Overview of hemolytic anemia Both Intra and Extravascular

Classification on hereditary and acquired basis as well as Intra and extra vascular Hemolysis
by solomon suasb
mphil student
uhs Lahore Pakistan

1. Overview of Hemolytic Anemia. i-e Intra & Extravascular Hemolysis Usman Ali Shams MLS M-Phil HaematoTechnology University of Health Sciences Lahore

2. Learning Outcomes In the end of the session students will be able to. Describe Normal RBC Destruction Briefly elaborate the Hemolytic Anemias. Classify the hemolytic Anemias. Describe Intra and Extra Vascular Hemolysis

3. Contents Normal RBC Destruction Introduction to Hemolytic Anemia. Classification of Hemolytic Anemia. Acquired and Hereditary Hemolytic Anemia. Intra and Extra Vascular Hemolysis. Classification of Intra and Extravascular Hemolysis.

4. Introduction to RBC Normal Destruction Red cell destruction usually occurs after a mean lifespan of 120 days when the cells are removed extravascularly by the macrophages of the reticuloendothelial (RE) system. The main sites of normal RBC destruction are mainly in marrow but also in the liver and spleen. As we know that RBC has no command center i-e Nucleus, so the RBC metabolism become progressively Worse as enzyme are degraded and finally the cell has no capability of survival.

5. Normal RBC Destruction The breakdown of Haem from hemoglobin liberates iron for recirculation via plasma transferrin mainly to marrow erythroblasts. Protoporphyrin, which is broken down to bilirubin. Bilirubin circulates to the liver where it is conjugated to glucuronides , which are excreted into the gut via bile and converted to stercobilinogen and stercobilin(excreted in feaces ) Stercobilinogen and stercobilin are partly reabsorbed and excreted in urine as urobilinogen and urobilin . Globin chains are broken down to amino acids which are reutilized for general protein synthesis in the body.

6. Normal RBC Destruction Haem Globin Iron Protopho-rphryin AminoAcid Protein Synthesis Marrow Erythroblast Via Transferrin Unconjugated Bilirubin Conjugated Bilirubin RBC Liver Exreted through Gut via Bile Bilirubin Gluconarides Stercobilin Stercobilinogen urobilinogen & urobilin Re-Absorbed In kidey Excreted in Feaces

7. Introduction to hemolytic anemias Hemolytic anemias are defined as anemias that result from an increase in the rate of immature red cell destruction. Because of erythropoietic hyperplasia and anatomical extension of bone marrow, red cell destruction may be increased several‐fold before the patient becomes anemic. The normal adult marrow, after full expansion, is able to produce red cells at 6–8 times the normal rate provided. Therefore, anemia due to hemolysis may not be seen until the red cell lifespan is less than 30 days.

8. Clinical features of Hemolytic Anemia Pallor of the mucous membranes Mild fluctuating jaundice and splenomegaly There is no bilirubin in urine, but this may turn dark on standing because of excess urobilinogen. Pigment (bilirubin) gallstones may complicate the condition Some patients (particularly with sickle cell disease) develop ulcers around the ankle. Aplastic crises may occur, usually precipitated by infection with parvovirus which ‘switches off’ erythropoiesis and are characterized by a sudden increase in anemia and drop in reticulocyte count.

9. Laboratory findings Can be divided into three categories. Features of increased red cell breakdown: (a) serum bilirubin raised, unconjugated and bound to albumin; (b) urine urinobilinogen increased; (c) serum haptoglobins absent because the haptoglobins become saturated with hemoglobin and the complex is removed by RE cells.

10. Features of increased red cell production : (a) Reticulocytosis ; (b) Bone marrow erythroid hyperplasia; the normal marrow myeloid:erythoid ratio of 2 :1 to 12 :1 is reduced to 1:1 or reversed. Laboratory findings CONT….

11. Laboratory findings CONT…. Damaged red cells: morphology (e.g., micro spherocytes, elliptocytes, fragments); osmotic fragility; specific enzyme, protein or DNA tests.

12. Laboratory Finding CONT……..

13. Classification of Hemolytic anemia

14. Classification based on Hereditary & Acquired Causes

15. Hereditary Hemolytic Anemia

16. Acquired Hemolytic Anemia

17. ExtraVascular Hemolysis Extravascular hemolysis occurs when RBCs are phagocytized by macrophages in the spleen, liver and bone marrow. During the normal aging of red blood cells in the circulation, effete RBCs are destroyed by macrophages, i.e. extravascular hemolysis is always occurring to some degree in our body when RBCs have finished living.

18. With extravascular hemolysis, the erythrocytes are degraded within macrophages. Hemoglobin is not released free into the cytoplasm. Thus, we do not see hemoglobinemia or hemoglobinuria with extravascular hemolysis alone, unless it is accompanied by intravascular hemolysis. ExtraVascular Hemolysis

19. ExtraVascular Hemolysis CAUSES Immune-mediated hemolytic anemia . Attachment of IgG or IgM causes fixation of complement (to C3b) on red cell membranes. Erythroparasites .   Mycoplasma haemofelis  (feline infectious anemia) Oxidant injury. Oxidant injury (e.g. acetaminophen toxicity in cats) can result in extravascular hemolysis. Histiocytic disorders. Normal RBC being Destructed by macrophages being stimulated by cytokines. Inherited red blood cell defects, Inherited defects of RBC enzymes (e.g. pyruvate kinase deficiency

20. Intravascular Hemolysis Intravascular hemolysis results from the rupture or lysis of RBC  within  the circulation, i.e. the RBC are lysing  in vivo . In Intravascular haemolysis , free haemoglobin is released which rapidly saturates plasma haptoglobins and the excess free haemoglobin is filtered by the glomerulus. If the rate of haemolysis saturates the renal tubular reabsorptive capacity, free haemoglobin enters urine. Iron released from haemoglobin in the renal tubules is seen as haemosiderin in a urinary deposit.

21. IntraVascular Hemolysis CONT….. Laboratory Features of Intravascular Hemolysis are. 1 Haemoglobinaemia and haemoglobinuria . 2 Haemosiderinuria . 3 Methaemalbuminaemia (detected spectrophotometrically).

22. Mismatched blood transfusion (usually ABO) G6PD deficiency with oxidant stress Red cell fragmentation syndromes Some severe autoimmune haemolytic anaemias Some drug‐ and infection‐induced haemolytic anaemias Paroxysmal nocturnal haemoglobinuria March haemoglobinuria Unstable haemoglobin IntraVascular Hemolysis CAUSES

23. Classification Based on Intra and Extra Vascular Hemolysis

24. Hemolysis on basis of Intra and Extravascular

25. Extravascular Hemolysis CONT…..

26. Extravascular Hemolysis CONT…..

27. Intravascular Hemolysis

28. Thank you