HEMATOLOGY 1

Question 1

What are the three major mechanisms that cause microcytic anemia? List examples of conditions associated with each mechanism.

Answer 1

 Reduced iron availability
 Iron deficiency
 Anemia of chronic disease  Reduced globin synthesis
 Thalassemia
 Reduced heme synthesis
 Lead poisoning
 Sideroblastic anemia

Question 2

what are the causes of normochromic normocytic anemia?

Answer 2

 Anemia of chronic disease
 Early (mild) iron deficiency
 Combined iron + B12/folate def.
 Renal failure
 Anemia of hypoendocrine states
 Sideroblastic anemia
 Aplastic anemia
 BM infiltration
 Acute bleeding
 Hemolysis

Question 3

What are the causes of macrocytic anemia, and how are they categorized based on the shape of red blood cells?

Answer 3

Macrocytichigh MCV > 100
Oval: Vit B12 Deficiency
Folate deficiency

Round: Hypothyroidism
Liver disease
Alcoholism
Reticulocytosis
Myelodysplasia

Question 4

Mechanism of anemia?

Answer 4

1. Decreased production in BM (“FACTORY/STIMULUS/NUTRIENTS”)
2. Increased loss (e.g. bleeding) 3. Increased destruction (e.g. hemolysis)

RETICULOCYTE COUNT - determines the cause of anemia

Question 5

DESCRIBE RETICULOCYTES

Answer 5

 Young RBCs
 Contain remnants of RNA and ribosomes
 # reticulocytes reflects erythropoietic activity
 Reticulocytes are bigger than RBCs
 May result in an elevated MCV
 Reported as polychromasia

Question 6

what is the Rate of Hb fall

Answer 6

 Total marrow shutdown of production will result in a Hb fall of no greater 1-1.5g/dl/wk
 A fall more rapid than this usually means bleeding or hemolysis

Question 7

What are the causes of decreased red blood cell production and associated anemias? FACTORY

Answer 7

 Pancytopenia (usually)
→Marrow infiltration
→ Aplastic anaemia

 Normochromic/normocytic anemia or Hipochromic/microcytic anemia →Anemia of chronic disease

 Marrow infiltration
→Leukemia, Lymphoma Metastasis Myelofibrosis

 Aplastic anemia (Stem cell problem)
→ Chemotherapy →Chloramphenicol
→Antithyroid drugs
→Chemicals Benzene
→Traditional medicine
→Radiation
→Viral infections (HIV, HBV, EBV, CMV)

 Anemia of chronic disease (cytokines)
 Chronic inflammation
 Chronic infection
 Neoplasia

REMEMBER Se-Ferritin is an acute phase reactant and will be usually be raised three-fold by inflammation

Question 8

causes of decreased production + associated anemia : stimulus

Answer 8

 Normo/normo anemia
 Chronic kidney disease
 Hypothyroidism
 Addison’s disease
 Parathyroid disease

Question 9

causes of decreased production: NUTRIENTS

Answer 9

 Iron-deficiency - Hipo/micro anemia
 Vit B12 + Iron deficiency - Oval macrocytes, Hypersegmented neutrophil, Defective DNA synthesis

Question 10

WHAT ARE THE CAUSES OF IRON DEFICIENCY

Answer 10

1.  Chronic blood loss: Menstruation, Gastrointestinal bleeding – peptic ulcer, cancer etc. , Epistaxis
2. Inadequate intake : vegetarians
3. Malabsorption: Gastrectomy, Low acid (PPI, H2RA, Atrophic gastritis), Coeliac disease
4. Increased demands: pregnancy, puberty

Question 11

what are the iron results in iron deficiency?

Answer 11

 S-Iron - LOW
 S-Tranferrin High
some labs report this as TIBC (total iron binding capacity)
 S-Transferrin saturation - LOW  S-Ferritin - LOW
 Bone marrow iron stores LOW

CHECK IDA VS ACD on slides NB!!

Question 12

when do we always exclude a GIT-bleed as a cause of an iron deficiency anemia especially

Answer 12

 Any GIT-symptoms, overt bleeding or melena
 Patients > 50yr
 Males
 Loss of weight
 Family history of colon cancer

Stool occult blood, Gastroscopy Ba-enema and/or colonoscopy

Question 13

what is the management of iron deficiency?

Answer 13

Investigation and treatment of underlying cause
 Treat anemia and replenish iron stores: Usually 6 MONTHS if underlying cause is found and reversed
 Oral iron vs  IV iron
 Bloodtransfusion only if patient is unstable
 A well compensated IDA of 5g/dL is NOT an indication to transfuse

Question 14

expected response to effective therapy

Answer 14

 Hb should rise at rate of 2g/dl every 3 weeks
 Reticulocyte response peaks at 7 to 10 days in those with moderate/severe anemia

Question 15

what to do if oral iron as intolerable side effects

Answer 15

 Nausea  Abdominal pain  Constipation  Diarrhoea

 Take dose with food (may reduce absorption)
 Alternate day dosing (if not already done)
 Switch formulation
 Switch from tablet to liquid formulation

Question 16

what if patient doesn’t respond to oral iron?

Answer 16

-presence of coexisting disease interfering with BM response
- diagnosis incorrect
- Poor compliance
- Poor absorption
- Need not met by oral intake

(check elaborations on slides- NB!)

Question 17

what are the indications for IV iron?

Answer 17

 Intolerable side effects of oral supplementation
 Pregnancy – 2nd and 3rd trimester
 Oral iron often not tolerated well
 Need to rapidly replace stores  Severe symptomatic anemia (may prevent blood transfusion)  Blood loss in excess of oral iron needs
 Malabsorption syndromes
 Inflammatory bowel disease
 Oral iron may worsen inflammatory bowel disease
 Haemodialysis and EPO therapy

Question 18

benefits of intravenous iron

Answer 18

 Rapid replenishment of stores  Earlier response
 New formulations
 Safer than old formulations (very few adverse reactions)
 Can give total dose infusion (completely fill the stores in one dose)

Question 19

what are the cause of VitB12 deficiency?

Answer 19

1. Malabsorption
   → Gastric cause : Gastrectomy, Low gastric acid, Pernicious anemia
   → Intestinal causes: Chron’s or resection of terminal ileum
   - Bacterial overgrowth anatomic(with stasis)/ functional (scleroderma,diabetes) “blind loop”
2. Inadequate intake - vegetarians

Question 20

what are the clinical associations of pernicious anemia?

Answer 20

• female > male
• blue eyes
• early greying
• northern European descent
  -familial
• blood group A

Question 21

what are the auto-immune associations of pernicious anemia?

Answer 21

• Vitiligo
• thyroid disease
  
  • Myxedema, hashimoto’s disease, thyrotoxicosis
• Addison’s disease
• Hypoparathyroidism

Question 22

development of pernicious anemia

Answer 22

• an auto-immune response directed against the IF producing parietal cells in gastric mucosa
  Auto-immune attack gastric mucosa
  ↓
  Atrophy and thinning stomach wall
  ↓
  Achlorhydria
  ↓
  Intestinal metaplasia
  ↓
  Carcinoma stomach

Question 23

treatment of pernicious anemia?

Answer 23

Pernicious anemia
 1000mcg B12 IM/day x 1 week  1000mcg B12 IM/week x 4 weeks
 1000mcg B12 IM/month for life

Question 24

describe B12 neuropathy

Answer 24

 Progressive sensory neuropathy
 Peripheral sensory nerves and post and lat columns
 Symmetrical and affects lower limbs > upper limbs
 Pt c/o tingling feet, difficulty walking and falling over in the dark
 Rarely optic atrophy or severe psychiatric Sx

 Always exclude B12 deficiency in any patient with dementia, as it is usually fully reversible!!!!!

Neurological problems
 Improves slowly over 6 months
 Degree of improvement inversely related to the extent and duration of disease

Question 25

what are the causes of folate deficiency?

Answer 25

 Inadequate intake  No vegies/fruits  Increased demands  Pregnancy  Hemolysis  Malabsorption  Drugs  Alcohol  Anticonvulsants  Methotrexate

Question 26

how is folate deficiency treated?

Answer 26

-  Folate deficiency  Folate 1-5mg/d for 1-4 months or until hematological recovery occurs  If underlying condition can not be reversed, give folate indefinitely  E.g. congenital hemolytic anemia  Folate may reverse some of the hematological manifestations of B12 deficiency, BUT neurological problems may worsen  ALWAYS  Give B12 and folate together until blood results are known  Never start folate blindly without testing for B12