HA 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
How are senescent RBCs removed?
→RES by the liver and spleen
Describe haemolysis
→Shortened red cell survival 30-80 days
→Compensation by Bone marrow to increase production
→Increased young cells in circulation = Reticulocytosis +/- nucleated RBC
→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
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
→Leg ulcers- local ischemia
→Folate deficiency - (increased use)
What are the lab investigations for HA?
→Peripheral blood film
What are features of the lab investigations for HA?
→polychromatophilia(much bigger),
→nucleated rbc,
→ thrombocytosis;
→neutrophilia with left shift
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?
→Erythroid hyperplasia of BM
→normoblastic reaction
→Reversal of Myeloid: Erythroid ratio
→Reticulocytosis
What are other findings of HA?
→Increased unconjugated bilirubin →Increased LDH (lactate dehydrogenase) →Decreased serum haptoglobin protein that binds free Hb →Increased urobilinogen →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
→ extravascular eg Autoimmune haemolysis
What are the classifications of origin of RBC damage in HA?
→Intrinsic (Intracorpuscular) eg G6PD deficiency
→Extrinsic
(Extracorpuscular) eg Delayed haemolytic transfusion reaction, Infections
What are some problems in intrinsic HA?
→Membrane defects
→Enzyme defects
→Haemoglobin defects
What are some problems in immune-mediated HA?
→Autoimmune
→Alloimmune
What things induce autoimmune HA?
→warm weather
→cold weather
→ drug induced
What are some problems in extrinsic HA?
→Red cell fragmentation syn →Microangiopathic HA- caused by fibrin or vascular endothelium →Infections: Malaria, clostridium →March haemoglubinuria →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
