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HEMOLYTIC ANEMIA

8th

12 March 2014

Approach to hemolytic diseases

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Learning objectives

✓ To be able to define haemolysis and haemolytic anaemia

✓ To be able to classify haemolytic anaemias

✓ To understand the difference between intravascular and extravascular haemolysis

✓ to recognize the clinical & laboratory features of hemolytic anemia

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Approach to hemolytic diseases

HEMOLYTIC ANEMIA

anemia which result from an increase in the rate of red cell destruction

(decreased red cell lifespan)

RBCs are destroyed faster than the bone marrow can produce them.

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Hemolytic anemia

Manifestation

Features of Increased Red Cell Destruction &

Features of Increased Red Cell Production : compensatory vigorous blood regeneration.

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Pathophsiology

1. Increased RBC destruction-anemia

2. Release of RBC contents- breakdown of Hb. –catabolism to bile pigment- jaundice.

3. Unconjugated is water insoluble (indirect hyperbiliurbinemia) - not cross GFR-acholuric jaundice

4. Increase conjugation in liver –pigmented stones

5. Increase marrow erythroid activity- reticulocytosis.

6. marrow expansion &hyperplasia- bone &skeletal changes

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Classification

On clinical presentation;

Acute (favism)

Chronic (spherocytosis)

Acute attack over chronic disorders

On site of hemolysis

Intravscular

(incompatibility, PNH, favism)

Extravascular:

(HS, thalassemia,immune)

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Extravascular haemolysis

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Extravascular haemolysis

It is the major pathogenetic mechanism of hemolysis in a variety of hemolytic anemias

Anemia

Jaundice

Splenomegaly:

No evidence of hemoglobinemia and hemoglobinuria

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Intravascular haemolysis

is the minor pathway of red cell destruction Hemoglobinemia

Decreased serum haptoglobin

Hemoglobinuria

Hemosiderinuria

splenomegaly is not found

Anemia

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Classification

On defect site

Intrinsic-intracorpusclar-

structural or functional defect within the red cell

sickle cell anemia and Glucose-6-Phosphate Dehydrogenase deficiency. (G6PD)

Extrinsic- extracorpuscular-

abnormality in the red cell environment(Marche hemoglobinuria,burn,infect)

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Classification

On etiology (most useful)

Inherited disorders

I. Genetic defect of hemoglobin ( SCD,Thalas. Unstable Hb.)

II. Abnormal RBC membrane (elliptocytosis,HS)

III.Abnormal RBC metabolism-enzyme deficiency- (G6PDdeficiency, pyruvate

kinase deficiency)

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Classification

Acqiured disorders

I. Immune HA (incompatibility, HDN, AIHA)

II. Traumatic &microangiopathic hemolysis (prosthetic valves,HUS,TTP,DIC)

III.Infection (malaria,clostridial)

IV. Chemicals,drugs,venoms

V. Physical injury,thermal ,marche hemoglobinuria

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Clinical features of HA

1. Anemia; chronic congenital- mild ,moderate. Acute attack – severe

2. Jaundice; mild, if severe : risk in neonates-kerinkterus. No bilirubin in urine (acholuric jaundice).

3. Splenomegaly; extravascular destruction.

4. Cholethiasis; black multiple small bile stones. Biliary colic ,cholangitis or Asymptomatic

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Clinical features of HA

5. Aplstic crisis; chronic congenital hemolysis. Transient arrest in RBC production due to parvo virus B19 infection

6. Leg ulcers; chronic congenital hemolysis, sluggish flow in capillaries. HS&SCD.

7. Skeletal changes; skull bossing, zygomatic prominence, maxillary ,dental abnormalities. Enlarging metacarpals bones

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Laboratory features

1. Excess RBC destruction

1. Increase S.bilirubin (indirect) <5mg/dl

2. Increase S.LDH

3. Low S. haptoglobin.

4. Increase urobilinogen in urine, no bilirubin in urine.

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Laboratory features

2. Intravascular hemolysis1. Hemoglobinemia;red color plasma

2. Hemoglobinuria; pink –dark color urine ( no microscopic RBC)

3. Haemosiderinuria; proximal tubules re absorption

4. Met-hemoglobinemia & Met-hemalbuminemia; coffee brown plasma

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Laboratory features

3. Accelerated erythropoiesis

1. Reticulocytosis.

2. Polychromasia,macrocytosis, nucleated RBC,

3. Thrombocytosis,leucocytosis.

4. BM erythroid hyperplasia

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Laboratory features

4. Radiological featuresWidening of marrow cavity,

thinning of cortex separation between cortices

Prominent trabecualae

Hair on end appearance

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Erythrocyte membrane structure

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Erythrocyte membrane defect

Disturbances (quantities or function); RBC destruction (extravascular) in spleen –hemolysis or loss of part of membrane in relation to volume (abnormal shape) & reduced survival

Classification according to

shape; (spherocyte , elleptocyte, stomatocyte)

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Hereditary spherocytosis

most common hereditary membrane defect

Deficiency in β spectrin or anykrin

Autosomal dominant,75%,+ve FH

Presentation1. At childhood, commonly manifested, as chronic mild –

moderate HA

Anemia, jaundice, gall stone, splenomegaly,bone changes

2. At neonatal ,prolonged neonatal jaundice (1st wk)

3. Delayed presentation at adulthood (6th decade)

4. Asymptomatic until-----------pregnancy

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Hereditary spherocytosis

It is chronic mild compensated hemolysis, may exacerbated by attack of

haemolytic crisis: acute severe (infection, vaccination).

Aplastic crisis

Megaloblastic crisis

Leg ulcers

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investigation

Features of extravascular hemolytsis

CBC; anemia ,spherocytes, polychromasia, reticulocytosis

Osmotic fragility test; increased sensitivity to lysis if incubated in hypotonic saline. (diagnosis & screen)

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spherocytosis

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Osmotic fragility test

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Differential diagnosis

Any cause of sperocytosis

1. Immune hemolytic anemia; +ve Coomb’s

2. HDN (neonatal jaundice)

Treatment:1. Folic acid ;1mg/day -5mg/week. Life long.

Alleviate anemia & prevent megloblastic anemia

2. Blood transfusion in acute hemolytic complication.

3. Exchange transfusion in neonate

4. splenectomy .31waseem al tameemi

splenectomy

o Correct anemia, improve RBC survival, relieve jaundice

Indications:

1. very severe chronic hemolysis

2. recurrent acute hemolytic crisis or acute aplastic crisis.

3. cholecystitis or biliary colic.

4. death in affected family member.

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Preparation & complications

o Delayed after 9-10 yrs.

o preoperative vaccine against encapsulated mo Streptococcus pneumonia

Hemophilius influenza.

Neisseria meningitidies

& influenza

o Followed by long term prophylaxis.

Surgical complications

Risk of infection, sepsis, malaria,

Thrombocytosis ; risk of thrombosis.

Pulmonary hypertension

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