Outcome : The student will know : -The types of hemolytic anemias
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Transcript of Outcome : The student will know : -The types of hemolytic anemias
Course title: Hematology (1)Course code: MLHE-201 Supervisor: Prof. Dr Magda SultanDate : 19/ 12 / 2013
Outcome :The student will know :-The types of hemolytic anemias-The diagnosis of hemolytic anemias -The types of hereditary hemolytic anemias.-The diagnosis of hereditary hemolytic anemias -The laboratory tests needed for diagnosis
1-Hemolytic anemia(HA)
• HA = decreased levels of red blood cells in circulating blood (anemia) because of their accelerated destruction (hemolysis)
• A red blood cell survives 120 days • The spleen (part of the reticulo-endothelial
system) is the main organ which removes old and damaged RBCs from the circulation.
• Breakdown of RBCs can exceed the rate that the body can make RBCs and so anemia can develop.
HEMOLYTIC ANEMIA Anemia of increased
destruction Normochromic, normocytic anemia Shortened RBC survival Reticulocytosis - Response to
increased RBC destruction Increased indirect bilirubin Increased LDH
Classification of hemolytic anemias
Causes of hemolytic anemias can be either:
1 - hereditary (genetic ) 2 - acquired.
Hemolytic anemia Hereditary
Defects of hemoglobin Thalassaemia, Sickle cell anemia
Defects of the red cell membrane Hereditary spherocytosis, Hereditary
elliptocytosis Defective red cell metabolism (enzymes)
G6PD deficiency. P K deficiency
Physiologic classification of anemia
Acquired Immune mediated : Autoimmune,
isoimmune, drugs Microangiopathic: DIC, HUS Hypersplenism Miscellaneous: drugs, toxin,
infection, burn, chemical
Mechanisms of hemolysis:
- intravascular - extravascular
Intravascular hemolysis :Red cell destruction occurs in vascular spacee.g eclinical states associated with Intravascular hemol acute hemolytic transfusion reactions severe burns physical trauma bacterial infections
Intravascular hemolysis :
- laboratory signs of intravascular hemolysis: tests for hemolysis and aditionally:
hemoglobinemia methemalbuminemia hemoglobinuria hemosiderinuria
Extravascular hemolysis :red cells destruction occurs in reticuloendothelial systeme.g
scyrestem - clinical states associated with extravascular hemolysis : autoimmune hemolysis delayed hemolytic transfusion reactions hemoglobinopathies hereditary spherocytosis hypersplenism hemolysis with liver disease- laboratory signs of extravascular hemolysis: tests for hemolysis
Signs of hemolytic anemia: Physical
• Symptoms of anemia• Jaundice• Pallor• Splenomegaly / hepatosplenomegaly
Laboratory features (1)*Morphology: anemia*Peripheral blood smear microscopy: **fragments of the red blood cells
("schistocytes") can be present **some red blood cells may appear
smaller and rounder than usual (spherocytes)
**reticulocytes are present in elevated numbers.
Normoblasts can be present.
Bone marrow smear microscopy: * Erytrhroid hyperplasia * The level of unconjugated bilirubin
in the blood is elevated.* The level of lactate dehydrogenase
(LDH) in the blood is elevated
Laboratory features (2)
*The direct CoombꞋs test is positive, if hemolysis is caused by an immune process.
*Increased excretion of urobilinogen in the urine
*Increased stercobilinogen in the stool.*Sometimes abnormal results of the
osmotic fragility test
Hereditary Hemolytic anemia
Defects of hemoglobin Thalassaemia, Sickle cell anemia
Defects of the red cell membrane
Hereditary spherocytosis, Hereditary elliptocytosis
Defective red cell metabolism G6PD deficiency. P K deficiency
. The abnormalities of the gene may result
from substitution of single amino acid like sickle cell anaemia or decrease synthesis of the whole globin chain (thalassaemia)
Haemoglobinopathy
Sickle cell anaemia Substitution of glutamic acid by valine The Hb is stable when oxygenated
state and become unstable and polymerized on deoxygenated state
Polymerization will lead to precipitation of Hb. The cell become deformed (sickle shape) and very sticky leading to vascular occlusion and small infarction to the affected areas.
Short life span of cells leading to chronic anaemia,
Sickle cell anaemia
The origin of the disease is a small change in the protein hemoglobinThe change in cell structure arises from a change inthe structure of hemoglobin.
A single change in an amino acid causes hemoglobinto aggregate.
Diagnosis Laboratory:Hb 6-9 g/dl, high retics (5-15%), Normocytic
anemia , target or anisocytosisSickling testHb electrophoresis Hb S 60-100 in
SS Parents sickle trait Hb AS
Sickle cell anaemia
Hgb Electrophoresis
Amino acids in globin chains have different charges
Separates hemoglobin according to charge
90% Hgb S, 10% Hgb F, small fraction of Hgb A2
Means defective synthesis of one or more of the
globin chains which form normal hemoglobin. In very severe form this globin is totally absent. The
defect may be in alpha chain ( thalassaemia),
Beta chain ( thalassaemia) or Delta chain ( thalassaemia)
Thalassaemia
HEMOGLOBIN NORMAL ADULT RBC CONSISTS OF
3 FORMS OF Hb: - HbA - 2 α and 2 β globin chains - HbA2 – 2 α and 2 δ globin chains - HbF - 2 α and 2 γ globin chains
THALASSEMIAS α and β
Different forms of thalassemia Alfa thalassemia Beta thalasemia: major, minor
(trait), intermedia Delta/Beta thalassemia Hereditary persistentce of fetal
hemoglobin (HPFH)
Beta ThalassaemiaDefective chain synthesis
Excess chain Precipitation
cell membrane damageCirculating Red cell
Anaemia
Bone marrow expansion
skeletal changes & hyper metabolism
Erythropoietin increased
Ineffective erythropoiesis
Bone marrow
blood transfusion
Iron overload
Complication and death
Hemolytic
Iron absorption
Beta-Thalassemia major laboratory features
Severe anemia Blood film: anisopoikilocytosis,
hypochromia, target cells, basophylic stippling, reticulocytes moderately increased and normoblasts .
Marrow: marked erythroid hyperplasia, increased sideroblasts
Shortened red cell survival Haemoglobin electrophoresis : Fetal hemoglobin > 90%, HbA
absent, HbA2 low/normal/high
HEREDITARY SPHEROCYTOSIS Defective or absent spectrin
molecule Leads to loss of RBC membrane,
leading to spherocytosis Decreased deformability of cell Increased osmotic fragility Extravascular hemolysis in spleen
Hereditary spherocytosis (HS) Laboratory features - hemolytic anemia - blood smear-microspherocytes - abnormal osmotic fragility test, acidified glycerol lysis time - negative direct Coombs test
G6PD DEFICIENCYFunction of G6PD
G6PD
GSSG 2 GSH
NADPH NADP
2 H2O H2O2
6-PG G6P
Hgb
Sulf-Hgb
Heinz bodies
Hemolysis
InfectionsDrugs
Glucose 6-Phosphate Dehydrogenase
Functions
Regenerates NADPH, allowing regeneration of glutathione
Protects against oxidative stress Lack of G6PD leads to hemolysis during
oxidative stress Infection Medications Fava beans
Oxidative stress leads to Heinz body formation, extravascular hemolysis
G6PD DEFICIENCY DIAGNOSIS : QUANTITATIVE ASSAY
DETECTING LOW ENZYME
TREATMENT – SUPPORTIVE AND PREVENTATIVE
Assignement :Student name : العاطي عبد مصطفي الشيماء
Title:Sickle cell anaemiaStudent name : يوسف اسعد اميره
Title : Haemoglobin electrophoresis .Student name : مرشدي صالح اميرهTitle :G6PD deficiency .Student name : الموجود عبد انجيTitle : Spherocytic anaemia . Student name : رياض مهدي بسمهTitle :Laboratory tests of hemolytic anaemias .
Training questions :What are the tests of hemolysis ? How to diagnose Sickle cell anaemia ? How to classify hemolytic anaemias ?
Reference book : Essential Hematology . Dacie .