Hemolytic Anemia

Shen Yan
The Second Affiliated Hospital of CQMU

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 Definition
• What is hemolytic anemia?

• At the end of the normal life span (about 120 days), red blood cells (RBCs) are
removed from the circulation.

• Hemolysis is the destruction of red blood cells in the circulation before their life span
is over. It involves premature destruction and a shortened RBC life span.

• Hemolytic anemia is a disorder in which the red blood cells are destroyed faster than
the bone marrow can produce them.

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 Pathogenesis

• Intrinsic causes
• Membrane abnormalities: hereditary spherocytosis, paroxysmal nocturnal
hemoglobinuria（PNH）

• Enzyme defects: glucose-6-phosphate dehydrogenase (G6PD) deficiency

• Abnormal hemoglobins: sickle cell disease, thalassemia

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 Pathogenesis
• Extrinsic causes
• Drugs and toxins: quinine, quinidine, penicillins, methyldopa, lead,
copper,etc

• Immunologic abnormalities: autoimmune hemolytic anemia

• Infections

• Mechanical injury: traumatic hemolytic anemia

• Reticuloendothelial hyperactivity: hypersplenism

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 Pathogenesis
• Intravascular hemolysis
Pathophysiologic characters:
plasma free hemoglobin
haptoglobin
hemoglobinuria,
hemosiderinuria

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 Pathogenesis
• Extravascular hemolysis
Pathophysiologic
characters:
indirect bilirubin
stercobilinogen (+) ,
urobilinogen (+)

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 Clinical features
• Acute (intravascular hemolysis): acute onset, fever, chills, lower back
pain, noticeable hemoglobinuria, heart failure, renal failure.

• Chronic (extravascular hemolysis): anemia, jaundice, enlargment of

liver, spleen, gall stones, liver failure, etc.

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Laboratory testing
• Documenting RBC destruction

• Documenting marrow compensation

• Defining the etiology

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Laboratory testing
• Documenting RBC destruction

CBC: anemia

Peripheral smear: abnormalities of RBC morphology

Serum bilirubin, LDH, haptoglobin, ALT

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Laboratory testing
• Documenting bone marrow compensation

Reticulocytosis：Reticulocyte is an immature red blood cell without a

nucleus, having a granular or reticulated appearance when suitably stained.
An elevation in the number of reticulocytes reflects the
rapid red blood cell production.

Normal: less than 1%.

Reticulocytosis: above 1%.

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 Laboratory testing
• Documenting bone marrow compensation

Bone marrow smear shows increased nucleated red cell precursors

with megaloblastoid changes. The megaloblastoid maturation is
secondary to folate deficiency because of rapid cell
turnover and depletion of folate stores.

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Laboratory testing
• Defining the etiology

• Consider risk factors (eg, geographic location, genetics, underlying

disorder)

• Examine the patient for splenomegaly

• Do a direct antiglobulin (direct Coombs) test

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 Laboratory testing
• Direct Antiglobulin (Direct Coombs) Test

• used to determine whether red blood cell (RBC)-binding antibody (IgG) or

complement (C3) is present on RBC membranes.

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 Laboratory testing
• Indirect Antiglobulin (Indirect Coombs) Test

• used to detect IgG antibodies against RBCs in a patient's plasma.

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Diagnosis
• History and physical examination

• Laboratory findings

• Post-diagnostic testing

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 Diagnosis
• History and physical examination: A systematic approach, starting with a
thorough history and physical examination is the cornerstone of the
evaluation. Helpful clues from the history and physical examination include
onset, jaundice, dark urine, LDH, blood transfusion, history of hemolytic
anemia, history of pigmented gallstones, splenomegaly

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 Diagnosis
• Laboratory findings: There is no single specific diagnostic test for
hemolytic anemia. However, the diagnosis can be accepted if most of
the following findings are present: anemia, increased reticulocyte
count, signs of RBC destruction

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 Diagnosis
• Post-diagnostic testing

• Anemia and thrombocytopenia with numerous schistocytes on the blood smear

suggests a TMA such as TTP, HUS, or drug-induced TMA.

• Rapid onset of fever, back pain, dark urine, and pink plasma following a blood
transfusion suggests an 'Acute hemolytic transfusion reaction.

• Lifelong anemia, splenomegaly, and RBC morphology typical of one of the inherited
disorders such as spherocytes , elliptocytes , or stomatocytes suggests a congenital
RBC membrane/cytoskeletal defect.
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 Diagnosis
• A blood smear characteristic of sickle cell disease or thalassemia in a patient with
classic findings suggests a hemoglobinopathy

• A rapid drop in hemoglobin level after exposure to a drug known to cause hemolysis
suggests drug-induced hemolytic anemia, which may be due to glucose-6-
phosphate dehydrogenase (G6PD) deficiency

• Hemoglobinuria associated with pancytopenia or acute onset thrombosis (especially

abdominal vein or central venous sinus thrombosis) suggests paroxysmal nocturnal
hemoglobinuria (PNH), which is evaluated with flow cytometry.
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 Diagnosis
• Coombs test interpretation
• Warm AIHA is generally due to an IgG that binds to RBCs at a temperature around 37°C,
and the DAT is typically positive with anti-IgG antisera or IgG plus complement at low
titer.
• Cold agglutinin disease is due to an IgM autoantibody that has an optimum
temperature of reaction at 4° C (thermal range 4 to 34°C) and strongly activates
complement. The DAT is positive with anti-complement antisera and a high titer of cold
agglutinins is found in the serum . Typically, spontaneous agglutination of RBCs occurs
at room temperature, sometimes invalidating automated blood counts and raising the
diagnostic suspect.

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Treatment
• Etiological treatment

• Immunosuppressant: corticosteroids, immunoglobulin,

rituximab

• Blood transfusion (washed RBC)

• Spleenectomy

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Hereditary spherocytosis(HS)
• Defect of RBC membrane, leading to spherocytosis

• Decreased deformability of cell

• Increased osmotic fragility

• Inherited in an autosomal

dominant manner

• Treatment : splenectomy, RBC

transfusions, folic acid, cholecystectomy

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 Glucose-6-phosphate dehydrogenase (G6PD)
Deficiency
• Depressed functions of G6PD

• Hemolysis during oxidative stress

(drugs, infection, fava beans-favism)

• Decreased generation of glutathione

• Deformed Hb leading to Heinz body formation

• Hereditary, X chromosome

• Treatment: Avoidance of triggers,

transfusions, supportive care

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Heinz body

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 Warm autoimmune hemolytic anemia (AHA)

• Antibodies or complements combine with RBC

• Macrophage recognizes Fc receptor of Ig or C3b, causing destruction of RBC

• Coombs test (+)

• Treatment: transfusion, underlying disorder, corticosteroid, rituximab, IVIG

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Thalassemia
Demographics:

Found most frequently in the Mediterranean, Africa, Western

and Southeast Asia, India and Burma

Classification:

according to which chain of the hemoglobin molecule is

affected : α- and β-thalassemias
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Thalassemia
• Both α- and β-thalassemias are often inherited in an
autosomal recessive manner.

• Hb Electrophoresis

• Gene mutation examination

• Treatment: red blood cell transfusion, with or

without iron chelation therapy. Splenectomy if
splenomegaly is present. Allogeneic stem cell
transplantation if possible.

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Paroxysmal nocturnal hemoglobinuria(PNH)

• Clonal cell disorder

• Aquired mutation in PIGA gene, deficit of GPI-associated protein

• Intravascular hemolysis , hemoglobinuria, pancytopenia and arterial and

venous thromboses

• Testing: Ham test(+), sugar-water test(+), CD55, CD59 (-) in RBC, WBC

• Treatment:supportive , eculizumab

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