1. Nada Mohamed Ahmed, MD, MT (ASCP)i

2. Objectives Intoduction Definition Classification Intravascular &extra vascular hemolysis Signs of hemolytic anemias Diagnosis of hemolytic anemia

3. Hemolytic Anemia Definition: – anemias which result from an increase in the rate of red cell destruction.

4. Introduction Anemias may result from increased erythrocyte loss or destruction When the rate of destruction exceeds the B.M capacity to produce red cell, anemia results The normal adult marrow, after full expansion, able to increase erythropoietic activity 6-8 times normal This may occur before the patient get anemic (compensated hemolytic disease)

5. HEMOLYTIC ANEMIAS A red blood cell survives 90 to 120 days in the circulation; about 1% of human red blood cells break down each day The spleen is the main organ which removes old and damaged RBCs from the circulation

6. Mechanisms of hemolysis Extravascular red cells destruction occurs in reticuloendothelial system Intravascular red cells destruction occurs in vascular space.

8. Signs of hemolytic anemias Symptoms of anemia – pallor, fatique, rapid pulse Jaundice Splenomegaly

9. Classification of hemolytic anemias 1.Hereditary a)Membrane defect (spherocytosis, elliptocytosis) b)Metabolic defect (Glucoze-6-Phosphate-Dehydrogenaze (G6PD) deficiency, Pyruvate kinase (PK) deficiency) c)Hemoglobinopathies (thalassemias, sickle cell anemia ) 2.Acquired a)Immune hemolytic anemias b)Nonimmune hemolytic anemias

10. Hereditary membrane defects 1.Spherocytosis The most common defect of red cell membrane protein (1/2000 birth) Inheritance - autosomal dominant Deficient of membrane protein causes change of shape (round, no central pallor) Clinical features: jaundice, gallstones, splenomegaly, constitutional Laboratory Diagnosis anemia, hyperbilirubinemia, retikulocytosis,  LDH)lactate Dehydrogenase enzym) - blood smear - microspherocytes - abnormal osmotic fragility test

12. Special test Spherocytes Cells are incubated in decreasing concentrations of NaCl. Spherocytes lyse sooner than normal red cells. osmotic fragility test

13. Hereditary metabolic defect Glucoze-6-Phosphate-Dehydrogenaze (G6PD) deficiency Glucoze-6-Phosphate-Dehydrogenaze (G6PD) deficiency – Hemolysis is induce by infections, drugs,soya beans. – Hemolysis is intravascular

14. Hereditary Hemoglobinopathies Thalassemias Thalassemias definition: Are a group of inherited hematologic disorders caused by defects in the synthesis of one or more of the hemoglobin chains.

15. SICKLE CELL ANEMIA Definition: chronic hemolytic anemia characterized by sickle-shaped red cells caused by homozygous inheritance of Hemoglobin S

16. SICKLE CELL ANEMIA- pathogenesis - Hemolysis - because sickle RBCs are too fragile to withstand the mechanical trauma of circulation - Occlusion in microvascular circulation caused by distorted, inflexible RBCs adhering to vascular endothelium

17. SICKLE CELL ANEMIA

18. 2. Acquired A A. Immune hemolytic anemias 1. Autoimmune hemolytic anemia - caused by warm-reactive antibodies - caused by cold-reactive antibodies 2. Alloimmune hemolytic anemia (transfusion of incompatible blood) B. Nonimmune hemolytic anemias 1. Chemicals 2. Bacterial infections, parasitic infections (malaria) 3. Hemolysis due to physical trauma (e.g. microangiopathic hemolytic anemia) 4. Hypersplenism 5. Paroxysmal nocturnal hemoglobinuria (PNH) unusual acquired hematologic disorder characterized by – Intravascular hemolysis – Bone marrow failure (cytopenias) – Thrombosis.

19. Autoimmune hemolytic anemia - AIHA Laboratory Diagnosis : direct Coombs test (direct antiglobulin test)

20. General Consideration in the Diagnosis Of Hemolytic Anemias In investigating patient with an anemia suspected of being hemolytic, three questions must be answered: 1.Is the anemia hemolytic? 2.If so, is the site of red cell destruction intravascular or extravascular? 3.What is the etiology?

21. Laboratory findings The lab. Findings are divided into 2 groups: 1- Features of increased red cell breakdown. 2- Features of increased red cell production.

22. Laboratory findings 1- Features of increased red cell breakdown: Raised Serum bilirubin, unconjugated and bound to albumin. Increased urine urobilinogen. Increased faecal stercobilinogen. Absent Serum.haptoglobins (saturated with Hb and removed by the RE cells).

23. Laboratory findings 2-Features of increased red cell production: Reticulocytosis Bone marrow erythroid hyperplasia. Circulating nucleated red cells

24. Reticulocytosis is a feature of increased red cell production.

25. Laboratory tests useful in differential diagnosis Examination of peripheral blood Special Lab. Examinations for speacial type of hemolytic anemia.

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