Introduction to

Hemolytic Anemias
HEMOLYTIC ANEMIAS
Introduction
 Definition
 Classification
 Pathogenisis
 General clinical features
 Laboratory evaluation of hemolysis
Hemolytic Anemias
Definition
 A group of disorders leading to anemia
caused by a reduction in red cell life span.
 RBC’s normally survive 60 - 120 days .
 Bone marrow has the capacity to increase
erythropoiesis 6 - 8 times than normal.
 Anemia is the result of premature
destruction of red cells exceeding the
erythropoietic capacity of the bone
marrow.
Hemolytic Anemias
Classification
 Hemolytic anemias may be classified as

I- Hereditary or acquired
or
II- Intracorpuscular or Extracorpuscular
Hemolysis may occur in two compartments
I- Intravascular
or
II- Extravascular ( eg: spleen )
 CLASSIFICATION

INTRA CORPUSCULAR EXTRA CORPUSCULAR

•Haemoglobinopathies •Familial hemolytic

•Enzymopathies uremic syndrome
HERIDITARY •Membrane cytoskeleton
defect

•Paroxysmal nocturnal •Mechanical

haemoglobinuria(PNH) destruction(microangiop
ACQUIRED athic)
•Toxic agents
•Drugs
•Infections
 Red cell destruction
Extravascular Intravascular

Hb RES Hpt and Hpx Free plasma Hb

Globin Haem+globin
methem
Haem Hb- Hpt complex
Plasma Haemopexin-methem
Plasma
protein pool
iron pool
Excess Hb
Protoporphyrin methaemalbumin
Liver
Expired CO Unconjugated
Kidney
bilirubin
Liver metHb
Hb Haemosiderin
Conjugated bilirubin
GI tract
Urine
Faeces Urobilinogen
Clinical Manifestations in Summary
 Onset may be acute or  Splenomegaly
insidious  Cholelithiasis (gall stones)
 Symptoms and signs of symptoms
anemia  Leg ulcers (sickle cell,
 Jaundice spherocytosis)

◦ Acholuric  Skeletal abnormalities

(thalassemia)
◦ Without pruritus  Crises (chronic hemolytic disease)
 Symptoms and signs
◦ Aplastic crises (HPV-B19)
specific to the type of
hemolytic anemia ◦ Hemolytic
 Symptoms related to the ◦ Megaloblastic
underlying disease  Changes in urine color
 LABORATORY FİNDİNGS
I- Increased RBC destruction

 Decreased RBC life span  > 1 g /dl /week fall in

 Increased haem(heme) blood Hb level*
catabolism  Reduced glycosylated Hb
◦ Increased serum  Signs of intravascular
unconjugated bilirubin* hemolysis
◦ Increased endogenous CO ◦ Hemoglobinemia*
production
◦ Hemoglobinuria*
◦ Increased urobilinogen
excretion ◦ Hemosiderinuria*
 Increased serum LDH* ◦ Methemalbuminemia
◦ Reduced serum
 Absence or decrease of
hemopexin level
serum haptoglobin*
 LABORATORY FİNDİNGS
II-Increased bone marrow activity and RBC production
 Blood
◦ Reticulocytosis  Ferrokinetic
◦ Macrocytosis ◦ Increased plasma iron
◦ Polychromatophilia turnover
◦ Erythroblastosis ◦ Increased RBC iron
◦ Leukocytosis and turnover
thrombocytosis  Biochemical
 Bone marrow ◦ Increased RBC creatine
◦ Erythroid hyperplasia ◦ Increased activity of
RBC enzymes eg:
hexokinase, etc
Laboratory Evaluation of Hemolysis
Extravascular Intravascular
Hematologic
 Blood film Polychromatophilia Polychromatophilia
 Reticulocyte Increased
Increased
 Bone marrow Erythroid hyperplasia Erythroid hyperplasia
Plasma or serum
 Bilirubin unconjugated unconjugated
 Haptoglobin , absent
absent
 Plasma free Hb N -
 LDH
Urine
 Bilirubin 0
0
 Hemosiderin 0 +
 Hemoglobin 0 + ( severe cases)
 Urobilinogen
Laboratory tests useful in differential
diagnosis
 Examination of peripheral blood
 Special Lab. examinations
 CLASSIFICATION

INTRA CORPUSCULAR EXTRA CORPUSCULAR

•Haemoglobinopathies •Familial hemolytic

•Enzymopathies uremic syndrome
HERIDITARY •Membrane cytoskeleton
defect

•Paroxysmal nocturnal •Mechanical

haemoglobinuria(PNH) destruction(microangiop
ACQUIRED athic)
•Toxic agents
•Drugs
•Infections
ACQUIRED HEMOLYTIC ANEMIAS
1.AUTOIMMUNE HEMOLYTIC ANEMIA

 Auto antibodies(warm antibody- agglutinate the RBC at

37 C or cold antibody- agglutinate at lower temp,0 to
4 C) develop against the erythrocytes.
 Warm antibodies generally belong to Ig G class,whereas
cold antibodies are immunoglobuline M (Ig M).
 In the warm antibody type,hemolysis takes place
extravascularly in the spleen,while in the cold antibody
type hemolysis occurs intravascularly or in the liver.
ETIOLOGY

CAUSES OF COLD AGGLUTININ CAUSES OF WARM AGGLUTININ

DISEASES DISEASES

VIRAL INFECTIONS IDIOPATHIC

INFECTIOUS MYCOPLASMA DRUGS(penicillin)

MULTIPLE MYLOMA SLE AND OTHER COLLAGEN

DISORDERS
KAPOSI,S SARCOMA ANTI PHOSPHOLIPID SYNDROME

WALDENSTROM’S LYMPHOMAS AND CLL

MACROGLOBULINEMIA
VENOM-ARTHROPODES AND
SNAKES
PATHOGENESIS
 Antibody is usually of IgG class
 Reacting with erythrocyte Rh antigen

complex
 Compliment activation may or may not

occur
 Antibody coated cells will be removed by

the splenic macrophages

 partially damaged erythrocytes may escape

destruction
 these repair themselves and appear as

spherocytes.
SPHEROCYTES
CLINICAL FEATURES
 Anemia
 Jaundice
 Splenomegaly
 Acute Massive Hemolysis With Shock And

Renal Failure
 Hemolytic anemia of the cold antibody
type may give rise to two clinical
syndromes on exposure to cold
environment.

1. Cold agglutinine syndrome

2. Paroxysmal cold hemoglobinuria
1. Cold agglutinine
syndrome

 Occurs in older patients,it presents with

 acrocynosis
 Raynaud’s phenominon
 Gangrene of fingertips and
 mild chronic hemolytic anemia
2.Paroxysmal cold hemoglobinuria
 First identified auto immune disease
described by Karl landsteiner,a pathologist
from Vienna.
 Antibody reacts with erythrocytes in the cold.
 In PCH sudden hemolysis develops and leads

to hemoglobinuria.
LAB INVESTIGATIONS

in peripheral blood film shows

 Marked anisopoikilocytosis
 Polychromasia
 Spherocytosis
 Increase reticulocytes.
 Neutrophil leukocytosis
 Rarely platelets may be reduced due to

development of antibodies against

them(Evan’s syndrome)
anisopoikilocytosis polychromasia
 The antibodies present on erythrocytes can
be demonstrated by direct coomb’s test.
 Free antibodies in the serum can be identified

by the indirect coomb’s test.