HEMOLYTIC ANEMIA

1)CONSEQUENCES OF RED CELL DESTRUCTION

i)Features of red cell destruction=A= Extra vascular hemolysis –Major .Macrophage
mediated .Liver ,Spleen, Bone marrow are various sites .So increased destruction of red cells
extravascularly causes C/F of ANEMIA,JAUNDICE(Both more pronounce than intravascular) and
SPLENOMEGALY(where extra RBC is destroyed)

Re cell lysis=Heme+GlobinHeme produce bilirubin and Globin leads to amino acid pool increase

B=Intravascular Hemolysis-Minor .In blood vessels. Due to mechanical

injury, parasites, toxins, complement.Hemoglobin forms a complex with Haptoglobin which is cleared by
Mononuclear Phagocyte system. But this being a minor mode of Hb destruction so there is less amount
of Haptoglobin the system so when intravascular Hemolysis increases Haptoglobin is not in sufficient
number to form complex with all increased hemoglobin leading to increased hemoglobin level in blood
causing HEMOGLOBINEMIA which passes in urine causing HEMOGLOBINURIA which is reabsorbed by
the PCT but is toxic to the tubules and so is converted Into HEMOSIDERING leading to
HEMOSIDERINURIA .Also HAPTOGLOBIN level is decreased due to its consumption by Hemoglobin
causing red. SERUM HAPTOGLOBIN levels. The hemolysis leads to NEMIA AND JAUNDICE which is less as
compared to extravascular Hemolysis. So increased destruction of red cells intravascularly causes
HEMOGLOBINEMIA, HEMOGLOBINURIA, HEMOSIDERINURIA, LOW SERUM HAPTOGLOBIN, ANEMIA,
JAUNDICE.

ii) Features of inc red cell production-Retiulocytosis(in PBS),Erythroid hyperplasia(Bone Marrow)

iii) Features of damaged red cells-Microspherocytes ,Ellipsiocytes ,Sickle cells ,Red cell fragments

2)CLASSIFICATION OF HEMOLYTIC ANEMIA

I)HEREDITARY
A) Abnormalities of red cell membrane-Hereditary Spherocytosis,Hereditary ellipsiocytosis

B) a) Enzyme defects-G6PD,Pyruvate Kinase,Hexokinase

b) Hemoglobinopathies-Qualitative(Defect in the GLOBIN CHAIN QUALITY)-Sickle cell disease

Quantitative(Defect in the GLOBIN CHAIN QUANTITY)-Thallasemia
I)ACQUIRED
A) Abnormalities of red cell membrane-PNH(Deficiency of phosphatidyl inositol linked glycoproteins)

B) Antibody mediated-Immune hemolytic Anemias

C) Mechanical trauma to RBC (DIC,TTP,HUS) && Defective cardiac valves

D) Direct toxic effects

E) Splenomegaly

(I)SICKLE CELL ANEMIA

It is a multisystemdisorder that is caused by a single gene mutation.

*ETIOLOGY-Point mutation in cdon 6 ofbetaglobin chain in which GLUTAMIC ACID(HbA) is replaced by

VALINE(HbS) .HbS being insoluble leadsto sickling

*PATOGENESIS-HbS on deoxygenation causes aagregation and polymerizationwhich leadsto HOLLY LEAF

shape or SICKLE CELL shape(Recersibleas adequate oxygeanation causes reversal of sickling to normal
shape) .Upon further deoxyenation and repaeated episodes it leads to damage of RBC Membrane
causing irreversible sickilng and release of hemoglobin in intravascular compartment causing features of
intravascular hemolysis.Microvascular occlusion occurs due to reduceddeformablity of RBCs and
inveased adhesiveness of Sickled cells.

**HbA and HbF decreases sickiling while increased HbC and MCHC increases sickilng.Also
fever,infections,acidosis favour sickling **

*TYPES-2/3rd- XTRAVASCULAR. 1/3rd INTRAVASCULAR

*C/F-(i)Symptoms appear after 6 monhs d/t protective action ofHbF before

(ii) Chronic Hemolysis causing ANEMIA and Chonic Hyperbilirubinemia causing JAUDICE

(iii) CRISIS-a)Vaso-occlusve crisis=Hypoxic injury or infarction causing severe pain.Manifests in

Bones(ONE PAIN), lungs(ACUTE CHEST PAIN) ,liver and spleen(ABDOMINAL PAIN) ,brain(STROKE), penis
(PRIAPISM)

b)Sequestration crisis-In children with intact spleen.massive sequestration of sickled RBC causing
splenomegaly,Hypovolemic shock.

c)Aplastic criisi-Parvovirus B19 infection

d)Hemolytic crisis-Marked fall in hemolysis causes rapid decrease in Hb.

(iv) Prone to infections-D/T splenic hypofunction and defects in alterbate pathway.Infection by H,
influenza and S, pneumonia causing septicemia and meningitis.

(v) Chronic organ damage-