1. HEMOLYTIC ANEMIA
HOSEA NJOKU
1405

2. CLASSIFICATION OF HEMOLYTIC ANEMIA
1. Intrinsic (intracorpuscular) abnormalities
   (A) HEREDITARY
     (i) Membrane abnormalities:  Membrane skeleton: Spherocytosis, Elliptocytosis,
Membrane lipids: Abetalipoproteinemia
     (ii) Enzyme deficiencies: Glycolytic enzymes: pyruvate kinase, hexokinase;
Enzymes of HMP shunt: G-6PD
     (iii) Disorders of Hemoglobin:  Deficient globin synthesis: Thalassemia syndromes;
Structurally abnormal globin: Sickle cell anemia, unstable Hb
   (B) ACQUIRED
    Membrane defect: Paroxysmal Nocturnal Hemoglobinuria
2. Extrinsic (extracorpuscular) abnormalities
   (A) ANTIBODY MEDIATED:  Isohemagglutinins: Transfusion reactions, Erythroblastosis fetalis;
Autoantibodies: idiopathic drug- associated, SLE
   (B) MECHANICAL TRAUMA: Microangiopathic hemolytic anemias: TTP, DIC, Defective cardiac valves
(C) INFECTIONS: Malaria

4. BASIC FEATURES
Abnormal and accelerated destruction of red cells and, in some anemias, their precursors
Increased breakdown of hemoglobin, which may result in:
increased bilirubin level (mainly indirect-reacting) with jaundice
increased fecal and urinary urobilinogen
Hemoglobinemia, methemalbuminemia, hemoglobinuria and hemosiderinuria (where there is significant intravascular hemolysis).
Bone marrow compensatory reaction:
Erythroid hyperplasia with accelerated production of red cells, reflected by reticulocytosis, and slight macrocytosis in peripheral blood
Expansion of bone marrow in infants and children with severe chronic hemolysis - changes in bone configuration visible on X-ray

5. CLINICAL FEATURES OF HEMOLYTIC ANEMIA
PALLOR
JAUNDICE
SPLENOMEGALY

6. GLOBIN > Amino Acids
Heme > Iron and Protoporphyrin
Protoporphyrin > Unconjugated bilirubin.

7. Extravascular Hemolysis
RBC is broken down by the Reticuloendothelial cell > Liver , Spleen, Kidney.
CLINICAL FEATURES OF EH
anemia with splenomegaly
Jaundice with unconjugated bilirubin
Marrow hyperplasia with corrected reticulocyte count of >3%

8. INTRAVASCULAR HEMOLYSIS
Rbc Broken Down In Blood Vessels
Hemoglobin Released
Hb Binds To Haptoglobin
CLINICAL FEATURES
Hemoglobinemia
hemoglobinuria
hemosiderinuria
decreased haptoglobin level in blood.

9. LABORATORY FEATURES -Anemia -reticulocytosis -increased serum iron
-antiglobulin coombs test is positive.

10. -Anisopoikilocytosis, sperocytosis
BLOOD SMEAR
-Anisopoikilocytosis, sperocytosis
-erythroblasts
-schistocytes
BONE MARROW SMEAR
-erythroid hyperplasia

11. PROGNOSIS
The prognosis for patients with hemolytic anemia depends on the underlying cause.
Overall, mortality rates are low in hemolytic anemias. However, the risk is greater in older patients and patients with cardiovascular impairment.
Morbidity depends on the etiology of the hemolysis and the underlying disorder, such as sickle cell anemia or malaria.

12. Heriditary Spherocytosis
Life span of RBC ↓10 to 20 days (normal: 120 days)
Mutations: mostly affect spectrin, ankyrin, band 3,or band 4.2

13. HERIDITARY ELIPTOCYTOSIS
Mutation in spectrin/band 4.1
Intrinsic defect with extravascular hemolysis

14. G6PD DEFICIENCY
GSH PRODUCTION is impaired- GSH is supposed to stop oxidants generated by phagocytes during an infection.
This resuults in hemolysis.
Could also be caused by Fava beans.
Oxidative stress causes the Hb to form heinz bodies.

15. PYRUVATE KINASE DEFICIENCY

16. HEMOGLOBINOPATHIES SICKLE CELL ANEMIA
Mutation in β-globin gene creates sickle hemoglobin (HbS) by the substitution of valine for glutamic acid at the 6th amino acid residue of β-globin

17. SIICKLE CELL ANEMIA…
Severe hemolytic anemia - life span of RBC only 20 days
Microvascular obstructions (Vaso-occlusive crises)
↑ transit time for red cells through the microvasculature (sluggish blood flow in spleen and bone marrow)
90% HbS, 8% HbF, 2% HbA2, (No HbA)

18. INCREASES RISKS FOR SICKLING
Hypoxemia
Acidosis
Dehydration
DECREASES RISKS FOR SICKLING
HbF

20. B- THALASSEMIA Mutations leading to aberrant RNA splicing most common
no mature mRNA, complete failure of β-globin production (β0)
New splice junctions in abnormal positions
normal & abnormal splicing, some normal β-globin mRNA (β+)
In β-globin promoter
↓transcription, some normal β-globin is synthesized (β+)
“Stop” codons - No synthesis of β-globin (β0)
Leading to poorly hemoglobinized RBC

23. A-THALASSEMIA More common in South East Asians and Africans
Deletions involving one or more of the α-globin genes
Severity of disease is proportional to missing α-globin genes

24. Paroxysmal Nocturnal Hemoglobinuria
Intrinsic defect with intravascular hemolysis
In paroxysmal nocturnal hemoglobinuria, hemolysis is due to intravascular complement-mediated destruction of erythrocytes. > lack of CD55.

25. Immunohemolytic Anemias
WARM TYPE ANTIBODIES
COLD TYPE ANTIBODIES

26. WARM TYPE ANTIBODIES CONFIRMATION- Direct coombs test.
Primary (idiopathic)
Secondary:
B cell neoplasms (e.g., chronic lymphocytic leukemia),
Autoimmune disorders (e.g., systemic lupus erythematosus),
Drugs(e.g., α-methyldopa, penicillin, quinidine)
CONFIRMATION- Direct coombs test.

27. COLD TYPE ANTIBODY. IgM against bodies own RBC
Infection- Mycoplasma Pneumonia, Infectious mononucleosis.

29. Hemolytic Disease of the Newborn
Maternal antibodies cross the placenta and react with fetal red cells causing hemolysis of fetal RBCs
Rh Incompatibility: maternal allo-immunization to fetal red cell antigens (D antigen of Rh blood group)
No problems during first pregnancy, but anti-Rh antibodies may cause problems in subsequent pregnancies

30. INFECTION
Malaria- intravascular hemolysis, severly called blackwater fever.

31. TREATMENT Definitive therapy depends on the cause:
Symptomatic treatment can be given by blood transfusion, if there is marked anemia.
In severe immune-related hemolytic anemia, steroid therapy is sometimes necessary.
Sometimes splenectomy can be helpful where extravascular hemolysis, or hereditary spherocytosis, is predominant (i.e., most of the red blood cells are being removed by the spleen

33. References
Current Medical Diagnosis and Treatment 2009 By Stephen J. McPhee, Maxine A. Papadakis page 436