HEREDITARY SPHEROCYTOSIS & APLASTIC ANEMIA

1. HEREDITARY SPHEROCYTOSIS & APLASTIC ANEMIA Dr.Sridevi.H.B

2. HEREDITARY SPHEROCYTOSIS

3. Overview of HS Introduction Pathogenesis Morphology Clinical features

4. Introduction A type of hemolytic anemia Prevalence of HS is highest in northern Europe, where rates of 1 in 5000 are reported. An autosomal dominant inheritance pattern is seen in about 75% of cases.

5. Overview Introduction Pathogenesis Morphology Clinical features

6. Normal red blood cells

8. Pathogenesis of HS Inherited disorder caused by intrinsic defects in the red cell membrane skeleton That render red cells spheroid, less deformable, Red cells becomes vulnerable to splenic sequestration and destruction.

9. Pathogenesis of HS HS is caused by diverse mutations that lead to an insufficiency of membrane skeletal components. As a result of these alterations, the life span of the affected red cells is decreased on average to 10 to 20 days from the normal 120 days. The pathogenic mutations most commonly affect ankyrin, band 3, spectrin, or band 4.2, the proteins involved in the first of the two tethering interactions, presumably because this complex is particularly important in stabilizing the lipid bilayer.

12. Overview Introduction Pathogenesis Morphology Clinical features

13. Morphology of HS Spherocytosis, apparent on smears as abnormally small, dark-staining (hyperchromic) red cells lacking the central zone of pallor Distinctive but not pathognomonic, since other forms of membrane loss, such as in autoimmune hemolytic anemias, also cause the formation of spherocytes.

14. Jaundice Red cells span decreased Increased heme conversion to BR Red cell loss in spleen Increased iron extracted during red cell destruction Feedback to the bone marrow to produce more red cells Hemosiderosis Erythroid hyperplasia More immature RBCs enter circulation Reticulocytosis

15. Morphology of HS Cholelithiasis (pigment stones) occurs in 40% to 50% of affected adults. Moderate splenic enlargement is characteristic (500–1000 gm); in few other hemolytic anemias is the spleen enlarged as much or as consistently. Splenomegaly results from congestion of the cords of Billroth and increased numbers of phagocytes needed to clear the spherocytes.

16. Her. Spherocytosis:

18. Overview Introduction Pathogenesis Morphology Clinical features

19. Clinical fearures of HS The diagnosis is based on family history, hematologic findings, and laboratory evidence. In two thirds of the patients the red cells are abnormally sensitive to osmotic lysiswhen incubated in hypotonic salt solutions, which causes the influx of water into spherocytes with little margin for expansion. HS red cells also have an increased mean cell hemoglobin concentration, due to dehydration caused by the loss of K+ and H2O.

20. Clinical fearures of HS The generally stable clinical course is sometimes punctuated by aplastic crises, usually triggered by an acute parvovirus infection. Parvovirus infects and kills red cell progenitors, causing red cell production to cease until an effective immune response commences, generally in 1 to 2 weeks. Because of the reduced life span of HS red cells, cessation of erythropoiesis for even short time periods leads to sudden worsening of the anemia.

21. Clinical fearures of HS Transfusions may be necessary to support the patient until the immune response clears the infection. Hemolytic crises are produced by intercurrent events leading to increased splenic destruction of red cells (e.g., infectious mononucleosis); these are clinically less significant than aplastic crises. Gallstones, found in many patients, can also produce symptoms. Splenectomy treats the anemia and its complications, but brings with it the risk of sepsis.

22. APLASTIC ANEMIA

23. Overview of Aplastic anemia Introduction Etiology Pathogenesis Morphology Clinical features Treatment

24. Introduction Refers to a syndrome of chronic primary hematopoietic failure and attendant pancytopenia Anemia, neutropenia, and thrombocytopenia In the majority of patients autoimmune mechanisms are suspected Inherited or acquired abnormalities of hematopoietic stem cells also seem to contribute

25. Overview of Aplastic anemia Introduction Etiology Pathogenesis Morphology Clinical features Treatment

26. Etiology of aplastic anemia Idiopathic:: Primary Stem cell defect, Immune Dose related Drug effect:: Alkylating, Antimetabolites, Benzene, Chloramphenicol, Arsenic Idiosyncratic Drug effect:: Chloramphenicol, Phenylbutazone, Phenytoin, Streptomycin, CPZ, DDT Irradiation Viral etiology:: Hepatitis, CMV, EBV, Herpes Inherited:: Fanconi Anemia

27. Overview of Aplastic anemia Introduction Etiology Pathogenesis Morphology Clinical features Treatment

28. Pathogenesis of aplastic anemia Not fully understood. Unlikely that a single mechanism underlies all cases. Two major etiologies have been invoked: An extrinsic, immune-mediated suppression of marrow progenitors; An intrinsic abnormality of stem cells

30. Overview of Aplastic anemia Introduction Etiology Pathogenesis Morphology Clinical features Treatment

31. Morphology of aplastic anemia Markedly hypocellular bone marrow largely devoid of hematopoietic cells Only fat cells, fibrous stroma, and scattered lymphocytes and plasma cells remain. Marrow aspirates often yield little material (a “dry tap”) Aplasia is best appreciated in marrow biopsies

32. Morphology of aplastic anemia Granulocytopenia and thrombocytopenia Systemic hemosiderosis can appear due to multiple transfusions The red cells are usually slightly macrocytic and normochromic. Reticulocytopenia is the rule.

33. Morphology of aplastic anemia

34. Overview of Aplastic anemia Introduction Etiology Pathogenesis Morphology Clinical features Treatment

35. Clinical features of aplastic anemia Can occur at any age and in either sex. Onset is usually insidious. Initial manifestations vary somewhat, depending on which cell line is predominantly affected, Pancytopenia ultimately appears, with the expected consequences.

36. Clinical features of aplastic anemia Anemia : progressive weakness, pallor, and dyspnea; Thrombocytopenia:petechiae and ecchymoses Neutropenia: frequent and persistent minor infections or the sudden onset of chills, fever, and prostration. Splenomegaly is characteristically absent; if it is present, the diagnosis of aplastic anemia should be seriously questioned.

37. Overview of Aplastic anemia Introduction Etiology Pathogenesis Morphology Clinical features Treatment

38. Treatment of aplastic anemia The prognosis is variable. Bone marrow transplantation is the treatment of choice in those with a suitable donor Provides a 5-year survival of over 75%. Older patients or those without suitable donors often respond well to immunosuppressive therapy.