one week, as many cases of mild neutropenia are transient. At the same time, and as part of the initial work-up, which other investigations should we request?

We should investigate the underlying cause by organising the following tests:

• As already mentioned, a repeat full blood count.

This in order to confirm whether the neutropenia is sustained and to check for other full blood count abnormalities.

• A blood film: which can identify abnormal cell morphology, immature cells, or blasts suggestive of bone marrow disease. It can also help detect features consistent with infection, nutritional deficiency, or autoimmune processes.

• Vitamin B12 and folate: because as we said earlier, deficiency can lead to ineffective neutrophil production.

• Ferritin and iron studies: given that iron deficiency not only causes anaemia, but can also reduce neutrophil production.

• Autoimmune screen because some autoimmune conditions can cause immune-mediated destruction of neutrophils or affect bone marrow function.

• HIV testing: because HIV can lead to neutropenia through direct bone marrow suppression, chronic immune activation, or associated infections. In these cases, HIV treatment can reverse the neutropenia and improve overall immunity.

• and finally, we should also request Hepatitis B and C serology: given that chronic viral hepatitis can impair bone marrow function and is also associated with splenomegaly, hypersplenism, and autoimmune cytopenias.

After we have done these tests, if the patient is well and the cause of the neutropenia remains unknown, our next steps will depend on the degree and persistence of the low neutrophil count.

Firstly, if the neutrophil count remains below 1.0 × 10⁹/l we will refer urgently to outpatient haematology. This is because even in the absence of symptoms, this level carries a meaningful risk of infection and warrants specialist assessment.

If the neutrophil count is between 1.0 and 1.5 × 10⁹/l, we will monitor the full blood count for 4–6 weeks. This is because many cases in this borderline range are temporary, and monitoring over several weeks helps determine whether the neutropenia is improving, stable, or worsening.

Then we will refer to haematology routinely if any of the following occur:

– First, if the neutrophil count remains below 1.5 × 10⁹/l

(or below 1.0 × 10⁹/l in African-Caribbean patients, due to constitutional neutropenia). This is to rule out the possibility of a chronic underlying cause.

– Also if there are other full blood count abnormalities suggesting that more than one blood cell line may be affected, raising concern for broader marrow pathology.

– and finally, if there is a history of infections or ulcers. This is because recurrent infections, mouth ulcers, or delayed healing are clinical signs that the neutropenia may be functionally significant, even if the absolute count is only mildly reduced. These symptoms suggest impaired neutrophil activity or insufficient neutrophil reserves, and they strengthen the case for specialist review.

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.