Nelson’s 14th Addition Chapter16 (pp.1232-1256)
Anemia’s
Anemia results when RBC’s can’t be produced in sufficient numbers to
replace those removed from circulation.
1. Congenital Pure RBC Anemia (ex. Congenital Hypoplastic Anemia)
 rare condition
 usually seen in early infancy
 characteristic diagnostic feature is deficiency of RBC precursor in
normal bone marrow
 genetic basis with male = female
 some pt.’s with tryptophan metabolism abnormality
 ADA (adenosine deaminase) activity increased in RBC
 Increased erythropoietin in serum and urine
Manifestations
 Pale appearance (50%)
 Profound anemia 2-6 months
 Heart failure and death without transfusion
 Macrocytic normochromic anemia
 Assay reveals young erythrocyte population
 Thrombocytosis and occasional neutropenia
 Despite increased erythropoietin there is lack of erythropoietic activity
 Diminished reticulocytes
Treatment
 Corticosteroids
 Transfusion is the only chance for survival if corticosteroids do not
produce remission
 10-15% do not respond to corticosteroids and require transfusion every
4-6 weeks
2. Acquired Pure RBC Anemia’s
 Cause unknown
 Removal of thymus tumor have led to remissions in some
 Associated in thymoma in children
 Erythropoietin inhibiting antibody, antibodies to erythroblasts and
inhibitors of heme synthesis have been identified in plasma
 May respond to corticosteroids
 Immunosuppressive's may be given if corticosteroids ineffective
 Markedly reduced erythrocyte precursors in marrow
 Decreased RBC survival rate is basis of aplastic crisis in some
hemolytic anemia’s
3. Anemia’s of Chronic Infection, Inflammation and Renal Disease
 Anemia complicates many systemic diseases (ex. Chronic pyogenic
infections)
 Important symptoms and signs underlie disease
 Normochromic normocytic anemia with low serum iron and elevated
serum ferritin (acute phase reactant)
 If underlying systemic disease is controlled, anemia spontaneously
remises
4. Physiologic Anemia of Infancy
 Progressive decline of hemoglobin levels within the 1st week of life
which persists for 6-8 weeks
 Several factors are operative
1. abrupt cessation of erythroporesis
2. shortened RBC survival
3. expansion of blood volume with rapid weight gain (1st 3 months)
 pre term infants have greater decline in hemoglobin concentrations
 dietary factors may aggravate anemia ( high portions of
polyunsaturated fatty acids with iron supplements)
 vitamin E deficiency presenting with “infantile pyknocytosis” (self
limited hemolytic process, large numbers of acanthocytes)
 diet with essential nutrients for hemopoietic process
5. Megaloblastic Anemia’s
 RBC’s are larger than normal in every stage
 Finely dispersed chromatin in nucleus
 Asynchrony between cell cytoplasm and nuclear maturity
 Increased RNA in proportion to DNA
 Uncommon in US
A. Folic Acid Deficiencies
 Caused by deficient folic acid due to decreased
intake/absorption
 Rapid growth or infection compounds deficiency
 Human and cow milk have adequate folic acid
Manifestations
 Low birth weight
 Peak incidence 4 – 7 months
 Irritability, fail to gain weight and chronic diarrhea
 Thrombocytopenic hemorrhages in advanced cases
 May accompany Kwashiorkor or Marasmiro
 Progressive anemia
 RBC count disproportionately lower than hematocrit
 RBC shape and size variations
 Low reticulocyte count
 Elevated serum activity of LDH (lactate dehydroginase)
Treatment
 Parenteral folic acid 2-5 mg/24 hr. x 3-4 weeks
 Transfusion with severe anemia
 Folic acid as low as 50 g/24 hr. can be used to test between
primary folic acid deficiency and B12.
1. Megaloblastic Anemia of Pregnancy
 Increased folate demand
 1 mg/24 hr. folate supplement
2. Folic Acid (FA) Deficiency of Malabsorption
 FA absorbed through small intestine
 Celiac disease, chronic infectious enteritis or any other
inflammatory or degenerative disease of intestine can
interfere with FA absorption
 Oral FA 1mg/24 hr. is treatment
3. Congenital Defect of FA Absorption
 Defect in intestinal absorption of FA
 Inability to transfer folate from plasma to CNS
 Oral folic acid 15-50mg/24 hr.
4. FA Deficiency complicating Hemolytic Anemia’s
 Chronic hemolysis may increase FA requirement
 Adults>children
 Transfusion may be needed
 Examine bone marrow if anemia worsens or there is an
increased need for transfusion
 Normal diets may eliminate need for FA supplement
5. FA Deficiency associated with Anticonvulsant's and Other
Drugs
 Anticonvulsant's may lead to decreased FA
 Usually no anemia or symptoms
 Possible displacement of FA from serum carrier
 FA therapy
B. Vitamin B12 Deficiencies
 Intrinsic factor needed for B12 absorption
 Absorbed in terminal ileum
 Dietary deficiency rare
 Seen in Vegans (no milk, eggs or animal products)
 Most cases due to absorption problem
Manifestations
 Juvenile onset 9 months to 10 years
 Irritability, anorexia and listlessness
 Painful smooth red tongue
 Neurological symptoms: ataxia, paresthesia, hyporeflexia, +
babinski’s, clonus and coma
 Serum iron and FA may be normal or elevated
 Moderate bilirubin levels
 Excessive excretion of methylmalonic acid in urine is reliable for
diagnosis
 B12 absorption assessed by schilling test
Treatment
 Parenteral B12 1 – 5 g/24 hr.
 Maintenance for life
 Oral therapy contraindicated
1. Transcobalamine Deficiency
 Transcobalamines I and II are plasma B12 binding proteins
with type II being primary
 Autosomal recessive
 Severe megaloblastic anemia in early infancy
 Massive parenteral B12 therapy
2. Vitamin B12 Deficiency in Older Children
 Atrophy of gastric mucosa and achlorhydria possible
 Cutaneous candidiosis and thyroid/endocrine deficiencies
possible
 Parenteral B12 regularly
 Structurally abnormal intrinsic factor seen
6. Microcytic Anemia’s
A. Iron Deficiency Anemia
 Lack of iron for hemoglobin synthesis
 Most common hemotologic disease in infancy and childhood
 8 – 15 mg iron in diet is necessary



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newborns iron mostly in circulating hemoglobin
usually during 1st 4 – 6 months due to dietary insufficiency
blood loss must be considered in every case
⅓ infants with severe iron deficiency in US have chronic intestinal
loss induced by exposure to a heat labile protein in whole cow’s
milk
Manifestations
 Pallor most important clue
 Few symptoms may be seen
 Spleen enlarged and palpable
 Obese or underweight children
 Pica may be prominent
 May have effects on neurological and intellectual function
 Serum ferritin is relatively accurate to iron stores
 RBC’s become smaller with less hemoglobin
 Reticulocyte count is normal
Treatment
 Oral administration of ferrous salts
 Parenteral therapy in calculated doses
 Diet considerations
B. Sideroblastic Anemia
 Heterogeneous
 Abnormal iron or heme metabolism
 Ringed marrow sideroblasts found
 X linked form appears in childhood
7. Hemolytic Anemia’s
 Shortened RBC survival
 Increased marrow activity
 Increased reticulocyte count
 X-ray changes seen in skull and fingers
 Elevated unconjugated bilirubin
 Plasma hemoglobin increases
 Isotopic techniques can estimate RBC survival
8. Intrinsic Abnormalities of the RBC
A. Hereditary Spherocytosis
 No abnormalities of hemoglobin except glucose-6-phosphate
dehydrogenase (G-6-PD) type
 Most common hereditary hemolytic anemia
 Most common among Northern Europeans
 Autosomal dominant – occasionally recessive
 Abnormality of spectrin (protein lattice of RBC’s shape and lipid
bilayer)
 Spleen involves-hemolytic process ceases after removal
 Onset in infancy
 50% of unsplenectomized patients form gallstones
 reticulocytosis, anemia and hyperbilirubinemia
 spherocytic RBC’s smaller than normal
 osmotic fragility studies indicated
Treatment
 splenectomy (over 5 years old) – eliminates aplastic crisis and
chance of gallstones
9. Enzymatic Defects of RBC’s
A. Pyruvate Kinase Deficiency
 Congenital – autosomal recessive (homozygous)
 Impaired ATP, Pyruvate and NAD
 Increased 2,3 DPG
 Reduced RBC life span
 Jaundice and anemia in neonatal period
 Spiculated pyknocytes present
 Diagnosis relies on reduced pyruvate kinase activity
Treatment
 Exchange transfusion
 Packed RBC transfusion
 Splenectomy
10.Glucose-6-Phosphate Dehydrogenase Deficiency
 Inherited
 More common in blacks
A. Drug Induced Hemolytic Anemia
 Males > Females
 No G-6-PD deficiency evident
 Antipyretics, sulfonamides, antimalarials and fava
beans(favism)
 Death may occur
 Premature black infants can have spontaneous hemolysis
 Heinz Bodies seen (only 1st 3-4 days of onset)
 Diagnosis based on decreased G-6-PD activity in RBC’s
11.Hemoglobin Disorders
A. Sickle Cell
 Severe chronic hemolytic disease
 Premature destruction of RBC’s
 RBC’s brittle
 Ischemic changes may also be involved
 No characteristics may be present
 Ischemic necrosis of small bones
 Acute painful vaso-occlusive episodes most frequent and
prominent
 Ischemic damage may also affect myocardium, liver and kidney’s
 Splenomegally enlargement possible
Treatment
 Maintain full immunization status
 Prophylactic PCN-G
 Oral acetaminophen for painful episodes or codeine if needed
B. Thalassemia Syndromes
 Heterogeneous and hypochromic
 Decreased or absence of mRNA for 1 or more globin chains
 Many mutations can occur
 Most prevalent of all genetic diseases
 Most prevalent regions are those associated with malaria from
Plasmodium Falciparum
1.  Thalassemia (Thalassemia Major AKA Cooley’s Anemia)
 2-6 months of life
 Regular transfusions necessary
 Thin bones which can lead to pathologic fractures
 Enlarged liver and spleen
 Diabetes Mellitus can occur
 Fragmented poikilocytes and target cells present
 Nucleated RBC’s
 Elevated unconjugated bilirubin
Treatment
 Transfusions
-Hemosiderosis is inevitable due to prolonged transfusion
therapy
*Thalassemia major is AKA Cooley’s Anemia and associated with
facial deformities such as severe maxillary hyperplasia and
malocclusion.
2.  Thalassemia
 Deficient  globulin chain(s)
 Most severe form results from deletion of all 4  globin
chains
12.Extrinsic Factors
A. Autoimmune Hemolytic Anemia’s(with “warm” antibodies)
 Uncertain pathology
 Possibly drugs or infectious agents
 Acute onset
 Pallor, jaundice, pyrexia and hemoglobinemia
 Splenomegally
 Response to corticosteroids and full recovery within 3 months are
characteristic of acute form
 Other form is chronic
 + direct coomb’s test
Treatment
 Transfusions
 Prednisone 2-5 mg/kg/24 hr.
 Remits spontaneously in weeks to months
B. Autoimmune Hemolytic Anemia’s(with “cold” antibodies)
1. Cold Agglutinin Disease
 Severe episodes of intravascular hemolysis with
hemoglobinemia and hemoglobinuria may occur
2. Paroxysmal Cold Hemoglobinuria
 Specific cold antibody – Donath-Landsteiner Hemolysin
 ⅓ cases associated with congenital or acquired syphilis
 transfusions for severe anemia
 avoid chilling patient
13.Intoxication’s and Infections
 Arsenic and phenylhydrazine produce hemolysis
 Hemolytic anemia’s may complicate various infections
 Septicemia may cause direct RBC damage
 Parasites can affect RBC’s