1. Red Cell Turnover and Life Span 2.5 million red cells are removed from the circulation every second. BM produces 200 billion new red cells (reticulocytes) each day. These cell survived for 120 days before they are removed by the RES ( BM, liver, spleen). HEMOLYTIC DESORDERS

2. Definition HA is a decrease in the total number of circulating e rythrocytes that is caused by the premature d estruction or removal of red cells from the circulation. Anaemia will result only if the rate of RBC destruction exceed the BM response (uncompensation). HEMOLYTIC ANAEMIA (HA)

3. Haemolytic anaemia cont. Because of erythropoietic hyperplasia and anatomical extension of bone marrow, red cell destruction may be increased several fold before the patient become anaemic --- compensated haemolytic anaemia. The normal adult marrow, after full expansion, is able to produce red cells at 6-8 times the normal rate. Therefore HA may not be seen until the red cell lifespan is less than 30 days.

4. RBC SURVIVAL (days ) Hg produced & degraded ( g/day) Total Hg (g)Hg g/dl. 120 6.7 80016.7 NORMAL 20 40 800 16.7 COMPENSATED 12 40 480 10 HAEMOLYTIC ANAEMIA

5. Classification of HA The HA can be classified in several different ways: 1- Site of haemolysis: Extravascular haemolytic disorders - macrophages of the RES Intravascular haemolytic disorders- within the circulatory system In many of the cases there is a combination of both extra and intravascular haemolysis.

6. Extravascular haemolysis Red cell destruction usually occurs in the cell of the RES.

7. Intravascular haemolysis Destruction of red cells occur inside the blood vessels.

8. Classification of HA 2- Site of defect: Intrinsic defect (intracorpuscular)- structural or functional defect within the red cell. Extrinsic defect (extracorpuscular)- an abnormality in the red cell environment.

9. Classification of HA 3- Inherited or acquired: Inherited HA are usually caused by intrinsic defect. While acquired HA are caused by an extrinsic defect. However there are some exceptions: Paroxysmal nocturnal haemoglobinuria (PNH) which is an acquired intrinsic defect, and severe hereditaryG6PD enz deficiency which requires the presence of an extrinsic trigger such as the antimalarial drug for the intrinsic defect to manifest.

10. Inherited & acquired HA Hereditary HA Membrane defects e.g hereditary spherocytosis Metabolic defect e.g G6PD deficiency. Haemoglobin defects e.g sickle cell disease. Acquired HA Immune - Autoimmune eg AIHA Alloimmune e.g Hemolytic Disease of Newborn, HaemolyticTransfusion Reaction Red cell fragmentation syndromes March haemoglobinaemia Infections Chemical and physical agents. PNH

11. Clinical features Pallor of the mucous membranes Mild fluctuating jaundice Splenomegaly Dark urine Pigmented gall stones. Ulcers around the ankle Aplastic crisis may complicate viral infections. Growth retardation Hypertrophic skeletal changes

12. Leg ulcers in patients with severe congenital haemolytic disorders. e.g sickle cell anaemia

13. Skeletal changes in patients with  thalassaemia.

14. I. signs of excessive RBC destruction: 1-Decrease RBC life span 2-I ncrease catabolism of heme. indirect hyperbilirubinaemia. increase rate of bilirubin production. increase rate of urobilinogen production Laboratory manifestation

15. 3-increase LDH activity 4-Absence of serum haptoglobin. 5-Signs of intra-vascular hemolysis. Hemoglobinaenemia. Hemoglobinuria. Haemosiderinuria. Methemealbuminaemia. Decrease hemopexin Decrease Hb level. Laboratory manifestation cont.

16. Intravascular haemolysis Free Hb will be released from damaged red cells. This free Hb will rapidly saturates plasma haptoglobins. The complex will be removed by the liver. The excess free Hb is filtered by the glomerulus, and free Hb will enter the urine, as iron is released, the renal tubules become loaded with haemosiderin. Methaemalbumin and haemopexin are also found in the process of IV haemolysis.

17. The process of intravascular haemolysis Liberation of free Hb Filtered through the kidney Appear in urine as haemoglobinuria

18. Haemoglobinuria Notice the dark colour of urine compared to the normal colour in the other container. This is a sign of intravascular haemolysis.

19. II. signs of accelerated erythropoiesis : Blood reticulocytosis (polychromasia in the blood film). Macrosytosis. Normoblastaemia. Leukocytosis and thrombocytosis. Bone marrow. Erythroid hyperplasia. Ferrokinetics: increase plasma iron turnover. increase erythrocyte iron turnover II. signs of accelerated erythropoiesis : Blood reticulocytosis (polychromasia in the blood film). Macrosytosis. Normoblastaemia. Leukocytosis and thrombocytosis. Bone marrow. Erythroid hyperplasia. Ferrokinetics: increase plasma iron turnover. increase erythrocyte iron turnover

20. : 1- Morphology (blood film findings): (spherocytes, elliptocytes, acanthocytes, stomatocytes, target cells, fragmented RBCs, Autoagglutination ) 2-Direct coomb’s test. 3-Osmotic fragility test 4-Auto-hemolysis test. 5-Hb-electorphoresis test. 6-Sickling test. 7-Ham’s test. 8-Screening test for G6PD deficiency III. Lab tests useful in the differential diagnosis

23. Reticulocytosis is a feature of increased red cell production. New methylene blue is used to stain the reticulocytes

24. Fragmented cells, and bitten cells are sings of damaged cells occurring in haemolysis

25. Approach to the diagnosis of haemolytic anaemias.

26. Patient’s history Good history is essential to provide guidance for the diagnosis of haemolytic disorders. The following points should not be neglected: Family history--- hereditary conditions, mode of inheritance. Ethnic origin--- G6PD deficiency is most common in Mediterranean and Chinese populations. Past history--- NNJ may be indicative of congenital conditions as HS or G6PD deficiency. Triggering events--- history of drugs, infections

27. Differential diagnosis of hemolytic anaemia Anaemia with increase reticulocyte count *Hemorrhage **Recovry from deficiency of iron,B12, folate. ***Recovery from marrow failure. Anaemia with acholuric jaundice *ineffective erythropoiesis. **Loss of blood in body cavity & tissue. Marrow invasion myoglobinuria