Laboratory Medicine

LABORATORY MEDICINE

MODULE

Red Blood Cell Disorders

Dr. Magdy Mohamed EIShamy

Professor of Pathology

Faculty of Medicine,

Tabuk University

Lab Med RBCs Disorders Or M EIShamy

Complete Blood Cell Count (CaC)

(Complete Blood Picture)

Components of a CBC:
1~ Hemoglobin (Hb), RBC count, Hematocrite (Hct) or Packed cell
volume (PCV)

2~ RBC indices, RBC distribution width (RDII\!)

3~ Total Leucocytic Count (TLC) with a Diffe..ential count,

4· Platelet count

5- Evaluation of the Pe ..iphe..al blood mo..phology: Blood film

1 Dr Magdy E1Shamy--RBCs Disorders--­

 Laboratory Medicine

T es of Normal Hb detected b Electro horesis in Adults:

- HbA has 2a12~ globin chains (97%).
- HbA2 has 2a/2li globin chains (2%).
- HbF has 2a12y globin chains (1%).

Erythropoiesis
- Erythropoiesis is the production of RBCs in the bone marrow and
- is dependent on the release of Erythropoietin from the kidneys.

DISORDERS OF RED BLOOD CELLS

~---,.~
Or less
n 18 commonly
P Iycythe -a

Lab Med. RI3Cs D~"'rJ Dr M EIShamy

Reticulocyte Count
- Marker of effective erythropoiesis (bone marrow response to anemia)
- Reported as a percentage of red cells present in peripheral blood. (normal = 1.5%).
- Corrected reticulocyte count: Corrects for degree of anemia
- 2 • 3% = Normal

- < 2%: poor bone marrow response;

- > 3%: good bone marrow response

Corrected reticulocyte count above 3%

- Good bone marrow response to anemia (Le., effective erythropoiesis)

~: - Hemolytic anemia: sickle, spherocytosis, G6PD, AIHA,

- Acute hemorrhage,
- After treatment of iron deficiency with iron, macrocytic anemia with Vit 812

Corrected reticulocyte count below 2%

- Poor bone marrow response [0 anemia
- Examples: - Aplastic anemia
- untreated iron deficiency anemia;

- Bone marrow metastasis

- Anemia of chronic disease

- Renal failure

Dr ~I FISh.my

2 Dr Magdy E1Shamy--RBCs Disorders--­

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Peripheral blood reticulocytes with methylene blue stain

Red blood cells (reticulocytes) showing thread-like material in the
cytoplasm representing residual RNA filaments (arrow).

Platelet Red Blood cells

Band Eos:inophil
Neutrophiil

Segmented

Lymphocyte
"':;;::=:===:1 iN eu tro phi I
~~~:::>-:

Basophil
Monocyte

Normal peripheral Blood

Showing different types of blood cells

Dr M ~ISh",ny 6

3 Dr Magdy ElShamy--RBCs Disorders--­

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Adult Reference Ranges for Red Blood Cells

Male F ale
-
Hemoglobin (Hb) 13.5 - 17.5 g/dl 12.0 - 16.0 g/dll _..
.. - ­
I
..

Haematocrit (Hct) 41- 53 % 36- 46 %

Packed cell volume (PCV)

..
RBC count 4.5 - 6.0 millionfmm:l 3.5·5.5 millionfmm:'
~

Red Cel'l '"dices:

Mean corpuscula.r vol!ume 80 -1'00 fI
;:(MCV) ( Microcytic Normocytic Macrocytic)
.­
.. I
Mean corpuscular hemoglobin 27 - 32 pg
I ,.

Mean corpuscular hemoglobin 30 - 35 gfdl

concentlration (MCHC) ( Hypochromic
-
Normochromic r MCHC)
Lab />led' RBC. DISorders Dr M EIShamy 7

POLYCYTHEMIA
Definition:
- Polycythaemia is an increase in the blood concentration of red cells, usually
with increase in haemoglobin concentration & haematocrit (packed
cell volume).

Etiology & Classification:

1- Relative Polycythemia: uncommon (Apparent polycythemia)
- results from any cause of dehydration as prolonged vomiting, diarrhea,

11- Absolute Polycythemia: (True polycythemia)

A- Secondary Polycythemia:
- due to i in erythropoietin levels caused by
1- Hypoxia: e.g. Chronic obstructive pulmonary disease (COPD),
high-altitude living, congenital cyanotic heart disease
2- Erythropoietin-secreting tumors:
e.g hepatocellular carcinoma, renal cell carcinoma
Lao Med RBC, Dis,,,d,,,s Dr M EI~j.tl':i1:I'f

4 Dr Magdy ElShamy--RBCs Disorders--­

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B- Primary Polycythemia (Polycythemia vera)

-The increase in red cell mass results from abnormal autonomous proliferation
of the trilineage myeloid stem cells -> 111 RBCs and 1 WBCs & platelets

Symptoms & sig ns: are the result of i blood viscosity

- headache, dizziness, visual disturbances
- Thrombotic events due to hyperviscosity (e.g., deep vein thrombosis)
- Splenomegaly
- Signs of increased histamine -> as ruddy face, pruritus, peptic ulcer disease

Laboratory findings in Polycythemia vera:

- 1 RBC
mass, THb up to 20 g/dl or more, Thaematocrit values up to 75%.

- Leukocytosis (leukocytes >12,000/IJL),

- Thrombocytosis (platelets >400,000/IJL)

- 1 Erythropoietin levels (Increased 02 content inhibits erythropoietin release)

- T Serum uric acid

Complications: Gout
- Due to T breakdown of nucleated cells with release of purines (converted to uric acid)

Lab Med RBCs D.. orP~" 9

ANEMIA
Definition:

Anemia is decrease in level of hemoglobin in the blood below the normal

range usually accompanied by decrease in red cell count and haematocrit

(packed cell volume) (M: 13.5-175 F: 11.5-16.0 g/dl)

General features of Anemia:

depend on the severity of anaemia

- Weakness, fatigue, palpitations, dyspnea on exertion, inability to concentrate an

dizziness.

- Pallor of skin, nails and mucous membranes

- Angina pectoris & intermittent claudication may occur in atherosclerosis

- Sign of an underlying disease

Dr M EISham~ 10

5 Dr Magdy ElShamy--RBCs Disorders--­

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Etiological Classification Of Anemias:

1- Blood Loss: Acute (post hemorrhagic anemia) or Chronic.

II~ Increased Red Cell Destruction (Hemolytic Anemias):

111- Impaired Red Cell Production: due to

1~ Bone marrow hypofunction:
- Aplastic anemia,
- Anemia of chronic disease: e.g. chronic renal failure,
chronic inflammation
- Anemias due bone rna rrow infiltrations by tumo rs

2- Deficiency anemias: e.g

- Iron deficiency anemia
- Megaloblastic anemia (deficiency of Vit. B12 or Folic acid)

Lab M(.~(j RUes DISQrdm:;, Or M EIShamy 11

Classification of anemia based on

size of red cells (MCV)

= Mean Corpuscular Volume (MeV)

=Average volume of RBCs =(Normal: 80-100 fl)

- Used to classify anemia into:

- Microcytic (MCV < 80): e.g - Iron deficiency anemia,
- Thalassemia,
- Anemia of chronic disease

• Macrocytic (MCV > 100): e.g. Folate deficiency or Vit. B12 deficiency

- Normocytic (MCV 80 -100): e.g - Hemolytic anemias,

Lol:) Me,j RBCs D'sorders
- Aplatic anemia,
- Anemia of ch ronic disease
- Bone marrow metastasis
- Chronic renal failure
Dr M EIStla,r,}' 12

6 Dr Magdy ElShamy--RBCs Disorders--­

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Classification of anemia based on

Mean Corpuscular Hemoglobin Concentration

(MCHC)

- Normal MCHC: ----> Normochromic (N= 30-35 g/dl)

- Decreased MCHC: -> Hypochromic

-Increased MCHC: ----> ego Hereditary spherocytosis

lab Mod' HBC. fJ<s=,,-,r. Dr M. E:Sr,amy 13

Anemias of blood loss

1- Acute blood loss (----> Acute post hemorrhagic anemia)
- It follows loss of large amounts of blood:
e.g. (traumatic Hge , perforated peptic ulcers, ruptured varices ... etc

- The anemia is Normocytic Normochromic

MechanislIJ of Recovery
- Rise in the erythropoietin level -> stimulates bone marrow hyperplasia -,
increased red cell production within several days -, peripheral blood shows
Reticulocytosis in 5-7 days

2- Chron·c blood loss:

- as from lesions of gastrointestinal tract, gynecologic disturbances

- With chronic blood loss -> iron stores are gradually depleted ----> iron
deficiency anemia

- Iron is essential for hemoglobin synthesis and effective erythropoiesis???

Lab Moo RBCs Disorders Dr M E4Sharny 14

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Aplastic Anemia
Definition:

- characterized by Pancytopenia with 1 hemopoietic tissue in bone marrow

Causes:

- usually acquired, may be secondary to drugs, cytotoxic drugs, chemicals, toxins,

irradiation, infections

- This leads to suppression or deficiency of multipotent myeloid stem cells

Clinical features:
- Weakness, Fatigue due to Anemia
- hemorrhagic manifestations, due to Thrombocytopenia
- fever and recurrent infections due to Neutropenia

Laboratory findings:
• Anemia: normocytic normochromic

- Leucopenia: (WBC ! 2000/cmm),

- Thrombocytopenia,

- ReticuJocytopenia ????

- Hypocellular bone marrow

- Complete recovery occurs in less than 10% of cases.

15
Dr M EISharTI,

Iron deficiency anemia

It is the most common anemia.

Iron deficiency --> Decreased synthesis of heme

Causes of iron deficiency:

1- Dietary deficiency: seen in elderly, in children and in poor.
2- Increased demand: in children and pregnant women.
3- Decreased absorption: malabsorption, after gastrectomy
4- Chronic blood loss due to gynecological (menstrual bleeding) or GIT
causes (hookworm infestation, Gastritis, carcinomas as colorectal cancer)

Clinical features:
1- General features of anemia
2- Special features: uncommon
- Koilonychia (concave nails), brittle hair,

- Glossitis, Angular cheilitis (painful fissuring of mouth corners)

- Plummer-Vinson syndrome (chronic iron deficiency + Dysphagia

due to the presence of esophageal web or mucosal fold in post-cricoid region)

- Features of underlying cause

L;:,b Mea R.Be!=! .l.:J,orders Dr. M EIShemy

8 Dr Magdy E1Shamy--RBCs Disorders--­

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!ngular cheilitis Angular cheilitis

& Glossitis

Koilonychia in Iron defiency

Lab Med RBC. Disorders Dr M EIShamy 17

Laboratory findings:
- Microcytic hypochromic anemia (l MCV, 1 MCHC)

- Decreased serum iron

- Decreased serum ferritin « 30 ng/mL)

- Increased total iron-binding capacity (TIBC) (N: 300 1J9/dL)

- Decreased % saturation of iron binding protein (transferrin) (N: 33%)

- Leukocyte count is usually normal. ± Eosinophilia occurs in hookworm

infestations.

- The platelet count is often raised (unknown),

Lab Mf!d. RUes Disorue:! S Dr M EISMmy 18

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Microcytic Hypochromic Anemia

The RBC's are smaller than normal and have an increased zone of

central pallor

19

Macrocytic anemias is defined as an anemia in which the MeV is

increased more than 100 fL

Megaloblastic anemias
Megaloblastic anemia is characterized by the appearance in the bone marrow

of abnormal large red cell precursors called megaloblasts.

Pathog enesis:

- Folate or vitamin 8 12 deficiency -> Impaired DNA synthesis -> Delayed

nuclear maturation -> Causes a block in cell division -> leading to large,

nucleated hematopoietic cells called Me aloblasts

- Cellular RNA and protein synthesis continue -, Cytoplasmic volume continues

to expand.

So,
- RBCs have megaloblastic maturation in bone marrow -> form
macro-ovalocytes in peripheral blood

- WBC proliferation -+ Giant metamyelocytes in bone marrow -)

H erse mented Neutro hils (>5 lobes) in peripheral blood

Lab Med' Rae. D,SQ, 'rs Dr M [IS~",,, II 20

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Megaloblastic Anemia due to

Vitamin 812 Deficiency

Causes of Vit 812 deficiency:

1- Dietary deficiency:
- Rare (because 812 is stored in the liver & suffcient for years),
- but seen in strict vegetarians (diet with no animal proteins)

2- Decreased absorption: which may be caused by

~ Decreased intrinsic factor (IF) associated with gastrectomy
or pernicious anemia

- Intestinal malabsorption due to parasites (fish tapeworm),

Bacterial overgrowth or Crohn's disease of ileum

Lab Med RBCs Disorder" Dr M EIShamy 21

Signs and symptoms of 812 deficiency:

1- Weakness due to anemia, glossitis (sore tongue) with atrophy of papillae
2- Mild jaundice
3- CNS symptoms: in P.A.
- Peripheral neuropathy affecting sensory neurones,
- Subacute combined degeneration of the spinal cord --->
spasticity, ! coordination, ! sensation in lower limbs, dementia

Laboratory findings:

1- Blood film: Macrocytic normocytic anemia with oval macrocytic RBCs

2- i MCV (> 100 fl)

3- Leucopenia with Hypersegmented Neutrophil (>5 lobes)

4- Mild Thrombocytopenia

5- Low serum B12 level

6- Serum autoantibodies against parietal cells or intrinsic factor (in P.A)

7- Schilling test: +ve in P.A. oral administration of radioactive vitamin 8 12

8- Gastric Function Test: reveals Achlorhydria (in P.A.)

Treatment: intramuscular vitamin 812

Lab Med R8Cs D,sorders Or M FISIl3Il',' 22

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Megaloblastic anaemia
Peripheral blood Showing enlarged red blood cells (oval macrocytes) and
hypersegmented neutrophil (arrow) with nine lobes.

labM"d RBCs Oi!ltll~ Dr M EISharny 23

Megaloblastic Anemia due to

Folate Deficiency

Causes i elude:
1- Decreased intake:
• Dietary deficiency, seen in chronic alcoholics & elderly

2- Decreased absorption: intestinal malabsorption

3- Increased requirement for folate: during pregnancy, in infancy

4- Decreased 'utilization:
- due to folate antagonists used in chemotherapy as methotrexate

N.B.: Body stores of folate are small and depleted within 3-4 months of
cessation of dietary intake

Lab Med RBe. DISorders Dr M EJ ill\'

12 Dr Magdy E1Shamy--RBCs Disorders--­

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Signs and symptoms of folate deficiency:

- Megaloblastic anemia

- But No neurologic symptoms

- Increased risk for open neural tube defects in the fetus:
due to decreased maternal intake of folate prior to conception

Laboratory findings:
1- Macrocytic anemia with oval macrocytic red cells, i Mev
2- Decreased serum folate but dereased Red Cell Folate level
is more accurate (best screening test)

Treatment:
Oral folic acid 5 mg daily for 4 months.

Lab Med H6C. Disorders Dr. M EIShamy

OLYTIC ANEMIAS
Definition:
are anemias that result from increased destruction of red cells
with a reduction of the circulating life-span (normally 120 days).

Destruction of red cells can occur intravascular or extravascular

AM Intravascular hemolysis:
- hemolysis occurs within the vascular system

- Examples: as in • immunohemolytic anemias,

• mechanical trauma (e.g. mechanical heart valve)

B- Extravascular hemolysis: (the more common)

- Red cell destruction occurs
largely within the mononuclear phagocytic cells
of the spleen (most common site) and liver.

WbJ·,kd R6Cs ~ot$

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Etiology of Hemolytic Anemias

A- Intrinsic (lntracorpuscular) Causes: mostly Hereditary
1- Membrane protein abnormlities: Hereditary spherocytosis

2- Enzyme deficiencies: G6PD deficiency

3- Disorders of hemoglobin synthesis (Hemoglobinopathy)

- Deficient globin synthesis: Thalassemia syndromes
- Abnormality in globin chain structure: Sickle cell anemia,

B- Extrinsic (Extracorpuscular) Causes: usually Acquired

1- Immunohemolytic anemias: Antibody mediated
a- Autoimmune hemolytic anemia (AIHA)
b-Incompatible blood transfusions
c- Hemolytic disease of the newborn: (Rh disease of newborn)
d- Drug induced hemolytic anemia

2- Infections: e.g. malaria

3- Trauma: e.g. in patients with mechanical heart valves.

Lab Mn.:i RBCs Dlsljlders Or ~.1 EI~h.my 27

General Features of Hemolytic Anemias

All are characterized by:
1· Increased rate of red cell destruction,

2- Erythroid hyperplasia within the bone marrow -> Reticulocytosis

3- Hemolytic jaundice: heme-> bilirubin -> unconjugated hyperbilirubinemia

4- Pigment stones in gall bladder (? 1 bilirubin in bile + long-standing hemolysis)

5- Generalized hemosiderosis or in severe cases, 2ndry hemochromatosis

due to excess iron accumulation

6- ExtramedUllary hematopoiesis in the spleen & liver of infants

7- Enlarged liver and spleen (splenomegaly) due to hyperplasia of the

mononuclear phagocyte system and extramedullary hematopoiesis.

8- Decreased serum hepatoglobin (hemoglobin-binding protein in the blood)

lab Med· RBC s Disorders Or M EI$hamy

14 Dr Magdy ElShamy--RBCs Disorders--­

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Hereditary Spherocytosis
Definition:
- Hereditary disorder characterized by
- defect in the red cell membrane proteins (mostly Spectrin)
-> lin the RBC surface membrane ---> red cells become Spherocytes

Pathog enesis:
- Spherocytes are less deformable,
- Destroyed in spleen by macrophages (i.e. Extravascular hemolysis)

Clinical features:
- Anemia, jaundice, increased risk for pigment gallstones,
- Splenomegaly (greater & more common than in any other HA)
- In long-standing cases there is prominent systemic hemosiderosis.

Lab Med HBCs DlsolJms Or M EISh.my 29

Lab Finding:
1- Blood film:
RBGs -, Spheroidal in shape with absence of the central zone of pallo

2- Decreased Hb level

3- Normal MCH with increased MCHC ? hyperchromic

4- General Findings of Hemolytic Anemia: as

- i Reticulocytic count (reticulocytosis),
- i Serum indirect bilirubin, i urine urobilinogen
- 1 Serum haptoglobin
5- Special test:

Increased osmotic fragility of RBCs if placed in hypotonic salt solutions

Treatment:
Splenectomy for those who are symptomatic
- It results into rise in Hb, disappearance of jaundice,
increase in red cell life span, but spherocytosis persists.
Lab Mad RBe. D,sorders Dr M EISh.my 30

15 Dr Magdy ElShamy--RBCs Disorders--­

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Hereditary spherocytosis
The blood smear shows many round erythrocytes with decreased diameter,
dense staining & No central area of pallor (Spherocytes). (arrows).

lab Med RBCs D'SDCdGrs Dr M EISharny 31

Sickle Cell Disease

Definition:
- Hereditary disorder characterized by
- presence of abnormal hemoglobin (Sickle hemoglobin, HbS)
- resulting from replacement of the normal glutamic acid by val ine at the sixth
position of the IJ-globin chain

Incidence: sickle cell anemia is the most common form offamilial hemolytic anemi

(N.B.: The normal adult red cell contains:

97% HbA (azlJz), + 2% HbAz (az~z) + 1% Fetal Hb (HbF, azyz).

Types of Sickle Cell Disease:

1- Homozygous state (55): ----> Disease = Sickle cell anemia
- In homozygotes All HbA is replaced by HbS

2- Heterozygous state (AS): ----> sickle cell trait

- Only about 40% of HbA is replaced by HbS.
- The RBCs of heterozygotes have little tendency to sickle in vivo. (?Iow HbS)
- Patients have Fewer symptoms than those with sickle disease
- Present in 8% of black Americans and in 30% of black Africans
L2Ib Med RBC:. DI:.rxap.rs Dr M EIShamy 32

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Pathogenesis:
Two mechanisms are responsible for clinical manifestations

First mechanism:
The sickled red cells are removed by mononuclear phagocyte cells ---. chronic
extravascular hemolytic anemia

Second mechanism:
- Upon deoxygenation ---> HbS -> undergo polymerization (crystallization) -)
RBCs assume a rigid crescentic, sickle or boat-like shape

- Reoxygenation -> unsickling of red cells; however,

- Repeated episodes of sickling & unsickling ---> irreversibly sickled red cells
-} become rigid & sticky ---> increased adherence to endothelial cells in the
microcirculation.

- Microvascular occlusions -> Vaso-occlusive crises -, ischemic tissue

damage & Pain crises

- Factors which can trigger the sickling of red cells: as

- hypoxemia, infection, inflammation, dehydration, acidosis
Lab Med RBCs D,sorders Dr M EIShamy 33

Clinical fe<l.tures:
- Sickle cell trait: -> Rarely causes symptoms

- Homozygous sickle cell disease: (symptoms appear after 6 th month of life)

1- Symptoms of chronic hemolytic anemia

2- Splenomegaly early in children -> eventually small fibrous nonfunction

spleen by adulthood (autosplenectomy). (?autoinfarction).

3- Sudden Vaso-occlusive or Pain crises:

attacks of Vascular congestion, thrombosis & infarction can affect any
organ, including:
bones, bone marrow (most common)

liver, kidney,

retina, brain,

lung, skin (producing leg ulcers).

4- Increased susceptibility of infections, risk for fatal septicemia,

5- The acute chest syndrome and central nervous system stroke

are the two leading causes of ischemia-related death.
Lab Med RBCs D,sordo'·5 0, M EIShamy

17 Dr Magdy EIShamy--RBCs Disorders--­

 Laboratory Medicine

Lab Finding:
· General Findings of Hemolytic Anemia: as
- ! Hb, ! hematocrit, marked reticulocytosis, hyperbilirubinemia.

- Blood film:
- In sickle cell disease: show some irreversibly sickled red cell
- In the sickle cell trait ~ Normal peripheral blood

· Sickling test: Using sodium metabisulfite ~ Sickling of red cells

· Hemog lobin Electrophoresis: * * * *

- show Abnormal Hemoglobin (HbS)
HbAS profile (Trait): - HbS 40 % HbA 60%,
HbSS profile (Disease): - HbS 95%, HbF 5%, No HbA

Prenatal diagnosis of sickle cell anemia:

- by Analysis of DNA in fetal cells to detect the point mutation

Lab Med' RBCs D.sorders Dr M EIShamy 35

Sickle cell anemia (homozygous)

showing many Sickled cells

Dr M [iShamy 36

18 Dr Magdy EIShamy--RBCs Disorders--­

 Laboratory Medicine

Thalassemias

Definition & Etiology:

- The thalassemias are a group of inherited disorders
- caused by mutations that decrease the rate of synthesis of
a- or ~-globin chains.

Types:
a~ Thalassemia
has decreased a-globin chains with relative excess p-chains

p~ Thalassemia
has decreased p-globin chains with relative excess a-chains

Lab Med ROCs Disorders Of M EIShamy 37

a~ Thalassemia

- There are four a-globin genes on chromosome 16,

- the deletion of one, two, three or all four results in a-thalassemia with various severity.

Clinical Disease states:

1- Silent~carrier state: (- a/aa)

- loss of a single a-globin gene -7 production of 75% a chains
- Individuals are completely asym~tomatic and all lab tests Normal

2~ a-thalassemia Trait: (- -/aa) in Asians (- a/- a) in African-Americans

- occur if two of a-globin genes are deleted (inactive) ---> production of 50% a chains

- is often asymptomatic + mild anemia (microcytic hypochromic)

Lab Mad RBCs DI~u:1'.!.e"s Dr M EISham\f 38

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3- Hemoglobin H disease: Hb H W4) (- -1- a)

- occur if three of the four a-globin genes are deleted --> production of 25% a chains

- increased formation of Hb H (~4)

- Marked Microcytic Hypochromic Anemia

4- Hydrops fetalis: Hb Bart (Y4) (- -1--)

- occur if all the four a-globin genes are deleted --> No a chains are produced

- It is a fatal condition characterized by still birth fetus (lethal in utero)

Dr M fISh'I1n,'

p. Thalassemia
-There are a total of two IJ-globin chai n genes on chromosome 11

- The l3-globin mutations associated with

(1) 1'0, in which no IJ-globin chains are produced; and
(2) I'+'
in which there is reduced p-globin synthesis.

Clinical Disease states: three molecular subtypes

1- n-Tlhalassemia Minor or II-Thalassemia Trait: (~/Wor ~/130)
- Asymptomatic or mildly symptomatic (mild hypochromic microcytic anemia)

2- l\-thatassemia Intermedia: ( 1'+/1'+)

- Severe hypochromic microcytic anemia (Hb 6-10 g/dl) but No transfusions needed

3- p-Thalassemia Major: (1'0/1'0, 1'°11'+)

- Failure of ~-globin chain synthesis with deposition of excess unpaired a chains in
red cells --> insoluble aggregates -, extravascular hemolysis

Lab fMc RBGs [);so,'dors Dr M ((Shanl)' o

20 Dr Magdy ElShamy--RBCs Disorders--­

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Clinical features in fJ-Thalassemia Major:

- Severe hemolytic anemia (hypochromic microcytic anemia)

- Splenomegaly, hepatomegaly, jaundice, & T risk of pigment gallstones

- Lifelong repeated blood transfusions: iron overload -> secondary hemochromatosi~

- Congestive heart failure from secondary hemochromalosis (common cause of death)

- Erythroid hyperplasia in lhe bone marrow

-> "crewcut" skull x-ray or hair-an-end appearance

Lab Findings:
- Severe microcytic hypochromic anemia + Numerous Target cells in blood film
- increased Reticulocyte count
- Serum iron is High
- Hemoglobin Electrophoresis:

Lao Med RBCs 0,,0'00 Dr. M EIShal'l)' 41

assemia
The peripheral blood erythrocytes are hypochromic and microcytic
and show anisocytosis, poikilocytosis, and target cells (arrows).

Lab Med RBCs O,;:;I1jor. 42

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 Laboratory Medicine

Glucose-6-Phosphate Dehydrogenase Deficiency

Definition & Etiology:

- X-linked disorder in which

- RBCs are deficient in glucose-6-phosphate dehydrogenase (G6PD

- resulting in decreased levels of the antioxidant glutathione
- making red cells susceptible to damage (hemolysis) by oxidants

Deficiency of G6PD is due to:

- decreased synthesis
- &/or a decreased half-life (decreased stability)

Lab Med RI3Cs D,sor<Jel" Dr M EI::>hamj' 43

Pathogenesis:
- G6PD deficiency produces No symptoms
- But when the patient is exposed to environmental oxidant injury -)
he develops Attack of red cell damage (Hemolysis)

Examples of oxidant injury: such as

- Drugs (antimalarials, sulfonamides)
- Aspirin (in large doses),
- Infections,
- Favism (due to ingestion of fava beans

How??

- Oxidation of hemoglobin -> forms Heinz bodies -> are "eaten" by splenic

macrophages (extravascular hemolysis)

Clinical features:
- The G6PD gene is on the X chromosome
- Thus, affected males are more susceptible to oxidant injury.
- whereas most carrier females are asymptomatic,

LBb Med RBes Diso"lers Dr M EIShamy 44

22 Dr ~1agdy ElShamy--RBCs Disorders--­

 Laboratory Medicine

Peripheral blood smear from a patient with Glucose-6-phosphate

dehydrogenase deficiency after exposure to an oxidant drug.

Inset: red cells with precipitates of denatured globin (Heinz bodies)

revealed by supravital staining.
Lab Mcd RBes Dls~,dDrs Dr M EIShamy 45

Hemolytic Disease of the Newborn (HDN)

(Erythroblastosis Fetalis)

(Rh Disease of Newborn)

Etiology & Pathogenesis:

- The mother is Rh-negative and the fetus is Rh-positive.

- Rh+ve fetal red cells

--> pass into maternal circulation of Rh-ve mother
-> production of Anti-Rh (anti-D) antibodies in the maternal blood

- In subsequent pregnancies, these IgG antibodies

--> cross the placenta to the blood of the next D-positive fetus
--> immune destruction of fetal red cells (hemolysis)

- Thus, the disorder does Not manifest in the first pregnancy.

Lab Mecl· RBes Disorders Dr. M EIShamy 46

23 Dr Magdy ElShamy--RBCs Disorders--­

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Clinical features:
- Severely affected fetuses may develop hydrops fetalis,
characterized by:
heart failure, generalized edema, jaundice, & intrauterine death

-In less severe cases, the neonate is pale and jaundiced at birth,

Treatment:
Exchange transfusion of the neonate to remove the fetus
antibody coated red cells

Prevention:
- Rh-ve pregnant mother is given injections of anti-D immunoglobulin

Lao Med' RBGs DISorders Dr M EIShamy 47

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