L12: Haemolytic Anaemias Flashcards
What is 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 difference in Hb between neonates and infants?
→Hb is higher than in infants
How long do RBCs go without nuclei or cytoplasmic cells?
→120 days
What is the width of capillaries?
→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
How are senescent RBCs removed?
what happens to RBCs when they are old?
→Reticular endothelial system (RES) of the liver and spleen
Describe the characteristics of haemolysis
→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
What is incomplete compensated haemolysis?
→RBC production unable to keep up with decreased RBC life span thus decreased HB
Why does reticulocytosis occur?
→due to reduced Hb
→the bone marrow may increase its output of red cells
→expanding the volume of active marrow
What are the clinical findings of haemolytic anaemia?
→Jaundice- increase in unconjugated bilirubin
→Pallor
→Fatigue
→Splenomegaly
What are the chronic clinical findings of haemolytic anaemia?
→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
What are the lab investigations for HA?
→Peripheral blood film
→ Bone marrow findings
→other findings
What are features of the lab investigations for HA (in peripheral blood film)? (what do you see in the blood film?)
→ 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)
What do morphological clues of HA lead to?
→underlying disorder
What are some morphological abnormalities of HA?
→Spherocytes,
→Sickle cell, Target cells,
→Schistocytes (fragmented, triangular rbc)
→acanthocytes
What are the bone marrow findings of HA?
compensatory mechanisms to haemolysis
→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)
What are other findings of HA?
→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
What is hemosidirin?
→brown iron-containing pigment usually derived from the disintegration of extravasated red blood cells
What are the different classifications of haemolytic anaemias?
→Inheritance
→Site of RBC destruction
→Origin of RBC damage
What are the inheritance classification of HA?
→hereditary eg Hereditary spherocytosis
→acquired eg Paroxysmal nocturnal haemoglobinuria, IHA
What are classifications of sites of RBC production in HA?
→intravascular eg Thrombotic thrombocytopenic purpura, haemolytic transfusion reaction
→ extravascular eg Autoimmune haemolysis
What are the classifications of origin of RBC damage in HA?
→Intrinsic (Intracorpuscular) -within RBC eg G6PD deficiency
→Extrinsic (Extracorpuscular) - outside RBC eg Delayed haemolytic transfusion reaction, Infections
What are some problems in intrinsic HA?
→Membrane defects e.g Hereditary Spherocytosis
→Enzyme defects e.g. G6PD; Pyruvate kinase deficiency
→Haemoglobin defects e.g. SCD; thalassaemias
What are some problems in immune-mediated HA?
→Autoimmune
→Alloimmune e.g. Haemolytic disease of newborn; haemolytic transfusion reaction
What things induce autoimmune HA?
→warm weather
→cold weather
→ drug induced
What are some problems in extrinsic non- immune HA?
→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
What is involved in the management of HS?
→Monitor
→Folic acid
→Transfusion
→Splenectomy
What are the observations in HS?
→microspherocytes-
→no central pallor,
→polychromatophilic-
→increased in RNA, no biconcave
What are the observations in HE?
→elongated with no pointed ends
What are the clinical features of HS?
→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
What is used to test for HS?
→eosin-5′-maleimide (EMA) binding test is aflow cytometric test
What is the role of Glucose-6-phosphate dehydrogenase?
→Role of the HMP shunt
What is the role of the HMP shunt?
→Generates NADPH & reduced glutathione
→Protects the cell from oxidative stress
What are the effects of HMP shunt deficiency?
→Oxidation of Hb by oxidant radicals
→Oxidised membrane proteins
reduced RBC deformability
What does oxidation of Hb lead to?
→resulting denatured Hb aggregates & forms Heinz bodies – bind to membrane.
What is the role of NADPH in the HMP shunt?
→converts oxidised glutathione to a reduced form- protects against oxidative stress that leads to haemolysis
What are the morphological findings of oxidative haemolysis?
→bite cells,
→blister cells & Ghost cells;
→Heinz bodies
What are bite cells?
→abnormally shaped mature red blood cell with one or more semicircular portions removed from the cell margin
What are Heinz bodies?
→lumps of damaged hemoglobin attached to your red blood cells
What should people with OH avoid?
→oxidative drugs like anti-malaria drugs
→ they have protection against malaria
What is the genotype of OH?
→X-linked
What is the genotype of PKD?
→Autosomal recessive
What pathway is PK involved in?
→Glycolytic Pathway
→generate ATP
What is thalassaemia?
→Defect in the rate of synthesis alpha- or beta-globin chain (structurally normal
→Excess unpaired globin chains are unstable
What are the clinical divisions of thalassaemia?
→Hydrop foetalis
→β-Thalassaemia major
→Thalassaemia intermedia
→Thalassaemia minor
What are the clinical features of beta thalassemia major?
→Severe anaemia
→Progressive hepatosplenomegaly
→Bone marrow expansion – facial bone abnormalities
→Transfusion dependent
→Mild jaundice
→Iron overload
→Intermittent infections, pallor
What are the morphological features of beta thalassaemia?
→Microcytic hypochromic with decreased MCV, MCH, MCHC
→Anisopoikilocytosis; target cells, nucleated RBC, tear drop cells
→Reticulocytes >2%
Why is the bone marrow expansion in beta thalassaemia?
→extensive erythroid hyperplasia
What are the features of beta thalassaemia minor?
→Asymptomatic
→Often confused with Fe deficiency
→α-thal trait often by exclusion
→HbA2 increased in b-thal trait – (diagnostic)
What are the features of Hb Barts hydrops syndrome of alpha thalassaemia?
→deletion of all 4 globin genes
→incompatible with life
What are the features of HbH disease of alpha thalassemia?
→Deletion of 3/4 α-globin genes
→moderate chronic HA
Splenomegaly, hepatomegaly
→hypochromic microcytic, poikilocytosis, polychromasia, target cells
What is the mutation in HbS?
→glutamic acid at position 6 → valine (HbS)
What are the clinically significant sickling syndromes?
→HbSS
→HbSC
→HbS- β thalassaemia
What are the diagnostic tests for SCA?
→Solubility test
→HLPC
What is thalassaemia intermedia?
→transfusion independent
→diverse clinical phenotype
→Increased bilirubin level
How many RBC produced a day and where?
2x10^11 RBC/day in the bone marrow
What is compensated heamolysis?
When RBC production kept up with destruction of RBC thus Hb levels are normal
What is jaundice?
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
What is splenomegaly?
Enlargement of spleen due to increase in RBC destruction (occurs in liver and spleen)
What is pallor?
Pale appearance due to decreased Hb
normal vs abnormal RBC destruction
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