Haemolytic Anaemias Flashcards
What is haemolytic anaemia?
Anaemia due to shortened Blood cell survival occurring by high rate of destruction of RBC
Describe the variation in blood Hb conc from neonates to adult?
VD
Describe the normal Blood cell lifestyle?
- 2 × 10 ^ 11 BC produced per day in the bone marrow
- They circulate in blood for 120 days without any organelles (300 miles travelled)
- When senescent (RBC become old), removal occurs by the reticular endothelial system (RES) of the liver + spleen
Describe how the haemolysis cycle occurs?
- Reticulocytosis is an increase in reticuloyctes (developing RBCs)
- Shortened red cell survival 30-80 days -> Compensation by Bone marrow to increase production -> Increased young cells in circulation = Reticulocytosis +/- nucleated RBC -> incompletely compensated haemolysis: RBC production unable to keep up with decreased RBC life span = Decreased Hb
State 4 clinical findings of haemolytic anaemia?
- Jaundine (yellowing of skin)
- Pallor (unhealthy pale appearance)
- Fatigue
- Splenomegaly (enlargement of the spleen)
State 3 chronic clinical findings of haemolytic anaemia?
- Chronic clinical findings:
- Gallstones - pigment
- Leg ulcers
- Folate deficiency (due to increased use of folate to compensate for lowered RBC count)
State features of a peripheral blood film of someone with HA?
- Polychromatophilia (increased immature RBCs)
- Nucleated RBCs
- Thrombocytosis (high platelet count)
- Neutrophilia with left shift
What morphological abnormalities in a peripheral blood film shows clue that HA is the underlying disorder?
- Spherocytes
- Sickle cell
- Target cells
- Schistosities (fragmented, triangular RBCs)
- Acanthocytes
State the major bone marrow findings for someone with HA?
- Reticulocytosis (variable % of reti. In BM)
- Mild (2-10%) caused via haemoglobinopathies
- Moderated to marked (10 to 60%) caused via IHAs (immune haemolytic anaemia), HS (hereditary spherocytosis), G6PD deficiency
State the other major bone marrow findings for someone with HA?
- Erthyroid hyperplasia of BM (increased erythronium precursor cell -› increase in immature RBCs)
- Normoblastic reaction (production of nucleated RBCs)
- Reversal of the myeloid:erythroid ratio
Apart from the major findings, state 5 factors which have increased and decreased in the Bone marrow findings with someone with HA? (Low-key go back and figure how these happen)
Increased factors:
- Unconjugated bilirubin
- LDH (lactate dehydrogenase)
- Urobilinogen (via metabolism of bilirubin)
- Urinary hemosiderin
Decreased factors:
- Serum haptoglobin protein that binds to free Hb
State the 3 major classifications of haemolytic anaemia stating examples for each sub-classification?
- Inheritance: Acquired, Paroxysmal nocturnal haemoglobinuria
b. Hereditary: Hereditary spherocytosis
- Inheritance: Acquired, Paroxysmal nocturnal haemoglobinuria
- Site of RBC destruction: Intravascular (within the vascular system): Thrombotic thrombocytopenia purpura/ haemolytic transfusion
B. Extravascular, II. Autoimmune haemolysis
- Site of RBC destruction: Intravascular (within the vascular system): Thrombotic thrombocytopenia purpura/ haemolytic transfusion
- Intrinsic (intracorpuscular)
b. Extrinsic (extracorpuscular)
- Intrinsic (intracorpuscular)
State the subtypes within the intrinsic (intracorpuscular) classification of HA stating examples for each?
- Membrane defects: Hereditary spherocytosis, H elliptocytosis, H pyropoikilocytosis
- Enzyme defects: G6PD, PK
- Hb defects: SCD, thalassamias
State the subtypes within the extrinsic (extracorpuscular) classification of HA stating examples within?
- Alloimmune = immune response to nonself antigens
from members of the same species , which are called alloantigens or isoantigens - Two major types of alloantigens are blood group antigens and histocompatibility antigens.
How is the haemolytic disease of the foetus and newborn similar to transfusion reaction?
- Hemolytic disease of the fetus and newborn is similar to a transfusion reaction
- in the sense that The mother’s antibodies cannot tolerate the fetus’s antigens
- Which happens when the immune tolerance of pregnancy is impaired.
Describe the sites of RBC destruction when it normally happens? (PART 1)
- The site of BC destruction is most commonly extravascular and specifically, in the spleen (as mentioned above).
- Macrophages facilitate most extravascular BC breakdown and the components they break RBCs down into are protoporphyrins that is eventually converted to bilirubin via the liver
- iron that binds to transferrin and globin that is broken down further to individual amino acids.
Describe the sites of RBC destruction when it abnormally happens? (PART 2)
- In intravascular haemolysis, rather than RBCs being systematically broken down, the haemoglobin content of RBCs is released into blood and becomes free haemoglobin that is excreted.
- Iron is also released into the blood from haemoglobin and can also be excreted via urine.
Describe normal extravascular haemolysis
- Normal (EV H) -> In Macrophages -> RBCs broken into -> protoporphyrins - converted to bilirubin via the liver
- (- excreted via gut/kidney, iron that binds to transferrin and globin that is broken down further to individual amino acids.
Describe abnormal intravascular haemolysis
Abnormal (IV H) -> RBCs lysed -> Hb released into blood + excreted via kidney
How do membrane disorders arise from haemolytic anaemia?
- Defects of integral proteins in BC membrane - Autosomal dominant mutations - herditary spherocytosis (- Vertical interaction D - spectrin, band 3, protein 4.2, ankyrin) OR H elliptocytosis (> horizontal interactions D - protein 4.1, glycophorin C + spectrin)
State the features of the blood film of hereditary spheroctosis and how it is managed?
- BF - Spherocytosis + elliptocytes
- Managed -> Monitor, folic acid, transfusion, splenectomy
State clinical features of haemolytic spherocytosis?
- Asymptomatic to severe haemolysis
- neonatal jaundice
- Jaundice, splenomegaly, pigment gallstones
- Eosin-5-maleimide (EMA) binding (binds band 3),
- Positive family history
- Negative direct AB test
Enzyme defects
What pathway is G6PD involved in?
- Glucose-6-phosphate dehydrogenase
- Used in hexose monophosphate shunt (- Generates NADPH + ‹ glutathione)
- Protects cell from oxidative stress
Enzyme defects
state the effects of G6PD deficiency?
Oxidative stress
- oxidation of Hb by oxidant radicals
(- denatured Hb aggregates + forms heinz bodies - binds membrane)
- oxidised membrane proteins (decreased RBC deformability)
- Oxidative haemolysis
Enzyme defects
Describe the morphology from the blood film of G6PD deficiency/oxidative haemolysis?
- Bite cells, blister cells, ghost cells + heinz bodies
PK
What pathway is pyruvate kinase used in, state its uses + what occurs if deficiency of it occur?
- Glycolytic pathway
- Generates energy in ATP
- Maintains BC + deformability
- Regulates IC cation conc. via cation pumps (Na+/K+ pump) - PK def. - affects these + autosomal recessive
- Causes chronic non spherocytic HA
