Guidance for Primary Care on the Interpretation of Haematinics B12, Folate and Ferritin

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Directorate of Laboratory Medicine, Department of Clinical Biochemistry Filename: CB-INF-HAEMATINICS, Version: 2.0 Date of issue: September 2021

Department of Clinical Biochemistry

Contents VITAMIN B12 ...... 1 FOLATE ...... 2 FERRITIN ...... 3

Directorate of Laboratory Medicine, Department of Clinical Biochemistry Filename: CB-INF-HAEMATINICS, version 2.0 Date of issue: Sep Page 1 of 3 Vitamin B12

 B12 deficiency does not usually require secondary care referral.  Replacement is usually given by IM injection. Oral replacement may be appropriate for mild deficiencies where the IFA result is negative.  It is not appropriate to measure B12 in patients on IM treatment. Monitor response to treatment using the full blood count (Hb and MCV).

B12 <150 ng/L B12 150 – 196 ng/L B12 197 – 771 ng/L B12 >771 ng/L

Probable/Mild B12 deficiency. B12 deficiency unlikely. High B12 in patients not on treatment may B12 deficiency highly likely. ? symptoms/clinical features Confirm with clinical findings If strong clinical suspicion remains, be due to consumption of OTC No consider a trial of replacement supplements or fortified food. It can also be Yes especially if B12 result borderline associated with the following conditions:

 Myeloproliferative disorders Commence replacement. (unlikely if FBC normal) Commence replacement (IM) Repeat in 6 – 8 weeks  Consider possible Liver disease Intrinsic factor antibodies (IFA) If B12 still low, consider  Renal failure underlying causes will be added by laboratory replacement and measure intrinsic Request intrinsic factor Please contact the Duty Biochemist if you Consider underlying cause factor antibodies (IFA) wish to discuss further. antibodies (IFA)

Causes of B12 deficiency Clinical features of B12 deficiency B12 levels are not easily correlated with clinical features, and low levels  Pregnancy, OCP, HRT (not thought to represent a functional B12 deficiency) may not represent a functional B12 deficiency.  Medications: metformin, PPI, anti-convulsants e.g. phenytoin, antibiotics, colchicine  Vegetarian/vegan/poor diet Features of B12 deficiency may include:  Malabsorption – consider other features of malabsorption/pancreatic insufficiency  Macrocytic anaemia (MCV >101 fl)*  Pernicious anaemia – consider history of autoimmune disease and/or family history  Glossitis  Folate deficiency  Paraesthesia, unsteadiness, peripheral neuropathy  Parasitic infection, HIV, *Note co-existing iron deficiency/thalassaemia trait may mask macrocytosis

Directorate of Laboratory Medicine, Department of Clinical Biochemistry Filename: CB-INF-HAEMATINICS, version 2.0 Date of issue: Sep Page 2 of 3 Folate

 It is not appropriate to measure folate in patients on supplements. Monitor response to therapy using the full blood count (Hb and MCV).  Serum folate should always be measured with B12; in the presence of true B12 deficiency, serum folate may be elevated.

Folate <3.0 μg/L Folate 3.0 – 3.9 μg/L Folate >3.9 μg/L

Folate deficiency unlikely. Folate deficiency. Possible folate deficiency. Serum folate reflects recent folate ingestion and Check B12 levels and commence folate recent high dose biotin intake may cause falsely replacement (symptoms of B12 deficiency can elevated results; please see ? Reduced intake over the previous few days be exacerbated if treated with folate https://tinyurl.com/BiochemInfo for more replacement alone) information on biotin interference. If strong clinical suspicion of deficiency remains, Consider underlying cause ? Symptoms/clinical features rule out B12 deficiency and consider discussion with haematology

Yes No

Check B12 levels Repeat in 6 – 8 weeks. Commence replacement. If still low, consider replacement.

Causes of Folate deficiency Clinical features of Folate deficiency

 Dietary deficiency/anorexia Features of folate deficiency include:  Pregnancy  Macrocytic anaemia (MCV >101 fl)*  Alcoholism  Angular cheilosis/stomatitis  Malabsorption – consider other features of malabsorption/pancreatic insufficiency  Haemolysis *Note: co-existing iron deficiency/thalassaemia trait may  Malignancy mask macrocytosis  Medications: Anti-convulsants  Sample collection immediately post-dialysis

Directorate of Laboratory Medicine, Department of Clinical Biochemistry Filename: CB-INF-HAEMATINICS, version 2.0 Date of issue: Sep Page 3 of 3 Ferritin

 For investigation of iron deficiency, serum ferritin is the recommended front line test and is superior to transferrin saturation.  Monitor response to iron therapy using FBC (Hb and MCV) initially. There is no need to re-check ferritin levels within 6 – 8 weeks.

>150 μg/L <15 μg/L 15 – 30 μg/L 30 – 150 μg/L

CRP <5 mg/L? Iron deficiency unlikely Iron deficiency confirmed. Iron deficiency likely. Consider clinical context and If Ferritin elevated above age and sex Evaluate underlying cause Yes No commence replacement if reference ranges and CRP normal and commence replacement. appropriate. Refer to https://tinyurl.com/BiochemInfo

Evaluate underlying cause Iron deficiency unlikely. for investigation of hyperferritinaemia.

Iron deficiency not excluded. Transferrin saturation will be added by laboratory For patients with chronic inflammatory conditions, interpret ferritin cautiously. F erritin levels are increased independently of iron status in acute and chronic inflammatory conditions, malignancy and liver disease which may mask deficiencies.

Review FBC parameters and transferrin saturation; if <16%, iron deficiency is possible. Note: transferrin saturation is non-specific as pregnancy, OCP and chronic illness can result in low transferrin saturation without iron deficiency.

Causes of iron deficiency Clinical features of iron deficiency

Features of iron deficiency include:  Inadequate diet or malabsorption  Microcytic hypochromic anaemia (MCV <79 fl)  Bleeding, e.g. GI bleeding, menorrhagia or blood donation  Chronic renal failure and haemodialysis  Symptoms of anaemia – fatigue, dyspnoea, pallor.  Infancy, pregnancy or lactation  Symptoms of iron deficiency may occur without anaemia: lack of concentration,  Increased red cell turnover irritability, hair loss, dry skin, angular cheilosis, atrophic glossitis, spoon-shaped nails, and unusual cravings for non-food items (phenomenon known as pica).