haemolytic anaemias

Question 1

describe haemolytic anaemia

Answer 1

anaemia due to shortened RBC survival

Question 2

describe normal RBC lifecycle

Answer 2

2x10^11 RBC day in bone marrow

RBC circulate for approx 120 days without nuclei or cytoplasmic organelles

300 miles travelled through microcirculation, as small as 3.5 microns

removal senescent RBC by RES

Question 3

haemolysis

Answer 3

1. shortened red survival 30-80 days
2. compensation by bone marrow to increase production
3. increased young cells in circulation = reticulocyotsis +/- nucleated RBC
4. incompletely compensated haemolysis: RBC production unable to keep up with decreased RBC lifespan = decreased Hb

Question 4

clinical findings

chronic clinical findings

Answer 4

jaundice
pallor
fatigue
splenomegaly

gallstones - pigment

leg ulcer
folate deficiency

Question 5

lab investigation for HA

Answer 5

peripheral blood film: polychromatophilia, nucleated RBC, thrombocytosis, neutrophilic with the left shift

bone marrow = compensatory mechanism to haemolysis

Question 6

further findings for lab investigation of HA

Answer 6

Increased unconjugated bilirubin		
Increased LDH (lactate dehydrogenase)	
Decreased serum haptoglobin protein that binds free Hb
Increased urobilinogen
Increased urinary hemosiderin

Question 7

classification of haemolytic anaemia

Answer 7

hereditary and acquired inheritance

site of RBC destruction = intravascular and extravascular

origin of RBC damage = intrinsic (G6PD deficiency) and extrinsic (delayed haemolytic transfusion reaction)

Question 8

describe intrinsic corpuscular

Answer 8

Membrane defects
Hereditary Spherocytosis
Hereditary Elliptocytosis
H. Pyropoikilocytosis

Enzyme defects
G6PD
PK

Haemoglobin defects
Sickle Cell Disease
Thalassamias

Question 9

describe extrinsic extracorpuscular: immune mediated

Answer 9

autoimmune
warm
cold
drug induced

alloimune
HDN
haemolytic = transfusion rxn

Question 10

describe extrinsic extra corpuscular: non immune

Answer 10

red cell fragmentation syndrome 
mechanical trauma 
microangiopathic HA 
drugs and chemicals
infections = malaria, clostridium 

march haemogluinuria
hypersplensim

Question 11

management of HS

Answer 11

monitor
folic acid
transfusion
splenectomy

Question 12

clinical features HS

Answer 12

asymptomatic to severe haemolysis

neonatal jaundice

jaundice, splenomegaly, pigment gallstones

reduced eosin-5-maleimide binding - binds to band 3

positive family history

negative direct antibody test

Question 13

glucose 6 phosphate dehydrogenase

Answer 13

role of HMP shunt:

• generates NADPH and reduced glutathione
• protects cell from oxidative stress

effects of deficiency:

• oxidative stress
  1. oxidation of Hb by oxidant radicals = results in denatured Hb aggregates and forms Heinz bodies, bind to membrane

2. oxidised membrane proteins = reduced RBC deformability

Question 14

describe the pyruvate kinase deficiency

Answer 14

Glycolytic Pathway
Generates energy in ATP;
to maintain red cell shape and deformability

To regulate intracellular cation conc. via cation pumps (Na/K pump),

Def in PK

affects the above.

Question 15

describe globin disorders

Answer 15

thalassaemias - quantitative = defect in rate of synthesis of alpha or beta-globin chain

variant haemoglobin = qualitative
- production of a structurally abnormal globin chain

Question 16

thalassaemias

Answer 16

imbalanced alpha and beta chain production

excess unpaired globin chains are unstable

heterogeneous gp genetic disorders
ineffective erythropoiesis

clinically divided:

• hydro foetalis
• B thalassaemia major, intermedia and minor

Question 17

beta thalassaemia major

Answer 17

clinical features:

• severe anaemia
• progressive hepatospelnomegaly
• bone marrow expansion - facial bone abnormalities
• mild jaundice
• iron overload
• intermittent infections, pallor

peripheral blood:
- microcytic hypo chromic with decreased mcv, much, much

anisopoikilocytosis = target cells, nucleated RBC, tear drop cells

reticulocytes >2%

Question 18

b- thalassaemia trait minor

Answer 18

asymptomatic
often confused with Fe deficiency

alpha-thalassaemia trait often by exclusion

HbA2 increased in B-thalassaemia trait

Question 19

alpha thalassaemias

Answer 19

Hb Barts hydrops syndrome (- -/- -)
deletion of all 4 globin genes
incompatible with life

HbH disease (- α/- -)

Deletion of 3/4 α-globin genes
Common in SE Asia
Clin Features: 
moderate chronic HA
Splenomegaly, hepatomegaly*
hypochromic microcytic, poikilocytosis, polychromasia, target cells
Electrophoresis - diagnostic

Thal trait (minor) (- α/αα; - α/- α; - -/αα)
Normal or mild HA
MCV & MCH low

Question 20

thalassaemia intermedia

Answer 20

disorder with clinical manifestation between major and minor

• transfusion independent
• diverse clinical phenotype
• varying symptoms
• increased bilirubin level
• diagnosis = largely clinical
• eg. include Be/mild B+

Question 21

sickle cell disease

Answer 21

SCD = refers to all diseases as a result of inherited HbS

Hb S caused by single nucleotide substitution

• HbSS = sickle cell anaemia (homozygous state )
• HbAS = sickle cell trait (heterozygous)

Question 22

name clinically significant sickling syndromes

Answer 22

HbSS
HbSC
HbS - B thalassaemia

Question 23

features of SCD

Answer 23

clinical :
Painful crises
Aplastic crises
Infections due to hyposplenism
Acute sickling:
Chest syndrome
Splenic sequestration
Stroke
Chronic sickling effects:
Renal failure
Avascular necrosis bone

lab:
Anaemia
Hb often 60-90
Reticulocytosis
Increased NRBC
Raised bilirubin
Low creatinine

Question 24

confirming diagnosis of sickle cell anaemia

Answer 24

solubility test:

• expose blood to reducing agent
• HbS precipitated
• positive in trait and disease