HEMOLYTIC ANEMIA
Hemo: Referring to blood cells
Poiesis: โThe development or production ofโ
The word Hemopoiesis refers to the production & development of all the blood cells:
Erythrocytes: Erythropoiesis
Leucocytes: Leucopoiesis
Thrombocytes: Thrombopoiesis.
Begins in the 20th week of life in the fetal liver & spleen, continues in the bone marrow till young adulthood & beyond!
2. Normal Red Cells
No nucleus
Biconcave discs
Center 1/3 pallor
Pink cytoplasm (Hb filled)
Cell size 7- 8 ยต - capill.
Negative charge
100-120 days life span
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3. The Factory โ Bone Marrow
Sternum, pelvis, vertebrae, long
bones, skull bones, Tibia (paed)
From stem cells (pleuripotent)
75% of marrow for WBC
25% of BM for Red cells
Erythrod / Granulocyte Ratio 1:3
Large white areas are marrow
fat
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6. HEMOPOIESIS
โข Hemo: Referring to blood cells
โข Poiesis: โThe development or production ofโ
โข The word Hemopoiesis refers to the production &
development of all the blood cells:
โ Erythrocytes: Erythropoiesis
โ Leucocytes: Leucopoiesis
โ Thrombocytes: Thrombopoiesis.
โข Begins in the 20th week of life in the fetal liver & spleen,
continues in the bone marrow till young adulthood &
beyond!
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7. Sites of erythropoiesis
โข Mesoblastic stage-
๏ in the yolk sac
๏ Starts at 2 weeks of intrauterine life
โข Hepatic stage-
๏ 2-7 months
๏ Both liver and spleen
โข Myeloid stage
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8. Myeloid stage
โข Occurs in bone marrow
โข Starts at 5 months of fetal life and takes over
completely at birth
โข Red bone marrow of all bone.
โข Late adult life, red marrow of flat bones
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9. SITES OF HEMOPOIESIS
โข Active Hemopoietic
marrow is found, in
children throughout the:
โ Axial skeleton:
โข Cranium
โข Ribs.
โข Sternum
โข Vertebrae
โข Pelvis
โ Appendicular skeleton:
โข Bones of the Upper &
Lower limbs
โข In Adults active
hemopoietic marrow is
found only in:
โ The axial skeleton
โ The proximal ends of the
appendicular skeleton.
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10. In adults extramedullary hematopoiesis may occur in
diseases in which the bone marrow becomes destroyed or
fibrosed
In children, blood cells are actively produced in the marrow
cavities of all the bones.
By age 20, the marrow in the cavities of the long
bones, except for the upper humerus and femur, has become
inactive .
Active cellular marrow is called red marrow; inactive marrow
that is infiltrated with fat is called yellow marrow.
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11. The bone marrow is actually one of the largest organs in the
body, approaching the size and weight of the liver. It is also
one of the most active.
Normally, 75% of the cells in the marrow belong to the white
blood cell-producing myeloid series and only 25% are
maturing red cells, even though there are over 500 times as
many red cells in the circulation as there are white cells.
This difference in the marrow reflects the fact that the
average life span of white cells is short, whereas that of red
cells is long.
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12. STEM CELLS
โข These cells have extensive proliferative capacity and
also the:
โ Ability to give rise to new stem cells (Self Renewal)
โ Ability to differentiate into any blood cells lines
(Pluripotency)
โข They grow and develop in the bone marrow.
โข The bone marrow & spleen form a supporting system,
called the
โข โhemopoietic microenvironmentโ
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13. Stem cells
โข Totipotential stem cells- convert into any tissue type
โข Pluripotent stem cell- Pluripotent hematopoeitic
stem cell
โข Committed stem cells- CFU E, CFU G, CFU M, etc
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15. Hematopoietic stem cells (HSCs) are bone
marrow cells that are capable of producing all
types of blood cells.
They differentiate into one or another type of
committed stem cells (progenitor cells). These in
turn form the various differentiated types of blood
cells.
There are separate pools of progenitor cells for
megakaryocytes, lymphocytes, erythrocytes, eosi
nophils, and basophils; neutrophils and
monocytes arise from a common precursor.
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17. PROGENITOR CELLS
โข Committed stem cells lose their capacity for self-
renewal.
โข They become irreversibly committed.
โข These cells are termed as โProgenitor cellsโ
โข They are regulated by certain hormones or substances
so that they can:
โ Proliferate
โ Undergo Maturation.
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19. ERYTHROPOIESIS
15-20ยตm- basophilic cytoplasm,
nucleus with nucleoli.
14-17ยตm-mitosis, basophilic
cytoplasm, nucleoli disappears.
10-15ยตm-โPOLYCHROMASIAโ
Hb appears, nucleus condenses.
7-10ยตm- PYKNOTIC Nucleus.
Extrusion, Hb is maximum.
7.3ยตm- Reticulum of basophilic
material in the cytoplasm.
7.2ยตm- Mature red cell with Hb.
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25. Reticulocytes
Young erythrocytes
Contain a short network of clumped ribosomes and RER.
Enter the blood stream
Fully mature with in 2 days as their contents are
degraded by intracellular enzymes.
Count = 1-2% of red cells
Provide an index of rate of RBC formation
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27. Duration
Differentiation phase- from pronormoblast to
reticulocyte phase- 5 days
Maturation phase: from reticulocyte to RBC- 2
days
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28. Factor needed of Erythropoiesis
1. Erythropoietin ( Released in response to Hypoxia)
2. Vitamin B 6 (Pyridoxine)
3. Vitamin B 9 (Folic Acid)
4. Vitamin B 12 (Cobolamin)
๏ตEssential for DNA synthesis and RBC
maturation
5. Vitamin C ๏ Helps in iron absorption (Fe+++ ๏
Fe++)
6. Proteins ๏ Amino Acids for globin synthesis
7. Iron & copper ๏ Heme synthesis
8. Intrinsic factor ๏ Absorption of Vit B 12
9. Hormones
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29. Hormonal factors:
Androgens: increase erythropoiesis by stimulating the production of
erythropoietin from kidney.
Thyroid hormones:
๏ผ Stimulate the metabolism of all body cells including the bone marrow cells,
thus, increasing erythropoiesis.
๏ผ Hypothyroidism is associated with anemia while hyperthyroidism is
associated with polycythaemia.
Glucocorticoids:
๏ผ Stimulate the general metabolism and also stimulate the bone
marrow to produce more RBCs.
๏ผ In Addisonโs disease (hypofunction of adrenal cortex) anemia
present, while in Cushingโs disease (hyperfunction of adrenal cortex)
polycythaemia present.
Factor needed of Erythropoiesis
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30. Factor needed of Erythropoiesis
Hormonal factors
Pituitary gland: Affects erythropoiesis both directly
and indirectly through the action of several
hormone.
Haematopoietic growth factors: Are secreted by
lymphocytes, monocytes & macrophages to
regulate the proliferation and differentiation of
proginator stem cells to produce blood cells.
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31. Factor needed of Erythropoiesis
State of liver & bone marrow
Liver - Healthy liver is essential for normal
erythropoiesis because the liver is the
main site for storage of vitamin B12 , folic
acid, iron & copper. In chronic liver
disease anemia occurs.
Bone marrow - When bone marrow is
destroyed by ionizing irradiation or drugs,
aplastic anemia occurs.
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33. Erythropoietin
โข Glycoprotein with 165 amino acids, 4
oligosaccharide chains and molecular weight of 34,000
โข Production- 85% by peritubular capillary bed interstitial
cells(Kidney) and 15% by perivenous hepatocytes( Liver)
โข Also seen in brain, salivary glands, uterus, oviducts
โข Site of Action: BONE Marrow
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35. Action of Erythropoietin:
1. Formation of Pronormoblast from stem cell
2. Speeds up the differentiation through various
stages of erythropoiesis
Mechanism of Action:
โข Formation of ALA synthetase
โข Activation of Adenylyl Cyclase
โข Synthesis of transferrin receptors
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36. Maturation factors
Vitamin B12 and Folic acid:
โ Essential for DNA synthesis (Thymidine triphosphate)
โ Abnormal and diminished DNA
โ Failure of division and maturation
โ Macrocytic / Megaloblastic anemia
Other factors
โ Cobalt
โ Copper
โ Vitamin C
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39. HAEMOLYTIC ANAEMIAS
โขThe normal red cell life is 110-120 days after
which the senile cells are removed by bone
marrow and splenic macrophages.
โขReduced red cell survival leads to increased red
cell production due to erythropoietin drive that can
compensate for the reduced red cell life and
maintain a normal Hb level.
โขThe mean red cell life is affected by molecular
changes in either the red cell membrane or
haemoglobin.
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40. โขA haemolytic state exists when the in vivo survival
of the RBC is shortened.
โขAnaemia occurs if the onset of haemolysis is
sudden with no time for marrow compensation or in
severe chronic haemolysis when the mean red cell
life is very short.
โขThe usual marrow response in acute hemolytic
anemia is reflected by a reticulocyte index of 2โ3,
whereas in long-standing chronic hemolysis, the
increase in erythropoiesis is approximately 6-fold.
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41. Correcting Retic Count
Retic Index = Retic % x Patient Hct
Normal Hct
Absolute Retic = Retic % x RBC/mm3
Retic Production Index = Retic Index
Days in circulation
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42. CLINICAL FEATURES
Jaundice: generally mild and often not noticed by the patient.
Anaemia: recent onset = acquired
long-standing = possibly congenital.
Haemoglobinuria: intravascular haemolysis.
Urobilinogenuria: increased Hb catabolism.
Splenic pain: spenomegaly or splenic infarction.
Leg ulcers: intrinsic red cell disorders, e.g. sickle cell disease.
Skeletal hypertrophy: severe congenital haemolytic anaemias
and thalassaemias.
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43. CLASSIFICATION OF HEMOLYTIC
ANEMIAS
The course of the
disease
acute chronic
The place of RBC
distraction
intravascular extravascular
The whence acquired inherited
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44. Haemolytic anaemia
Intravascular vs. Extravascular
Intravascular
โข red cells lyse in the
circulation and release
their products into the
plasma fraction.
โข Anemia
โข Decreased Haptoglobin
โข Hemoglobinemia
โข Hemoglobinuria
โข Urine hemosiderin
โข Increased LDH
Extravascular
โข ingestion of red cells by
macrophages in the
liver, spleen and bone
marrow
โข Little or no hemoglobin
escapes into the
circulation
โข Anemia
โข Decreased Haptoglobin
โข Normal plasma
hemoglobin
โข Increased LDHdrpankajyadav05@gmail.com
54. Warm vs. Cold Auto
WARM
โข Reacts at 37 degC
โข Insidious to acute
โข Anemia severe
โข Fever, jaundice frequent
โข Intravascular not common
โข Splenomegaly
โข Hematomegaly
โข Adenopathy
โข None of these
COLD
โข Reacts at room
temperature
โข Often chronic anemia
โข 9-12 g/dL (less severe)
โข Autoagglutination
โข Hemoglobinuria,
acrocyanosis and
raynaudโs with cold
exposure
โข No organomegaly
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57. Etiologic and Pathogenetic
Classification of the Hemolytic
Disorders
I. Inherited Hemolytic Disorders
A. Defects in the erythrocyte membrane
1. Hereditary spherocytosis
D. Deficiencies of enzymes involved in the pentose phosphate
pathway and in glutathione metabolism
1. Glucose-6-phosphate dehydrogenase (G6PD)
E. Defects in globin structure and synthesis
1. Unstable hemoglobin disease
2. Sickle cell anemia
3. Other homozygous hemoglobinopathies (CC, DD, EE; Chapter
52)
4. Thalassemia major
5. Hemoglobin H disease
6. Doubly heterozygous disorders (such as hemoglobin SC disease
and sickle thalassemia)
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58. Etiologic and Pathogenetic
Classification of the Hemolytic
Disorders
II. Acquired Hemoltyic Anemias
A. Nonimmune: due to
1. Traumatic and microangiographic hemolytic anemias
2. Infectious agents
3.Chemicals, drugs, and venoms
4. Physical agents
5. Hypophosphatemia
6. Spur-cell anemia in liver disease
7. Vitamin E deficiency in newborns
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59. Etiologic and Pathogenetic
Classification of the Hemolytic
Disorders
II. Acquired Hemoltyic Anemias
B. Immunohemolytic anemias
1. Iso (allo) immune:
transfusion of incompatible blood
Hemolytic disease of the newborn
2. Heteroimmune:
Virus, bacterial infections, chemical, Drug-induced
3. Autoimmune hemolytic anemia
Idiopathic (the essential cause is unknown)
Secondary or symptomatic (in case of lymphoma, chronic lymphocytic leukemia,
Other malignant disease, Immune-deficiency states, Systemic lupus
erythematosus and other autoimmune disorders, Virus and
mycoplasma infections)
Autoimmune hemolytic anemia caused by warm-reactive antibodies (Coombโs
positive).
Autoimmune hemolytic anemia caused by cold-reactive antibodies
Cold hemagglutinin disease
Paroxysmal cold hemoglobinuria
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60. Etiologic and Pathogenetic
Classification of the Hemolytic
Disorders
II. Acquired Hemoltyic Anemias
C. Paroxysmal nocturnal hemoglobinuria
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61. The Three Primary Measures
Measurement Normal
Range
A. RBC count (RCC) 4- 5.7 million
B. Hemoglobin 12 to 17
Hematocrit (PCV) 38 to 50
A x 3 = B x 3 = C - This is the rule of thumb
Check whether this holds good in a given result
If not -indicates micro or macrocytosis or
hypochro.
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62. The Three Derived Indicies
Measurement Normal
Range
A. RCC 4 to 5.7
B. Hemoglobin 12 to 17
C. Hematocrit 38 to 50
MCV C รท A x 10
MCH B รท A x 10
MCHC (%) B รท C x 100drpankajyadav05@gmail.com
63. Hemolytic Anemia
Anemia of increased RBC destruction
โ Normochromic, normocytic anemia
โ Shortened RBC survival
โ Reticulocytosis โ due to โ RBC destruction
Will not be symptomatic until the RBC life
span is
reduced to 20 days โ BM compensates 6
times
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