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

2. 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 days.

3. 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.

4. 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

5. 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).

6. 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

7. 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.

8. 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

9. Mechanism and Consequences of Hemolysis

10. 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).

11. 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.

12. Hemoglobinuria

13. 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

15. 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

16. 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

17. 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.

18. 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.

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

20. 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,

21. 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

22. 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.

23. Note the erythroid hyperplasia

24. 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.

25. 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.

26. CLASSIFICATION OF HEMOLYTIC ANEMIAS

27. CLASSIFICATION OF HEMOLYTIC ANEMIAS

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

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