What are the two types of macrocytic anaemias?
- Megaloblastic
- Non-megaloblastic
These types are distinguished based on bone marrow findings.
What characterizes megaloblastic anaemia?
- Presence of megaloblasts
- Delayed nuclear maturation
- Defective DNA synthesis
Megaloblasts are large erythroblasts with immature nuclei.
What are the haematological findings in megaloblastic anaemia?
- MCV > 96 fL
- Oval macrocytes
- Hypersegmented polymorphs
- Possible leucopenia and thrombocytopenia
- Elevated LDH
These findings reflect ineffective erythropoiesis.
What is the biochemical basis of megaloblastic anaemia?
- Block in DNA synthesis
- Inability to methylate deoxyuridine monophosphate to thymidine
This is due to deficiencies in folate and vitamin B12.
What is the role of intrinsic factor in vitamin B12 absorption?
- Binds to vitamin B12
- Carries it to ileal receptors
Intrinsic factor is secreted by gastric parietal cells.
What are the causes of vitamin B12 deficiency?
- Pernicious anaemia
- Malabsorption (e.g., pancreatitis, coeliac disease)
- Dietary deficiency (e.g., veganism)
Pernicious anaemia is the most common cause in adults.
What are the clinical features of pernicious anaemia?
- Insidious onset of anaemia
- Lemon-yellow color( d/t anaemia & mild jaundice)
- Glossitis & angular stomatitis
- Neurological changes d/t vit b12 defficiency
Neurological changes can be irreversible if untreated.
What are the investigations for vitamin B12 deficiency?
divide into Investigations to confirm Vit b12 deff and To identify cause
To confirm Vit B12 def :-
* Haematological findings of megaloblastic anaemia
* Serum vitamin B12 < 160 ng/L
* Elevated serum methylmalonic acid and homocysteine
Holotranscobalamin is a better marker for deficiency than serum B12 concentration.
What is the main dietary source of folate?
- Green vegetables
- Offal (liver, kidney)
Cooking can lose 60% to 90% of folate.
What are the causes of folate deficiency?
- Poor intake (Major cause) - Starvation, alcoholism
- Antifolate drugs (MTX/anti epileptics/trimethoprim)
- Excessive utilization - Physiological (pregnancy & lactation) & Pathological (High cell turnover states e.g Haem malignanciea)
- Malabsorption
Poor intake is the major cause.
What are the clinical features of folate deficiency?
- May be asymptomatic
- Symptoms of anaemia
- Glossitis
Neuropathy does not occur with folate deficiency.
What is the minimal daily requirement of folate?
100 μg
Folate is essential for DNA synthesis and amino acid metabolism.
What is a concentration below 150 μg/L (340 nmol/L) indicative of?
Folate deficiency
RBCs measure tissue folate over their lifetime.
Name the major causes of folate deficiency.
- Poor intake
- Gastrointestinal disease
- Antifolate drugs
- Excess utilization
- Malabsorption
Nutritional causes include poor social conditions, starvation, and alcohol excess.
List some gastrointestinal diseases that can cause folate deficiency.
- Partial gastrectomy or bariatric surgery
- Coeliac disease
- Crohn’s disease
These conditions can impair folate absorption.
What are some antifolate drugs that can lead to folate deficiency?
- Anticonvulsants
- Phenytoin
- Primidone
- Methotrexate
- Pyrimethamine
- Trimethoprim
These medications interfere with folate metabolism.
What physiological conditions can lead to excess utilization of folate?
- Pregnancy
- Lactation
These conditions increase the body’s demand for folate.
Name some pathological conditions that can cause excess utilization of folate.
- Haematological disease with excess red blood cell production
- Malignant disease with increased cell turnover
- Inflammatory disease
- Metabolic disease (e.g., homocystinuria)
- Haemodialysis or peritoneal dialysis
These conditions can increase the need for folate.
What should be suspected if the cause of folate deficiency is not obvious?
Occult GI disease
Appropriate investigations, such as small bowel biopsy, may be performed.
What is the management for vitamin B12 deficiency?
- Hydroxocobalamin 1000 μg intramuscularly
- Total of 5 to 6 mg over 2 weeks
- 1000 μg every 3 months for life
Clinical improvement may occur within 48 hours.
What can occur 2 to 3 days after starting treatment for vitamin B12 deficiency?
Reticulocytosis
This peaks at 5 to 7 days after starting therapy.
What is the recommended daily dose of folic acid for correcting folate deficiency?
5 mg
Treatment should continue for about 4 months to replace body stores.
What is the prophylactic dose of folic acid recommended for females planning a pregnancy?
400 μg daily
This helps reduce the risk of neural tube defects.
What is a common physiological cause of macrocytosis?
Pregnancy
Macrocytosis can also occur in newborns.
