Haemolytic Anaemias Flashcards
Define Anaemia
reduced haemoglobin level for the age and gender of the individual
What is haemolytic anaemia?
anaemia due to shortened RBC survival
What is the normal RBC lifecycle
- 2x1011 RBC/day in the 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
Describe the process of haemolysis
- Shortened red cell survival to 30-80 days
- Bone marrow compensates by increasing production
- There are increased reticulocytes in circulation with or without nucleuses
What are the clinical findings in anaemia ?
- Jaundice
- Pallor
- fatigue
- Splenomegaly (enlarged spleen)
What are the chronic clinical findings
- Gallstones - pigment stones
- Leg ulcers - not healing due to lack of O₂ delivery
- Folate deficiency - due to increased use
What are the lab investigations carried out for HA
- Bone marrow findings
- Peripheral blood film
What would be seen in a Bone marrow investigation in HA
- Erythroid hyperplasia of BM, with normoblastic rxn, higher ratio of erythroid cells than myeloid cells
- Reticulocytosis – variable
Mild (2-10%) - Haemoglobinopathies
Moderate to marked (10-60%) - IHAs, HS, G6PD-def.
what would be seen in a peripheral blood film in HA
- Polychromatophilia, nucleated rbc, thrombocytosis; neutrophilia with left shift;
- Morphologic abnormalities provides clue to underlying disorder: e.g. Sickled cells, Spherocytes, Target cells, Schistocytes (fragmented, triangular rbc) acanthocytes
What are some other findings of HA
- Increased unconjugated bilirubin
- Increased LDH (lactate dehydrogenase)
- Decreased serum haptoglobin protein that binds free Hb
- Increased urobilinogen
- Increased urinary hemosiderin
How can Haemolytic anaemia’s be classified
Inheritance:
- Hereditary
Hereditary spherocytosis - Acquired
Paroxysmal nocturnal haemoglobinuria
Origin of RBC damage:
- Intrinsic (Intracorpuscular)
G6PD-deficiency - Extrinsic (Extracorpuscular)
Delayed Haemolytic Transfusion Rxn
Site of RBC destruction:
- Intravascular
Thrombotic Thrombocytopenic Purpura - Extravascular
Autoimmune Haemolysis
What is the site of RBC destruction
Extravascular - Liver then excreted in faeces
Intravascular - Kidney then excreted in urine
What are the intrinsic causes of HA
Membrane defects:
- Hereditary Spherocytosis (HS)
- Hereditary Elliptocytosis (HE)
- H. Pyropoikilocytosis
Enzyme defects:
- G6PD
- PK
Haemoglobin defects:
- Sickle Cell Disease
- Thalassaemia’s
What are the Immune-Mediated Extrinsic causes of HA
Autoimmune:
- Warm
- Cold
- Drug induced
Alloimmune:
- HDN
- Haemolytic Transfusion
What are the Non-Immune-Mediated Extrinsic causes of HA
Red cell fragmentation syn:
- Mechanical trauma
e.g. artificial valve - Microangiopathic HA
e.g. HUS, TTP, DIC
Drugs & chemicals
Infections:
- Malaria, clostridium
March haemoglubinuria
Hypersplenism
What are the features of membrane disorders in HS
- Asymptomatic to severe haemolysis
- Neonatal jaundice
- Jaundice, splenomegaly, pigment gallstones
- *Reduced eosin-5-maleimide (EMA) binding – binds to band 3
- Positive family history
- Negative direct antibody test
What are the Enzyme effects that cause HA
- Defect in Glycolytic (Embden-Meyerhof) pathways
- Defect in Glucose-6-phosphate dehydrogenase
Explain how the defect works in the glycolytic pathway
RBC is unable produce ATP which is needed in powering Na/K pumps and needed in changing shape to fit though capillaries.
This way RBC can’t return to their original shape and lyse.
Explain how the defect works in the G6PD shunt
G6PD is needed in the management of oxidants.
If not present in RBC oxidants can cause the RBC to lyse
List all the globin disorders
Thalassaemia - quantitative:
defect in the rate of synthesis a globin chain (structurally normal)
SCD - variant haemoglobins: - qualitative
production of a structurally abnormal globin chain
What causes thalassaemia disorders
- Imbalanced alpha and beta chain production
- Excess unpaired globin chains are unstable
- Heterogenous gp genetic disorders.
- Ineffective erythropoiesis
- Clinically divided:
Hydrop foetalis
β-Thalassaemia major
Thalassaemia intermedia
Thalassaemia minor
What are the clinical features of B-thalassaemia major
- Severe anaemia
- Progressive hepatosplenomegaly
- Bone marrow expansion – facial bone abnormalities
- Mild jaundice
- Intermittent infections, pallor
- Iron overload
What does a peripheral blood sample show for B-thalassaemia major
- Microcytic hypochromic with decreased MCV, MCH, MCHC
- Anisopoikilocytosis; target cells, nucleated RBC, tear drop cells
- Reticulocytes >2%
What are some traits in B-thalassaemia minor
- Asymptomatic
- Often confused with Fe deficiency
- α-thal trait often by exclusion
- HbA2 increased in β-thal trait – (diagnostic)
What are some Alpha (α)-thalassaemia disorders
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
What are the clinical features in Alpha Thalassaemia
- 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
What are the characteristics of Thalassaemia intermedia?
Disorder with clinical manifestation between major and minor; e.g. βE/mild β+ (HbE- β-thal)
- transfusion independent
- diverse clinical phenotype
- Varying symptoms
- Increased bilirubin level
- diagnosis – largely clinical
What is sickle cell disease?
SCD – refers to all diseases as a result of inherited HbS;
Hb S caused by single nucleotide substitution.
HbSS is sickle cell anaemia (homozygous state)
HbAS – sickle cell trait (heterozygous)
What causes SCD
- Point mutation in the β globin gene: e.g. glutamic acid at position 6 → valine (HbS)
- Insoluble Hb tetramer when deoxygenated → polymerisation
- “Sickle” shaped cells
What are the clinical findings for SCD
Crises: Painful, Aplastic
Infections due to hyposplenism
Acute sickling:
- Chest syndrome
- Splenic sequestration
- Stroke
Chronic sickling effects:
- Renal failure
- Avascular necrosis bone
What are the Laboratory findings for SCD
- Anaemia: Hb often 60-90
- Reticulocytosis, Increased NRBC
- Raised bilirubin, Low creatinine
What is the solubility test for SCD
- Expose blood to reducing agent
- HbS precipitated
- Positive in trait and disease
