Transcript SZPICZAK MNOGI Definicja choroby: Choroba proliferacyjna

Hemolytic anemias
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Objectives
1. Define Haemolytic anaemias and their classification.
2. Define the terms "intravascular hemolysis" and "extravascular
hemolysis" and identify which mechanism predominates in normal red
cell destruction.
3. Describe the fate of free hemoglobin following red blood cell
destruction.
4. Listing the lab. Findings in extra & intravascular hemolysis.
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Definition
• This is a Normocytic, normochromic anemia
• Hemolytic Anemias are defined as those anaemias
which result from an increase in the rate of red cell
destruction.
• Any condition which leads to a reduction in the
mean lifespan of the red cell is a hemolytic disorder
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• In a healthy person, a red blood cell survives 90 to 120 days in
the circulation, so about 1% of human red blood cells break
down each day. The bone marrow is the main organ that
removes old and damaged RBCs from the circulation. In
healthy individuals, the breakdown and removal of RBCs from
the circulation is matched by the production of new RBCs in
the bone marrow.
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In conditions where the rate of RBC breakdown is
increased, the body initially compensates by
producing more RBCs; however, breakdown of RBCs
can exceed the rate that the body can make RBCs,
and so anemia can develop.
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• The normal adult marrow, after full expansion, is
able to produce red cells at 6-8 times the normal
rate and this leads to reticulocytosis.
• Therefore Hemolytic Anemias may not be seen
until the red cell lifespan is less than 30 days.
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Normal Red cell Break down
• Occurs extravascularly by macrophages of RE
system, especially Bone marrow, but also in liver
& spleen.
• Red blood cells have no nucleus, so they cannot
replace metabolism enzymes which deteriorate.
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Mechanisms of hemolysis:
- intravascular
- extravascular
Intravascular hemolysis has a very little or NO role in
Normal red cell break down. It occurs inside blood
vessels. Hb is liberated and binds Haptoglobin. The
complex is removed from plasma by RES.
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Classification of Hemolytic anemias
A. Hereditary (intracorpuscular : inside RBCs)
1. Membrane defects (Hereditary spherocytosis,
Hereditary elliptocytosis)
2. Metabolic defects (Glucoze-6-PhosphateDehydrogenaze (G6PD) deficiency, Pyruvate kinase
(PK) deficiency)
3. Hemoglobinopathies (unstable Hb, thalassemias,
Hb S, Hb C )
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B. Acquired (Extracorpuscular : outside RBCs)
A. Immune hemolytic anemias
1. Autoimmune hemolytic anemia
- caused by warm-reactive antibodies
- caused by cold-reactive antibodies
2. Alloimmune hemolytic anemia
-caused by hemolytic transfusion reaction
- caused by hemolytic disease of newborn
3. Drug associated
B. Nonimmune hemolytic anemias
1. Chemical & physical agents (drugs, industrial, burns)
2. Infections (parasitic or bacterial : malaria, clostridia)
3. Red cell fragmentation syndromes
- hemolytic - uremic syndrome (HUS)
- thrombotic thrombocytopenic purpura (TTP)
- prosthetic heart valves
4. Paroxysmal Nocturnal Hemoglobinuria (PNH)
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PNH : Paroxysmal Nocturnal Hemoglobinuria is an
exception of this classification , as it is an acquired
disease but the red cells has an intrinsic defect.
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Clinical features:
- pallor to mucus membranes
- jaundice
- splenomegaly
- pigment gallstones
- leg ulcers
- a plastic crisis usually due to infections
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Jaundiced Urine
Normal Urine
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Jaundice = Raised Serum bilirubin
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leg ulcers in sickle cell anemia
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Laboratory findings
• The lab. Findings are divided into 3 groups:
1- Features of increased red cell breakdown.
2- Features of increased red cell production.
3- Damaged red cells.
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1-Features of increased red cell breakdown:
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•
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Raised Serum bilirubin
Increased urine urobilinogen.
Increased faecal stercobilinogen.
Absent Serum haptoglobins (saturated with Hb
and removed by the RE cells).
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2-Features of increased red cell production:
• Reticulocytosis
• Bone marrow erythroid hyperplasia. (normally,
myeloid : erythroid ratio is 2 : 1 to 12 – 1
This is reduced to 1 : 1 or even reversed.
• Polychromatic cells
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• Polychromatic cells
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3-Damaged red cells:
• Morphology– microspherocytes, elliptocytes,
fragmented cells ,bite cells ….. etc
• Special tests: Osmotic fragility, ham test
autohaemolysis, Coomb’s Test
• Red cell survival is shortened; this is best shown
by 51Cr labelling with study of the sites of
destruction.
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Fragmented cells = Schistocytes
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Spherocytes are red blood cells that are almost spherical in
shape. They have no area of central pallor .
Microspherocytes
Macrospherocytes
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Causes of Intravascular hemolysis :
1. Mismatched blood transfusion (usually ABO)
2. G6PD deficiency with oxidant stress
3. Red cell fragmentation syndromes
4. Some autoimmune hemolytic anemias
5. Some drug and infection - induced hemolytic
anemias
6. Paroxysmal Nocturnal Hemoglobinuria (PNH)
7. Unstable Hb
8. March Hemoglobinuria
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Lab. Findings in Intravascular hemolysis :
1. Erythroid hyperplasia
2. Hemoglobinemia
3. Methemoalbuminemia
4. Hemoglobinuria
5. Absence or reduced of free serum haptoglobin
6. Hemosiderynuria
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