1. Anemia
April 4, 2011
Clinical Medicine I
Patrick Carter MPAS, PA-C

2. Objectives
• Define anemia.
• For aplastic anemia, discuss its:
– Etiology
– Clinical manifestations
– Laboratory findings
– Diagnostic evaluation
– Treatment
• For the following disorders, describe the pathophysiology, clinical
presentation, significant historical and physical findings, diagnostic work-
up, management and patient education issues for:
– Iron deficiency anemia
– Hemolytic anemia
– Vitamin B12 deficiency
– Hereditary spherocytosis
– Folic acid deficiency
– G6PD deficiency

3. Objectives
• Describe the pathophysiology, clinical presentation, significant historical
and physical exam findings, diagnostic work-up, management, prognosis
and patient education issues associated with:
– Sickle cell anemia and related syndromes
– Beta thalassemia major
– Alpha thalassemia trait
– Beta thalassemia minor
• For anemia of chronic disease, discuss its relationship to and significance
as it pertains to:
– Renal failure
– Hypothyroidism
• For acute blood loss anemia, explain its clinical manifestations, laboratory
findings and therapy.
• Discuss the clinical presentation, significant historical and physical exam
findings, diagnostic work-up and treatment for polycythemia vera.

4. Objectives
• For the following disorders, describe the pathophysiology, clinical
presentation, significant historical and physical findings, diagnostic
work-up, management and patient education issues for:
• Hemolytic anemia
• Vitamin B12 deficiency
• Hereditary spherocytosis
• Folic acid deficiency
• G6PD deficiency
• Describe the pathophysiology, clinical presentation, significant
historical and physical exam findings, diagnostic work-up,
management, prognosis and patient education issues associated
with sickle cell anemia and related syndromes

5. Objectives
• For aplastic anemia, discuss its:
• Etiology
• Clinical manifestations
• Laboratory findings
• Diagnostic evaluation
• Treatment

6. Anemia
• For adults, anemia is present if the Hgb/Hct is:
– < 13.5/41 in men
– < 12/37 in women
• Pathophysiologic classification
– Cell Size
– Diminished production
– Accelerated Loss

7. Anemia
• MCV – mean corpuscular volume
– Measure of avg size of a single RBC
– NL range is 80-95 fL
– Microcytic (<80) – heme and globin synthesis
– Macrocytic (>100) – DNA synthesis
– Normocytic – Hypoproliferative disorder

8. Anemia

9. Anemia

10. Anemia
• MCHC – mean corpuscular
hemoglobin concentration
– Measure of the avg
concentration of Hgb
within a single RBC
– Hypochromic – cell has a
deficiency of Hgb
– Normochromic – values are
normal

11. Iron Deficiency Anemia
• Essentials of diagnosis
– Microcytic, hypochromic anemia
– Serum ferritin < 12 mcg/L
– Caused by bleeding in adults unless proven otherwise
– Responds to iron therapy
• General considerations
– Most common cause of anemia worldwide
– Iron is needed in the synthesis of hemoglobin
– AA/ Hispanic women > Caucasian women > men

12. Iron Deficiency Anemia
• General considerations
– Most of the rest is stored as ferritin
– Average American diet contains 10-15 mg of iron per day
• Only 10% of this is absorbed
• Absorption occurs in the stomach, duodenum, and upper jejunum
• Bioavailability best with heme iron (red meat)
– Menstrual losses can be significant in women
• With heavy menses, women must absorb 3-4 mg of iron
from their diet each day
• Require iron supplementation

13. Iron Deficiency Anemia
• General considerations
– Iron requirements also increased in pregnancy, periods
of rapid growth
– Decreased iron absorption after gastric surgery
– Most important cause is blood loss in adults
• GI bleeding
• Chronic aspirin use
• Must search for source of GI blood loss in adults

14. Iron Deficiency Anemia
• Signs and symptoms
– Pica
– Fatigue
– Tachycardia/Palpitations
– Tachypnea on exertion
– pallor
• Severe deficiency
– Smooth tongue
– Koilonychia
• "spoon nails." It refers to abnormally thin nails
(usually of the hand) which have lost their
convexity, becoming flat or even concave in
shape
– Cheilosis
• inflammatory lesion at the labial commissure, or
corner of the mouth, and often occurs bilaterally. The
condition manifests as deep cracks or splits. In severe
cases, the splits can bleed when the mouth is opened
and shallow ulcers or a crust may form

15. Iron Lab Studies
• Ferritin – storage protein of iron
• Transferrin – plasma protein that transports
iron to the bone marrow
– What is measured with serum iron
• TIBC – total iron binding capacity
– What degree of transferrin is open for binding of
iron

16. Iron Deficiency Anemia
• Laboratory findings
– Decreased serum ferritin
– Decreased serum iron
– Decreased MCV
– Increased total iron-binding capacity (TIBC)
– Peripheral blood smear
• Hypochromic, microcytic cells
• Anisocytosis (unequal size)
• Poikilocytosis (abnormally shaped)
– Target cells
– Pencil-shaped cells

17. Iron def anemia
Normal

18. Iron Deficiency Anemia
• Differential diagnosis
– Anemia of chronic disease
– Thalassemia
– Sideroblastic anemia (usually normocytic)
• Treatment
– Ferrous sulfate 325 mg TID
• May cause constipation
• Take on empty stomach or with acidic juice (OJ) to increase
absorption
• Hct should return to normal within 2 months
• Continue 3-6 months after Hct has returned to normal

19. Iron Deficiency Anemia
• Treatment
– Parenteral iron
• Indications
– Intolerance to oral iron
– Refractory disease
– GI disease or previous surgery
• Risk of anaphylaxis
• Preferred drug is sodium ferric gluconate (Ferrlecit)
– IV dose 1.5 – 2 g given over 4-6 hours

20. Anemia of Chronic Disease
• Essentials of Diagnosis
– Anemia (normocytic or microcytic)
– Normal or Increased Ferritin
– Underlying Chronic Disease
• Chronic infection
• Chronic inflammation
• Cancer
• Liver disease
• Renal failure – decrease in EPO

21. Anemia of Chronic Disease
• Signs and symptoms
– Clinical features of the causative condition
• Laboratory findings
– Hct mildly or moderately reduced
– MCV usually normal
– Serum ferritin normal or increased
• Treatment
– Not usually needed
– EPO for renal failure or cancer or Inflammatory Bowel
• Very expensive
• Reserved for patients dependent on transfusions

22. The Thalassemias
• Essentials of diagnosis
– Microcytosis out of proportion to the degree of
anemia
– Positive family history or lifelong history of
microcytic anemia
– Abnormal RBCs (microcytes, acanthocytes, and
target cells)
– With β-thalassemia, elevated levels of hemoglobin
A2 or F

23. The Thalassemias
• General considerations
– Hereditary disorders
– Reduction in the synthesis of globin chains
– Normal adult hemoglobin
• 98% hemoglobin A (α2β2)
• 1-2% hemoglobin A2 (α2δ2 )
• 1-2% hemoglobin F (α2γ2)
– α-thalassemia has reduced α-globin chains
– β-thalassemia has reduced β-globin chains

24. The Thalassemias
– Clinical severity varies widely depending on the
degree to which the synthesis of the affected
globin is impaired
– Described as “trait” when there are lab features
without significant clinical impact
– Described as “major” when the disorder is life-
threatening

25. The Thalassemias
• Signs and symptoms
– Alpha-thalassemias
• Most commonly in persons from southeast Asia or
China, and less so in African Americans
• Normally adults have 4 copies of the alpha globin
chaing (gene)
• 3 alpha-globin chains = silent carrier (hematologically
NL)
• 2 alpha-globin chains = alpha-thalassemia trait
– Clinically normal with normal life expectancy
– Mild microcytic anemia

26. The Thalassemias
• Signs and symptoms
– Alpha-thalassemias
1 alpha-globin chain = Hgb H disease
 Chronic hemolytic anemia
 Pallor and splenomegaly
 Transfusions may be required in times of stress
• No alpha-globin chains = hydrops fetalis
– Stillbirth

27. The Thalassemias
• Laboratory findings
– Alpha-thalassemia trait
• Mild anemia
• Hct between 28 – 40%
• MCV strikingly low (60-75)
• RBC normal or increased
• PBS shows microcytes, hypochromia, some target cells
and acanthocytes
• Hemoglobin electrophoresis
– No increase in hemoglobin A2 or F
– No hemoglobin H (β4 tetramer)

28. The Thalassemias
Acanthocytes

29. The Thalassemias
• Laboratory findings
– Hemoglobin H disease ( one alpha globin gene)
• More marked hemolytic anemia
• Hct between 22 – 32%
• MCV low (60-70)
• PBS abnormal with microcytes, hypochromia, target
cells and poikilocytosis
• Elevated reticulocyte count
• Hemoglobin electrophoresis
– Hemoglobin H 10 – 40%

30. The Thalassemias

31. The Thalassemias
– Beta-thalassemias
• Most often persons of Mediterranean descent, less so
southeast Asians, Chinese and African Americans
• Beta-thalassemia major
– Homozygous for beta-thalassemia
– Normal at birth until 6 months of age
– Severe anemia requiring transfusions
– Growth failure
– Bony deformities
– Hepatosplenomegaly
– Jaundice

32. The Thalassemias
• Signs and symptoms
– Beta-thalassemias
• Beta-thalassemia intermedia
– Homozygous but a milder form
– Chronic hemolytic anemia
– Transfusions in times of great stress
• Beta-thalassemia minor
– Heterozygous
– Clinically insignificant microcytic anemia

33. The Thalassemias
• Laboratory findings
– Beta-thalassemia minor
• Modest anemia
• Hct between 28 – 40%
• MCV low (55-75)
• RBC normal or increased
• PBS mildly abnormal with microcytes, hypochromia,
and target cells
• Hemoglobin electrophoresis
– Elevation of hemoglobin A2 (4-8%)
– Occasional elevation of hemoglobin F (1-5%)

34. The Thalassemias
• Laboratory findings
– Beta-thalassemia major
• Severe anemia
• Hct less than 10% without transfusion
• PBS bizarre with severe poikilocytosis, microcytes,
hypochromia, target cells, basophilic stippling,
nucleated RBCs
• Hemoglobin electrophoresis
– Little or no hemoglobin A
– Hemoglobin F is the major type present

35. The Thalassemias
Target cells basophilic stippling

36. The Thalassemias

37. The Thalassemias
• Differential diagnosis
– Iron deficiency
– Other hemoglobinopathies
• Treatment
– Mild thalassemia requires no treatment
– Hemoglobin H disease
• Folate supplements
• Avoid iron supplements and oxidative drugs like
sulfonamides

38. The Thalassemias
• Treatment
– Severe thalassemia
• Regular transfusion schedule
• Folate supplements
• Splenectomy, if needed for hypersplenism
• Deferoxamine (chelates iron)
• Beta thalassemia major
– Allogeneic bone marrow transplantation

39. Sideroblastic Anemia
• Essentials of Diagnosis
– Elevated Serum Iron & Transferrin Levels
– Bone marrow shows ringed sideroblasts
• Acquired Bone Marrow Disorder
– Myelodysplasia that terminates in Acute Leukemia
– Chronic ETOH Abuse
– Lead Poisoning
• Failure to incorporate heme into protoporphyrin
to form hemoglobin
• Iron accumulates in the mitochondria

40. Sideroblastic Anemia
• Signs & Symptoms
– Generalized anemia symptoms
• Laboratory
– Moderate anemia with Hct 20-30%
– Serum Iron & Transferrin elevatd
– MCV usually normal or slightly
elevated
– Diagnosis made with Bone Marrow
biopsy
• Ringed sideroblasts

41. Sideroblastic Anemia
• Treatment
– Occasionally require transfusion is required
– Does not respond to Erythropoietin Therapy

42. Macrocytic Anemias
• Vitamin B12 deficiency
• Folic acid deficiency
• When either is lacking there is a defect in DNA
synthesis that affects the rapidly dividing cells
in the bone marrow

43. Macrocytic Anemias
*note that the RBCs are larger than the WBC)

44. Vitamin B12 Deficiency
• Essentials of Diagnosis
– Macrocytic Anemia
– Macro-ovalocytes and hypersegmented
neutrophils on PBS
– Serum Vitamin B12 level less than 100 pg/ml

45. Vitamin B12 Deficiency
 General Considerations
 All vitamin B12 is absorbed from the diet (foods of
animal origin)
 After ingestion, vitamin B12 binds to intrinsic factor,
a protein secreted by gastric parietal cells
 Avg Western diet contains 5-30μg daily
 Body stores are typically between 2-3mg, sufficient
for 3-4 years if supplies are completely cut off

46. Causes of vitamin B12 deficiency
• Decreased IF production • Alteration in release of
– pernicious anemia (most B12 from dietary protein
common cause) – Helicobacter pylori
– chronic atrophic gastritis infection
– Gastrectomy – PPI, H2 antagonist,
antacids
• Decreased B12 absorption
– surgical resection of the • Dietary deficiency (only
ileum in vegans)
– severe Crohn's disease

47. Vitamin B12 Deficiency
• Signs and Symptoms
– May be asymptomatic
– As anemia becomes more severe
• Pallor
• Glossitis
• Gastrointestinal disturbances (eg, anorexia, diarrhea)
• Neurologic manifestations
– Paresthesias
– Difficulty with position/vibration sensation and balance
– In advanced cases - cerebral function altered, dementia
– Megaloblastic anemia (MCV >100), which may be
severe
– If Neurological symptoms present and normal MCV
• Check B12 level

48. Vitamin B12 Deficiency
• Differential Diagnosis
– Folic acid deficiency
– Myelodysplastic syndrome
– Other cause of peripheral neuropathy, ataxia, or
dementia

49. Vitamin B12 Deficiency
• Laboratory Tests
– CBC
• Hematocrit may be as low as 10–15%
• MCV
– Strikingly elevated: 110–140 fL
– May be normal if coexistent thalassemia or iron deficiency is
present
– Low serum vitamin B12 level, often < 100 ng/L
(normal 160-200 ng/L), establishes diagnosis

50. Vitamin B12 Deficiency
• Laboratory Tests
– Peripheral blood smear
• Macro-ovalocytes are characteristic
• Hypersegmented neutrophils with mean lobe count > 4,
or 1 six-lobed neutrophil
• Anisocytosis and poikilocytosis
– Reticulocyte count reduced
– Pancytopenia present in severe cases

51. Vitamin B12 Deficiency

52. Vitamin B12 Deficiency
 Treatment
 Vitamin B12, 100 μg IM QD for 1 week, then every
week for 1 month, then every month for life
 Oral cobalamin, 1000 μ g PO QD, may be tried
instead of parenteral therapy but must be
continued indefinitely

53. Vitamin B12 Deficiency
 Follow-Up
 Brisk reticulocytosis occurs 5–7 days after therapy,
and the hematologic picture normalizes in 2
months
 Follow serum vitamin B12 levels
 CNS symptoms and signs are reversible if the onset
is <6 months, otherwise may be permanent

54. Folic Acid Deficiency
• Essentials of Diagnosis
– Macrocytic anemia
– Macro-ovalocytes and hypersegmented
neutrophils on PBS
– Normal Serum Vitamin B12 Levels
– Reduced Folate Level

55. Folic Acid Deficiency
 General considerations
 Folic acid is present in most fruits and vegetables
(especially citrus fruits and green leafy vegetables)
 Daily requirements of 50–100 μg/day usually met in
the diet
 Total body stores of folate is 10mg, enough to supply
requirements for 2–3 months
 Folate is absorbed rapidly from the upper small
intestine
 Transported in the plasma either unbound or bound to
albumin

56. Folic Acid Deficiency
–Causes
• Most common is inadequate dietary intake
 Alcoholics, anorectic patients, persons who do not
eat fresh fruits and vegetables, those who overcook
food
• Decreased absorption (gluten-induced enteropathy)
• Antifolate drugs - phenytoin, methotrexate,
trimethoprim-sulfamethoxazole)
• Increased requirement - chronic hemolytic anemia,
pregnancy,
• Increased loss – dialysis
• Alcohol

57. Folic Acid Deficiency
 Signs & Symptoms
 Similar to Vitamin B12
 No neurologic abnormalities, unlike vitamin B12
deficiency
 Laboratory
 Megaloblastic anemia identical to that in vitamin B12
deficiency (eg, macro-ovalocytes, hypersegmented
neutrophils
 Red Blood Cell Level < 150 ng/mL
 Serum vitamin B12 level normal
 Distinguish from anemia of liver disease
 macrocytic anemia with target cells but no megaloblastic
changes

58. Folic Acid Deficiency
 Treatment
 Folic acid, 1 mg PO Daily
 Rapid improvement in sense of well-being,
reticulocytosis in 5–7 days, and total correction of
hematologic abnormalities within 2 months
 MAKE SURE that your patient does not also have B12
deficiency – folate can improve their symptoms but
not prevent the neurological damage

59. Hemolytic Anemias
• General considerations
– Coombs positive hemolytic anemia may be
autoimmune or related to drugs, infection,
lymphoproliferative disease, Rh or ABO
incompatibility
– Coombs negative hemolytic anemia may be intrinsic
RBC disease
• Abnormal hemoglobin: sickle cell disease, thalassemia,
methemoglobinemia
• Membrane defect: hereditary spherocytosis, hereditary
elliptocytosis, paroxysmal nocturnal hemoglobinuria
• Enzyme defect: G6PD deficiency, pyruvate kinase deficiency

60. Hemolytic Anemias
• General considerations
– Coombs negative hemolytic anemia may be extrinsic
• Microangiopathic hemolytic anemia
• Thrombotic thrombocytopenic purpura (TTP)
• Hemolytic-uremic syndrome (HUS)
• Prosthetic valve hemolysis
• Vasculitis
• Malignant hypertension
• Splenic sequestration
• Plasmodium, Clostridium, Borrelia infection
• Burns

61. Hereditary Spherocytosis
• Essentials of Diagnosis
– Positive Family History
– Splenomegaly
– Sperhocytes and Increased Reticulocytes on PBS
– Microcytic / Hyperchromic Anemia (if present)
• General considerations
– Disorder of RBC membrane, leading to chronic hemolytic
anemia
– Autosomal dominant disease of variable severity
– Hemolysis occurs because of trapping of RBCs within the
spleen

62. Hereditary Spherocytosis
 Clinical Findings
 Often diagnosed in childhood, but milder cases
discovered incidentally late in life
 Anemia may or may not be present because bone
marrow may be able to compensate for shortened RBC
survival
Signs & Symptoms
 Severe anemia (aplastic crisis) may occur with folic acid
deficiency or infection
 Jaundice and pigment (calcium bilirubinate) gallstones
and cholecystitis in chronic hemolysis
 Palpable spleen

63. Hereditary Spherocytosis
 Diagnosis
 Anemia my or may not be present
 If present, anemia is Microcytic and variable severity;
hematocrit may be normal
 Hyperchromic - increased mean corpuscular hemoglobin
concentration, often > 36 g/dL
 Reticulocytosis ALWAYS present
 Peripheral blood smear shows small percentage of
spherocytes, small cells that have lost their central pallor
 Indirect bilirubin often increased
 Coombs test negative
 Increased osmotic fragility

64. Hereditary Spherocytosis
• Treatment
– Folic acid, 1 mg PO Daily
– Splenectomy, which eliminates site of hemolysis
– Splenectomy may not be necessary in very mild
cases discovered late in adult life

65. Glucose 6-phosphate
Dehydrogenase Deficiency
 Essentials of Diagnosis
 X-linked recessive disorder affects 10–15% of African
American males
 Episodic hemolysis
 Minimally abnormal PBS
 Reduced levels of G6PD between hemolytic episodes
 General considerations
 Hereditary enzyme defect causes episodic hemolytic
anemia from RBC's decreased ability to deal with oxidative
stresses
 Hemoglobin may become oxidized, forming precipitants
(Heinz bodies) which cause membrane damage, leading to
removal of RBCs by spleen

66. Glucose 6-phosphate
Dehydrogenase Deficiency
• Vast majority of patients are asymptomatic
throughout lifetime without chronic
hemolytic anemia, but are at risk of
hemolytic anemia when challenged with
oxidative agents
• 3 Triggers of hemolysis
 Fava beans
 Infection
 Drugs (antimalarials; sulphonamides; antibiotics – Cipro,
Macrobid; analgesics – pryidium, aspirin; Vit C >1g)

67. Glucose 6-phosphate
Dehydrogenase Deficiency
• Signs & Symptoms – when hemolytic anemia
is present
– Pallor
– Fatigue/weakness
– Tachycardia
– Jaundice
– Splenomegaly
– Dark, tea-colored urine (due to hemoglobinuria)

68. Glucose 6-phosphate
Dehydrogenase Deficiency
• Laboratory
– Coombs test - negative
– CBC with peripheral smear
• CBC is normal between hemolytic episodes
• During hemolytic episode
– Normocytic, normochromic anemia (varying severity)
– Reticulocytosis
• RBC smear, although not diagnostic, may reveal "bite" cells
• Heinz bodies may be seen on peripheral blood smear with crystal
violet stain
– G6PD enzyme assays negative or <12 IU/g
– G6PD enzyme assays may be misleadingly normal if
performed shortly after hemolytic episode when enzyme-
deficient RBCs have been removed – may need to repeat
test 3-4 weeks later

69. Glucose 6-phosphate
Dehydrogenase Deficiency
Bite cells Heinz bodies

70. Glucose 6-phosphate
Dehydrogenase Deficiency
• Treatment
– Avoid known oxidative triggers
– Typically, no treatment necessary, unless anemia is severe
which may require transfusion
– Hemolytic episode self-limited, even with continued
use of offending drug, because older RBCs (with low
G6PD activity) removed and replaced with young RBCs
(with adequate G6PD activity)
– Few patients will have chronic hemolytic anemia

71. Sickle Cell Anemia

72. Sickle Cell Anemia
• Essentials of Diagnosis
– Recurrent Painful Episodes
– Positive Family History
– Irreversibly sickled cells on PBS
– Hemoglobin S is the major hemoglobin seen on
electrophoresis
• General Considerations
– Hemoglobin S gene is carried in 8% of African
Americans
– Sickle cell anemia (Hgb S) occurs in 1 birth in 400 in
African Americans
– Onset during first year of life, when hemoglobin F
levels fall

73. Sickle Cell Anemia
• General Considerations
– When deoxygenated, Hgb S can form gelatinous polymers
that stiffen the RBC membrane, increase viscosity, and
cause dehydration – leading to the sickled shape
– The rigid and adherent cells clog small capillaries and
venules, causing tissue ischemia, acute pain and gradual
end-organ damage
– They also possess altered sticky membranes (retic) that are
abnormally adherent to the endothelium of small venules
– Sickling is increased by increased RBC hemoglobin S
concentration, RBC dehydration, acidosis, and hypoxemia
– Sickling is retarded by hemoglobin F; high hemoglobin F
levels are associated with more benign course

74. Sickle Cell Anemia
• Patients with heterozygous genotype (Hgb AS) have
sickle cell trait
• Patients with homozygous genotype (Hgb S) have
sickle cell disease

75. Sickle Cell Trait (Hgb AS)
• Signs & Symptoms
 Clinically normal
 Acute vasoocclusion occurs only under extreme conditions (vigorous
exertion at high altitude)
 Painless hematuria sometimes present in adolescent males
• Diagnostic testing
– CBC and PBS normal
– Hemoglobin electrophoresis shows that Hgb S comprises ~40% of
hemoglobin and Hgb A 60%
• Treatment
– No treatment necessary
– Genetic counseling appropriate

76. Sickle Cell Anemia (Hgb SS)
• Signs and Symptoms
– Vary significantly – some pt are virtually asymptomatic
while others suffer repeated crises requiring
hospitalization
– Chronic hemolytic anemia produces
• Jaundice
• Pigment (calcium bilirubinate) gallstones
• Splenomegaly (early childhood only)
• Splenic Infarct and atrophy in adulthood or Splenectomy
• Poorly healing ulcers over the lower tibia

77. Sickle Cell Anemia (Hgb SS)
• Signs and Symptoms
– Pulmonary hypertension is associated with
decreased survival
– Increased susceptibility to infection occurs as a
result of hyposplenism and complement defects
– Anemia may be life-threatening during hemolytic
or aplastic crises
– Aplastic crises occur when bone marrow
compensation is reduced by infection or folate
deficiency

78. Sickle Cell Anemia (Hgb SS)
• Signs and Symptoms
– Pain crisis - acute painful episodes (from vasooclusion)
• Manifested by acute pain and tenderness, fever, tachycardia
and anxiety
• Bones, priapism, stroke – but can occur anywhere in the body
• last hours to 2 weeks
• Frequency and severity vary greatly
• Repeated crises requiring hospitalization (>3/yr) correlate with
reduced survival in adult life
• Provocative factors – infection, fever, excessive exercise,
anxiety, abrupt changes in temperature and hypoxia

79. Sickle Cell Anemia (Hgb SS)
• Signs and Symptoms
– Acute chest syndrome
• Chest pain, tachypnea, fever, cough, and arterial O2
desaturation
• Can mimic pneumonia, PE, bone marrow infarction,
myocardial ischemia or lung infarction
• Thought to reflect in situ sickling within the lung
producing pain and temporary pulmonary dysfunction
• Repeated episodes correlate with reduced survival
– Renal necrosis – leads to failure in adults, a
common late cause of death

80. Sickle Cell Anemia (Hgb SS)
• Signs and Symptoms
– Repeated vasoocclusion affects
• Eyes (retinopathy)
• Heart (cardiomegaly, hyperdynamic precordium, systolic murmurs)
• Lungs (Pulm HTN)
• Spleen (infarction, asplenia)
• Kidney (infarction of renal medullary papillae, renal tubular
concentrating defects, and gross hematuria)
• Bone (ischemic necrosis, staphylococcal or salmonella
osteomyelitis)

81. Sickle Cell Anemia (Hgb SS)
• Laboratory Tests
– Elevated serum indirect bilirubin and lactase
dehydrogenase (LDH); serum haptoglobin low
– CBC and PBS
• Hematocrit usually 15–30%
• Reticulocyte count elevated
• PBS: irreversibly sickled cells comprise 5–50% of RBCs;
reticulocytosis (10–25%); nucleated RBCs; Howell-Jolly
bodies and target cells
• White blood cell count characteristically elevated to
12,000–15,000/L; thrombocytosis may occur

82. Sickle Cell Anemia (Hgb SS)
• Laboratory Tests
– Hemoglobin electrophoresis confirms diagnosis
• Sickle cell anemia (homozygous S)
– HgbS 95-97%
– Hgb F 2-5%
– No hemoglobin A
• Imaging Studies
– Chest radiograph in acute chest syndrome
– Bone radiographs show characteristic
abnormalities

83. Sickle Cell Anemia (Hgb SS)
• Treatment
– Folic acid, 1 mg PO QD
– Hydroxyurea
• Consider in pts experiencing repeated episodes of
acute chest syndrome or with >3 pain crises a year
requiring hospitalization
• Increases Hgb F levels
• Reduces frequency of painful crises in patients whose
quality of life is disrupted by frequent pain crises
• Long-term safety uncertain

84. Sickle Cell Anemia (Hgb SS)
• Treatment
– Acute painful episodes
• Identify precipitating factors
• Treat infections if present
• Aggressive analgesia administration
• Vigorous hydration
• Administer oxygen ONLY if hypoxic
• Transfusion for extreme cases (doesn’t shorten the
crisis)

85. Sickle Cell Anemia (Hgb SS)
• Treatment
– Acute chest syndrome
• Medical emergency, treat in ICU
• O2 if sat <90%
• Maintain HCT >30
• Exchange transfusion primarily indicated for
treatment of intractable pain crises, priapism, and
stroke
• Allogeneic bone marrow transplantation under
investigation as possible curative option for
severely affected children

86. Sickle Cell Anemia (Hgb SS)
• Treatment
– Prenatal diagnosis and genetic counseling should be
made available to those with personal or family history
– No specific treatment is available for sickle cell anemia
– Pneumococcal and H. flu vaccination reduces incidence
of infections
• Prognosis
– With improved supportive care, average life
expectancy is between ages 40 and 50

87. Autoimmune Hemolytic Anemia
• Essentials of Diagnosis
– Acquired anemia caused by IgG autoantibody
– Spherocytes on PBS
– Elevated Reticulocyte Levels
– Postive Coombs Test
• General Considerations
– Acquired Disorder
– 50% idiopathic
– Associated with SLE, Chronic Lymphocytic
Leukemia, and Lymphoma

88. Autoimmune Hemolytic Anemia
• Signs & Symptoms
– “Rapid Onset” Anemia
– May be “Life Threatening”
– Fatigue
– Angina
– CHF
– Jaundice
– Splenomegaly

89. Autoimmune Hemolytic Anemia
• Laboratory
– Anemia is variable but can have Hct < 10%
– Elevated Reticulocyte level
– PBS demonstrates Spherocytes
– Elevated Indirect Bilirubin
– Positive Direct Coombs Test
• Differential
– Important to exclude drug induced hemolytic
anemia

90. Autoimmune Hemolytic Anemia
• Treatment
– Prednisone
– Rituximab
– Immunosuppressive Agents
– High Dose Immune Globulin
– Splenectomy if prednisone ineffective or recurs
• Prognosis
– Good if no underlying SLE, Leukemia, or Lymphoma

91. Cold Agglutinin Disease
• Essentials of Diagnosis
– Elevated Reticulocyte Level
– Spherocytes on PBS
– Coombs test positive for complement only
– Positive Cold Agglutinin Test
• General Considerations
– Acquired hemolytic anemia – most idiopathic
• Can see in post infectious mycoplasma or mononucleosis
– IgM autoantibody directed at I antigen on RBC
– Occurs at temps less than 37 degrees Celsius in
fingers, toes, ears, nose

92. Cold Agglutinin Disease
• Signs & Symptoms
– Mottled or numb fingers or toes when exposed to
cold
– Episodic hemoglobinuria when exposed to cold
• Laboratory
– Mild anemia
– Elevated Reticulocyte Level
– PBS shows spherocytes
– Direct Coombs test positive to complement only
– Positive Cold Agglutinin Test

93. Cold Agglutinin Disease
• Treatment
– Avoid the cold
– Hemolysis takes place in liver so Prednisone &
Splenectomy ineffective
– Rituximab is treatment of choice
– High Dose Immune Globulin
– Immunosuppressive agents

94. Aplastic Anemia
• Essentials of Diagnosis
– Pancytopenia
– No abnormal cells seen on PBS
– Hypocellular Bone Marrow
• General Considerations
– Condition of Bone Marrow Failure
– Results from Injury to or Abnormal expression of stem
cells
– Age distribution is biphasic
• Peak in the teens-twenties and a second peak in the
elderly

95. Aplastic Anemia

96. Aplastic Anemia
• Signs & Symptoms
– Weakness, Fatigue
– Vulnerability to Infections easily
– Mucosal and skin bleeding
– Pallor
– Purpura
– Petechiae
– NOT PRESENT
• Hepatosplenomegaly
• Lymphadenopathy
• Bone Tenderness

97. Aplastic Anemia
• Laboratory Tests
– Pancytopenia, although in early disease only one
or two cell lines may be reduced
– Anemia may be severe
– Reticulocytes ALWAYS decreased
– Large RBCs (macrocytosis)
– Neutrophils and platelets reduced in number, no
immature or abnormal forms seen

98. Aplastic Anemia
• Laboratory Tests
– Severe aplastic anemia defined by neutrophils <
500/μL, platelets < 20,000/μL, reticulocytes < 1%,
and bone marrow cellularity < 20%
• Diagnostic Procedures
– Bone marrow aspirate and bone marrow biopsy
appear hypocellular, with scant amounts of
normal hematopoietic progenitors; no abnormal
cells are seen
– In severe cases the biopsy if virtually 100% fat

99. Aplastic Anemia
• Treatment
– Supportive measures only for mild cases
– Antibiotics to treat infections
– Red blood cell and platelet transfusions as necessary
– Bone marrow transplant is treatment of choice for
children and young adults
– Immunosuppressant for older adults
• Prognosis
– Median survival without treatment is 3 months
– Bone Marrow transplant is highly successful in
children and young adults