Podcast - The Art of Interpreting a FBC - turning the nightmare into a sweet dream
38m | Feb 26, 2024The video version of this episode can be found here:
My summary of the guidance consulted can be found here:
· https://1drv.ms/b/s!AiVFJ_Uoigq0mQ4ZjYGRH1wkGBdc?e=Zuxx84
This episode refers to guidelines produced by a number of organisations. Please note that the content 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 go through the interpretation of an abnormal full blood count, always focusing on what is relevant in Primary Care only.
I am not giving medical advice; this video is intended for health care professionals; it is only my summary and my interpretation of the information consulted. You must always use your clinical judgement.
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
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
· Medscape / Kevin Fernando- management of abnormal blood tests: https://1drv.ms/b/s!AiVFJ_Uoigq0mQPPwvFNZtsUSpIr?e=xYthDn
· Oxford hospital referral pathway: https://nssg.oxford-haematology.org.uk/general-haematology/documents/general-haematology/raised-haematocrit.pdf
· GP notebook: https://gpnotebook.com/en-GB/pages/general-information/abnormal-fbc-in-adults
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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 go through the interpretation of full blood counts, including follow up management, always focusing on what is relevant in Primary Care only.
I will be covering several areas:
1. Review of haematological indices
2. Polycythaemia
3. Anaemia
4. Thrombocytosis
5. Thrombocytopenia
6. Neutrophilia
7. Neutropenia
8. Lymphocytosis
9. Lymphopenia
10. Eosinophilia
11. Monocytosis
I have put time stamps throughout the video so that you can skip to the section that you are interested in.
I have based this episode on a variety of sources, primarily Haematological guidance by Camden CCG, Manchester Foundation Trust and King’s Health Partners, although other sources like Medscape and GP notebook were also reviewed. I have put links to them in the episode description. They are worth having a look as they have flowcharts and other information that you may find useful.
Make sure to stay for the entire episode because at the end, I will tell you how to access my summary of the recommendations, which I hope that you will find helpful.
Right, there is a lot of information to cover, so let’s jump into it.
I will now go through the blood indices on the full blood count and I will also touch on iron investigations such as ferritin and total iron binding capacity. So, let’s look at them one at a time:
· The Platelet Count gives us the absolute number of platelets
· The Mean Platelet Volume or MPV gives us the average size of platelets. New platelets are larger, and an increased MPV occurs when increased numbers of platelets are being produced, for example during infection or inflammation.
· The White Blood Cell Count or WBC, gives the absolute number of white blood cells present. Leucocytosis is when the White Blood Cell Count is raised and leucopenia when it is low. In these situations, we need to look at the subtypes of the white blood cells, that is, we need to look at the:
· WBC Differential, which looks at the number and proportion of the different types of WBC. We have five types: neutrophils, lymphocytes, monocytes, eosinophils, and basophils.
· The Red Blood Cell Count or RBC is the absolute number of red cells. It is an important value but we often rely on other red blood cell indices to interpret the results correctly
· Haemoglobin or Hb is crucial for the diagnosis of anaemia but, again, other indices are needed for the final interpretation.
· The Haematocrit or HCT measures how much volume is taken up by red blood cells and it is expressed either as a percentage (that is from 0 to 100) or a proportion (that is, from 0 to 1). The haematocrit is therefore influenced not only by the number of red blood cells but also the amount of plasma present.
· The Mean Corpuscular Volume or MCV refers to the average size of each RBC. An elevated MCV or macrocytosis is when the RBCs are larger than normal, for example in vitamin B12 or folic acid deficiency. A low MCV or microcytosis is when the RBCs are smaller than normal which may indicate, for example, iron deficiency anaemia.
· The Mean Corpuscular Haemoglobin or MCH measures the average haemoglobin per red cell. Since macrocytic or larger RBCs tend to carry more haemoglobin that normal, they would normally have higher MCH values.
· The Mean Corpuscular Haemoglobin Concentration or MCHC is about concentration, that is, the amount of haemoglobin relative to the size of the cell. A decreased MCHC or hypochromia is seen in conditions such as in iron deficiency anaemia, chronic inflammation or thalassaemia. An increased MCHC or hyperchromia is seen when the haemoglobin is abnormally concentrated in the cells, such as in spherocytosis.
· The Red Cell Distribution Width or RDW measures how uniform the red cells are in size. A high RDW indicates a mix of small and large cells, which can happen in some anaemias, such as iron deficiency or vitamin B12 deficiency. An increase in RDW happens when red blood cells have different sizes also called anisocytosis, or different shapes also called poikilocytosis.
· Ferritin is the most useful indicator of iron deficiency, as it can drops before any decrease in levels of iron in the blood occurs. Ferritin is the main form of iron storage and is present mostly in the liver. Ferritin levels are low in long-term iron deficiency. Ferritin may also be decreased if protein levels are very low, like in malnutrition. Ferritin is high in states of iron overload, especially in haemochromatosis. However, ferritin can be high for a number of other reasons including inflammatory conditions, infection and liver disease.
· Total Iron Binding Capacity, or TIBC, measures the total capacity to bind iron in the blood. TIBC correlates with the amount of transferrin, and while both tests (TIBC and transferrin) are different, they measure essentially the same thing and most laboratories only measure one or the other. The amount of transferrin transporting iron is called transferrin saturation. Iron deficiency results in a low transferrin saturation, but an increased TIBC. In iron overload, such as in haemochromatosis, iron and transferrin saturation will be high and TIBC will be low or normal. Because transferrin is made in the liver, TIBC and transferrin will also be low in liver disease.
Now let’s start looking at the different haematological conditions. And the first section refers to polycythaemia.
Polycythaemia is judged on basis of HCT and it can be diagnosed if the HCT > 0.52 in men and > 0.48 in women.
Polycythaemia is also sometimes referred to as Erythrocytosis but this is not always correct. Why? Well, erythrocytosis indicates an excess number of erythrocytes or red blood cells and, as we have said, polycythaemia is judged on haematocrit, not red blood cells.
And this is because there are two types of polycythaemia, absolute polycythaemia, that is, when erythrocytosis is present, and relative or apparent polycythaemia, when this is not the case.
For example, in apparent or relative polycythaemia, the HCT increases as a result of a reduced plasma volume rather than an increased red blood cell mass. It is common in obese men, and it is also associated with smoking, diuretics, alcohol, hypertension, stress, and dehydration. Despite the potentially reversible causes, these patients are also at risk of occlusive vascular episodes.
On the other hand, we have absolute polycythaemia, which can be primary or secondary. The primary cause is Polycythaemia Vera. Well over 90% of PV patients have an acquired mutation in a gene called JAK2 that regulates erythropoiesis. These patients do not need as much erythropoietin or EPO to drive red cell production. So, the features of PV are a positive test to the JAK2 mutation, and a low serum EPO level. It also has a low ferritin secondary to the excess production of red cells, which consumes a significant amount of iron. Being a myeloproliferative disorder, it can also sometimes be associated with raised WBC and / or platelets.
Secondary Polycythaemia is due to the physiological response to increased EPO levels. It can be an appropriate response to hypoxia like in COPD, heart disease and smoking or to an inappropriate response due to an EPO producing tumour like in some Renal & liver tumours or fibroids. Other possible causes are anabolic steroids and testosterone therapy, as androgens can also stimulate EPO production. In cases of secondary polycythaemia, the JAK2 mutation is negative, EPO levels are high and ferritin, WBC and platelets are normal.
Criteria for urgent referral are a HCT >0.60 in men or >0.56 in women or also if there is recent thrombosis, abnormal bleeding, or neurological or visual symptoms.
If the criteria for urgent referral are not met, we should confirm the results by repeating the blood test. In order to differentiate between apparent and absolute polycythaemia, the blood sample should be uncuffed and we should ensure that the patient has not fasted, is well hydrated, and has been advised about alcohol and smoking.
In this blood test, we should request a:
· Repeat FBC
· A blood film and screen for diabetes, hyperlipidaemia and hypertension, checking
· HbA1c
· Lipids
· Ferritin
· Renal and liver function tests. Additionally, if we suspect absolute polycythaemia, we should also request
· Genetic testing for the JAK2 mutation and do
· EPO levels.
Criteria for routine referral are unexplained persistently elevated HCT >0.52 in men or >0.48 in women, taking into account that we should refer at lower limits if there is associated iron deficiency. “Persistently” means at least two readings above these levels 4 weeks apart.
Alternatively, routine referral is also justified if the HCT >0.52 in men or >0.48 in women without waiting for a second test if there are associated symptoms of concern like pruritus, raised WBC and / or platelets or splenomegaly, or if there is a past (not recent) history of arterial or venous thrombosis.
Right, let’s move on to the next chapter, which is a very important and common one, anaemia.
Anaemia presents as a low haemoglobin and is not a disease in itself, but may reflect an underlying disease process. It may also result from an increase in plasma volume and a dilutional effect, like in pregnancy. There may be local variations in the thresholds for diagnosis but the WHO uses the following haemoglobin thresholds to define anaemia at sea level in adults:
· women - 12 g/dl (reduced to 11 g/dl in pregnancy)
· men - 13 g/dl
So, I will be using these thresholds in this episode.
Also, I will be focusing on what we normally see in Primary Care, that is, chronic anaemia rather than anaemia secondary to acute bleeding requiring admission. Hospital admission will also be required with very severe anaemias, for example when the Hb <50 or even at higher levels if the patient is very symptomatic
The first thing to look after a low haemoglobin is the mean corpuscular volume or MCV. Depending on this value, the anaemia can be described as:
· Microcytic if the MCV is below 80
· Macrocytic if it is over 100 and
· Normocytic if it is between 80 and 100
· Bearing in mind that there may be mixed deficiencies, so we should look at the whole picture.
So, let’s look at the microcytic anaemias first. The most common cause of microcytosis is iron deficiency, so we will repeat the full blood count and check the patient’s iron status.
As we said earlier, ferritin can be an acute phase reactant so it can be raised in cases like, for example, inflammation, malignancy, alcohol excess, liver or renal disease and infection. If we suspect any of this, we should check ferritin together with iron studies or transferrin saturation to get a clearer picture. If the ferritin is >50mcg/L and transferrin saturation is >20%, then iron deficiency can be excluded. In that situation, we will consider haemoglobinopathy screening in order to exclude thalassaemia or other haemoglobin variants and, if positive, we will refer to haematology as necessary.
If the haemoglobinopathy screen is normal or if testing is not considered necessary , then we will think about the following conditions:
· One, Anaemia of chronic disease and we will look for causes of:
o Chronic inflammation: for example, autoimmune diseases, malignancy or tuberculosis
o Endocrine problems: for example, hypothyroidism, hypopituitarism or Addison’s and
o Other conditions such as CKD, liver disease or malnutrition
· Two, Myelodysplastic syndrome, usually presenting as lone unexplained and persistent anaemia and
· Three, We will also consider haemochromatosis where ferritin is raised.
And we will refer to the appropriate service if necessary.
On the other hand, if ferritin is:
· <30 mcg/L or
· <100 mcg/L with transferrin saturation less than 20%
We will regard it as iron deficiency anaemia. We will then enquire about upper and lower GI symptoms and we will consider an urgent cancer referral for upper and lower GI endoscopy after requesting a FIT test if:
· There are red flag symptoms
· There is an unexplained drop in Hb to below 110 in men and below 100 in non-menstruating women or if
· There is a strong family history of colorectal cancer, that is, two first degree relatives with the diagnosis or one first degree relative with a diagnosis before the age of 50.
If there are no criteria for urgent referral, and the cause of the iron deficiency is unknown, we will look for other possible causes, for example:
· Testing for coeliac serology and refer to gastroenterology if it is positive.
· Enquire about Heavy menstrual bleeding
· Consider Dietary causes
· Do Urinalysis to test for haematuria (as 1% of IDA have a renal malignancy)
· Do Stool testing for parasitology and we will also
· Consider aspirin, NSAIDs and anticoagulants as an aggravating factor but we will still investigate these patients fully.
When the cause of the iron deficiency anaemia is known, we will give iron therapy and treat the underlying cause accordingly and then recheck the Hb and ferritin within 3 months. If the deficiency has not resolved and it is not due to menstrual loss, we will refer to gastroenterology or other specialist services depending on the presentation and our clinical judgement.
Let’s now look at macrocytic anaemias, that is, when the MCV is >100.
If there is macrocytosis, with or without anaemia we should consider some of the possible causes and:
· Check alcohol intake
· Enquire about family history
· Review medication that could cause it, for example methotrexate, metformin, and some anticonvulsants, amongst others and
· remember that a high MCV can be a normal physiological finding in pregnancy.
Initial investigations will include:
· A Repeat FBC
· A Blood Film
· Vitamin B12 and folate levels
· Renal and liver function tests, including GGT
· TFTs
· Ferritin, iron studies
· Myeloma screen, including bone profile, serum immunoglobulins, serum Free Light Chains and Urinary Bence Jones protein
· And finally, we will also check the Reticulocyte count and LDH levels, looking for evidence of haemolysis, bearing in mind that markers of haemolysis include a raised reticulocyte count, a high bilirubin and a high LDH
Criteria for urgent referral to haematology are:
· Leucoerythroblastic features or blasts seen on blood film
· Unexplained symptomatic and progressive anaemia and if there is
· Associated splenomegaly, lymphadenopathy or other significant cytopenias
If the urgent criteria are not met, we will then act on the results and refer the patient accordingly. That is:
· If the reticulocyte count is high: we will look for evidence of bleeding or haemolysis and refer to the appropriate department.
· If there is CKD related anaemia: we will refer to the renal team
· If the TFTs are abnormal, we will treat the dysfunction and repeat the FBC 4-6 weeks later
· If vitamin B12 and / or folate levels are low: we treat the deficiencies and assess for the underlying cause. For example:
o In vitamin B12 deficiency, we will check for intrinsic factor Antibodies and Parietal Cell Antibodies and treat as pernicious anaemia if positive and
o In both vitamin B12 and folate deficiencies we will do a coeliac screen.
Criteria for routine haematology referral are:
· If paraprotein is detected
· If all results are normal, but there is persistent unexplained anaemia
· If there is persistent unexplained macrocytosis with an MCV >100 as this can be a feature of myelodysplasia
· If there is persistent unexplained vitamin B12 deficiency because persistent unexplained vitamin B12 deficiency can also occur in myelodysplastic syndromes
· If there is anaemia with associated abnormalities in other blood cells
· If the reticulocyte count is low or the picture is unclear and
· If there is an abnormal blood film
Finally, let’s now look at normocytic anaemias, that is, when the MCV is between 80 and 100.
Possible causes of normocytic anaemias are:
· A mixed haematinic deficiency
· Myelodysplastic syndrome
· Recent blood loss
· Anaemia of chronic disease like in:
o Chronic inflammation
o Endocrine problems or
o Other conditions such as CKD, liver disease or malnutrition
· And haemochromatosis if ferritin is raised.
In these cases, we will investigate similarly to macrocytic anaemias, that is, we will check the following:
· A repeat FBC with a Blood Film
· Vitamin B12 and folate levels
· Renal and liver function tests, including GGT
· TFTs
· Ferritin, iron studies
· Myeloma screen
· And finally, we will also check the Reticulocyte count and LDH levels, looking for evidence of haemolysis
And we will act on the results and refer the patient accordingly.
The next section refers to thrombocytosis or a raised platelet count above 450 x 109/L.
Possible causes of thrombocytosis are:
· Iron Deficiency Anaemia
· Malignancies especially the LEGO cancers, that is:
o Lung
o Endometrium
o Gastric
o Oesophageal
· Inflammation
· Infection
· Post-Splenectony and Hyposplenism like in Coeliac Disease
· Post-Operatively situations and finally a
· primary Myeloproliferative Disorder
But before moving on, let’s clarify a concept: should we call it thrombocytosis or thrombocythemia? Well, in fact, there is a difference. In summary, thrombocytosis is more common and arises as a secondary response, and therefore it is also referred to as reactive thrombocytosis. On the other hand, thrombocythemia, also referred to as primary or essential thrombocythemia, is less common and is a form of myeloproliferative disorder. Another key difference if that people with reactive thrombocytosis have normal platelets and therefore, also have a lower risk of blood clots and bleeding whereas those with thrombocythemia have abnormal platelets and also a higher risk of clots and bleeding. Thrombocythemia often presents with splenomegaly and a platelet count >1000.
Therefore, criteria for urgent haematology referral are if:
· The PLT count exceeds 1000 x 109 / L
· There is splenomegaly
· There is a recent history of thromboembolism
· The PLT count is >600 x109/L and the patient is at high risk of thromboembolism or CVD
· There are neurological symptoms
· There is abnormal bleeding
· There are any signs of malignancy or
· There are any other significant abnormal FBC indices
If the urgent referral criteria are not present, we will then look for causes by doing the following initial investigations:
· A repeat FBC
· A blood film
· Inflammatory markers like ESR and CRP
· Ferritin and iron studies and we will also
· consider doing a coeliac screen as it can be associated with thrombocytosis
If the patient is asymptomatic and there is no obvious cause, we will repeat the FBC 4-6 weeks later. If the thrombocytosis persists >450, we will refer to haematology routinely.
The next section is thrombocytopenia, which is defined as a low platelet count below 150 x 109/L. We need to remember that thrombocytopenia can frequently be an artefact, stemming from platelet clumping, rather than reflecting an actual decrease in platelet count. We should always confirm it with a second FBC and a blood film report.
We will enquire about travel, drugs and alcohol because possible causes of thrombocytopenia include:
· Alcohol excess
· Recreational drugs
· Malaria
· TB
· Liver & Renal disease
· Medications, for example, NSAIDs, Heparin, Digoxin, Quinine, anti-epileptics, antipsychotics, and PPIs
· B12 and folate deficiency
· Viral infection including:
o EBV (it usually resolves within few weeks in this case)
o HIV and
o Hepatitis B and C
· Malignancy
· Bone marrow failure like in aplastic anaemias
· Immune thrombocytopenic purpura or ITP and
· Autoimmune diseases, like SLE
Baseline investigations will include:
· Repeat FBC and blood film
· Vit B12 and folate
· Ferritin and iron studies
· Inflammatory markers such as ESR and CRP
· Autoimmune profile
· Renal, liver and thyroid function tests
· HIV, hepatitis B and C serology and
· Any other test suggested by the clinical history or examination findings
We should arrange a hospital urgent same day assessment if the platelet count is <20 with:
· Active Bleeding
· An abnormal blood film like Blasts or Fragments on the blood film or an
· Altered Conscious Level Or Confusion
We should make an urgent referral to haematology if:
· The platelet count is 50-100 and there is splenomegaly, lymphadenopathy, other cytopenias, the patient is pregnant or there is upcoming surgery or if
· The platelet count is <50. In this case, we will stop all antiplatelet agents and anticoagulants as it would be unsafe to continue.
If the platelet count is over 50 and the urgent referral criteria are not present, we will repeat the FBC after 4-6 weeks and refer to haematology routinely if the thrombocytopenia persists and remains unexplained.
Now, next, let’s have a look at neutrophilia, which is when the neutrophil count is raised, that is, over 7.5.
Infection is the most common cause but other possible causes are:
· Infection
· Inflammation
· Steroids
· Pregnancy
· Smoking
· Underlying Malignancy including Lymphoma and Leukaemia
· Connective tissue disease like RA
· Haemorrhage
· Haemolysis
· Hypoxia and
· Tissue damage including infarction
If the cause is unclear, we will investigate further by doing:
· A repeat FBC
· A Blood Film
· Inflammatory markers such as ESR and CRP
· Renal and liver function tests
· Autoimmune screen and
· Any other tests led by history
Criteria for urgent haematology referral will include a high suspicion of leukaemia because of:
· A leucoerythroblastic film or an
· Absolute Neutrophil count, ANC > 50 x109/L
We will make an early routine haematology referral, that is, without waiting for a repeat FBC, if the neutrophil count is >15 and:
· There is splenomegaly or
· There are other FBC abnormalities.
Otherwise, we will repeat the FBC 6 weeks later and we will refer to haematology routinely if:
· The neutrophilia persists and remains unexplained
Let’s now look at neutropenia, which is when the neutrophil count is low. A normal neutrophil count in adults is from 2.0 to 7.5. However, an isolated low neutrophil count is very common and a neutrophil count of between 1-5 -2.0 x 109/l, whilst below the normal range, is unlikely to be of any clinical significance. Also, people of Afro-Caribbean or Middle Eastern ethnicity have a lower normal range between 1 and 1.8 x 109/l, which is also referred to as constitutional or ethnic neutropenia. This is of no clinical consequence and we should only refer them if their neutrophils are <1.0 x 109/l on repeat testing.
For everybody else and for the purpose of this episode, we will say that neutropenia is when the neutrophil count is below 1.5.
Possible causes of neutropenia are:
· Drugs e.g. Phenytoin, Carbimazole, Antipsychotics and Clotrimoxazole
· Malignancy, like myeloma, bone marrow infiltration and chemo or radiotherapy
· Vitamin B12 and / or folate deficiency
· Iron deficiency
· Autoimmune diseases
· Any viral infection including EBV, HIV and Hepatitis B and C
· Excess alcohol
· Liver disease and cirrhosis and, as already mentioned, the
· Ethnic variation in people of Afro-Caribbean and Middle Eastern descent
We should send the patient to hospital as an emergency if:
· There is any evidence of sepsis
· The neutrophil count is <1 and:
o The patient is on chemotherapy
o There is lymphadenopathy
o There is splenomegaly or
o There is other cytopenia
We should make an urgent haematological referral on a cancer pathway if:
· The neutrophil count is <0.5 and the patient is otherwise well
If the neutrophil count is >0.5 and the patient is well, we will repeat the blood test within 1 week and investigate the cause by doing:
· A repeat FBC
· A blood film
· Vitamin B12
· Folate
· Ferritin and iron studies
· Autoimmune screen
· HIV and
· Hepatitis B and C serology
If the patient is well and the cause remains unknown, we will:
· Refer to haematology urgently if the neutrophil count remains <1 but
· If the neutrophil count is between 1 and 1.5, we will monitor the FBC for 4-6 weeks and refer to haematology routinely if:
o The neutrophil count remains below 1.5 (or 1 in African-Caribbean patients)
o There are other FBC abnormalities or
o There is a history of infections or ulcers
The next section refers to lymphocytosis, which is when the lymphocyte count is high that is, more than 3.5 x109 / L.
Possible causes of lymphocytosis are:
· Viral infections especially
o Glandular fever but also others such as:
o Measles, mumps, rubella
o EBV and
o CMV
· Bacterial infections, e.g. pertussis infection or whooping cough
· Lymphoproliferative disorders (such as Acute or Chronic Lymphatic Leukaemia or non-Hodgkins lymphoma)
· Post-splenectomy
· Rheumatoid arthritis
· Smoking
· Stress and
· Vigorous exercise
If there are features of acute or recent viral illness and the patient is otherwise well, we will repeat the FBC once resolved after 4-6wks.
We will refer to haematology urgently if:
· The Lymphocytosis is >20x109/L
· There are other cytopenias
· There is Lymphadenopathy
· There is Splenomegaly or if
· There are B symptoms, that is:
o Unexplained fever >38
o Drenching night sweats
o Weight loss
Otherwise, if the lymphocyte count is >5, we will repeat the blood in 4 to 6 weeks and investigate the cause by doing:
· A repeat FBC
· A Blood film
· Inflammatory markers such as ESR and CRP
· Glandular fever screen or other virology serology where indicated due to the clinical presentation and we will also request
· Immunophenotyping screen
And after this, we will refer to haematology routinely if the lymphocytosis persists and remains unexplained.
The next section is lymphopenia, when the lymphocyte count is low, that is below 1 x 109/L.
Possible causes of lymphopenia are:
· Elderly patients
· Excess alcohol
· Malnutrition
· Medication, for example steroids and chemotherapy
· Infection including legionella, HIV and hepatitis B and C and post viral lymphopenia is common
· Malignancy for example, lymphoma, bone marrow infiltration, and myeloma and we should consider a myeloma screen if there are suggestive symptoms.
· Renal or hepatic impairment
· Autoimmune conditions like RA and SLE
· Sarcoidosis
· Anorexia Nervosa and
· Primary immune deficiency
We will refer to haematology urgently if the lymphocyte count is <1 and there are any red flags. Red Flag signs in lymphopenia are:
· Recurrent infections or
· B symptoms, that is :
o Unexplained fever >38
o Drenching night sweats
o Weight loss
If there are no red flags, we will do a new blood test in 6 weeks and look for causes. So, we will do:
· A repeat FBC
· A blood film
· Renal and liver function tests
· Inflammatory markers such as ESR and CRP
· Autoimmune profile
· Viral serology as appropriate depending on the clinical presentation and a
· Myeloma screen if symptoms justify it
If the cause is found, we will refer to the appropriate specialist department. However, if it persists and remains unexplained, we will refer routinely to haematology.
There may be times when, if the lymphocyte count is >0.5x109/L and the patient is >70 years of age and otherwise well, we could consider just monitoring the FBC, but this will depend on our clinical judgement.
The next section refers to eosinophilia, when the eosinophil count is high. There may be local variations in the threshold but, in general, eosinophilia is defined as an eosinophil count over 0.5 x 109/L.
Examples of possible causes of eosinophilia are:
· Asthma
· Skin disease like eczema, atopic dermatitis, urticaria, and psoriasis
· Infections: especially those due to parasites (like hookworm, schistosomiasis and giardiasis), fungal infections as well as TB and malaria.
· Drugs such as penicillin, allopurinol, amitriptyline, and carbamazepine but in fact any drug is a possible cause
· Connective tissue disease like rheumatoid arthritis, and polyarteritis nodosa,
· Solid malignancies, for example breast, renal, stomach and lung cancer
· Myeloproliferative disorders like leukaemia and lymphoma
· Respiratory diseases such as bronchiectasis, and cystic fibrosis
· Endocrine conditions like Addison’s and
· Post-splenectomy
If the eosinophil count is >2.5, we will look for signs of organ damage and consider urgent admission if there are red Flags like:
· Severe symptoms secondary to organ involvement like:
o difficulty breathing
o chest pain
o abdominal pain, or
o neurological symptoms or
· other Complications such as tissue damage, venous thromboembolism, or end-organ damage like AKI or heart failure.
Criteria for urgent referral to haematology are:
· Leucoerythroblastic film or an
· Absolute Eosinophil Count > 5 x109/L,
If the eosinophil count is >0.5 and the patient is well, we will check the travel and drug history and check for any evidence of atopy. We will then repeat the blood test within 1 to 2 weeks and look for possible causes.
Initial investigations will include:
· A repeat FBC
· Blood film
· Inflammatory markers like ESR and CRP
· Immunoglobulin E
· Autoimmune profile
· Renal and liver function tests
· Bone profile
· LDH
· Vitamin B12 and folate
· Chest X-ray (e.g. if TB or pulmonary sarcoidosis are suspected)
· Stool culture for ova, cysts and parasites
· Serological antibodies for threadworm or other nematode infection and
· Serological antibodies for Schistosomiasis depending on the travel history and after discussion with microbiology
If the cause is found, we will treat it accordingly. However, we will refer to haematology routinely if the eosinophilia remains unexplained and
· It is more than 1.5 for 3 months or longer or
· if it is rising without an obvious cause.
The final section refers to monocytosis when the monocyte count is raised, that is over 0.8 x 109/L.
Possible causes of monocytosis include:
· CMML or Chronic Myelomonocytic Leukemia
· Myelodysplasia
· Hodgkins’s lymphoma and
· Infections such as:
o Malaria
o Tuberculosis
o Brucellosis
o Infective endocarditis and
o Rickettsial infections
Criteria for urgent haematology referral would be:
· Evidence of CMML features on blood film
· A persistently raised monocyte count >1.5 (which is typical of CMML)
· Associated cytopenias, particularly if involving multiple blood cell lineages or of there is any
· Clinical Suspicion of Hematologic Malignancy
If the monocyte count is >0.8 and the patient is well, we will check the travel history and check for any evidence of malignancy. We will then repeat the blood test and look for possible causes.
Initial investigations could include:
· A repeat FBC
· A blood film
· Inflammatory markers like ESR and CRP
· Any investigation as appropriate based on clinical suspicion, for example:
o A chest X-ray to screen for Tb
o Malaria parasites, and
o Serological tests for infectious diseases such as Brucella, Epstein-Barr virus, and cytomegalovirus
If the monocytosis remains unexplained and over 0.8 we will refer to haematology.
Well, this is the end of the clinical scenarios. I have created a quick reference guide based on the guidance by Camden CCG, Manchester Foundation Trust and King’s Health Partners which you are welcome to have a look at. Where there was a discrepancy between their guidance, I have generally opted for the most conservative approach, for example, if one neutropenia guideline recommends referral if the neutrophil count is <1 and another when it is <1.5, my summary will show <1.5. If you are in any doubt, please consult the original guidance or seek local specialist guidance. I have included links to sources consulted in the document itself, which you will be able to download in the episode description.
We have come to the end of this episode. Remember that this is not medical advice and it is only my summary and my interpretation of the guidelines. You must always use your clinical judgement.
Thank you for listening and goodbye.
