pathogenesis & lab diagnosis of hemolytic anemia
TRANSCRIPT
![Page 1: Pathogenesis & Lab diagnosis of Hemolytic Anemia](https://reader034.vdocuments.site/reader034/viewer/2022050907/55a732391a28ab76028b46e4/html5/thumbnails/1.jpg)
Pathogenesis & Lab Diagnosis
of
Sickle Cell Anemia & Thalassemia
![Page 2: Pathogenesis & Lab diagnosis of Hemolytic Anemia](https://reader034.vdocuments.site/reader034/viewer/2022050907/55a732391a28ab76028b46e4/html5/thumbnails/2.jpg)
Pathogenesis
Of
Hemolytic Anemia
Intravascular Extravascular
Abnormal
RBCs
Destruction at
Splenic sinusoids
Release of
hemoglobin Hb transported
![Page 3: Pathogenesis & Lab diagnosis of Hemolytic Anemia](https://reader034.vdocuments.site/reader034/viewer/2022050907/55a732391a28ab76028b46e4/html5/thumbnails/3.jpg)
Fate of Hemoglobin
Porphyrin portion of Heme - Bilirubin
Iron portion of Heme – Bone Marrow stores
Globin – Amino acids recycled
Reduced RBC number
Rebound erythropoiesis
Ineffective Erythropoiesis Extra Medullary Erythropoiesis
![Page 4: Pathogenesis & Lab diagnosis of Hemolytic Anemia](https://reader034.vdocuments.site/reader034/viewer/2022050907/55a732391a28ab76028b46e4/html5/thumbnails/4.jpg)
Pathogenesis
Of
Hemolytic Anemia
Intravascular Extravascular
Abnormal
RBCs
Destruction at
Splenic sinusoids
Release of
hemoglobin
Peripheral Smear
RBC count
Hb%Decreased
Haptoglobin levels
Hb transported
![Page 5: Pathogenesis & Lab diagnosis of Hemolytic Anemia](https://reader034.vdocuments.site/reader034/viewer/2022050907/55a732391a28ab76028b46e4/html5/thumbnails/5.jpg)
Fate of Hemoglobin
Porphyrin portion of Heme - Bilirubin
Iron portion of Heme – Bone Marrow stores
Globin – Amino acids recycled
Reduced RBC number
Rebound erythropoiesis
Ineffective Erythropoiesis Extra Medullary Erythropoiesis
S. Bilirubin
S. Iron
Hepato splenomegaly
Crew hair cut appearance
BM – M:E ratio reversed
Reticulocyte count
![Page 6: Pathogenesis & Lab diagnosis of Hemolytic Anemia](https://reader034.vdocuments.site/reader034/viewer/2022050907/55a732391a28ab76028b46e4/html5/thumbnails/6.jpg)
Pathogenesis
Of
Hemolytic Anemia
Intravascular Extravascular
Abnormal
RBCs
Destruction at
Splenic sinusoids
Release of
hemoglobin Hb transported
?
![Page 7: Pathogenesis & Lab diagnosis of Hemolytic Anemia](https://reader034.vdocuments.site/reader034/viewer/2022050907/55a732391a28ab76028b46e4/html5/thumbnails/7.jpg)
Abnormal RBCs
Abnormal membrane : Hereditary Spherocytosis
Abnormal Enzymes : G6PD deficiency
Abnormal Hemoglobin
Deficiency
Thalassemia
Heme
MethemoglobinemiaAltered
Sickle Cell Disease
Globin
![Page 8: Pathogenesis & Lab diagnosis of Hemolytic Anemia](https://reader034.vdocuments.site/reader034/viewer/2022050907/55a732391a28ab76028b46e4/html5/thumbnails/8.jpg)
Pathophysiology of Sickle Cell Disease
Robbins & Cotran’s Pathological Basis of Disease
![Page 9: Pathogenesis & Lab diagnosis of Hemolytic Anemia](https://reader034.vdocuments.site/reader034/viewer/2022050907/55a732391a28ab76028b46e4/html5/thumbnails/9.jpg)
Abnormal RBCs
Abnormal membrane : Hereditary Spherocytosis
Abnormal Enzymes : G6PD deficiency
Abnormal Hemoglobin
Deficiency
Thalassemia
Heme
MethemoglobinemiaAltered
Sickle Cell Disease
Globin
Hb Electrophoresis
HPLC
Hb F levels
![Page 10: Pathogenesis & Lab diagnosis of Hemolytic Anemia](https://reader034.vdocuments.site/reader034/viewer/2022050907/55a732391a28ab76028b46e4/html5/thumbnails/10.jpg)
Electrophoretic pattern of Sickle Cell Disease
PJ Russell, iGenetics 3rd ed
![Page 11: Pathogenesis & Lab diagnosis of Hemolytic Anemia](https://reader034.vdocuments.site/reader034/viewer/2022050907/55a732391a28ab76028b46e4/html5/thumbnails/11.jpg)
Functional Assays for sickling
Sickling test:
2% Sodium Metabisulphite reduces oxygen
tension
Induces sickling.
Solubility test:
HbS precipitates in high molarity phosphate
(2.24M) buffer – due to reduced state.
![Page 12: Pathogenesis & Lab diagnosis of Hemolytic Anemia](https://reader034.vdocuments.site/reader034/viewer/2022050907/55a732391a28ab76028b46e4/html5/thumbnails/12.jpg)
Pathophysiology of Thalassemia
Inclusion bodies : β4 inclusion body
Heinz bodies: denatured hemoglobin
Howell Jolly bodies: DNA inclusion body
![Page 13: Pathogenesis & Lab diagnosis of Hemolytic Anemia](https://reader034.vdocuments.site/reader034/viewer/2022050907/55a732391a28ab76028b46e4/html5/thumbnails/13.jpg)
Robbins & Cotran’s Pathological Basis of Disease
![Page 14: Pathogenesis & Lab diagnosis of Hemolytic Anemia](https://reader034.vdocuments.site/reader034/viewer/2022050907/55a732391a28ab76028b46e4/html5/thumbnails/14.jpg)
Electrophoretic pattern of Thalassemia
![Page 15: Pathogenesis & Lab diagnosis of Hemolytic Anemia](https://reader034.vdocuments.site/reader034/viewer/2022050907/55a732391a28ab76028b46e4/html5/thumbnails/15.jpg)
NESTROFT
A screening test for β Thalassemia trait.
Reduced Osmotic Fragility of RBCs.
Normal Osmotic Fragility 0.5 to 0.32%
Negative Positive
DW 0.36% Saline DW 0.36% Saline
Piplani et al., Journal of Clinical and Diagnostic Research, August 2014
![Page 16: Pathogenesis & Lab diagnosis of Hemolytic Anemia](https://reader034.vdocuments.site/reader034/viewer/2022050907/55a732391a28ab76028b46e4/html5/thumbnails/16.jpg)
A word on
Prenatal Diagnosis & Neonatal screening
![Page 17: Pathogenesis & Lab diagnosis of Hemolytic Anemia](https://reader034.vdocuments.site/reader034/viewer/2022050907/55a732391a28ab76028b46e4/html5/thumbnails/17.jpg)
Summary
RBC indices Normal Male Normal female Β Thalassemia
major
Β Thalassemia
trait
Mean
corpuscular
volume (MCV
fl)
89.1±5.01 87.6±5.5 50-70 <79
Mean
corpuscular
hemoglobin
(MCH pg)
30.9±1.9 30.2±2.1 12-20 <27
Hemoglobin
(Hb g/dL)15.9±1.0 14.0±0.9 <7
Males: 11.5-
15.3
Females: 9.1-
14
Galanello R et al., Hemoglobin. 1979
![Page 18: Pathogenesis & Lab diagnosis of Hemolytic Anemia](https://reader034.vdocuments.site/reader034/viewer/2022050907/55a732391a28ab76028b46e4/html5/thumbnails/18.jpg)
Peripheral Smear: Sickle cells – SCD
Target cells, Heinz bodies, Inclusion bodies - Thalassemia
Hb Electrophoresis
Hb variants – Hb F in SCD & Thalassemia major
Hb A2 in Thalassemia minor
Sickling tests.
Genetic Mutational Analysis.
![Page 19: Pathogenesis & Lab diagnosis of Hemolytic Anemia](https://reader034.vdocuments.site/reader034/viewer/2022050907/55a732391a28ab76028b46e4/html5/thumbnails/19.jpg)
Thank You!