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RED BLOOD CELLS. by Mary Yvonnette C. Nerves, MD, FPSP. Erythropoiesis. A process by which early erythroid precursor cells differentiate to become the mature RBCs Primary regulator: ERYTHROPOIETIN - stimulates red cell precursors at all levels of maturation to hasten the maturation process

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red blood cells

RED BLOOD CELLS

by

Mary Yvonnette C. Nerves, MD, FPSP

erythropoiesis
Erythropoiesis
  • A process by which early erythroid precursor cells differentiate to become the mature RBCs
  • Primary regulator:ERYTHROPOIETIN

- stimulates red cell precursors at all levels of maturation to hasten the maturation process

- responsible for stimulating the premature release of reticulocytes into the bloodstream.

slide4

Erythropoiesis

  • Total erythropoiesis:

- total number of red blood cells (RBCs)

- measured by the myeloid-erythroid (M:E) ratio from aspirate smears plus the estimate of cellularity from biopsy sections

slide6
Effective erythropoiesis:

- number of viable and functional RBCs available for physiologic needs

- reflects the balance between the number of cells produced and their life span

- measured by the reticulocyte count, which is normally 1% of the total RBC count

stages of maturation
Stages of Maturation
  • Pronormoblast (Rubriblast)
  • Basophilic Normoblast (Prorubriblast)
  • Polychromatophilic Normoblast (Rubricyte)
  • Orthochromatic Normoblast (Metarubricyte)
  • Reticulocyte
  • Erythrocyte
pronormoblast
Pronormoblast
  • Earliest recognizable and largest cell of the erythrocyte series
  • Morphology:

- Size: 12 – 20 um

- Nucleus: large round, oval, dark violet; fine chromatin; 1 – 2 nucleoli

- Cytoplasm: deep blue spotty, basophilic w/ a perinuclear halo

- N/C Ratio: 8:1

- BM (%): 1

basophilic normoblast
Basophilic Normoblast
  • Hemoglobin synthesis begins at this stage
  • Morphology:

- Size: 10 – 15 um

- Nucleus: large round to sl oval; condensed, coarse chromatin; 0 – 1 nucleoli

- Cytoplasm: deeply basophilic; clusters of free ribosomes

- N/C Ratio: 6:1

- BM (%): 1-4

polychromatic normoblast
Polychromatic Normoblast
  • Increased production of hemoglobin pigmentation and decreasing amounts of RNA
  • Last stage in which the cell is capable of mitoses
  • Morphology:

- Size: 10 - 15 um

- Nucleus: round nucleus, deep staining, may be centrally or eccentrically located; coarse & clumped chromatin

- Nucleoli: 0

slide14

Morphology:

- Cytoplasm: abundant blue-gray (RNA) to pink-gray (hemoglobin)

- N/C Ratio: 4:1

- BM (%): 10-20

orthochromatic normoblast
Orthochromatic Normoblast
  • The last nucleated stage
  • Cannot synthesize DNA and cannot undergo cellular division
  • The NRBC sometimes seen in the peripheral circulation
slide17

Morphology:

- Size: 8 - 10 um

- Nucleus: small pyknotic nucleus; dense chromatin; 0 nucleoli

- Cytoplasm: abundant red-orange cytoplasm uniform in color

- N/C Ratio: 1:2

- BM (%): 5-10

reticulocyte
Reticulocyte
  • Slightly larger than the mature RBC with residual amts of RNA
  • Reticulocyte count: an index of bone marrow activity or effective erythropoiesi
  • Morphology:

- Size: 8 - 10 um

- Nucleus: anucleate cell containing small amt of basophilic reticulum (RNA)

- Nucleoli: 0

- Cytoplasm: large amt of blue-pink staining hemoglobin cytoplasm

erythrocyte
Erythrocyte
  • A biconcave 6 – 8 um disc
  • Life span: 120 days
  • Main function: to transport hemoglobin, a protein that delivers oxygen from the lungs to tissues and cells
  • Contains 90% hemoglobin and 10% H2O
  • normal conc of RBCs varies w/ age, sex & geographic distribution
slide23

Morphology:

- Size: 7 - 8 um

- Nucleus: anucleated cell

- Nucleoli: 0

- Cytoplasm: pink staining, zone of central pallor is 1/3 of cell diameter devoid of hemoglobin

- N/C Ratio: NA

hemoglobin structure function
Hemoglobin: Structure & Function
  • A conjugated protein that serves as the vehicle for the transportation of O2 and CO2
  • When fully saturated, each gram of Hgb can hold 1.34 mL of O2
  • A molecule of Hgb consists of 2 pairs of polypeptide chains (“globin”) and 4 prosthetic heme grps each contg 1 atom of ferrous iron
description of terms
DESCRIPTION of TERMS

SIZE DESCRIPTORS

  • Anisocytosis: variation in the sizeof the RBCs due to a pathologic condition
slide32
Microcytic: Smaller RBCs less than 6 um

- MCV < 80 fl

- Defect / Change: abn size due to failure of hgb synthesis

- Dse: IDA, Thalassemia, Chronic dse

  • Macrocytic: Larger RBCs greater than 9um

- MCV > 90 fl

- Defect / Change: impaired DNA synthesis / stress erythropoiesis

- Dse: Megaloblastic anemia / liver dse / MDS / Alcoholism / Malaria

slide33

Macrocytic

Microcytic

slide35
CHROMICITY DESCRIPTORS
  • Normochromic: normal in color; pale central area occupies less than 1/3

- Defect / Change: normal amt of Hgb

- Normal indices

  • Hypochromic: an RBC that has a decreased Hgb complement

- central pallor exceeds 1/3 of diameter of cell

- Defect / Change: reduced Hgb content ( MCHC)

- Assoc conditions: IDA / Thalassemia

slide37

“Hyperchromic”: no central pallor

- Defect / Change: greater than normal MCHC

- Assoc condition: Spherocytosis

“Hyperchromic”

Hypochromic

slide38
Polychromasia: blue-gray coloration

- Defect / Change: presence of RNA

- Assoc condition: increased erythropoietic activity / hemorrhage / hemolysis

slide40

SHAPE DESCRIPTORS

  • Poikilocytosis:variation in shape of the RBC

- Defect / Change: irreversible alteration of membrane

- Assoc conditions: Anemia / Hemolytic states

slide41

Discocyte: normal biconcave erythrocyte - 6 – 8 um diameter; 0 – 2 um thickness

- Aka: Normocyte

Normal Red Cells (SEM)

slide42

Acanthocyte: spheroid w/ 3 – 12 irreg spikes or spicules

- Aka: spur cell

- decreased cell volume

- Defect / Change: inc ratio of chole to lecithin

- Assoc conditions:

end-stage liver dse

Pyruvate kinase def

Hemolytic anemia

Abetalipoproteinemia

slide44

Blister cell: contains 1 or more vacuoles

- Aka: Bite cells

- thinned periphery

- Defect / Change: formed by removal of Heinz bodies

- Assoc conditions:

Hemolytic episodes

G6PD def

Hemoglobinopathies

slide46

Codocyte : peripheral rim of Hgb surr by clear area & central hemoglobinized area (bull’s eye)

- Aka: target cell

- Defect / Change: excess of surface to volume ratio

- Assoc conditions:

Hemoglobinopathies

Thalassemia

Liver dse

Postsplenectomy

slide48
Dacryocyte: teardrop or pear-shaped w/ single elongated point or tail

- Aka: tear drop cell

- Defect / Change: squeezing & fragmentation during splenic passage

- Assoc conditions:

Myeloid metaplasia

Thalassemia

Megaloblastic anemia

Hypersplenism

slide50
Drepanocyte: crescent-shaped cell that lacks zone of central pallor

- Aka: Sickle cell

- Defect / Change: polymerization of deoxygenated Hgb

- Assoc conditions:

Sickle cell anemia

SC disease

S-thalassemia

slide52
Echinocyte: regular 10-30 scalloped short projections evenly distributed / spiny-like

- Aka: Burr cell / crenated RBC

- Defect / Change: Depletion of ATP

Exposure to hypertonic soln

Artifact in air drying

- Assoc conditions:

Uremia

Cirrhosis / Hepatitis

Chronic renal dse

slide54
Ovalocyte: egglike or oval-shaped cell

- Defect / Change:

Hgb has bipolar arrangement

Reduction in membrane chole

- Assoc conditions:

Megaloblastic BM

Myelodysplasia

Sickle cell anemia

slide55
Elliptocyte: rod or cigar shape, generally narrower than ovalocytes

- Defect / Change: polarization of Hgb

- Assoc conditions:

Thalassemia

Iron def

Hereditary elliptocytosis

slide57
Schistocyte: Fragmented RBCs varying in size & shape

- Aka: Helmet cells

- Defect / Change: extreme fragmentation produced by damage of RBC by fibrin, altered vessel walls, prosthetic heart valves

- Assoc conditions:

DIC / TTP / Burns

Microangiopathic hemolytic anemia

slide59
Spherocyte: smaller in diameter than normal RBC w/ concentrated Hgb content; no visible central pallor

- Defect / Change:

lowest surface area to volume ratio

defect of loss of membrane

- Assoc conditions:

Hereditary spherocytosis

Iso- & autoimmune hemolytic anemia

Severe burns

Hemoglobinopathies

slide61
Stomatocyte: normal sized cell w/ slitlike area in center

- Defect / Change:

artifact of slow drying

known to have inc permeability to Na+

- Assoc conditions:

Hereditary stomatocytosis

Acute alcoholism

Liver dse

red cell inclusions
RED CELL INCLUSIONS
  • Basophilic Stippling

- cytoplasmic remnants of RNA

- Fine: thin round dark blue granules uniformly distributed

- Defect/Change: represents polychromasia (reticulocyte)

- Coarse: medium sized uniformly distributed

- Defect/Change: represents impaired erythropoiesis

slide64
Basophilic Stippling

- Assoc conditions:

Thalassemia

Lead Poisoning

Increased reticulocytosis

slide66

Cabot Ring

- rings, loops, or figure eights; red to purple

- Defect / Change: remnants of microtubules of mitotic spindle

- Assoc conditions:

Megaloblastic anemia

Dyserythropoiesis

slide68

Heinz bodies

- deep purple irregularly shaped inclusions found on RBC inner surface of membrane

- Defect / Change: represent precipitated, denatured Hgb due to oxidative injury

- Assoc conditions:

Hereditary defects in HMS

G6PD def

Unstable Hgbs

Splenectomized pts

Thalassemia

slide70

Howell-Jolly bodies:coarse round densely stained purple 1-2 um granules eccentrically located on periphery of membrane

- Defect / Change: nuclear remnants; contain DNA

- Assoc conditions:

Megaloblastic anemia

Severe hemolytic process

Thalassemia

Accelerated erythropoiesis

slide72

Pappenheimer bodies:small, 2-3 um irregular basophilic inclusions that aggregate in small clusters near periphery w/ Wright’s stain

- Defect / Change: unused iron (nonheme) deposits

- Assoc conditions:

Sideroblastic anemia

Defective erythropoiesis

MDS

Hemolytic anemia

Thalassemia

slide74

Ringed Sideroblasts

- Nucleated RBC that contains nonheme iron particles (siderotic granules) arranged in ring form

- Defect / Change: excessive iron overload in mitochondria of normoblasts

- due to defective heme synthesis

- Assoc conditions:

Sideroblastic anemia

MDS

slide76

Ringed Sideroblasts

Prussian blue iron stain showing excess accumulation of iron as ferritin in mitochondria ringing nucleus.

slide77

Siderocyte:non-nucleated cell containing iron granules

- Defect / Change: excessive iron overload in mitochondria of normoblasts

- due to defective heme synthesis

- Assoc conditions:

Sideroblastic anemia

MDS

slide78

Autoagglutination:clumping of RBCs

- Defect / Change: presence of antibody

- Assoc conditions:

Cold agglutinin

AHA

slide79
Rouleaux Formation:alignment of RBCs linear appearing as stacks of coins

- Defect / Change: concentration of fibrinogen & immunoglobulin

- Assoc conditions:

MM / Waldenstrom’s macroglobulinemia

slide81

Hematologic testsused to measure several important parameters that reflect rbc structure and function:

1) Hemoglobin determination

2) Erythrocyte count

3) Hematocrit

4) Erythrocyte Indices: MCH, MCHC, MCV

5) Reticulocyte Count

6) Osmotic Fragility Test

7) Erythrocyte Sedimentation Rate (ESR)

slide84

Hemoglobin

- involves lysing the erythrocytes, thus producing an evenly distributed solution of hemoglobin in the sample

- Hemiglobincyanide Mtd:blood is diluted in a soln of K3Fe(CN6). The K3Fe(CN6) oxidizes Hgbs to hemiglobin (metHgb) and K cyanide provides cyanide ions to form HiCN, w/c has a broad absorption max at a wl of 540 nm

slide85

Erythrocyte Count

- involves counting the number of rbcs per unit volume of whole blood.

- expressed as number of cells per unit volume, specifically cells/µL

- NV: Female = 4.2 - 5.4 x 106/µL

Males = 4.7 - 6.1 x  106/µL

slide86

Hematocrit

- sometimes referred to as the Packed Cell Volume (PCV) or volume of packed red cells

- is the ratio of the volume of RBCs to that of the whole blood

- varies with age and sex

- expressed as a percentage or as a decimal fraction

Plasma

Buffy coat

Red cells

slide87

Erythrocyte Indices

1) Mean Cell Volume (MCV)

- average volume of red cells

- calculated from the Hct and RBC count

MCV = Hct x 1000

RBC (in millions/uL)

- expressed in femtoliters (fl) or cubic micrometers

slide88

2) Mean Cell Hemoglobin (MCH)

- content (weight) of Hgb of the average red cell

- calculated from the Hgb and RBC count

MCH = Hgb (in g/L)

RBC (/L)

- value is expressed in picograms (pg)

slide89
3) Mean Cell Hemoglobin Concentration (MCHC)

- the average conc of Hgb in a given volume of packed red cells

- calculated from the Hgb conc & the Hct

MCHC = Hgb (in g/dL)

Hct

- expressed in g/dL

slide91

Reticulocyte Count

- Principle: Reticulocytes are immature non- nucleated red cells that contain RNA and continue to synthesize Hgb after the loss of the nucleus

- Supravital staining: blood is briefly incubated in a soln of new MB or BCB, the RNA is precipitated as a dye-ribonucleoprotein complex  dark blue network (reticulum or filamentous strand)

- NV: 0.5 – 1.5% or 24 – 84 x 109/L

slide93

Osmotic Fragility Test (OFT)

- a measure of the ability of red cells to take up fluid without lysing

- Red cells are suspended in a series of tubes contg hypotonic solns of NaCl solns varying from 0.9% to 0.0%, incubated at room temp for 30 mins and centrifuged

- the percent hemolysis in the supernatant solns is measured & plotted for each NaCl conc.

slide94
- The larger the amount of red cell membrane (surface area) in relation to the size of the cell, the more fluid the cell is capable of absorbing before rupturing

- Cells that are more spherical, w/ a decreased surface/volume ratio, have a limited capacity to expand in hypotonic solns & lyse at a higher conc of NaCl than do normal biconcave cells  OFT

slide95
- Cells that are hypochromic & flatter have a greater capacity to expand in hypotonic solns, lyse at a lower conc than do normal cells, & are said to have decreased osmotic fragility

- Cells with increased surface/volume ratio are osmotic resistant  IDA, thalassemia, liver dse, & reticulocytosis

slide97

Erythrocyte Sedimentation Rate (ESR)

- detect and monitor an inflammatory response to tissue injury (an acute phase response) in which there is a change in the plasma conc of several proteins

-Principle:When well-mixed venous blood is placed in a vertical tube, RBCs will tend to fall toward the bottom. The length of the fall of the top of the column of RBCs in a given interval of time is called the ESR

slide98
- ESR is affected by (3) FACTORS:

a) erythrocytes

b) plasma composition

c) mechanical / technical factors

- Red Cell Factors:

  • Anemia increases ESR (change in RBC plasma ratio favors rouleaux fotn)
  • ESR is directly proportional to the weight of the cell aggregate & inversely proportional to the surface area
  • Microcytes sediment slower than macrocytes
  • Rouleaux accelerate the ESR
  • Red cells w/an abnormal or irregular shape hinder rouleaux fotn & lower the ESR
slide99
- Plasma Factors:
  • Elevated levels of fibrinogen accelerate ESR
  • Albumin & lecithin retard ESR
  • Cholesterol accelerate ESR

- Mechanical / Technical Factors:

  • A tilt of 3o can cause errors up to 30%  ESR
  • ESR increases as the temp increases
  • ESR tubes with a narrower than standard bore will generally yield lower ESR
  • ESR stands fro > 60 mins  falsely elevated ESR
  • Greater conc of EDTA  falsely low ESR

- Methods:Westergren Mtd / Wintrobe Mtd

slide102
Two main disorders affecting RBCs:

1. Polycythemia (Erythrocytosis)

- an elevated Hct level above the normal range

2. Anemia

- a reduction below normal limits of the total circulating red cell mass

polycythemia
POLYCYTHEMIA
  • May be classified into (2) major conditions:

1) Relative Polycythemia

- an increase in the Hct or red cell count as a result of decreased plasma volume

- total red cell mass is NOT increased

- Assoc conditions: acute dehydration or hemoconcentration / pts on diuretic therapy / Gaisbock’s syndrome (psedopolycythemia or stress erythrocytosis)

- BM: Normal

slide105
2) Absolute (or Secondary) Polycythemia

- an erythropoietin mediated increase in RBCs and Hgb due primarily to a hypoxic situation

- increase in the total red cell mass in the body assoc w/ normal or sl increased plasma volume

- Assoc conditions: tumors / anabolic steroids / & renal dso such as cystic dse, hydronephrosis / & adrenal cortical hyperplasia

- BM: Erythroid hyperplasia

slide106

3) Polycythemia rubra vera

(Primary Erythrocytosis)

- an absolute increase in all cell types, RBCs, WBCs and platelets

- not dependent on erythropoietin levels

- BM: all three cell lines increased (panhyperplasia)

anemia
ANEMIA
  • Decreased oxygen carrying capacity of the blood
  • Anemia may also be "defined" in terms of the Hb content

Hb < 12 g/dL in an adult male

Hb < 11 g/dL in an adult female

slide111
ANEMIAS SECONDARY TO BLOOD LOSS
  • Acute: e.g., hemorrhage due to trauma, massive GI bleeding, or child delivery. Usually the iron stores remain normal.
  • Chronic: e.g., bleeding peptic ulcer or excessive menstrual bleeding.
hypoproliferative anemias impaired production
HYPOPROLIFERATIVE ANEMIAS (Impaired Production)
  • reduced production of red cells can be subdivided into:
    • deficiency of haematinics
      • iron deficiency
      • B12 and folate deficiency
    • dyserythropoiesis (production of defective cells)
      • anaemia of chronic disorders (AOCD)
      • myelodysplasia
      • sideroblastic anaemia
    • marrow infiltration (myelophthisic anemia)
    • aplasia (failure of production of cells)
      • aplastic anaemia
      • red cell aplasia
slide114

Iron Deficiency Anemia

  • Normal forms of iron (Fe) and iron metabolism
    • Functional iron is found in Hb, myoglobin, and enzymes (catalase & cytochromes)
    • Ferritin: physiological storage form
    • Hemosiderin: degraded ferritin + lysosomal debris (Prussian blue positive)
    • Iron is transported by transferrin
slide115
causes:
    • Dietary deficiency: elderly, children and poor
    • Increased demand: children & pregnant women
    • Decreased absoprtion:

generalized malabsorption

after gastrectomy

    • Chronic blood loss:

GI bleeding (e.g. peptic ulceration, carcinoma of stomach or colon)

menorrhagia

urinary tract bleeding

Hook worm (Ancylostoma duodenale adult worm sucks 0.2 ml blood/day)

slide116

Lab Findings:

    • Microcytic, hypochromic anemia. Low serum iron
    • BM: show absence of iron
    • Ferritin: Low serum ferritin indicates low body stores of iron
    • Transferrin: These carrier proteins will be unsaturated and available to bind iron, hence the Total Iron Binding Capacity (TIBC) is increased with anemia.
slide121

Anemia of Chronic Disease (AOCD)

  • Char by iron being trapped in BM macrophages
  • Can be grouped in 3 categories:

- chronic microbial infections (eg. Osteomyelitis)

- chronic immune disorders (eg. RA)

- Neoplasms (eg. lymphoma, breast/lung CA)

  • Chronic inflamm dso inc IL-1, TNF, IF-Gamma 

- reduction in renal erythropoietin  marrow erythroid precursors do notproliferate

- hepcidin synthesis in liver inhibits release of iron

slide122
Labs: low serum iron

increased serum ferritin

decreased TIBC

normochromic, normocytic anemia or hypochromic, microcytic anemia

slide123

Megaloblastic Anemia

  • A group of dso in which the blood and BM hematopoietic cells display changes
  • Pathogenesis: impaired DNA synthesis (delayed mitoses) while RNA is not impaired; this produces nuclear-cytoplasmic asynchrony
  • Megaloblastic anemias can be divided into groups:

- anemia caused by B12 deficiency

- anemia caused by folate deficiency

- anemias nonresponsive to either therapy

slide124
important background knowledge:
    • B12:
      • vitamin B12 is required for DNA replication and inhibition of transcription of DNA to RNA
      • B12 is normally absorbed from gut by the following mechanism:
        • secretion of intrinsic factor by parietal cells in stomach
        • binding of intrinsic factor and vitamin B12 in lumen
        • intrinsic factor- B12 complex is absorbed in terminal ileum through pinocytotic vesicles
    • Folate:
        • folate is required for DNA replication and inhibition of transcription of DNA to RNA
    • lack of B12 or folate means that RNA builds up and the cells become too large
slide125
Causes:
    • causes of vitamin B12 deficiency (pernicious anaemia)
      • lack of intrinsic factor
        • atrophic gastritis - parietal cells are destroyed
        • gastrectomy
      • malabsorption of B12 not related to lack of intrinsic factor
        • tropical sprue or bacterial overgrowth of terminal ileum
        • ileal disease (e.g. Crohn's disease affecting the terminal ileum)
        • fish tape-worm (these attach to intestinal wall, and therefore in large enough numbers, may prevent B12-intrinsic factor complex absorption in terminal ileum)
        • poor diet - rare
slide126
causes of folate deficiency
    • poor diet - especially in alcoholics
    • malabsorption - coeliac disease
    • increased cell turnover (e.g. leukaemia, chronic haemolysis, pregnancy)
    • antifolate drugs (e.g. phenytoin)
slide129
Morphologic Abnormalities:
      • Large RBC's with nuclear-cytoplasmic dyssynchrony
      • Ovalocytes: The large RBC's tend to have an oval-shape.
slide130
Hypersegmented Neutrophils: One of the earliest signs of disease. 5 or 6 lobes
  • Howell-Jolly Bodies: Nuclear fragments seen in Megaloblastic anemia.
slide131

Aplastic Anemia

  • pancytopenia associated w/ a severe reduction in the amt of hematopoietic tissue that results in deficient production of blood cells
  • Etiology:
    • Acquired
      • idiopathic
      • Chemical agents
      • Physical agents
      • Viral infections
    • Inherited
      • Fanconi’s anemia
slide132
Pure red cell aplasia: erythrocyte stem cells are suppressed, but the other formed elements of blood are unaffected
      • Anemia due to isolated depletion of erythroid precursors in the marrow, and may be acute or chronic.
  • Lab Findings:

- Normochromic, normocytic or macrocytic anemia

- Reticulocytes are decreased or absent because it is hypoproliferative.

- BM: hypocellular or dry tap

reduction in all cell lines

hemolytic anemias increased destruction
HEMOLYTIC ANEMIAS (Increased Destruction)
  • Grp of dso that can be inherited, acquired,or drug-induced
  • Char by an increased red cell destruction or shortened survival of the RBC
  • Char by increased BM activity, polychromasia, nucleated RBCs and an increased reticulocyte count w/ stress reticulocytes
slide135

Hemolytic anemias share the ff. features:

1. shortened red cell life span, that is, premature destruction of red cells

2. elevated erythropoietin levels and increased erythropoiesis in the marrow & other sites

3. accumulation of products of Hgb catabolism, due to an increased rate of red cell destruction

slide136
HEMOLYTIC ANEMIAS
  • Acquired
    • Immune-mediated

- Autoimmune

- Alloimmune (Transfusion)

- Drug-induced

    • Microangiopathic
    • Infection
  • Hereditary
    • Enzymopathies
    • Membranopathies
    • Hemoglobinopathies
slide137

INTRINSIC DEFECTS

Hereditary Spherocytosis

  • abnormal cell membrane assoc cytoskeleton causing red cells to be spherical and fragile
  • principle defect is an abnormality of the membrane protein ankyrin
  • Lab findings: Normocytic, hyperchromic anemia (normal MCV and increased MCHC)

- increased pigment catabolism, erythroid hyperplasia, & reticulocytosis

- red cells with increased OFT

slide139
Glucose-6-Phosphate Dehydrogenase Deficiency
  • Normal: G6PD metabolises glucose, and forms small amounts of ATP (which maintains the cell cytoskeleton and membrane) and NADPH (which mops up free radicals)
  • G6PD def renders the cell susceptible to damage by free radicals
  • an X-linked recessive condition, in which haemolytic crises are precipitated by infections or certain drugs
  • Lab findings: poikilocytes & spherocytes, & Heinz bodies (stain w/ methyl violet)
slide141
HEMOGLOBINOPATHIES
  • Normal Hgb:

HbA / HbF / HbA2 (adult)

Hb Gower-1 and 2 / Hb-Portland (embryonic)

slide142
THALASSEMIA
  • Caused by impaired production of one of the polypeptide chains of the Hb molecule
  • Epidemiology: Mediterranean, African & Asian ancestry
  • autosomal recessive disease
  • Types according to clinical severity:

thalassaemia major = homozygote;

thalassaemia minor = heterozygote

  • Types according to molecular defect:

beta thalassaemia

alpha thalassaemia

slide143
Beta-Thalassemia
  • Major (Homozygous state):

- severe hypochromic, microcytic anaemia, hepato- splenomegaly, marrow hyperplasia causing skeletal deformities, haemochromatosis develops with repeated transfusions

  • Minor (Heterozygous states):

- reduction in HbA, but increase in HbA2; mild anaemia with hypochromia

slide145
Alpha-Thalassemia
  • note that there are 4 copies of the alpha globin gene (not 2), and therefore four possible degrees of alpha thalassaemia exist
        • 3 good copies - silent carrier
        • 2 good copies - mild anaemia with microcytosis
        • 1 good copy - moderate haemolytic anaemia with hypochromia and mycrocytosis; HbH (tetramer of beta)
        • 0 good copies - lethal in utero (hydrops fetalis)
slide149

Thalassemia Major

Patient with thalassemia major due to heterozygous hemoglobin E/B thalassemia. Note prominent target cells, anisopoikilocytosis, and three nucleated red cells (normoblasts)

slide150
Sickle Cell Disease
  • Endemic to Sub-saharan Africa, due to heterozygous advantage conferred against Falciparum Malaria (infected RBC's preferentially sickle and are thus taken to the spleen and sequestered, limiting the spread of infection)
  • PATHOGENESIS: Point-mutation of Glu  Val at 6th position of beta-globin chain
  • Pathophysio:abn Hgb polymerises at low O2 saturation causing abnormal rigidity and deformity of red cells and become abnormality fragile (and undergo haemolysis and sludge in small vessels)
  • autosomal recessive, with a point mutation in beta gene forming an abnormal HbS; more common in Negroes
slide151
Lab. Findings

Smear:normochromic, normocytic anemia, increased polychromasia, normoblasts are present, numerous target cells, Howell-Jolly and Pappenheimer bodies are present, sickle cells

OFT decreased

BM: normoblastic hyperplasia w/ increased iron storage

Electrophoresis: no HbA, 80% HbS (SCD)

slide152

Sickle Cells (SEM)

Scanning electron micrograph (SEM) showing sickle cells obstructing small vessel.

slide156
EXTRINSIC DEFECTS

Immune Hemolytic Anemias

  • Dso in w/c erythrocyte survival is reduced because of the deposition of Ig &/or ` complement on the red cell membrane
  • Classification:

1. Autoimmune Hemolytic Anemia

2. Isoimmune Hemolytic Anemia

3. Drug-induced Hemolytic Anemia

  • LAB: (+) direct & indirect antiglobulin tests
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Traumatic Hemolytic Anemia
  • Char by striking morphologic abn of the red cells, w/c include fragments (schistocytes) & irregularly contracted cells (triangular cells, helmet cells)
  • MICROANGIOPATHIC HEMOLYSIS: RBC's being damaged by intravascular fibrin-clots, in small vessels. DIC, TTP, HUS.
  • MACROANGIOPATHIC HEMOLYSIS: Damage by artifical heart valves.