HEMOLYTIC ANEMIA. 8 th 12 March 2014 Approach to hemolytic diseases. waseem al tameemi

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2 HEMOLYTIC ANEMIA 8 th 12 March 2014 Approach to hemolytic diseases 2

3 Learning objectives To be able to define haemolysis and haemolytic anaemia To be able to classify haemolytic anaemias To understand the difference between intravascular and extravascular haemolysis to recognize the clinical & laboratory features of hemolytic anemia 3

4 Approach to hemolytic diseases HEMOLYTIC ANEMIA anemia which result from an increase in the rate of red cell destruction (decreased red cell lifespan) RBCs are destroyed faster than the bone marrow can produce them. 4

5 Hemolytic anemia Manifestation Features of Increased Red Cell Destruction & Features of Increased Red Cell Production : compensatory vigorous blood regeneration. 5

6 Pathophsiology 1. Increased RBC destruction-anemia 2. Release of RBC contents- breakdown of Hb. catabolism to bile pigment- jaundice. 3. Unconjugated is water insoluble (indirect hyperbiliurbinemia) - not cross GFRacholuric jaundice 4. Increase conjugation in liver pigmented stones 5. Increase marrow erythroid activity- reticulocytosis. 6. marrow expansion &hyperplasia- bone &skeletal changes 6

7 Classification On clinical presentation; Acute (favism) Chronic (spherocytosis) Acute attack over chronic disorders On site of hemolysis Intravscular (incompatibility, PNH, favism) Extravascular: (HS, thalassemia,immune) 7

8 Extravascular haemolysis 8

9 Extravascular haemolysis It is the major pathogenetic mechanism of hemolysis in a variety of hemolytic anemias Anemia Jaundice Splenomegaly: No evidence of hemoglobinemia and hemoglobinuria 9

10 Intravascular haemolysis is the minor pathway of red cell destruction Hemoglobinemia Decreased serum haptoglobin Hemoglobinuria Hemosiderinuria splenomegaly is not found Anemia Jaundice 10

11 Classification On defect site Intrinsic-intracorpusclarstructural or functional defect within the red cell sickle cell anemia and Glucose-6- Phosphate Dehydrogenase deficiency. (G6PD) Extrinsic- extracorpuscularabnormality in the red cell environment (Marche hemoglobinuria,burn,infect) 11

12 Classification On etiology (most useful) Inherited disorders I. Genetic defect of hemoglobin ( SCD,Thalas. Unstable Hb.) II. Abnormal RBC membrane (elliptocytosis,hs) III.Abnormal RBC metabolism-enzyme deficiency- (G6PDdeficiency, pyruvate kinase deficiency) 12

13 Classification Acqiured disorders I. Immune HA (incompatibility, HDN, AIHA) II. Traumatic &microangiopathic hemolysis (prosthetic valves,hus,ttp,dic) III.Infection (malaria,clostridial) IV. Chemicals,drugs,venoms V. Physical injury,thermal,marche hemoglobinuria 13

14 Clinical features of HA 1. Anemia; chronic congenital- mild,moderate. Acute attack severe 2. Jaundice; mild, if severe : risk in neonates-kerinkterus. No bilirubin in urine (acholuric jaundice). 3. Splenomegaly; extravascular destruction. 4. Cholethiasis; black multiple small bile stones. Biliary colic,cholangitis or Asymptomatic 14

15 Clinical features of HA 5. Aplstic crisis; chronic congenital hemolysis. Transient arrest in RBC production due to parvo virus B19 infection 6. Leg ulcers; chronic congenital hemolysis, sluggish flow in capillaries. HS&SCD. 7. Skeletal changes; skull bossing, zygomatic prominence, maxillary,dental abnormalities. Enlarging metacarpals bones 15

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18 Laboratory features 1. Excess RBC destruction 1. Increase S.bilirubin (indirect) <5mg/dl 2. Increase S.LDH 3. Low S. haptoglobin. 4. Increase urobilinogen in urine, no bilirubin in urine. 18

19 Laboratory features 2. Intravascular hemolysis 1. Hemoglobinemia;red color plasma 2. Hemoglobinuria; pink dark color urine ( no microscopic RBC) 3. Haemosiderinuria; proximal tubules re absorption 4. Met-hemoglobinemia & Methemalbuminemia; coffee brown plasma 19

20 Laboratory features 3. Accelerated erythropoiesis 1. Reticulocytosis. 2. Polychromasia,macrocytosis, nucleated RBC, 3. Thrombocytosis,leucocytosis. 4. BM erythroid hyperplasia 20

21 Laboratory features 4. Radiological features Widening of marrow cavity, thinning of cortex separation between cortices Prominent trabecualae Hair on end appearance 21

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24 Erythrocyte membrane structure 24

25 Erythrocyte membrane defect Disturbances (quantities or function); RBC destruction (extravascular) in spleen hemolysis or loss of part of membrane in relation to volume (abnormal shape) & reduced survival Classification according to shape; (spherocyte, elleptocyte, stomatocyte) 25

26 Hereditary spherocytosis most common hereditary membrane defect Deficiency in β spectrin or anykrin Autosomal dominant,75%,+ve FH Presentation 1. At childhood, commonly manifested, as chronic mild moderate HA Anemia, jaundice, gall stone, splenomegaly,bone changes 2. At neonatal,prolonged neonatal jaundice (1 st wk) 3. Delayed presentation at adulthood (6 th decade) 4. Asymptomatic until pregnancy 26

27 Hereditary spherocytosis It is chronic mild compensated hemolysis, may exacerbated by attack of haemolytic crisis: acute severe (infection, vaccination). Aplastic crisis Megaloblastic crisis Leg ulcers 27

28 investigation Features of extravascular hemolytsis CBC; anemia,spherocytes, polychromasia, reticulocytosis Osmotic fragility test; increased sensitivity to lysis if incubated in hypotonic saline. (diagnosis & screen) 28

29 spherocytosis 29

30 Osmotic fragility test 30

31 Differential diagnosis Any cause of sperocytosis 1. Immune hemolytic anemia; +ve Coomb s 2. HDN (neonatal jaundice) Treatment: 1. Folic acid ;1mg/day -5mg/week. Life long. Alleviate anemia & prevent megloblastic anemia 2. Blood transfusion in acute hemolytic complication. 3. Exchange transfusion in neonate 4. splenectomy. 31

32 splenectomy o Correct anemia, improve RBC survival, relieve jaundice Indications: 1. very severe chronic hemolysis 2. recurrent acute hemolytic crisis or acute aplastic crisis. 3. cholecystitis or biliary colic. 4. death in affected family member. 32

33 Preparation & complications o Delayed after 9-10 yrs. o preoperative vaccine against encapsulated mo Streptococcus pneumonia Hemophilius influenza. Neisseria meningitidies & influenza o Followed by long term prophylaxis. Surgical complications Risk of infection, sepsis, malaria, Thrombocytosis ; risk of thrombosis. Pulmonary hypertension 33