Flashcards in Macrocytic Anaemias Deck (28)
What is macrocytic anaemia?
Macrocytic anaemia is a condition in which your body has overly large red blood cells and not enough normal red blood cells.
Types of macrocytic anaemia
Megaloblastic macrocytic anaemia
Most macrocytic anaemias are also megaloblastic. Megaloblastic anaemia is a result of errors in RBC DNA production. Leads to incorrect DNA production
Possible causes include:
Vitamin B-12 deficiency
some medications, such as chemotherapy drugs like hydroxyurea, antiseizure medications, and antiretroviral drugs used for people with HIV
Nonmegaloblastic macrocytic anaemia
Nonmegaloblastic forms of macrocytic anaemia may be caused by a variety of factors.
These can include:
Drugs –chemotherapy (anti-folates,anti-purines) and anti-HIV drugs
Raised reticulocyte count
Myelodysplasia, including acquired sideroblastic anaemia
Aplastic anemia and red cell aplasia
Myeloma and other paraproteinaemias
How does vitamin B12 deficiency present?
Classically presents with megaloblastic anaemia.
But can also present with peripheral neuropathy and neuropsychiatric complaints.
Typical patients with vitamin B12 deficiency?
People with chronic malabsorption,
Patients with Hx of gastric resection or bypass.
People taking metformin and PPI.
Causes of vitamin B12 deficiency?
Decreased dietary intake (vegan, poor diet, pregnancy)
Diminished gastric breakdown of vitamin B12 from food.
Malabsorption from the GUT (Crohn's disease, coeliac disease, bacterial overgrowth substances, surgery, pernicious anaemia, fish tapeworm, ileal resection)
Signs & Symptoms of vitamin B12 deficiency?
Pallor in conjunctiva, nails and lips.
Stomatitis (angular cheilosis- inflammation of the corners of the mouth)
Neuropathy- peripheral, optic and dementia (early diagnosis is key in halting the progression of neuropathy)
Risk factors of vitamin B12 deficiency
Age > 65 years
Hx of gastric surgery
Chronic GI illnesses (IBD)
Use of known causative medications
Tests and investigations for vitamin B12 deficiency?
FBC- elevated MCV, low haematocrit
Serum vitamin B12
Methylmalonic acid (elevated)- a marker for vitamin B12 deficiency.
Homocysteine (elevated)- a marker for vitamin B12 deficiency.
IF antibody -positive if pernicious anaemia is the cause
Differentials for vitamin B12 deficiency
Folic acid deficiency
Alcoholic liver disease
Vitamin B12 absorption in the body
The stomach and salivary glands are critical to the absorption of B12.
Transcobalamin I (TCN1), also known variously as haptocorrin, R-factor, and R-protein, is a glycoprotein produced by the salivary glands of the mouth.
It primarily serves to protect cobalamin (Vitamin B12) from acid degradation in the stomach by producing a Haptocorrin-Vitamin B12 complex.
Once the complex has travelled to the more neutral duodenum, pancreatic proteases degrade haptocorrin, releasing free cobalamin (i.e. free B12), which now binds to intrinsic factor (IF) for absorption by the enterocytes of the terminal ileum.
How is IF critical to the absorption of B12?
IF is critical to the absorption of B12 and this is secreted by the stomach parietal cells. IF is a glycoprotein, with a molecular weight of 45 kDa.
In the duodenum, the free vitamin B12 binds to IF to create a vitamin B12-IF complex. This complex then travels through the small bowel and reaches the terminal ileum, which has on its surface specialized receptors called cubilin receptors.
These identify the B12-IF complexes and take them up into the circulation via endocytosis-mediated absorption.
Lack of IF results in pernicious anaemia.
Management of B12 deficiency?
Patients with severe haematological or neurological symptoms of vitamin B12 deficiency require immediate treatment with an intensive regimen of cyanocobalamin or hydroxocobalamin over 1 month, followed by ongoing maintenance doses.
What is folate deficiency?
Normal folate stores only last 2-3 months.
Diagnosis is confirmed by the presence of low serum folate.
Vitamin B12 deficiency must be ruled out before initiating folic acid therapy.
Signs & symptoms of folate deficiency
Similar to B12 deficiency but often only sensory peripheral neuropathy.
Causes of folate deficiency
Nutritional- poor diet, chronic alcohol intake
Surgical- coeliac disease, jejunal resection
Physiological- pregnancy, prematurity
Disease states- chronic haemolysis, severe skin disease
Iatrogenic- methotrexate, anticonvulsants, dialysis
NB: Deficiency in pregnancy is associated with an increased incidence of NTDs in babies.
What is aplastic anaemia?
A rare disease in which the haematopoietic stem cells of the bone marrow are damaged.
This causes a deficiency of all 3 blood cell types (pancytopenia)- anaemia, leukopenia and thrombocytopenia.
Causes of aplastic anaemia
Exposure- radiation, chemicals (benzene), drugs (phenytoin, quinine, chloramphenicol, carbamazepine)
Infection- acute renal hepatitis, parvovirus B19, autoimmune disorders.
Diagnosis of aplastic anaemia
Bone marrow biopsy:
Normal bone marrow has 30-70% blood stem cells, but in aplastic anaemia, these cells are mostly gone and replaced by fat.
Management of aplastic anaemia
Immunosuppressive drugs typically either anti-lymphocyte globulin combined with corticosteroids and ciclosporin.
Haematopoietic stem cell transplantation is also used especially for patients under 30 years of age.
What is red cell aplasia?
Anaemia affecting erythroblasts.
Types of red cell aplasia
Acquired Pure Red Cell Aplasia
Transient or Acute Self-limited PRCA
Inherited or Congenital Pure Red Cell Aplasia (Diamond-Blackfan Anaemia)
What is acquired red cell aplasia?
This is a very rare condition and usually affects adults.
It is characterized by an absence of red cell precursors (reticulocytes) in the marrow and a low red blood cell count.
The amounts of white blood cells and platelet remain normal.
What is transient or acute self-limited PRCA?
This is the most common type of PRCA. It is identical to acquired PRCA except that, at some point, it simply goes away.
Transient PRCA is usually triggered by a virus or drug. In most cases, when the virus clears, or the responsible drugs are eliminated, the PRCA will disappear.
This is most dangerous to patients who already have chronic hemolytic anaemia.
Patients with otherwise normal functioning bone marrow may even recover without having known they had it.
What is inherited PRCA?
Diamond-Blackfan anaemia is a genetic condition usually diagnosed during the first two years of life.
About half of the patients also have physical malformations or mental retardation.
Only several hundred cases have been reported worldwide. The severity of the disease varies by patient.
Causes of red cell aplasia
Infections- HIV, herpes, parvovirus B19, hepatitis
Lymphoproliferative- T-cell large granular lymphocytic leukaemia
Drugs- Mycophenolate, EPO
Congenital- Diamond-Blackfan anaemia, autosomal dominantly inherited defects in ribosomal proteins.