11/13/24, 7\:32 PM Guide | Haematinics interpretation

Haematinics interpretation

Table of contents

Introduction

Haematinics are the nutrients needed by the bone marrow to make blood cells in the process of haematopoiesis. Without
adequate amounts of these nutrients, cytopenia(s) and related symptoms can develop. Excess amounts can also be
pathological and can point to various underlying disease states.
This guide to haematinics interpretation will focus on de
(cobalamin), vitamin B9 (folate), and iron.
Other haematinics not covered in this guide include\:
Vitamin A
Vitamin B2 (ribo
Vitamin B3 (nicotinic acid)
Vitamin B6
Vitamin C
Vitamin E
Copper
Cobalt
It is essential to consider the history and examination
change depending on the patient context and should be interpreted alongside a thorough clinical assessment.

Iron

Investigating a patient’s iron status can become complicated as no single test accurately represents all stages of iron
metabolism and some of the available tests can be a
Given how common iron de is, it is important to understand the tests used to investigate iron de
how to interpret results correctly.

When to investigate

Iron de
Most of these symptoms are related to anaemia, such as fatigue, shortness of breath, weakness and reduced exercise
tolerance. Other symptoms can include pica (e.g. ice craving) and restless leg syndrome.
Typical clinical
General and conjunctival pallor
Atrophic glossitis
Angular cheilitis
Koilonychia (spoon-shaped nails) - less common

Initial screening investigations

If iron de is suspected, initial screening investigations should include\:
Full blood count (FBC)
C-reactive protein (CRP)
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Serum ferritin
Full blood count (FBC) and red cell parameters
These tests allow the identi
which is typically seen in iron de
To gain more information about iron status, review the mean corpuscular volume (MCV), mean corpuscular haemoglobin
(MCH) and mean corpuscular haemoglobin concentration (MCHC). These may be low in iron de
distribution width (RDW) may be elevated.
These
For more information, see the Geeky Medics guide to full blood count interpretation.
Serum ferritin
Ferritin is an intracellular protein complex that binds iron and is responsible for most iron storage in the body.
Small amounts of ferritin are released into the serum to transport and absorb excess iron and therefore act as a surrogate
serum marker for body iron storage.
There is a direct correlation between serum ferritin levels and overall iron stores in health. However, serum ferritin is an acute-
phase protein, and so increases in inchronic kidney disease, liver disease, and malignancy.
The British Society for Haematology (BSH) guidelines suggest a serum ferritin level of \<15 μg/l is indicative of an iron de
in those aged >5 years.
A level of \<150 μg/l should act as a trigger to consider further investigations for potential iron de
concurrent in
Therefore, CRP is suggested as part of the initial screening test, as serum ferritin within the normal range cannot exclude iron
de
Figure 1. Summary of ferritin interpretation. Adapted from BSH guidelines.

Secondary investigations

If the
requesting secondary investigations which are listed below.
Transferrin saturations
Transferrin saturation is the ratio of total serum iron (or the total iron-binding capacity) to transferrin expressed as a
percentage.
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Transferrin is the primary serum iron transporter molecule in the body. In an iron-de
transferrin to increase the total iron-binding capacity and so acquire more iron for its cells.
There is no strong evidence for a diagnostic threshold, but the BSH consensus guidelines suggest levels \<16% as supportive of
a diagnosis of iron de
Blood
A blood
conclusion that a patient is iron de
Blood
cells, and elliptocytes.
Advanced red cell parameters
These are available on modern analysers and most UK laboratories would be able to run these tests relatively easily. Di
analysers will run slightly di
cells that are hypochromic, and reticulocyte haemoglobin equivalent.
Given that they are relatively easy to perform, BSH suggest they can be used as part of secondary testing. Mean reticulocyte
haemoglobin of \<29 pg can be supportive of a diagnosis of iron de
patients with chronic kidney disease.

Other investigations of iron metabolism

These are not usually required to diagnose iron-de but are available from most laboratories and can support
the diagnosis. Below is a list of the more common investigations.
Serum iron
Serum iron only measures a fraction of the iron in the blood. It can only measure the ferric form (Fe3+) and not the iron
incorporated in haemoglobin molecules.
Serum iron levels show diurnal variation and are sensitive to recent iron intake therefore, measuring serum iron in isolation has
no role in determining a patient’s iron stores.
Total iron-binding capacity (TIBC)
The TIBC is calculated by taking a serum sample and adding excess iron to fully saturate the iron carrying molecules.
The TIBC is a measurement of the total iron concentration in the sample when fully saturated.
TIBC can rise in an iron-de
iron stores.
Transferrin
Transferrin is the main serum iron transporter molecule which can be measured in a patient’s serum.
Like TIBC, transferrin can rise in iron de
is a negative acute-phase protein and so decreases in in
Soluble transferrin receptor (STFR)
Transferrin receptors are present on developing red cells and can be detected in their soluble form in peripheral blood.
In iron de
iron, this increase can be measured in the serum.
Unlike ferritin, this is not a
de
A rise in STFR is not speci
anaemia, and hypoxia. STFR can also be normal in mild de
Due to the lack of speci
de

Summary table

Table 1. Interpreting iron studies.
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Iron de
Ferritin ↓/Normal Normal ↑↑
Transferrin/TIBC ↑ Normal/↓ ↓↓
Transferrin saturations ↓ Normal/↓-
STFR ↑/Normal Normal -
Treatment of iron de
For most patients, oral iron is a safe, e
C improves the absorption of oral iron.
Traditional dosing guidelines suggested aiming for 100-200mg of elemental iron a day however, more recent studies
performed in iron de
is more e
one tablet of either ferrous fumarate 210mg or ferrous sulphate 200mg. A response in the haemoglobin count should
be seen within a few weeks of starting therapy.
In certain scenarios, intravenous iron may be preferred. This includes patients with chronic kidney disease, in
bowel disease, those intolerant of oral iron, those needing rapid replacement due to the degree of anaemia or certain
pregnant patients. The safety proanaphylactoid
reactions and permanent skin staining.

Vitamin B12

Testing for a patient’s vitamin B12 and folate status is challenging as existing investigations are not sensitive or speci
show wide variability between di
For this reason, routine screening is not indicated for any patient group. Instead, investigations should be performed in
response to speci
As vitamin B12 and folate share a close relationship in human metabolism and so present with similar features, they should be
investigated simultaneously.

Clinical features of vitamin B12 de

B12 de
Patients with B12 de
reduced exercise tolerance as well as neuropsychological features (motor and sensory peripheral neuropathies, ataxia,
retinopathy, optic atrophy, cognitive impairment etc.) and glossitis.
In severe de
Importantly, not all patients with clinical vitamin B12 de
Therefore, if a patient presents with clinical features of B12 de
identi
Infants can also present with faltering growth, movement disorders or developmental delay.
Causes of vitamin B12 de
Causes of vitamin B12 de
Malabsorption\: pernicious anaemia, Crohn’s, coeliac disease, gastric/bariatric surgery, atrophic gastritis
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Dietary\: vegetarians/vegans
Infection\: H.pylori, giardia, tapeworm
Infants\: congenital causes

Speci

Medications
Certain medications can a
de
Metformin, anti-convulsants, proton pump inhibitors/H2 antagonists, hormone replacement therapy/combined oral
contraceptive pill, colchicine and certain antibiotics can all decrease serum B12 levels.
Gastrointestinal surgery
Patients who have undergone gastric surgery or bariatric surgery can often develop vitamin B12 de
These patients should undergo monitoring of B12 levels and receive advice on adopting a diet rich in B12 (red meat, salmon,
milk, cheese etc.). Intramuscular replacement should be commenced if levels are falling despite this.
Pregnancy
A physiological reduction in serum B12 levels occurs in up to 30% of individuals by the third trimester of pregnancy,
complicating assessment. If in doubt about the relevance of results, seek specialist advice.
Multiple myeloma
The presence of paraproteins can reduce serum B12, but rarely re

Primary testing

Serum cobalamin is the primary investigation suggested by BSH and should only be requested in the presence of objective
clinical markers of de
serum cobalamin, full blood count, and a blood
Serum cobalamin
The most common investigation in the UK for vitamin B12 is serum cobalamin, but levels do not always correlate clinically.
It is possible to be clinically de
False normal results can occur in the presence of very high titres of anti-intrinsic factor antibodies in pernicious anaemia.
Falsely low serum levels may occur in concurrent folate de
While there is no agreed normal level, most UK labs use a cut-o
clinical features are present.
BSH guidelines di
these results (see
Full blood count (FBC) and red cell parameters
Features which might suggest a vitamin B12 de
However, it is possible to be B12 de
marrow cannot make new cells without vitamin B12.
Blood
A blood
can include macrocytosis, hypersegmented neutrophils and oval macrocytes.

Investigating the cause

If a patient with B12 de
is important to investigate for pernicious anaemia. BSH suggest screening for pernicious anaemia in patients with both clinical
features and laboratory con
Anti-intrinsic factor antibodies (Anti-IF)
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Anti-intrinsic factor antibodies are found in pernicious anaemia and have a low false-positive rate with a high positive
predictive value. They are present in 40-60% of pernicious anaemia cases. False-positive results can occur following recent
B12 injections.
Anti-gastric parietal cell antibodies
Anti-gastric parietal cell antibodies are less speci
pernicious anaemia. However, they are found in up to 80% of patients with the disease.

Summary charts of BSH guidance

Interpreting serum cobalamin (with clinical features)

Secondary testing

Depending on the clinical presentation, secondary testing may be required. Secondary testing is indicated if a patient presents
with convincing clinical features of vitamin B12 de
but has normal serum cobalamin levels.
Secondary testing for B12 de
Total plasma homocysteine\: raised in B12 de
disease, and hypothyroidism.
Plasma methylmalonic acid\: raised in B12 de
overgrowth.
Holotranscobalamin\: more sensitive but not available in all labs. It is low in vitamin B12 de
Table 2. Interpreting secondary tests for B12 de
B12 de
Plasma homocysteine ↑ ↑
Plasm methylmalonic acid ↑-
Holotranscobalamin ↓-
Treatment of B12 de
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In the United Kingdom, guidelines for the treatment of B12 de
injections with the dosing and frequency depending on symptoms and response\:
If no neurological symptoms\: 1mg IM three doses a week for 2 weeks, then every 3 months
If neurological symptoms present\: 1mg IM alternate days until no further improvement in symptoms (minimum 3
weeks), then every 2 months
Once treatment is commenced, an increase in reticulocyte count should occur in the

Folate

Folate is the term for all biological forms of vitamin B9, while folic acid refers to the synthetic form used for treatment.
Both forms are absorbed in the terminal ileum, and half of the body’s folate is found in the liver. It is often measured
simultaneously with vitamin B12 as they share a close relationship in human metabolism with similar clinical features in
de
As folate is important in DNA synthesis, the rapidly dividing cells of the body are those
Symptoms of folate de
ulcers/glossitis. Therefore, folate levels are generally measured in similar scenarios to vitamin B12.
An isolated folate de
before initiating folate replacement due to the risk of precipitating subacute degeneration of the spinal cord.
Causes of folate de
Causes of folate de
increasing the body’s requirements for folate\:
Dietary\: diet de
Alcoholism\: alcohol intake >80g/10 units a day
Gastrointestinal disorders\: coeliac or any disorder a
Pregnancy\: preferential delivery of folate to foetus rather than mother’s tissues, de
neural tube defects
Haematological disorders\: increased red cell destruction (sickle cell anaemia, haemolytic anaemias) and those with
abnormal haematopoiesis
Exfoliative skin disorders (e.g. psoriasis)
Medications\: anti-epileptics

Primary testing

If folate de
Serum folate
The serum folate level is the most useful initial screening test. No internationally recognised level de
level \<7nmol/l is generally used. Below this level, the risk of megaloblastic anaemia sharply increases.
Therefore, there is a grey area from 7-10nmol/l, in which case a treatment trial may be helpful.
Serum folate is not a perfect test as several conditions can cause false results.
Falsely low levels can occur in anorexia, acute alcohol intake, pregnancy, anti-epileptic therapy, and post-haemodialysis.
Falsely high levels can occur if the test is performed too soon after oral folate ingestion.
Full blood count/blood
The development of anaemia due to folate de
leads to the presence of large, abnormal red cells called megaloblasts in peripheral blood. This causes a raised MCV on the
full blood count.
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Secondary testing

If the clinical suspicion of folate de
secondary testing. These can include\:
Red cell folate\: lots of laboratory variables limiting use, time-consuming and expensive
Plasma total homocysteine\: high in folate de
disease and hypothyroidism
Treatment of folate de
If a patient is folate de
If a patient is de
worsening neurological features of B12 de
The usual treatment of folate de
de

Reviewer

Reviewer

Dr Tom Fail
Haematology SpR

References

Fletcher, A., Forbes, A., Svenson, N., Wayne Thomas, D. (2022), Guideline for the laboratory diagnosis of iron de
adults (excluding pregnancy) and children. Br J Haematol, 196\: 523-529.
Devalia, V., Hamilton, M.S., Molloy, A.M. and (2014), Guidelines for the diagnosis and treatment of cobalamin and folate
disorders. Br J Haematol, 166\: 496-513.
Camaschella C. (2015) Iron-de
Source\: geekymedics.com
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