Red Blood Cell Disorders

Question 1

Erythropoiesis

pg. 279

Answer 1

Erythropoiesis and erythropoietin

1. -Definition of erythropoiesis
   a. Production of red blood cells (RBCs) in the bone marrow
   b. Dependent on the release of erythropoietin (EPO) from the kidneys
2. EPO synthesized in the renal cortex by interstitial cells in the peritubular capillary bed.

EPO: synthesized in interstitial cells of peritubular capillary bed

3.Stimuli for EPO release include:

• Hypoxemia (↓arterial PO2), severe anemia, left-shifted O2-binding curve (OBC), high altitude, and decreased O2 saturation (SaO2; carbon monoxide poisoning, methemoglobinemia)

EPO stimuli: ↓PaO2/↓SaO2, left-shifted OBC, high altitude

4.Increased O2 content suppresses EPO release (e.g., polycythemia vera).

↑O2 content ↓EPO

Question 2

Reticulocytes and the reticulocyte count

Answer 2

Reticulocytes and the reticulocyte count

1. Importance of reticulocytes
   a. Newly released RBCs from the bone marrow
   b. Peripheral blood markers of effective erythropoiesis
   c. Effective erythropoiesis refers to a good bone marrow response to anemia.

*Correlates with an increase in synthesis/release of reticulocytes from the bone marrow

Reticulocyte count: measure effective erythropoiesis

Effective erythropoiesis: good bone marrow response to anemia; ↑reticulocyte synthesis/release

2.Easily identified in the peripheral blood with supravital stains.

•Stains detect thread-like RNA filaments in the cytoplasm of young RBCs.

Question 3

Tissue Hypoxia

Answer 3

A. Hypoxia

1. Definition—inadequate oxygenation of tissue
2. Factors contributing to the total amount of O2 carried in blood
   a. Normally, O2 diffuses down a gradient from the atmosphere to the alveoli, to plasma, and into the red blood cells (RBCs), where it attaches to heme groups.
   (1) In the alveoli, O2 increases the partial pressure of O2 (PAO2).
   (2) In the plasma of the pulmonary capillaries, O2 increases the partial pressure of O2 (PaO2).
   (3) In the RBC, O2 attaches to heme groups and increases the O2saturation (SaO2).

O2 diffusion: O2 in atmosphere → ↑PAO2 → ↑PaO2 → ↑SaO2

b. PaO2 and SaO2 are reported in arterial blood gas analyses.
c. O2 content is a measure of the total amount of O2 carried in blood and includes the hemoglobin (Hb) concentration as well as the PaO2and SaO2.

• Decrease in O2 content due to a decrease in Hb, PaO2, or SaO2causes an increase in erythropoietin (EPO).

O2 content = (Hb g/dL × 1.34) × SaO2 + PaO2 × 0.003

3. In hypoxia, there is decreased synthesis of adenosine triphosphate (ATP).
   a. ATP synthesis occurs in the inner mitochondrial membrane by the process of oxidative phosphorylation.
   b. O2 is an electron acceptor located at the end of the electron transport chain (ETC) in complex IV of the oxidative pathway.
   c. Lack of O2 and/or a defect in oxidative phosphorylation culminates in a decrease in ATP synthesis.

Thus–> Hypoxia: ↓ATP synthesis by oxidation phosphorylation.

Question 4

What are the clinical findings of hypoxia?

Answer 4

1- Cyanosis (bluish discoloration of skin and mucous membranes).

2- Confusion

3- Cognitive impairment

4- Lethargy

Question 5

Causes of hypoxemia:

Ischemia

Answer 5

1. Ischemia

Definition—decreased arterial blood flow to tissue or venous outflow of blood from tissue.

b. Examples—coronary artery atherosclerosis, decreased cardiac output, and thrombosis of the superior mesenteric vein
c. Consequences of ischemia
(1) Atrophy (reduction in cell/tissue mass)
(2) Infarction of tissue (localized area of tissue necrosis)
(3) Organ dysfunction (inability to perform normal metabolic functions)

Question 6

Causes of hypoxia:

Hypoxemia

Answer 6

Definition—decrease in PaO2 measured in an arterial blood gas.

Hypoxemia: ↓PaO2

b.Normal PaO2 depends on percent O2 in inspired area, ventilation, perfusion, and diffusion of O2 from the alveoli into the pulmonary capillaries.

Causes of hypoxemia

(1) Decreased inspired PO2 (PiO2)

•Examples—breathing at high altitude and breathing reduced %O2 mist

(2) Respiratory acidosis

(a) Respiratory acidosis is defined as retention of CO2 in the lungs.
(b) Carbon dioxide (CO2) retention in the alveoli always produces a corresponding decrease in Alveolar PO2 (PAO2) which, in turn, decreases both PaO2 and SaO2.
(c) A partial list of causes of respiratory acidosis includes depression of the medullary respiratory center (e.g., barbiturates), paralysis of the diaphragm (e.g., amyotrophic lateral sclerosis), and chronic bronchitis.

Question 7

Causes of hypoxemia:

Ventilation Defect

Answer 7

Ventilation defect

(a) Definition—alveoli are perfused; however, there is impaired O2 delivery to alveoli.
(b) _Respiratory distress syndrome (_RDS; refer to Chapter 17) is an example of a diffuse ventilation defect, where a lack of surfactant causes collapse of the distal airways (called atelectasis) in both lungs (note the arrows in Fig. 2-3).

–Ventilation defect: lung perfused but not ventilated.

Diffuse ventilation defects produce intrapulmonary shunting of blood characterized by pulmonary capillary blood having the same PO2 and PCO2 as venous blood returning from tissue (i.e., a large fraction of pulmonary blood flow has not been arterialized).

Ventilation defect: produces intrapulmonary shunting

Question 8

Causes of Hypoxemia:

Perfusion Defect

Answer 8

Perfusion defect

Definition—alveoli are ventilated but there is no perfusion of the alveoli

Examples—pulmonary embolus and fat embolism.

(b) Perfusion defects produce an increase in *pathologic dead space.

•In pathologic dead space, the exchange of O2 and CO2 does not occur (normal dead space includes the mouth to the beginning of the respiratory bronchioles).

Perfusion defect: ↑dead space

(c) Inspired %O2 from 24% to 28% or greater increases the PaO2 in perfusion defects, because they tend to be less extensive than ventilation defects.

•Other parts of ventilated and perfused lung have normal gas exchange; hence compensating for most perfusion defects (e.g., pulmonary embolus).

Question 9

Causes of Hypoxemia:

Diffusion defect

Answer 9

Definition—decreased diffusion of O2 through the alveolar-capillary interface into the pulmonary capillaries

(b) Examples—interstitial fibrosis, pulmonary edema

Cyanotic congenital heart disease (Tetralogy of fallot) is another cause of hypoxia

• Shunting of venous blood into arterial blood causes a drop in the PaO2.

Question 10

Causes of hypoxia related to Hemoglobin (Hb) abnormalities:

Anemia

Answer 10

Anemia

(1) Definition—decrease in Hb concentration

Anemia: ↓Hb concentration; ↓O2 content

(2) Causes of anemia
(a) Decreased production of Hb (e.g., iron deficiency)
(b) Increased destruction of RBCs (e.g., hereditary spherocytosis)
(c) Decreased production of RBCs (e.g., aplastic anemia)
(d) Increased sequestration of RBCs (e.g., splenomegaly)

Anemia: ↓production Hb/RBCs; ↑destruction/sequestration RBCs

(3) PaO2 and SaO2 are normal.

•Total amount of O2 delivered to tissue is decreased (↓O2content), which has no effect on normal O2 exchange in the lungs.

Anemia: normal Pao2/Sao2; ↓O2 content

Question 11

Methemoglobinemia (metHb)

Answer 11

Methemoglobinemia (metHb)

(1) Definition—Hb with oxidized heme groups (Fe3+)

MetHb: heme Fe3+; cannot attach to O2

MetHb reduction: NADH electrons → cytochrome b5 → cytochrome b5 reductase → heme Fe2+

(2) Causes
(a) Oxidant stresses

• Examples—nitrite- and/or sulfur-containing drugs, nitrates (fertilizing agents), and sepsis

(b) Congenital deficiency of **cytochrome b5 reductase
(3) Pathogenesis of hypoxia
(a) Fe3+ cannot bind O2; hence PaO2 is normal, but SaO2 is decreased.

• ↓SaO2 decreases O2 content, causing an increase in EPO.

MetHb: heme Fe3+; normal PaO2, ↓SaO2

(b) Ferric heme groups impair unloading of O2 by oxygenated ferrous heme in the RBCs (impairs cooperativity).

• MetHb shifts the O2-binding curve to the **left.

MetHb: shifts OBC to left; lactic acidosis.

(4) Clinical findings
(a) Cyanosis at low levels (levels <20%)
(b) Headache, anxiety, dyspnea, tachycardia (levels >20%)
(c) Confusion, lethargy, lactic acidosis (levels >40%)

•Lack of O2 causes a shift to anaerobic glycolysis leading to lactic acidosis.

Question 12

Carbon Monoxide poisoning

Answer 12

CO: leading cause of death due to poisoning

(2) Produced by incomplete combustion of carbon-containing compounds.
(3) Causes include:

•Automobile exhaust, smoke inhalation, wood stoves, indoor gasoline powered generators, and clogged vents for home heating units (e.g., methane gas)

↑CO: car exhaust, smoke inhalation, wood stoves

(4) Pathogenesis of hypoxia
(a) CO has a high affinity for heme groups and competes with O2for binding sites on Hb.

• This decreases SaO2 (if blood is measured with a co-oximeter) without affecting the PaO2.

(b) CO inhibits cytochrome oxidase in the ETC.

• Cytochrome oxidase normally converts O2 into water.
• Inhibition of the enzyme prevents O2 consumption, shuts down the ETC, and disrupts the diffusion gradient that is required for O2 to diffuse from the blood into the tissue.

(c) Similar to metHb, CO attached to heme groups impairs unloading of O2 from oxygenated ferrous heme in RBCs into tissue (impairs cooperativity).

• CO shifts the O2-binding curve to the left.

(d) ↓SaO2 decreases O2 content causing an increase in EPO.
(5) Clinical findings
(a) Cherry-red discoloration of the skin and blood.
(b) Headache (first symptom at levels of 10%–20%)
(c) Dyspnea, dizziness (levels of 20%–30%)
(d) Seizures, coma (levels of 50%–60%)
(e) Other findings—atraumatic rhabdomyolysis (myoglobin binds CO and prevents normal muscle function), delayed neurologic deficits (e.g., memory deficits, apathy)

Laboratory findings

a) ↑CO levels in blood if measured with a co-oximeter.
(b) Lactic acidosis (shift to anaerobic glycolysis)

CO poisoning: normal PaO2, ↓SaO2, lactic acidosis (hypoxia)

Treatment

(a) Administer 100% O2 therapy with nonrebreather mask or endotracheal tube.
(b) Hyperbaric oxygen therapy

Question 13

Factors causing a left-shift of the OBC

Answer 13

Decreased 2,3-bisphosphoglycerate (2,3-BPG)

(a) 2,3-BPG is an intermediate of glycolysis in RBCs and is formed by conversion of 1,3-BPG to 2,3-BPG.
(b) Stabilizes the taut form of Hb, which ↓O2 affinity and allows O2 to move into tissue.
(2) Other factors include CO, alkalosis, metHb, fetal Hb, and hypothermia

COHb and MetHb: ↓SaO2, normal PaO2, left-shifted OBC

(3) All factors that shift the OBC to the left increase affinity of Hb for O2 with less release of O2 to tissue.

•Example—at the capillary PO2 concentration in tissue, a right-shifted OBC (↑2,3-BPG, acidosis, fever) has released most of its O2 to tissue (80% to tissue), whereas a left-shifted OBC still has most of its O2 attached to heme groups (only 20% to tissue; see Fig. 2-5).

Right-shifted OBC: ↑2,3-BPG, fever, acidosis, high altitude

Question 14

Thalassemia

Answer 14

1. Epidemiology
   a. Definition—decrease in α- or β-globin chain synthesis
   b. Autosomal recessive disorders
   c. α-thal is common in Southeast Asians, people who live on the African west coast, and in blacks (prevalence of 5%).
   d. β-thal is common in blacks, Greeks (prevalence 15% to 30%), and Italians.

Blacks can have α- or β-thalassemia

Question 15

What is the Pathogenesis of alpha-Thalassemia?

Answer 15

Decrease in α-globin chain synthesis is due to gene deletions.

• Four genes control α-globin chain synthesis.
  b. One gene deletion produces a silent carrier.

•Not associated with anemia

c. Combination of two gene deletions is called α-thal trait.
(1) Produces a mild anemia with a normal to increased RBC count.

•There is no consensus as to why the RBC count is normal to increased, when the Hb and Hct are decreased; however, it is a very useful clinical finding.

α-thal trait: mild anemia; N/↑RBC count.

(2) In the black population, it is associated with a loss of one gene on each chromosome (trans: α/− α/−; see Fig. 12-11A)

Black α-thal trait: trans α/− α/−

(3) In the Southeast Asian population, it is associated with a loss of both genes on the same chromosome (cis: −/− α/α; see Fig. 12-11B)

•Increased risk for developing more severe types of α-thal, because one chromosome completely lacks α-globin genes.

Southeast Asian α-thal trait: cis −/− α/α; danger severe types

d. Combination of three gene deletions is called HbH (four β-chains) disease.
(1) Associated with a severe hemolytic anemia

• Excess β-chain inclusions cause macrophage destruction of RBCs (hemolytic anemia).

(2) Hb electrophoresis detects HbH.

HbH: 3 gene deletions; 4 β-chains; severe hemolytic anemia.

e. Combination of four gene deletions is called Hb Bart (four γ-chains) disease
(1) This combination is incompatible with life.
(2) Hb electrophoresis shows an increase in Hb Bart.

Hb Bart: 4 γ-chains; incompatible with life.

Question 16

Laboratory findings in alpha-thal trait:

Answer 16

f. Laboratory findings in α-thal trait
(1) Decreased MCV, Hb, and Hct
(2) Increased RBC count
(3) MCV/RBC count ratio <13.
(4) Target cells inconsistently present
(5) Teardrop RBCs inconsistently present
(6) Normal RDW, serum ferritin, serum FEP, and Hb electrophoresis.

α-thal trait: ↓HbA, HbA2, HbF (normal electrophoresis); ↑RBC count

Hemoglobin electrophoresis is normal in α-thal trait, because all Hb types require α-globin chains. The Hb concentration is decreased; however, the relative proportions of the normal Hbs remains the same.

g.α-thal trait is a diagnosis of exclusion.

•Usually there is a family history of members with a mild microcytic anemia, normal Hb electrophoresis, and normal iron studies.

h.There is no treatment

Question 17

What si the pathogenesis of Beta-thalassemia?

Answer 17

a. Decrease in β-globin chain synthesis.
(1) Mild anemia is most often due to DNA splicing defects.
(2) Severe anemia is due to a nonsense mutation with formation of a stop codon.

•Premature termination of β-globin chain synthesis or absent β-globin chain synthesis

β-thal: mild—DNA splicing defect; severe—stop codon

b.Normal synthesis of α-, δ-, and γ-globin chains

*Normal β-globin chain synthesis is designated β; some β-globin chain synthesis is designated β+; absence of β-globin chain synthesis is designated β°.

β-thal minor: β/β+

(1) Mild microcytic anemia
(2) Decreased MCV, HB, and Hct
(3) Increased RBC count
(4) MCV/RBC count ratio <13
(5) Target cells consistently present
6) Teardrop RBCs present (see Fig. 12-12B)

•Due to damage of the RBC membrane from removal of excess globin chains by splenic macrophages

(7) Normal RDW, serum ferritin, and serum FEP

•Serum FEP is normal because heme synthesis is normal.

(8) Hb electrophoresis (see Fig. 12-7C)
(a) HbA (α2/β2) is decreased, because β-globin chains are decreased.
(b) Corresponding increase in HbA2 (2α/2δ) and HbF (2α/2γ)

β-thal minor: ↓HbA; ↑RBC count, HbA2, HbF; normal RDW; target cells, tear drop cells

(9) No treatment

Question 18

Beta-thalassemia Major (Cooley anemia)

Answer 18

β-Thal major (Cooley anemia; βo/βo or βo/β+)

β-thal major: β°/β° or βo/β+

(1) Severe hemolytic anemia
(a) RBCs with α-chain inclusions are removed by splenic macrophages

•Marked increase in unconjugated bilirubin (UCB; jaundice)

(b) RBCs with α-chain inclusions undergo apoptosis in the bone marrow (ineffective erythropoiesis).

β-thal major: severe hemolytic anemia; EMH; **hair-on-end skull x-ray

(2) EMH and accelerated erythropoiesis
(a) Hepatosplenomegaly from excessive hematopoiesis
(b) Radiographs of the skull show a hair-on-end appearance (see Fig. 12-3).
(3) Increased RDW due to increased size variation (see Fig. 12-12B)
(4) Increase in reticulocytes, teardrop cells, Howell-Jolly bodies (nuclear remnants), and nucleated RBCs (see Fig. 12-12B)
(5) Hb electrophoresis (see Fig. 12-7D)
(a) No synthesis of HbA
(b) Corresponding increase in HbA2 and HbF

β-thal major: no HbA; ↑HbA2, HbF, RDW, reticulocytes

(6) Treatment
(a) Blood transfusion

• Danger of iron overload (called hemosiderosis)
• Requires chelation therapy with desferrioxamine

(b)Bone marrow transplantation (only curative approach)

Question 19

Sickle Cell Disease

Answer 19

1. Epidemiology
   a. Autosomal recessive disorder
   b. Most common hemoglobinopathy in individuals of African descent

•Highest prevalence (~30%–40%) is in sub-Saharan Africa

HbSS anemia: intrinsic defect, predominantly extravascular hemolysis.

•Mild component of intravascular hemolysis

d. Missense point mutation with substitution of valine for glutamic acid at the sixth position of the β-globin chain
e. Heterozygote condition (sickle cell trait, HbAS) has no anemia.

•Present in ~10% of the black population

f. Homozygous condition (HbSS) produces severe anemia.
g. Using an example of a pedigree with two people with sickle cell trait:
(1) Normal child 25%
(2) Sickle cell trait 50%
(3) Sickle cell disease 25%
h. Protective against Plasmodium falciparum malaria

Trait × trait: 25% normal, 50% trait, 25% disease

Question 20

What is the pathogenesis of Sickle Cell Disease?

Answer 20

Pathogenesis

a. Hemoglobin S molecules aggregate and polymerize into long needle-like fibers when deoxygenated.
(1) RBCs assume a sickle or boat-like shape.
(2) O2 inhibits sickling.

HbS molecules aggregate and polymerize when deoxygenated; O2 inhibits sickling

b. Causes of sickling
(1) Sickle hemoglobin (HbS) concentration >60% is the most important factor for sickling.

•HbS concentration is too low in HbAS (<50%) to produce sickling in the peripheral blood.

(2) Factors that increase the concentration of deoxyHb and increase the risk for sickling include:
(a) Acidosis, which shifts the OBC to the right, causing O2 release from RBCs and leading to an increase in deoxyHb

(b) Volume depletion, where intracellular dehydration causes an increase in concentration of deoxyHb

(c) Hypoxemia, where a decrease in arterial P O2 decreases the O2 saturation of Hb, which increases the amount of deoxyHb

Sickling: ↑HbS, ↑deoxyHb (acidosis, volume depletion, hypoxemia)

c. Reversible and irreversible sickling
(1) Initial sickling is reversible with administration of O2.

•O2 inhibits sickling.

(2) Recurrent sickling causes irreversible sickling due to membrane damage.
(a) Influx of calcium ions cross-links membrane proteins, causing the egress of K+ and H2O and leaving the cell dehydrated.
(b) Number of irreversibly sickled cells correlates with the severity of hemolysis.
(c) Irreversibly sickled cells are sequestered and are extravascularly removed by macrophages in the spleen and liver.

Irreversibly sickled cells: dehydrated; correlate with degree of severity of hemolysis; extravascular removal.

d. Microvascular occlusions (vasoocclusive crises) produce ischemic damage.

(1) Sickled cells are sticky because of increased expression of adhesion molecules on their surface; this enables them to stick to and damage endothelial cells in the microvasculature.
(2) Microvascular occlusion leads to ischemic damage of tissue.

Sickle cells: ↑expression of adhesion molecules; stick to and damage endothelial cells in microvasculature

e. HbF prevents sickling

(1) Increased HbF at birth prevents sickling in HbSS until 5 to 6 months of age.
(2) Hydroxyurea increases the synthesis of HbF.
(3) HbF has a high affinity for O2, which inhibits sickling.

HbF prevents sickling: hydroxyurea ↑HbF synthesis

f. Key pathologic processes in homozygous sickle cell disease include:
(1) Severe hemolytic anemia
(2) Painful vasoocclusive crises

HbSS anemia: severe hemolytic anemia; vasoocclusive crises

Question 21

What are the clinical findings of Sickle Cell Disease?

Answer 21

3. Clinical findings in homozygous sickle cell disease (HbSS)
   a. Dactylitis (hand-foot syndrome)
   (1) Painful swelling of the hands and feet

•Infarctions in the metacarpal bones (aseptic necrosis)

(2) Occurs in infants (usually 6–9 months old) and is rarely seen after 2 years of age

Dactylitis: aseptic necrosis in metacarpal bones; MC presentation in infants

b.Acute chest syndrome

(1)Definition

•New segmental lung infiltrate associated with chest pain.

(2) Most common cause of death in young people with sickle cell disease
(3) Causes include:
(a) Pneumonia

•Streptococcus pneumoniae, Mycoplasma, Chlamydia, viruses

(b) Bone infarction with fat embolism
(4) Clinical findings include:

• Chest pain, wheezing, dyspnea, pleuritic chest pain, pleural effusion, and cough.

(5) Arterial blood gas shows hypoxemia
(6) Chest x-ray shows lung infiltrates

Acute chest syndrome: MCC death in young people

c. Avascular necrosis of femoral head

d.Autosplenectomy

(1) Spleen is enlarged but dysfunctional by age 10 to 12 months.

• Nuclear remnants (Howell-Jolly bodies) appear in RBCs, indicating loss of macrophage function in the spleen (see Fig. 12-24C).

(2) Spleen is fibrosed and smaller in young adults.

•Most authors refer to this stage as “autosplenectomy.”

Howell-Jolly bodies: sign of splenic dysfunction

Autosplenectomy: spleen fibrosed/smaller

e. Increased susceptibility to infections
(1) Risk for infection is due to a dysfunctional spleen with impaired opsonization of encapsulated bacteria.
(2) Children are at risk for S. pneumoniae sepsis.
(a) This is a common cause of death in children.
(b) Prophylactic penicillin is recommended.
(3) Increased risk for osteomyelitis

• Most often due to Salmonella paratyphi and less frequently to Staphylococcus aureus

Pathogens: S. pneumoniae sepsis, Salmonella paratyphi osteomyelitis

f.Aplastic crisis

(1) Most frequently associated with a parvovirus infection
(2) No reticulocytes in the peripheral blood (reticulocytopenia)

Aplastic crisis due to parvovirus; no reticulocytes

g.Sequestration crisis

(1) Associated with rapid splenic enlargement and entrapment of sickled RBCs (drop in hemoglobin) and blood causing hypovolemia
(2) Usually occurs in the first 2 years of life
(3) Reticulocytosis present in the peripheral blood

Sequestration vs. aplastic crisis: reticulocytosis, reticulocytopenia, respectively

h. Increased risk for calcium bilirubinate gallstones.

Calcium bilirubinate gallstones

i. Strokes may occur in children between ages 2 and 5 years.

(1) Common cause of death in children
(2) 70% recurrence rate

Strokes common in children; common cause of death in children

j. Recurrent leg ulcers

•Commonly occur above the medial or lateral malleolus

Recurrent leg ulcers around malleoli

k. Proliferative retinopathy

•Commonly leads to blindness

Proliferative retinopathy → blindness

l. End-stage renal failure occurs after 40 years of age.

End-stage renal failure after 40 years old

Question 22

Renal findings in Sickle Cell Trait:

Answer 22

Sickling occurs in peritubular capillaries in the medulla

• O2 tension is normally low enough in the medulla to induce sickling in trait and disease.

b. Microhematuria occurs because of microinfarctions in the kidneys.

• Always order a sickle cell screen in any black person with unexplained hematuria.

c. Renal papillary necrosis may occur.

•Loss of the renal papillae results in a loss of concentration and dilution of urine.

Sickle cell trait: no anemia; microhematuria; potential for renal papillary necrosis

Question 23

Laboratory findings in sickle cell trait and disease

Answer 23

a.Sickle cell screen

•Sodium metabisulfite reduces O2 tension, which induces sickling in a test tube.

Screen: sodium metabisulfite ↓O2 tension, induces sickling

b. Hb electrophoresis (see Fig. 12-7E and F)
(1) HbAS (trait) profile: HbA 55% to 60%, HbS 40% to 45%
(2) HbSS (disease) profile: HbS 90% to 95%, HbF 5% to 10%, no HbA
c. Peripheral blood findings
(1) Normal peripheral blood smear in HbAS
(2) Sickle cells, target cells, nucleated RBCs, and Howell-Jolly bodies in HbSS (seeFig. 12-24A)
d. Prenatal screening

•Analysis of fetal DNA is used to detect the point mutation.

HbAS: HbA 55%–60%, HbS 40%–45%

HbSS: HbS 90%–95%, HbF 5%–10%, no HbA

Target cells: excess RBC membrane; sign hemoglobinopathy or alcohol excess