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Extravascular Hemolysis

  • Hemolysis predominantly at Spleen

1.Hereditary Spherocytosis

  • Genetic Problem Problem in maintaining Bi-concave Shape of RBC

  • Autosomal Dominant Ankyrin 80% patients

  • Autosomal Recessicve SPectrin mutation
  • Band 3 mutation ➡️ Pincer cells/Mushroom cells
  • High risk on B19 infection ➡️ Apalstic Crisis

graph TD
    X1[Autosomal dominant Ankyrin defect] 
    X2[Autosomal recessive Spectrin defect ] 
    X3[Band 3 defect  ]
    X1 ==>X
    X2 ==> X
    X3 ==> X

    X[Spherocytes] ==> xa[Small blebs in RBC membrane ]
    xa ==> Xb[ membrane Eaten by macrophages]
    Xb ==> x1c[Older cells ➡️ small in size
    New RBC ➡️ larger in size]
    X ==>|Spherical RBC enters Spleen cell | X1a[stuck  spleen sinusoids]
    X1a ==> X1ab[Hemolysis]

labs

  • Spherical RBC(Spherocytes in RBC)
  • Jaundice ( ⬆️ unconjucated bilirubin)
  • Gall stones(Gall bladder concentrating bilirubin)
  • ⬆️ RDW (older cell more damage than new cells)
  • ⬆️ MCHC (⬇️ in RBC size but same Hemoglobulin ,increase the Concentration per size of cell)
  • Splenomegaly (macrophages hypertrophy for destruction)

Diagnostic test

  • Osmotic Fragility test

    add hypotonic solution to RBC > Normal RBC burst at 0.5-0.3 % nacl concentration > Structural protein deficiency ➡️ cell burst at 0.5% -0.7% NACl concentration

Treatment

  • Splenectomy (site of Hemolysis) ➡️ Howel-Jelly bodies RBC with nucelus presence

2.Sickle Cell anemia

  • Missese mutation of beta-chain on Chromosome 11 ,leads to switching Glutamic acid to Valine amino acids on Translation

  • When 2 abnoraml Beta genes are present

Thalassemia Sickle Cell anaemia
Type of Muttion Abnormal mutation Mis-sense mutation
Effect of Mutation low/No Beta- chain expression Glutamic Acid to Valine
Diseases Microcytic Hypochromic Anemia, Hemolysis by spleen only Hemolytic anemia
Special Symptoms ChipMunk face ,Crew cut
  • HbS[alpha2,sickled beta2] RBC gets Sickled on
  • Acidosis
  • Hypoxia

  • Dehydration

  • Then back to Normal shape on Oxygenation

graph TD
    X11[Normal Shaped HbS RBC]
    X11 ==>|Acidosis
    Hypoxia
    Dehydration| X1a[Sickling]
    X1a ====>|Oxygenation| X11;
    X1a -.-> |Cannot withhold stress of Sickling and Unsickling| X1n[Intravascular hemolysis];
    X1a ==>|into spleen| X1aa[Stuck in sinusoids ]
    X1aa ==> X1aab[Hemolysis]
    X1a -.-> X22[Permanent Sickling];
    X22 ===> X22a["`Vaso-occlusion`"];
    X22a ==> ya[Dactilitis] & yn[Auto-splenctomy] & yw[Acute Chest Syndrome]  & yy[Renal Papillary Necrosis];
  • Vaso-occlusion of Permananet Sickled RBC
  • Dactylitis vado-occlusive infarcts on bones (swelling of hands and foots at 6months of age)
  • M/C death in Kids Auto-splenectomy (Obstruction of Spleen vessels ➡️ fibrotic spleen), Howell Jolly bodies as no spleen ,Risk of encapsulated organism infection(no germinal centre region to produce Antibodies)
  • *** M/C death in adults* Acute Chest Syndrome ➡️ Chest Pain,Shortness of breath

    Pneumonia ➡️ Vasodilation ➡️ Sickling of RBC ➡️ obstruction of Pulmonary Vessels .

  • Renal Papillary necrosis

Sickle Trait [alpha2, 1 sickle beta- 1 normal beta]

  • < 50 % HbS,so no sickling in blood vessels
  • Except in renal mudulla sickling due to hypoxia,Hypotonicity ➡️ micro infraction in renal medulla ➡️hematuria.

Labs

  • Target cell (shape problem)
  • Sickle cell
  • No sickle or Target cell in Sickle Trait
  • Diagnosis Sickle train HbA[alpha2, 1sickle beta - 1 normal beta] add Metabisulphate leads sickle trait cell to sickle.
  • Electrophorosis HbS [ 90% HbS,8% HbF,2% HbA2] ,Sickle Trait [55% HbA,43% HbSickle, 2% HbA2]

Treatment

  • Hydroxyurea (⬆️ HbF synthesis)

Hemoglobin C

  • AR mutation of beta chain , Glutamic acid to Lysine
  • less common
  • mild anemia
  • HbC crystal in smear (like H.pylori rod shaped)