APPROACH TO A PATIENT WITH HEMOLYTIC ANEMIA By Dr. Ramlah Hasan H.O MU-II

1. APPROACH TO A PATIENT WITH HEMOLYTIC ANEMIA By Dr. Ramlah Hasan H.O MU-II

2. Definition Hemolytic are a group of disorders characterised by shortened survival of RBCs in circulation .

3. An introduction Consequences of hemolysis Shortening of red cells survival does not always cause anemia as there is a compensatory increase in red cell production by the bone marrow.If the red cell loss can be contained within the marrow�s capacity for increased output,then a hemolytic state can exist without anemia (compensated hemolytic disease). The bone marrow can increase its output by 6 to 8 times by increasing the proportion of cells committed to erythropoiesis (erythroid hyperplasia) and by expanding the volume of active marrow. In addition, immature cells (reticulocytes) are released prematurly.

4. Sites of hemolysis Extra vascular hemolysis In most hemolytic conditions red cell destruction is extra vascular. The red Cells are removed from the circulation by macrophages in the reticuloendothelial system, particularly the spleen.

5. Sites of Hemolysis (contd.) Intra vascular Hemolysis When red cells are rapidly destroyed within the circulation Hb is liberated. This is initially bound to plasma haptoglobin but these soon become saturated. Excess free plasma Hb is filtered by the glomerulus and enters the urine, although small amounts are reabsorbed by the renal tubules. In the renal tubular cells Hb is broken down and becomes deposited in the cells as haemosiderin.

6. Classification of Hemolytic Anemias Intra corpuscular Hereditary Membrane Defects Hereditary Spherocytosis Hereditary Elliptocytosis Enzyme Deficiency G6PD Deficiency Pyruvate Kinase Deficiency Haemoglobinopathies Sickle Cells Anemia Unstable Haemoglobins Acquired Paroxysmal Nocturnal Haemoglobinuria

7. Classification of Hemolytic Anemias Extra corpuscular Autoimmune Hemolytic Anemias Associated with warm antibodies Associated with cold antibodies Isoimmune Hemolytic Anemias Drug induced Hemolytic Anemias Infections Plasmodiam, Clostridium Microangiopathic Hemolytic Anemias Hypersplenism

8. Clinical Approach History Examination Investigation Treatment

9. History Age Hemolytic anemia can occur at any age. Hereditary disorders usually are evident early in life. AIHA is more likely to occur in middle-aged and older individuals. Sex Most cases of hemolytic anemia are not specific to any gender. Autoimmune hemolytic anemia (AIHA) is slightly more likely to occur in females than in males. G-6-PD deficiency is an X-linked recessive disorder. Males usually are affected, and females are carriers

10. History (contd.) Symptoms Pallor, Fatigue, Worsening of preexisting, angina, Palpitation, Postural dizziness Mottled or Numb fingers or toes Pigment gall stone Reddish Brown first morning urine Symptoms due to splenomegaly like dragging sensation in abdomen Acute painful episode include the bones (especially the back and long bones) and the chest.

11. History (contd.) Family History Positive Medical History for Associated Diseases Drug Hsitory Analgesics Anti-malarials Anti-bacterials

12. Examination Pallor Jaundice Tachycardia Flow murmurs Signs of congestive cardiac failure Poorly healing ulcers over lower tibia Splenomegaly Cholelithiasis

13. Investigations Blood Complete Picture Hb ? or N TLC PLT Red Cell Indices MCV MCHC Reticulocytosis Bone Marrow Examination Erythroid Hyperplasia Serum Levels Bilirubin The level of unconjugated bilirubin never exceeds 4 to 5 mg/dl. Haptoglobin Plasma Haemoglobin Lactate Dehydrogenase Positive Urinary Haemosiderin

14. Peripheral Blood Film

15. Hereditary Spherocytosis

16. Sickle Cell Anemia

17. Other Investigations Osmotic fragility test Specific enzymatic assays Hb electrophoresis

18. Evaluation of Hemolysis

19. Treatment More than 200 types of hemolytic anemia exist, and each type requires specific treatment. Therefore, only the aspects of medical care relevant to most cases of hemolytic anemia are discussed. Transfusion therapy Avoid transfusions unless absolutely necessary, but they may be essential for patients with angina or severely compromised cardiopulmonary status. Administer packed RBC slowly to avoid cardiac stress. In AIHA, type matching and crossmatching may be difficult. Use the least incompatible blood if transfusions are indicated. The risk of acute hemolysis of transfused blood is high, but the degree is dependent on the rate of infusion. Slowly transfuse by administering half units of packed red cells to prevent rapid destruction of transfused blood. Discontinuing medications Discontinue penicillin and other agents that can cause immune hemolysis and oxidant medication such as sulfa drugs

20. Treatment (contd.) Administer folic acid because active hemolysis may consume folate and cause megaloblastosis. Corticosteroids are indicated in AIHA. IV immunoglobulin G (IgG) has been used for patients with AIHA, but only a few patients have responded, and the response has been transient. Iron therapy This is indicated for patients with severe intravascular hemolysis in which persistent hemoglobinuria has caused substantial iron loss. Before iron is administered, document the iron deficiency by serum iron studies and, possibly, by assessing iron stores in bone marrow aspirates. Because iron stores increase in hemolysis, iron administration generally is contraindicated in hemolytic disorders, particularly those that require chronic transfusion support.

21. Treatment (contd.) Surgical Care: Splenectomy may be the first choice of treatment in some types of hemolytic anemia such as hereditary spherocytosis. In other cases, it is recommended when other measures, such as in AIHA, have failed. Splenectomy usually is not recommended in hemolytic disorders such as cold agglutinin hemolytic anemia. Immunize against infections with encapsulated organisms, such as Haemophilus influenzae and Streptococcus pneumoniae, as far in advance of the procedure as possible.

22. Points to Remember Peripheral smear is the most important initial investigation and Coombs test with anti-IgG and anti-complement in diagnosing hemolytic anemia.