L12: Haemolytic Anaemias

Question 1

What is anaemia?

Answer 1

→reduced haemoglobin level for the age and gender of the individual

Question 2

What is haemolytic anaemia?

Answer 2

→anaemia due to shortened RBC survival

Question 3

What is the difference in Hb between neonates and infants?

Answer 3

→Hb is higher than in infants

Question 4

How long do RBCs go without nuclei or cytoplasmic cells?

Answer 4

→120 days

Question 5

What is the width of capillaries?

Answer 5

→3.5 microns
RBC are 8 microns - thus able to deform thanks to cytoplasmic enzymes, allowing them to go through small widths and thus survive for 120 days

Question 6

How are senescent RBCs removed?

what happens to RBCs when they are old?

Answer 6

→Reticular endothelial system (RES) of the liver and spleen

Question 7

Describe the characteristics of haemolysis

Answer 7

→Shortened RBC survival 30-80 days
→Compensation by Bone marrow to increase production
→Increased young cells in circulation = Reticulocytosis (increase in reticulocytes) +/- nucleated RBC seen in blood film
→RBC production unable to keep up with decreased RBC life span
→Decreased Hb

Question 8

What is incomplete compensated haemolysis?

Answer 8

→RBC production unable to keep up with decreased RBC life span thus decreased HB

Question 9

Why does reticulocytosis occur?

Answer 9

→due to reduced Hb
→the bone marrow may increase its output of red cells
→expanding the volume of active marrow

Question 10

What are the clinical findings of haemolytic anaemia?

Answer 10

→Jaundice- increase in unconjugated bilirubin
→Pallor
→Fatigue
→Splenomegaly

Question 11

What are the chronic clinical findings of haemolytic anaemia?

Answer 11

→Gallstones - pigment due to bilirubin
→Leg ulcers in lower leg- due to vasculastasis or local ischemia in the area
→Folate deficiency - due to increased use of folate to compensate for loss of RBC

Question 12

What are the lab investigations for HA?

Answer 12

→Peripheral blood film

→ Bone marrow findings
→other findings

Question 13

What are features of the lab investigations for HA (in peripheral blood film)? (what do you see in the blood film?)

Answer 13

→ polychromatophilia (much bigger and RBC basophilic in colour due to increased RNA content),
→ nucleated RBC,
→ thrombocytosis (increase in platelets)
→ neutrophilia with left shift (immature neutrophils)

Question 14

What do morphological clues of HA lead to?

Answer 14

→underlying disorder

Question 15

What are some morphological abnormalities of HA?

Answer 15

→Spherocytes,
→Sickle cell, Target cells,
→Schistocytes (fragmented, triangular rbc)
→acanthocytes

Question 16

What are the bone marrow findings of HA?

compensatory mechanisms to haemolysis

Answer 16

→Erythroid hyperplasia of BM (excessive count of erythroid precursors - immature RBC) with:
→normoblastic reaction (increase in normoblasts)
→Reversal of Myeloid: Erythroid ratio (normally 2-5:1; HA as a result of erythroid hyperplasia: 1:4)

→Reticulocytosis (variable- depending on what stage of HA)

Question 17

What are other findings of HA?

Answer 17

→Increased unconjugated bilirubin (due to increased RBC breakdown)
→Increased LDH (lactate dehydrogenase)
→Decreased serum haptoglobin protein that binds free Hb (increased Hb in plasma = increased binding to Hb because decreased serum haptoglobin protein and decreased Hb)
→Increased urobilinogen (due to bilirubin metabolism)
→Increased urinary hemosiderin

Question 18

What is hemosidirin?

Answer 18

→brown iron-containing pigment usually derived from the disintegration of extravasated red blood cells

Question 19

What are the different classifications of haemolytic anaemias?

Answer 19

→Inheritance
→Site of RBC destruction
→Origin of RBC damage

Question 20

What are the inheritance classification of HA?

Answer 20

→hereditary eg Hereditary spherocytosis

→acquired eg Paroxysmal nocturnal haemoglobinuria, IHA

Question 21

What are classifications of sites of RBC production in HA?

Answer 21

→intravascular eg Thrombotic thrombocytopenic purpura, haemolytic transfusion reaction
→ extravascular eg Autoimmune haemolysis

Question 22

What are the classifications of origin of RBC damage in HA?

Answer 22

→Intrinsic (Intracorpuscular) -within RBC eg G6PD deficiency

→Extrinsic (Extracorpuscular) - outside RBC eg Delayed haemolytic transfusion reaction, Infections

Question 23

What are some problems in intrinsic HA?

Answer 23

→Membrane defects e.g Hereditary Spherocytosis
→Enzyme defects e.g. G6PD; Pyruvate kinase deficiency
→Haemoglobin defects e.g. SCD; thalassaemias

Question 24

What are some problems in immune-mediated HA?

Answer 24

→Autoimmune

→Alloimmune e.g. Haemolytic disease of newborn; haemolytic transfusion reaction

Question 25

What things induce autoimmune HA?

Answer 25

→warm weather →cold weather → drug induced

Question 26

What are some problems in extrinsic non- immune HA?

Answer 26

→Red cell fragmentation syndrome →Mechanical trauma e.g. artificial valve →Microangiopathic HA- caused by fibrin deposition in vascular endothelium →Infections e.g. Malaria, clostridium →March haemoglubinuria (hameolysis occurring between toes when marching) →Hypersplenism

Question 27

What is involved in the management of HS?

Answer 27

→Monitor →Folic acid →Transfusion →Splenectomy

Question 28

What are the observations in HS?

Answer 28

→microspherocytes- →no central pallor, →polychromatophilic- →increased in RNA, no biconcave

Question 29

What are the observations in HE?

Answer 29

→elongated with no pointed ends

Question 30

What are the clinical features of HS?

Answer 30

→Asymptomatic until more severe haemolysis →Neonatal jaundice →Jaundice, splenomegaly, pigment gallstones →*Reduced eosin-5-maleimide (EMA) binding – binds to band 3- flow cytometry →Positive family history →Negative direct antibody test →Pigment gallstones

Question 31

What is used to test for HS?

Answer 31

→eosin-5′-maleimide (EMA) binding test is a flow cytometric test

Question 32

What is the role of Glucose-6-phosphate dehydrogenase?

Answer 32

→Role of the HMP shunt

Question 33

What is the role of the HMP shunt?

Answer 33

→Generates NADPH & reduced glutathione →Protects the cell from oxidative stress

Question 34

What are the effects of HMP shunt deficiency?

Answer 34

→Oxidation of Hb by oxidant radicals →Oxidised membrane proteins reduced RBC deformability

Question 35

What does oxidation of Hb lead to?

Answer 35

→resulting denatured Hb aggregates & forms Heinz bodies – bind to membrane.

Question 36

What is the role of NADPH in the HMP shunt?

Answer 36

→converts oxidised glutathione to a reduced form- protects against oxidative stress that leads to haemolysis

Question 37

What are the morphological findings of oxidative haemolysis?

Answer 37

→bite cells, →blister cells & Ghost cells; →Heinz bodies

Question 38

What are bite cells?

Answer 38

→abnormally shaped mature red blood cell with one or more semicircular portions removed from the cell margin

Question 39

What are Heinz bodies?

Answer 39

→lumps of damaged hemoglobin attached to your red blood cells

Question 40

What should people with OH avoid?

Answer 40

→oxidative drugs like anti-malaria drugs → they have protection against malaria

Question 41

What is the genotype of OH?

Answer 41

→X-linked

Question 42

What is the genotype of PKD?

Answer 42

→Autosomal recessive

Question 43

What pathway is PK involved in?

Answer 43

→Glycolytic Pathway | →generate ATP

Question 44

What is thalassaemia?

Answer 44

→Defect in the rate of synthesis alpha- or beta-globin chain (structurally normal →Excess unpaired globin chains are unstable

Question 45

What are the clinical divisions of thalassaemia?

Answer 45

→Hydrop foetalis →β-Thalassaemia major →Thalassaemia intermedia →Thalassaemia minor

Question 46

What are the clinical features of beta thalassemia major?

Answer 46

→Severe anaemia →Progressive hepatosplenomegaly →Bone marrow expansion – facial bone abnormalities →Transfusion dependent →Mild jaundice →Iron overload →Intermittent infections, pallor

Question 47

What are the morphological features of beta thalassaemia?

Answer 47

→Microcytic hypochromic with decreased MCV, MCH, MCHC →Anisopoikilocytosis; target cells, nucleated RBC, tear drop cells →Reticulocytes >2%

Question 48

Why is the bone marrow expansion in beta thalassaemia?

Answer 48

→extensive erythroid hyperplasia

Question 49

What are the features of beta thalassaemia minor?

Answer 49

→Asymptomatic →Often confused with Fe deficiency →α-thal trait often by exclusion →HbA2 increased in b-thal trait – (diagnostic)

Question 50

What are the features of Hb Barts hydrops syndrome of alpha thalassaemia?

Answer 50

→deletion of all 4 globin genes | →incompatible with life

Question 51

What are the features of HbH disease of alpha thalassemia?

Answer 51

→Deletion of 3/4 α-globin genes →moderate chronic HA Splenomegaly, hepatomegaly →hypochromic microcytic, poikilocytosis, polychromasia, target cells

Question 52

What is the mutation in HbS?

Answer 52

→glutamic acid at position 6 → valine (HbS)

Question 53

What are the clinically significant sickling syndromes?

Answer 53

→HbSS →HbSC →HbS- β thalassaemia

Question 54

What are the diagnostic tests for SCA?

Answer 54

→Solubility test | →HLPC

Question 55

What is thalassaemia intermedia?

Answer 55

→transfusion independent →diverse clinical phenotype →Increased bilirubin level

Question 56

How many RBC produced a day and where?

Answer 56

2x10^11 RBC/day in the bone marrow

Question 57

What is compensated heamolysis?

Answer 57

When RBC production kept up with destruction of RBC thus Hb levels are normal

Question 58

What is jaundice?

Answer 58

Clinical finding in HA because increase in RBC breakdown - Hb broken down into Heme and global - heme further broken down into Fe and protoporphyrin - protoporphyrin broken in bilirubin (yellow pigment) thus increase in uncongugated protoporphyrin thus increase in bilirubin

Question 59

What is splenomegaly?

Answer 59

Enlargement of spleen due to increase in RBC destruction (occurs in liver and spleen)

Question 60

What is pallor?

Answer 60

Pale appearance due to decreased Hb

Question 61

normal vs abnormal RBC destruction

Answer 61

see slide