Introduction to Hemolytic Anemias

Introduction to Hemolytic Anemias. HEMOLYTIC ANEMIAS Introduction Definition Pathogenesis Classification General clinical features Laboratory evaluation

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Introduction to

Hemolytic Anemias


• Definition

• Pathogenesis

• Classification

• General clinical features

• Laboratory evaluation of hemolysis

Hemolytic AnemiasDefinition• 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


• Hemolytic anemias may be classified as

I- Hereditary or acquired


II- Intracorpuscular or Extracorpuscular

Hemolysis may occur in two compartments

I- Intravascular


II- Extravascular ( eg: spleen )

Red cell destruction

Extravascular Intravascular




Plasma iron pool

Plasma protein pool


Expired CO Unconjugated bilirubin


Conjugated bilirubin

GI tract



Free plasma Hb

Hb- Hpt complex


Hpt and Hpx


Excess Hb



Hb Haemosiderin




• In some types of hemolytic anemias hemolysis occurs particularly as an intravascular hemolysis.eg: Paroxsysmal nocturnal hemoglobinuria

Traumatic or microangiopathic hem. anemia

(eg:cardiac hemolytic anemia,march hemoglobinuria,TTP)

Acute hemolytic transfusion reaction etc

1- Abnormalities of RBC interior

a. Enzyme defects

b. Hemoglobinopathies & Thalassemia Maj

2-RBC membrane abnormalities

a. Hereditary spherocytosis, elliptocytosis etc

b. Paroxysmal nocturnal hemoglobinuria c. Spur cell anemia

3- Extrinsic factors

a. Hypersplenism b. Antibody : immune hemolysis c. Traumatic & Microangiopathic hemolysis d. Infections , toxins , etc












A Simple Classification of Hemolytic Anemias

Clinical Manifestations in Summary• Onset may be acute or


• Symptoms and signs of anemia

• Jaundice

– Acholuric

– Without pruritus

• Symptoms and signs spesific to the type of hemolytic anemia

• Symptoms related to the underlying disease

• Splenomegaly– Most congenital hem. anemias except

sickle cell– Some of the acquired hem. anemias

• Cholelithiasis (gall stones) symptoms• Leg ulcers (sickle cell, spherocytosis)

• Skeletal abnormalities (thalassemia)

• Crises (chronic hemolytic disease)

– Aplastic crises (HPV-B19)

– Hemolytic

– Megaloblastic

• Changes in urine color

Laboratory findings

I- Increased RBC destruction• Decreased RBC life span• Increased haem(heme)

catabolism– Increased serum

unconjugated bilirubin*– Increased endogenous CO

production– Increased urobilinogen excretion

• Increased serum LDH* • Absence or decrease of serum


• > 1 g /dl /week fall in blood Hb level*

• Reduced glycosylated Hb• Signs of intravascular

hemolysis– Hemoglobinemia*– Hemoglobinuria*– Hemosiderinuria*– Methemalbuminemia– Reduced serum

hemopexin level

*common practice

Laboratory findingsII-Increased bone marrow activity and RBC production

• Blood– Reticulocytosis

– Macrocytosis

– Polychromatophilia

– Erythroblastosis

– Leukocytosis and thrombocytosis

• Bone marrow– Erythroid hyperplasia

• Ferrokinetic– Increased plasma iron


– Increased RBC iron turnover

• Biochemical– Increased RBC creatine

– Increased activity of RBC enzymes eg: hexokinase, etc

Laboratory Evaluation of Hemolysis

ExtravascularHematologic• Blood film Polychromatophilia• Reticulocyte Increased• Bone marrow Erythroid hyperplasiaPlasma or serum• Bilirubin unconjugated• Haptoglobin , absent• Plasma free Hb N - • LDHUrine• Bilirubin 0• Hemosiderin 0• Hemoglobin 0• Urobilinogen


Polychromatophilia IncreasedErythroid hyperplasia

unconjugated absent

0++ ( severe cases)

Laboratory tests useful in differential diagnosis

• Examination of peripheral blood

• Special Lab. examinations

Morphologic abnormalities in hemolytic anemias

• Polychromasia

• Spherocyte :

• Elliptocytes:

• Stomatocytes:

• Acanthocytes:

• Echinocytes:

: Reticulocytes

Her. Spherocytosis, immune hem. anemia,

burns, chemical injury to RBC

Hereditary ovalocytosis,

Hereditary stomatocytosis, alcoholism

Spur cell anemia with liver disease,


Pyruvate kinase deficiency, uremia

Morphologic abnormalities in hemolytic anemias

• Sickle cell:

• Target cels:

• Schistocytes:

• Agglutination:

• Heinz bodies:

Sickle cell anemia

Thalassemia, HbC disease, liver disease,


Microangiopathic hem anemia, uremia, DIC,

malignant hypertesion, eclampsia,

disseminated vasculitis or malignancy,

Cold agglutinin disease

Unstable Hb, G6PD deficiency and oxidant


• Bite cells -Blister cells

– G6PD deficiency

– Unstable Hemoglobin

• RBC fragmentation– Helmet Cell, schistocytes

• Thrombotic Thrombocytopenic Purpura (TTP),

• Hemolytic uremic syndrome (HUS)

• Disseminated Intravascular Coagulation

• Vaskulitis

• Renal graft rejection

• Malignant hypertention

• Burns

• Artificial cardiac valves

• March hemoglobinuria

• Target cells– Liver disease

– Thalassemia

– Hb C

– Splenectomy

– Sickle cell anemia

– Iron deficiency

• Howell-Jolly bodies

– Splenectomy

– Hyposplenism

– Megaloblastic anemia

– Hemolytic anemia

(Nuclear remnants)

• Basophylic stippling

– Lead poisoning– Thalassemia, – Unstable hemoglobines– MDS– Megaloblastic anemia– Other hemolytic anemia

• Eg. 5-Nucleotidase deficiency

Ribosomes/RNA/mitochondrial bodies

• Heinz Bodies

– RBC Enzyme defects– Unstable hemoglobin– Thalassemia– Sickle cell anemia

(Denaturated Hemoglobin)

Special Lab. Examinations• Coombs antiglobulin test - immune hemolysis• Osmotic fragility test - spherocytosis• Autohemolysis- G6PD,PK, spherocytosis• Membrane protein analysis- membrane defects• Red cell sickling- sickle cell anemia • Hemoglobin electrophoresis and HbA2, Hb F , HHb,etc -

Hemoglobinopathies and thalassemias• Red cell enzyme assays- RBC enzyme defects• HAM and sucrose lysis tests and GPI-linked protein analysis by

flow cytometry- PNH• Oxygen dissociation curve- High oxygen affinity Hb

Diagnostic approach

• Is there anemia?

• Detailed history including disease related symptoms, bleeding, drugs,ethnics, occupation , toxic exposure etc. family history

• Physical exam.: Signs of hemolytic anemia (common and specific ) in addition to anemia and any signs of underlying disease

Diagnostic approach• What are the changes in red cell morphology?

– Smear examination– Red cell indexes

• Are there any changes in other cell lines ?

• Is there evidence of increased red cell production? Reticulocytes

• Is there evidence of hemolysis?

• What is the type/diagn. of hemolysis?– Special tests

• Is there evidence of intravascular hemolysis?