Haematinics Flashcards
What are the causes of megaloblastic anaemia
B12 deficiency or abnormalities of B12 metabolism
Folate deficiency or abnormalities of folate metabolism
Antifolate medications e.g. methotrexate
Cases unrelated to B12/folate i.e due to defects in DNA synthesis
Myelodysplasia, AML
Medications interfering with DNA synthesis e.g. cytarabine, hydroxyurea, 6-mercaptopurine
Orotic aciduria (responds to uridine)
Lesch-Nyhan syndrome (responds to adenine)
Thiamine responsive megaloblastic anaemia (diabetes + hearing loss + megaloblastic)
Where is folate absorbed in the GI tract?
Jejunum
Where is B12 absorbed in the GI tract?
Ileum
Causes of B12 deficiency
- Decreased intake → Vegan diet, Malnutrition - elderly, anorexia, poverty, Breast fed babies of vegetarian mothers
- Gastric causes → Atrophic gastritis with achlorhydria, gastrectomy, Zollinger-Ellison syndrome (too much acid)
Pernicious anaemia = severe lack of IF due to gastric atrophy - Failure of trypsin release of B12 from R binding proteins → Pancreatic insufficiency
- Impaired intestinal absorption due to failure of intrinsic factor uptake in the ileum → Ileal resection or disease (eg Crohn’s), Tropical sprue, Parasites eg giardia, bacterial overgrowth, fish tapeworm
- Abnormal transport proteins →Haptocorrin deficiency, Transcobalamin deficiency
- Increased demand → Haemolysis
- Drugs → Alcohol (absorbance impeded secondary to gastritis), PPIs and H2 receptor antagonists – reduced gastric acid production, Metformin - impedes absorption
Colchicine reduces IF-B12 receptors - Congenital → Maternal cobalamin deficiency, Intrinsic factor or IF receptor deficiency/defect
Inborn errors of cobalamin metabolism
Causes of folate deficiency
- Reduced intake - Poor diet, especially alcoholics, Premature babies, Babies fed on goat milk
- Malabsorption - Coeliac disease, Tropical sprue, Small bowel resection/malabsorption syndrome
- Drugs - cotrimoxazole, sulphasalazine, MTX, phenytoin, Na valproate
- Hereditary hyperhomocysteinaemia
- Increased folate turnover - Pregnancy, Increased requirements from breastfeeding, Skin disease (eg. severe psoriasis), Haemodialysis, Haemolysis – haemoglobinopathy, PNH, AIHA
Causes of reduced B12 assay
- B12 deficiency (multiple causes)
- Pregnancy
- Drugs - OCP, omeprazole, colchicine, metformin
- Congenital transcobalamin deficiency
Causes of high B12 level
- Supplementation
- Liver disease
- MPNs
Causes of falsely normal B12 assay
- Early deficiency
2. High titre IF antibodies
Causes of falsely low B12 assay
Pregnancy - reduced haptocorrin but normal transcobalamin. OCP Haptocorrin deficiency Elderly Myeloma HIV
How is ESR measured?
Westergren method
Whole blood in EDTA is diluted in microvette tube then drawn up capillary tube (Westergren tube) to “O” mark. Sedimentation is recorded in mm per 1 hr.
Causes of error for ESR?
- Old sample
- Warm sample (increases ESR)
- Hct - anaemia increases ESR, polycythaemia reduces ESR
- Dilution
- Agglutination
- Tilting tube, vibrations, direct sunlight, draught
- Can’t read tube if there are bubbles, haemolysis, lipaemia
Causes of an increased ESR
- Inflammation
- Anaemia
- Pregnancy
- Old age
Causes of increased hepcidin?
- Inflammation
2. Iron overload
Causes of decreased hepcidin?
- Appropriate
- Iron deficiency
- Anaemia with increased erythropoiesis
- Hypoxia - Inappropriate
- Ineffective erythropoiesis e.g. thalassaemia
- Hereditary Haemochromatosis
Regulation of iron absorption
- Hepcidin
- DMT-1 - upregulated in response to low iron status in enterocytes
- Iron response elements on mRNA (up or down regulate gene expression of proteins involved in iron metabolism)
