HAEM: Anaemia II - Macrocytic Anaemia

Question 1

What is the DDX for macrocytic anaemia?

Answer 1

Megaloblastic:

• Vitamin B12 deficiency.
• Folate deficiency.

Non-megaloblastic:

• Alcoholism.
• Drugs/medications.
• Liver disease.
• Hypothyroidism.
• Bone marrow disorders (multiple myeloma, myelodysplasia, acute leukaemia)

Question 2

• What is the pathology of megaloblastic anaemia?
• Discuss the structure of the RBCs and neutrophils.

Answer 2

• A macrocytic anaemia resulting from impaired DNA production during erythropoiesis.
  
  • Cells cannot progress from G2 to M phase, causing growth without division and hence macrocytosis.
• The resulting RBCs are immature, large and oval shaped. Neutrophils are hypersegmented.

Question 3

What are the common causes of megaloblastic anaemia?

Answer 3

B12 deficiency:

1. Low intake: dietary deficiency (vegans).
2. Low absorption: GI issues (coeliac) or lack intrinsic factor (pernicious anaemia).
3. High excretion (alcoholism).
4. High use/demand (pregnancy).

Folate deficiency:

1. Dietary.
2. Low absorption (coeliac).
3. Rapid cell division using up folate (cancer, pregnancy, prematurity; haemolytic anaemia).
4. Increased loss (dialysis).
5. Some drugs (alcohol, methotrexate, some anticonvulsants).

Question 4

How does megaloblastic anaemia present for:

• B12 deficiency.
• Folate deficiency.

Answer 4

If caused by B12 deficiency:

• Pallor (from anaemia).
• Glossitis.
• GI disturbances.
• Weight loss.
• Peripheral neuropathy.
• Subacute degeneration of posterior columns (vibration, proprioception etc).
• Psychiatric disturbances.
• If caused by folate deficiency, as above but no neurological sequelae.

Question 5

What are the tests you would do and results indicating megaloblastic anaemia?

Answer 5

FBP: (tells you there is macrocytic anaemia) - high MCV - low Hb - platelet & neutrophil count may be low in severe disease Blood films: (determines megaloblastic vs non-megalo) - macro-ovalocyte red cells - hypersegmented neutrophils - low level of reticulocytes B12 & folate levels: (look for cause of megaloblasty) - one is low depending on cause - if B12 is borderline test for active B12 - if neither is low consider bone marrow biopsy (possible myelodysplasia) *note in developed countries folate deficiency is rare due to fortification If B12 low, test for Intrinsic Factor (IF) antibodies to screen for pernicious anaemia (70% of P.A. patients will have them).

Question 6

What is the treatment for megaloblastic anaemia?

Answer 6

Depends on cause. B12 deficiency: - supplement with cobalamin (B12) either oral or IM - pernicious anaemia requires ongoing IM cobalamin Folate: - supplement - address any underlying cause (ie malignancies)

Question 7

What is pernicious anaemia?

Answer 7

Autoimmune condition with antibodies against the Intrinsic Factor in the stomach which allows B12 to be absorbed in the Ileum.

Question 8

What is the pathology of haemolytic anaemia?

Answer 8

1. red blood cells are destroyed 2. EPO increases to enhance erythropoeisis and replace the RBCs. Increased destruction: - Increased bilirubin o Dark urine (increased urobilinogen) - Increased lactate dehydrogenase - Reduced haptoglobin (binds free haemoglobin) Increased production: - Increased reticulocyte count - Reduced folate stores - Erythroid hyperplasia in bone marrow

Question 9

What are the causes of haemolytic anaemia?

Answer 9

There are many causes of haemolytic anaemia, generally divided into: - RBC defects o Membrane (Hereditary elliptocytosis or spherocytosis) o Enzyme (G6PD deficiency, PK deficiency) o Haemoglobin (thalassemia, sickle cell anaemia) - External to RBC causes o Malaria/Other infections o Trauma o Autoimmune haemolytic anaemia

Question 10

What is hereditary spherocytosis/elliptocytosis?

Answer 10

Autosomal dominant disorder. Abnormal cytoskeleton protein = spherical RBC with reduced deformity = shorter life span. Seen on blood films. Clinical spectrum, if severe splenectomy may reduce symptoms. HEREDITARY ELLIPTOCYTOSIS = similar but less severe phenotype

Question 11

What is G6PD deficiency?

Answer 11

X-linked disorder, deficiency in enzyme which causes problems with the hexose monophosphate shunt (substitute glucose oxidation pathway). Increased haemolysis in times of oxidative stress (infection, acidosis, eating broad beans). Blood films = bite/blister cells and Heinz bodies.

Question 12

What is autoimmune haemolytic anaemia? (AIHA)

Answer 12

Production of auto-antibodies directed against RBCs. Causes standard haemolytic FBP: - normocytic/macrocytic anaemia - low haptoglobin (binds free Hb) - high lactate dehydrogenase (marker of tissue breakdown, in this case erythrocyte destruction). - Increased bilirubin (component of the pathway that breaks down RBCs) + SPECIFIC TO AIHA = positive coombs test (direct antiglobulin test)

Question 13

What are the 2 types of AIHA? How are they treated

Answer 13

AIHA can be IgG (warm antibody, reacts at body temp) or CD3 (cold antibody, reacts at room temp) WARM TREATMENT: - Rituximab - Steroids, oral, daily - Splenectomy - IV immunoglobulin - Other immunosuppressants COLD TREATMENT - Rituximab

Question 14

What is traumatic haemolytic anaemia? What else is it called?

Answer 14

Traumatic HA causes red cell fragmentation and is also called microangiopathic haemolytic anaemia. Red cells become fragmented when they come into contact with fibrin, these fragments (schistocytes) can be seen on a blood film. Causes: trauma, heart valve replacement, drugs (cyclosporin), pre-eclampsia, disseminated intra-vascular coagulation.