HEMOLYTIC ANEMIA Dr Ramadas Nayak Professor & Head of the department of Pathology Yenepoya Medical College, Mangaluru

Hemolytic anemias Definition Hemolytic anemias are defined as anemias that result due to increase in the rate of red cell destruction. Normal life span of red cells is ~120 days Premature or increased rate of destruction of circulating RBCs- hemolysis. Hemolytic anemias -major feature is reduction in red cell life span which may be as low as 10-15 days.

Hemolytic anemias If the compensatory marrow regeneration (by increased erythropoiesis) is adequate-patient does not manifest anemia-referred to as compensated hemolytic disease. Moderate to marked hemolysis- compensatory mechanisms are not adequate-patients develop clinical features of hemolytic anemias.

Mechanism and Consequences of Hemolysis These may be divided into three major categories. A. Features of Increased Red Cell Destruction B. Features of Increased Red Cell Production C. Damaged Red Cells

A. Features of Increased Red Cell Destruction Normal life span of 120 days Physiological destruction of RBCs takes place mainly (80-90%) extravascularly within the mononuclear phagocytic (RE) cells of the spleen, liver and bone marrow. In hemolytic anemia, there is excessive destruction of RBCs (hemolysis).

A. Features of Increased Red Cell Destruction Increased hemolysis accumulation of hemoglobin degradation products released from lysed RBCs. They result in: Increased unconjugated bilirubin in blood: Jaundice. Increased stercobilinogen in stool causing dark colored stool. Increased urobilinogen in urine leading to high colored urine. Increased iron stores—iron released from heme is stored in bone marrow

A. Features of Increased Red Cell Destruction Site of RBCs destruction: Extravascular or intravascular. Extravascular red cell destruction Major mechanism of destruction of normal RBCs and also in a variety of hemolytic anemias. Destruction occurs within the mononuclear phagocytes of the reticuloendothelial (RE) system. The contents of red cells are not detected in the plasma because it is degraded inside the phagocytic macrophages-hence referred to as extravascular hemolysis (macrophage-mediated hemolysis). Extravascular hemolysis “work” hyperplasia of organs like spleen, liver and bone marrow.

A. Features of Increased Red Cell Destruction Characteristic findings of extravascular hemolysis are: Anemia: Due to excessive destruction of RBCs. Jaundice: Due to excessive production of bilirubin. Splenomegaly: Due to hyperplasia of the mononuclear phagocyte system. With extravascular hemolysis, hemoglobinemia and hemoglobinuria are not observed

Mechanism and Consequences of Hemolysis

A. Features of Increased Red Cell Destruction Intravascular red cell destruction: Minor pathway of normal red cell destruction. Can be a major pathological process in few hemolytic anemias. Hemolysis occurs within the circulation with release of red blood cell contents, including hemoglobin directly into the plasma. Intravascular hemolysis may be caused by mechanical injury (e.g. trauma by heart valves), intracellular parasites (e.g. malarial parasites), complement fixation (e.g. binding of antibodies against red cell antigens) or exogenous toxic injury (e.g. clostridial sepsis).

A. Features of Increased Red Cell Destruction Characteristic findings of intravascular hemolysis are: 1. Hemoglobinemia: Intravascular hemolysis releases free hemoglobin which binds to haptoglobin in plasma. The hemoglobin and haptoglobin complex formed is rapidly cleared by the mononuclear phagocyte system, thus preventing hemoglobin excretion into the urine. 2. Decreased serum haptoglobin: Characteristic of intravascular hemolysis. 3. Hemoglobinuria: When the plasma hemoglobin exceeds the haptoglobin binding capacity, free elevated hemoglobin is detected in the urine (hemoglobinuria). Hemoglobinuria may impart dark red or brown (cola/root beer) color to the urine because of its oxidation to brown colored methemoglobin.

Hemoglobinuria

A. Features of Increased Red Cell Destruction Characteristic findings of intravascular hemolysis are: 4. Hemosiderinuria: In hemoglobinuria of chronic intravascular hemolysis, iron released from hemoglobin may be reabsorbed by the renal proximal tubular cells. Iron accumulates within tubular cells as hemosiderin and can be detected in the urine sediment by Prussian blue reaction. 5. Anemia: Due to excessive destruction of blood cells. 6. Jaundice: Due to excessive production of bilirubin. Known as hemolytic or prehepatic jaundice. 7. Unlike in extravascular hemolysis, splenomegaly is not found. 8. Plasma lactate dehydrogenase (LDH): Increased

B. Features of Increased Red Cell Production Compensatory mechanism to hemolysis increased production of red cells. Anemia +tissue hypoxiaincreased erythropoietin production by kidneystimulates bone marrowcompensatory erythroid hyperplasiaincreased reticulocytes in the peripheral blood

C. Damaged Red Cells Morphological features: These include presence of microspherocytes, elliptocytes, red cell fragments, etc. in the peripheral blood. Red cell survival is shortened

Clinical Features Depend upon the severity, duration and type of hemolytic anemia. Anemia: General symptoms of anemia are fatigue, dyspnea on exertion and tachycardia. Jaundice: Increased bilirubin gives rise to yellowish discoloration of sclera and skin. Splenomegaly: due to increased red cell destruction by phagocytic macrophages (work hyperplasia) of the spleen and also due to foci of extramedullary hematopoiesis. In sickle cell anemia, repeated episodes of splenic infarcts result in autosplenectomy.

Clinical Features Gall stones (cholelithiasis): Excessive excretion of bilirubin in the bile pigment gallstones.. Skeletal deformities: Chronic hemolytic anemia causes persistent marked bone marrow hyperplasia. In children since bones are still developing, it may cause bone deformities. Leg ulcers: Especially in patients with hereditary spherocytosis and sickle cell anemia secondary to stasis.

Laboratory Findings in Hemolytic Anemias Peripheral Blood Hemoglobin: Decreased and varies with the type and duration of hemolytic anemia. Reticulocyte count: Increased.

Laboratory Findings in Hemolytic Anemias Peripheral smear: Most important investigation in hemolytic anemia. RBCs : Markedly increased reticulocyte count-appear as large polychromatophilic red blood cells in the peripheral blood. Nucleated RBCs Red cell morphology provides a clue to the underlying hemolytic disorder like: Spherocyte , sickle cell,

Laboratory Findings in Hemolytic Anemias Peripheral smear: WBCs: Neutrophilia with shift to left and presence of metamyelocytes and myelocytes is seen in active hemolysis. Platelets: In acute hemolysis, there is thrombocytosis with numerous large platelets

Laboratory Findings in Hemolytic Anemias Bone Marrow Not necessary for the diagnosis of hemolytic anemia. Cellularity: increased due to erythroid hyperplasia, Erythropoiesis: Anemia hypoxiaincreased production of erythropoietincauses erythroid hyperplasia -> increased number of erythroid precursors (normoblasts) in the marrow. M:E ratio: Myeloid-erythroid ratio is decreased with a reversal ranging from 1:1 to 1:6.

Note the erythroid hyperplasia

Laboratory Findings in Hemolytic Anemias Extramedullary Hematopoiesis Develops when marrow erythroid hyperplasia is not able to ameliorate moderate to severe anemia because of “ineffective erythropoiesis”. Ineffective erythropoiesis=developing erythroid precursors die within the marrow without producing mature cells. Extramedullary hematopoiesis can appear in the liver, spleen and lymph nodes.

CLASSIFICATION OF HEMOLYTIC ANEMIAS Classified in a variety of ways. Location of hemolysis: intravascular and extravascular Source of defect causing hemolysis: Intrinsic to the red cell itself (intracorpuscular defect) Abnormality outside the red cell (extracorpuscular mechanism). Mode of onset: Hereditary Acquired disorders.

CLASSIFICATION OF HEMOLYTIC ANEMIAS

CLASSIFICATION OF HEMOLYTIC ANEMIAS

What do you have to remember Anemia + Retikulocytosis  bilirubin (unconjugated),  LDH  haptoglobin Haemoglobin and haemosiderin in urine

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