Transcript Hemolytic Anemias

Introduction to
Hemolytic Anemias
HEMOLYTIC
ANEMIAS
Introduction
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Definition
Pathogenesis
Classification
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 )
Red cell destruction
Extravascular
Hb
Intravascular
Hpt and Hpx
RES
Free plasma Hb
Globin
Haem
Haem+globin
Hb- Hpt complex
Plasma
protein pool
Plasma
iron pool
methem
Haemopexin-methem
Excess Hb
Protoporphyrin
Expired CO
Liver
Unconjugated
bilirubin
Liver
Conjugated bilirubin
GI tract
Faeces
methaemalbumin
Kidney
Hb
Urine
Urobilinogen
metHb
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
A Simple Classification of Hemolytic Anemias
1- Abnormalities of RBC interior
a. Enzyme defects
Hereditary
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
Acquired
Clinical Manifestations in Summary
• Onset may be acute or
insidious
• 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
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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 haptoglobin*
• > 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 findings
II-Increased bone marrow activity and RBC production
• Blood
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Reticulocytosis
Macrocytosis
Polychromatophilia
Erythroblastosis
Leukocytosis and
thrombocytosis
• Bone marrow
– Erythroid hyperplasia
• Ferrokinetic
– Increased plasma iron
turnover
– Increased RBC iron
turnover
• Biochemical
– Increased RBC creatine
– 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
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• Hemoglobin
0
+ ( severe cases)
• Urobilinogen
Laboratory tests useful in differential
diagnosis
• Examination of peripheral blood
• Special Lab. examinations
Morphologic abnormalities in hemolytic anemias
• Polychromasia : Reticulocytes
• Spherocyte : Her. Spherocytosis, immune hem. anemia,
burns, chemical injury to RBC
• Elliptocytes: Hereditary ovalocytosis,
• Stomatocytes: Hereditary stomatocytosis, alcoholism
• Acanthocytes: Spur cell anemia with liver disease,
abetalipoproteinemia
• Echinocytes: Pyruvate kinase deficiency, uremia
Morphologic abnormalities in hemolytic anemias
• Sickle cell:
Sickle cell anemia
• Target cels:
Thalassemia, HbC disease, liver disease,
splenectomy
• Schistocytes: Microangiopathic hem anemia, uremia, DIC,
malignant hypertesion, eclampsia,
disseminated vasculitis or malignancy,
• Agglutination: Cold agglutinin disease
• Heinz bodies: Unstable Hb, G6PD deficiency and oxidant
stress
• Bite cells -Blister cells
– G6PD deficiency
– Unstable Hemoglobin
• RBC fragmentation
– Helmet Cell, schistocytes
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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
(Nuclear remnants)
– Splenectomy
– Hyposplenism
– Megaloblastic anemia
– Hemolytic anemia
• Basophylic stippling
Ribosomes/RNA/mitochondrial bodies
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Lead poisoning
Thalassemia,
Unstable hemoglobines
MDS
Megaloblastic anemia
Other hemolytic anemia
• Eg. 5-Nucleotidase deficiency
• Heinz Bodies
(Denaturated Hemoglobin)
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RBC Enzyme defects
Unstable hemoglobin
Thalassemia
Sickle cell anemia
Special Lab. Examinations
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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?