Anemia

1. ANEMIAANEMIA
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2. ANEMIAANEMIA
any condition in which the number of red
cells, the amount of hemoglobin or the
volume of packed red blood cells per unit
volume is less than normal.
a pathophysiological condition in which
the body cannot meet its demands for
oxygen.
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3. WBC 4,800-10,800/mm
3
RBC M: 4.7-6.1 mil/mm
3
F: 4.2-5.4 mil/mm
3
( or x 10
6
/mL)
Plt 130,000-400,000/mm
3
Hgb M: 14.0-18.0 g/dL F: 12.0-16.0 g/dL
Hct M: 42-52% F: 37-47%
MCV [= Hct(%) / RBC count(x10
6
/mL)/10] 80-100m
3
(or fL)
MCH [= Hgb(g/dL) / RBC count(x10
6
/mL)/10] 27-33 pg
MCHC [= Hgb(g/dL) / Hct(%)/100] 32-36 g/dL
RDW 8.5-11.5 %
reticulocyte (absolute number) 40,000-100,000 /mL
Blood Reference ValuesBlood Reference Values
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4. Erythrocyte IndicesErythrocyte Indices
•Hemoglobin (Hgb)
•Hematocrit (Hct)
•Mean Corpuscular Volume (MCV)
•Mean Corpuscular Hemoglobin (MCH)
•Mean Corpuscular Hemoglobin Concentration
(MCHC)
•Red Cell Distribution Width (RDW)
•[Packed Cell Volume (PCV)]
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5. RBC “rule of 3’s”RBC “rule of 3’s”
For normal erythrocytes:
hemoglobin (g/dL) @ 3 x RBC count (millions)
hematocrit (%) @ 3 x hemoblobin (g/dL) ± 3%
Failure to obey this “rule of 3’s” suggests an
abnormality in erythrocytes (sickle cells, etc)
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6. classification of anemia by colorclassification of anemia by color
1.hypochromic (decreased color)
•increased central pallor
2.normochromic (normal color)
•central pallor ~1/3 of the RBC diameter
3.hyperchromic (increased color)
(~spherocytosis)
•loss of central pallor
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7. anemiaanemia
M: Hb<13.5Hct<41
F: Hb<12 Hct<36
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9. ANEMIAANEMIA
morphologic classificationmorphologic classification
microcytic
MCV <80
normocytic
MCV 80-100
macrocytic
MCV >100
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10. ANEMIA ANEMIA
classification by volumeclassification by volume
I.microcytic anemia (MCV <80)
II.normocytic anemia (MCV 80-100)
III.macrocytic anemia (MCV >100)
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11. ANEMIA ANEMIA
classification by volumeclassification by volume
I.microcytic anemia (MCV <80)
1.iron deficiency anemia
2.thalassemia syndromes
3.anemia of chronic disease
4.sideroblastic anemia
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12. ANEMIA ANEMIA
classification by volumeclassification by volume
•microcytic anemia (MCV <80)
•normocytic anemia (MCV 80-100)
1.anemia of blood loss
2.hemolytic anemia
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13. ANEMIA ANEMIA
classification by volumeclassification by volume
•microcytic anemia (MCV <80)
•normocytic anemia (MCV 80-100)
•macrocytic anemia (MCV >100)
1.megaloblastic anemia
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14. ANEMIA ANEMIA
classification by volumeclassification by volume
I.microcytic anemia (MCV <80)
1.iron deficiency anemia
2.thalassemia syndromes
3.anemia of chronic disease
4.sideroblastic anemia
II.normocytic anemia (MCV 80-100)
1.anemia of blood loss
2.hemolytic anemia
III.macrocytic anemia (MCV >100)
1.megaloblastic anemia
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15. ANEMIA ANEMIA
pathophysiologic classificationpathophysiologic classification
I RBC loss
1. blood loss
2. ↑ RBC destruction
a. intrinsic abnormality
b. extrinsic abnormality
II ↓RBC production
1. stem cell abnormality
2. erythroblast abnormality
3. unknown/multiple mechanism
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16. ANEMIA ANEMIA
pathophysiologic classificationpathophysiologic classification
I RBC loss
1.blood loss
a. acute : trauma, massive hemorrhage
b. chronic : GI lesion, GYN lesion
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17. ANEMIA ANEMIA
pathophysiologic classificationpathophysiologic classification
I RBC loss
1. blood loss
2.↑ RBC destruction
a.intrinsic abnormality
b.extrinsic abnormality
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18. ANEMIA ANEMIA
pathophysiologic classificationpathophysiologic classification
I RBC loss
1. blood loss
2.↑ RBC destruction
a.intrinsic abnormality
i.membrane disorder
ii.enzyme disorder
iii.Hgb synthesis disorder
iv.acquired memb. defect
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19. ANEMIA ANEMIA
pathophysiologic classificationpathophysiologic classification
I RBC loss
1. blood loss
2.↑ RBC destruction
a.intrinsic abnormality
–membrane disorder
–enzyme disorder
–Hgb synthesis disorder
–acquired memb. defect
hereditary spherocytosis
hereditary elliptocytosis
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20. ANEMIA ANEMIA
pathophysiologic classificationpathophysiologic classification
I RBC loss
1. blood loss
2.↑ RBC destruction
a.intrinsic abnormality
i.membrane disorder
a)hereditary spherocytosis
b)hereditary elliptocytosis
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21. ANEMIA ANEMIA
pathophysiologic classificationpathophysiologic classification
I RBC loss
1. blood loss
2.↑ RBC destruction
a.intrinsic abnormality
–membrane disorder
–enzyme disorder
–Hgb synthesis disorder
–acquired memb. defect
pyruvate kinase def.
G6PD def.
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22. ANEMIA ANEMIA
pathophysiologic classificationpathophysiologic classification
I RBC loss
1. blood loss
2.↑ RBC destruction
a.intrinsic abnormality
–membrane disorder
–enzyme disorder
1)pyruvate kinase def.
2)G6PD def.
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23. ANEMIA ANEMIA
pathophysiologic classificationpathophysiologic classification
I RBC loss
1. blood loss
2.↑ RBC destruction
a.intrinsic abnormality
–membrane disorder
–enzyme disorder
–Hgb synthesis disorder
–acquired memb. defect
Thalassemia
sickle cell disease
Hb C disease
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24. ANEMIA ANEMIA
pathophysiologic classificationpathophysiologic classification
I RBC loss
1. blood loss
2.↑ RBC destruction
a.intrinsic abnormality
–membrane disorder
–enzyme disorder
–Hgb synthesis disorder
1)Thalassemia
2)sickle cell disease
3)Hb C disease
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25. ANEMIA ANEMIA
pathophysiologic classificationpathophysiologic classification
I RBC loss
1. blood loss
2.↑ RBC destruction
a.intrinsic abnormality
–membrane disorder
–enzyme disorder
–Hgb synthesis disorder
–acquired memb. defect
PNH
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26. ANEMIA ANEMIA
pathophysiologic classificationpathophysiologic classification
I RBC loss
1. blood loss
2.↑ RBC destruction
a.intrinsic abnormality
–membrane disorder
–enzyme disorder
–Hgb synthesis disorder
–acquired memb. defect
1)PNH
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27. ANEMIA ANEMIA
pathophysiologic classificationpathophysiologic classification
I RBC loss
1. blood loss
2.↑ RBC destruction
•intrinsic abnormality
•extrinsic abnormality
i.mechanical trauma
ii.chemical injury
iii.infection
iv.immunologic injury
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28. ANEMIA ANEMIA
pathophysiologic classificationpathophysiologic classification
I RBC loss
1. blood loss
2.↑ RBC destruction
•intrinsic abnormality
•extrinsic abnormality
i.mechanical trauma (microangiopathic HA)
1)TTP/HUS, DIC
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29. ANEMIA ANEMIA
pathophysiologic classificationpathophysiologic classification
I RBC loss
1. blood loss
2.↑ RBC destruction
•intrinsic abnormality
•extrinsic abnormality
–mechanical trauma
–chemical injury
1)lead poisoning
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30. ANEMIA ANEMIA
pathophysiologic classificationpathophysiologic classification
I RBC loss
1. blood loss
2.↑ RBC destruction
•intrinsic abnormality
•extrinsic abnormality
–mechanical trauma
–chemical injury
–infection
1)malaria
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31. ANEMIA ANEMIA
pathophysiologic classificationpathophysiologic classification
I RBC loss
1. blood loss
2.↑ RBC destruction
•intrinsic abnormality
•extrinsic abnormality
–mechanical trauma
–chemical injury
–infection
–immunologic injury
1)autoimmune hemolytic anemia
2)drug mediated injuries
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32. ANEMIA ANEMIA
pathophysiologic classificationpathophysiologic classification
I RBC loss
1. blood loss
2.↑ RBC destruction
a.intrinsic abnormality
i.membrane disorder
ii.enzyme disorder
iii.Hgb synthesis disorder
iv.acquired memb. defect
b.extrinsic abnormality
i.mechanical trauma
ii.chemical injury
iii.infection
iv.immunologic injury
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33. ANEMIA ANEMIA
pathophysiologic classificationpathophysiologic classification
I RBC loss
1. blood loss
2. ↑ RBC destruction
II ↓ RBC production
1. stem cell abnormality
2. erythroblast abnormality
3. unknown/multiple mechanism
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34. ANEMIA ANEMIA
pathophysiologic classificationpathophysiologic classification
I RBC loss
1. blood loss
2. ↑ RBC destruction
II ↓ RBC production
1.stem cell abnormality
i.aplastic anemia
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35. ANEMIA ANEMIA
pathophysiologic classificationpathophysiologic classification
I RBC loss
1. blood loss
2. ↑ RBC destruction
II ↓ RBC production
1. stem cell abnormality
2. erythroblast abnormality
i.megaloblastic anemia
ii.iron deficiency anemia (defective Hb synthesis)
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36. ANEMIA ANEMIA
pathophysiologic classificationpathophysiologic classification
I RBC loss
1. blood loss
2. ↑ RBC destruction
II ↓ RBC production
1. stem cell abnormality
2. erythroblast abnormality
3. unknown/multiple mechanism
i.sideroblastic anemia
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37. Hereditary SpherocytosisHereditary Spherocytosis
intrinsic defect in the membrane cytoskeleton
genetic: autosomal dominant
pathoetiology:spectrin deficiency
→ decreased RBC surface memb.
→ loss of biconcavity
anemia: moderate anemia
normocytic
hyperchromic
reticulocytosis
entrapment of spherocytes in the spleen
(splenomegaly)
(extravascular hemolysis)
increased erythrocyte osmotic fragility
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38. Hereditary SpherocytosisHereditary Spherocytosis
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39. Hereditary SpherocytosisHereditary Spherocytosis
Sx:1. mild to moderate hemolytic anemia
2. splenomegaly
3. marked compensatory erythroid hyperplasia in BM
4. jaundice, pigment cholelithiasis ← ( ↑ bilirubin )
5. increased risk for acute red-cell aplasia due to
parvovirus B19 infection
Lab:1. increased osmotic fragility
2. normal MCV with increased MCHC
Tx:splenectomy
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40. Hereditary ElliptocytosisHereditary Elliptocytosis
intrinsic defect in the membrane cytoskeleton
genetic: autosomal dominant
pathoetiology: impaired aggregation of spectrin
anemia: 90% of pt. are non-anemic
non-hypochromic elliptocytes >25%
(nl=<15%)
Sx:splenomegaly
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41. Embden-Meyerhof glycolytic pathway
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42. Pyruvate Kinase DeficiencyPyruvate Kinase Deficiency
•autosomal recessive
•most common red cell enzyme deficiency involving
Embden-Meyerhof glycolytic pathway
•inability to maintain normal ATP levels
•mild to moderate hemolysis
•splenomegaly
•patients tolerate anemia rather well (¬ high levels of
2,3-DPG)
Dx: - fluorescent spot test
- enzyme assay
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43. X
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44. fluorescent spot testfluorescent spot test
Pyruvate kinase catalyzes the phosphorylation of ADP to
ATP with the formation of pyruvate. Pyruvate then
reduces any NADH present to NAD with formation of
lactate. Loss of florescence of NADH under ultra-violet
light is observed as evidence of the presence of pyruvate
kinase.
phosphoenol pyruvate pyruvate lactate
PK
ADP ATP *NADH NAD
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45. www.freelivedoctor.com

46. G6PD DeficiencyG6PD Deficiency
Pathophysiology: decreased half life of G6PD
increased vulnerability to oxidative denaturation due to limited
generation of NADPH (older RBCs are preferentially destroyed)
Genetics:
high genetic heterogeneity
x-linked recessive (® full expression in male hemizygote)
Sx:
hemolysis after exposure to oxidant stress
- drugs: primaquine, chloroquine, sulfonamides, nitrofurantoins
- infections: viral hepatitis, pneumonia, typhoid fever
“favism” : hemolysis after ingestion of fava beans (Mediterranean type)
Lab:
- poikilocytes, some spherocytes
- Heinz bodies : precipitates of denatured hemoglobin material
- “bite cells”
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47. G6PD DeficiencyG6PD Deficiency
bite cellHeinz bodies
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48. ANEMIA ANEMIA
pathophysiologic classificationpathophysiologic classification
I RBC loss
1. blood loss
2.↑ RBC destruction
a.intrinsic abnormality
–membrane disorder
–enzyme disorder
–Hgb synthesis disorder
1)Thalassemia
2)sickle cell disease
3)Hb C disease
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49. hemoglobin molecule
two a chains
two b chains
four a-globin genes
two b-globin genes
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50. globin genesglobin genes
CH16
CH11
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51. Thalassemia SyndromesThalassemia Syndromes
heterogeneous hemolytic disorders characterized by quantitative
abnormalities of hemoglobin synthesis
•genetic defect in globin production
•selective depression or absence of a- or b- chain of hemoglobin
•broad spectrum of presentation
•predominantly seen in persons of Mediterranean, African and
Asian ancestry
α-thalassemia : α-chain deficiency due to gene deletion
β-thalassemia : β-chain deficiency due to point mutation
(Cooley’s anemia)
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52. Thalassemia SyndromesThalassemia Syndromes
pathophysiologypathophysiology
Two (2) pathological mechanisms to contribute to
develop anemia
1. inadequate Hgb formation
® low MCHC, hypochromasia
2. relative excess of unaffected Hgb chain
® aggregation and precipitation of excess chain
® damage to the cell membrane
® loss of K+ and impaired DNA synthesis
® apoptosis of RBCs in BM
(“ineffective erythropoiesis”)
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53. Thalassemia SyndromesThalassemia Syndromes
pathophysiologypathophysiology
ineffective erythropoiesis
+ ® severe erythroid hyperplasia
hemolysis excess absorption of iron
¯
severe iron overload
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54. αα-thalassemia-thalassemia
a1
a2
a a / a a normal
a1
a2
- a / a a a
+
-thal heterozygote
(mild)
a1
a2
- - / a a a
0
-thal heterozygote
(moderate)
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55. αα-thalassemia-thalassemia
a1
a2
- a / - a a
+
-thal homozygote
(moderate)
a1
a2
- - / - a a
0
-thal x a
+
-thal
(severe)
a1
a2
- - / - - a
0
-thal homozygote
(lethal)
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56. ββ-thalassemia-thalassemia
clinical classification of β thal is based on the severity of
the anemia (based on the type of genetic defect and
gene dosage)
β
+
→ some β chain production
β
0
→ no β chain production
clinical manifestation
homozygous (β
+
/β
+
or β
0
/β
0
) severe
heterozygous (β
+
/β or β
0
/β) mild
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57. ββ-thalassemia-thalassemia
promoter gene mutation:
75-80% reduction of transcription rate (b
+
thal)
chain termination mutation:
premature termination of mRNA translation (b
0
thal)
splicing mutation:
aberrant splicing (b
0
& b
+
thal)
most common cause of thal
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58. ““Thalassemia Major”Thalassemia Major”
•homozygous β
+
/β
+
or β
0
/β
0
•severe anemia at 6 to 9 months of age requiring blood
transfusion
•death at early age, if not transfused
•severe erythrophagocytosis and extramedullary
hematopoiesis
® hepatosplenomegaly
•marked red marrow expansion ® “Crew-Cut” sign
•hemosiderosis
•heart disease 2º to hemochromatosis is the major
cause of death in older patients
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59. ““Thalassemia Major”Thalassemia Major”
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60. ““Thalassemia Major”Thalassemia Major”
Dx:
•anemia work up
•hemoglobin electrophoresis ® no or very low HbA
markedly elevated HbF
•DNA analysis
Rx:
•blood transfusion with iron chelators
•improvement of anemia
•suppression of secondary features related to excessive
erythropoiesis
•BM transplantation
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61. ““Thalassemia Minor”Thalassemia Minor”
•much more common than Thalassemia major
•heterozygous b
+
/b or b
0
/b
•peripheral smear:hypochromia, microcytosis,
basophilic stippling, target cells
•may be resistant against falciparum malaria
•usually asymptomatic or mild anemia (microcytic
anemia)
DDx: iron deficiency anemia
serum iron
total iron binding capacity
serum ferritin
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68. Sickle Cell DiseaseSickle Cell Disease
prototype of hereditary hemoglobinopathies
structurally abnormal hemoglobin from a point mutation
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69. Sickle Cell DiseaseSickle Cell Disease
- severe anemia ® generalized growth and developmental
impairment
- vaso-occlusive complications
- painful crisis: bones, lungs, liver, brain, spleen, penis
- acute chest syndrome
- aplastic crisis
- sequestration crisis (splenic hyperplasia  pooling of blood)
- chronic hyperbilirubinemia
- increased susceptibility to infection ® septicemia, meningitis
(encapsulated bacteria)
Dx:clinical findings
peripheral blood smear
hemoglobin analysis
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70. Sickle Cell TraitSickle Cell Trait
- heterozygous (Ss) Hb S -- 30-40%
- approx. 10% of American blacks
- normal peripheral blood count and RBC life
span
- rare sickling with low oxygen tension, low pH
(local ischemia, high altitude, pneumonia, etc.)
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71. Paroxysmal Nocturnal Paroxysmal Nocturnal
Hemoglobinuria (PNH)Hemoglobinuria (PNH)
an acquired clonal disorder of stem cells, and results
from a somatic mutation in phosphatidylinositol glycan A
(PIGA) gene that is essential for the synthesis of the
glycosylphosphatidylinositol (GPI) anchor protein of the
membrane, and makes RBCs very sensitive to
complement-mediated cell lysis due to the deficiency of
proteins that regulate complement activity
GPI-linked complement reg. Proteins
CD55 (DAF)
CD59
CD8 binding protein
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72. Paroxysmal Nocturnal Paroxysmal Nocturnal
Hemoglobinuria (PNH)Hemoglobinuria (PNH)
clinical:
- chronic hemolysis without dramatic hemoglobinuria
(75%)
- paroxysmal and nocturnal intravascular hemolysis
(25%)
- venous thromboses in hepatic, portal or cerebral veins
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73. TTP / HUSTTP / HUS
Thrombotic Thrombocytopenic Purpura (TTP)
Hemolytic Uremic Syndrome (HUS)
- widespread formation of hyaline thrombi in
microcirculation
- endothelial injury and activation of intravascular
thrombosis seem to be the initiating mechanisms
- may have diverse causes
- verotoxins ( E.coli O157:H7)
- viral infection
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74. TTP / HUSTTP / HUS
TTP (Thrombotic Thrombocytopenic Purpura)
adult female with pentad
1. Fever
2. Thrombocytopenia
3. Microangiopathic hemolytic anemia
4. Transient neurologic deficits
5. Renal failure
HUS (Hemolytic Uremic Syndrome)
child with acute renal failure
microangiopathic hemolytic anemia
thrombocytopenia
no neurologic symptoms
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75. Disseminated IntravascularDisseminated Intravascular
Coagulation (DIC)Coagulation (DIC)
- an acute, subacute, or chronic thrombohemorrhagic
disorder occurring as a secondary complication in a
variety of diseases
- activation of clotting system resulting in wide spread
formation of microthrombi throughout the microcirculation
- as a consequence, causing consumption of platelets,
fibrin and coagulation factors, and activation of
thrombolytic mechanism
Two major triggering mechanisms
1. release of tissue factor or thromboplastic substance
2. widespread endothelial injury
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76. Disseminated IntravascularDisseminated Intravascular
Coagulation (DIC)Coagulation (DIC)
Pathology:- wide spread thrombi
(brain, heart, lungs, kidneys, adrenals,
spleen , liver)
- microinfarcts
Clinical:- ~50% associated with obstetric
complications
- ~30% with carcinomatosis
- microangiopathic anemia
- dyspnea, cyanosis
- convulsions, coma
- oliguria, acute renal failure
- shock, circulatory failure
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77. Lead PoisoningLead Poisoning
- inhibition of 5’-nucleotidase and sodium-potassium pump
® decreased RBC survival
- intestinal absorption of Pb is enhanced by def. of calcium, iron or
zinc
- blood accumulates 5-10% of absorbed Pb
- Pb clearance:
from blood ® rapidly cleared
from bone ® slow (half-life = 30 yrs)
Lab: basophilic stippling
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78. MalariaMalaria
- intracellular protozoan parasite (Plasmodium)
P.falciparum:worldwide infection affecting 100 million people
1 to 1.5 million deaths each year
other malaria parasites:
P.vivax
P.ovale
P.malariae
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79. Immunohemolytic AnemiaImmunohemolytic Anemia
several subtypes
(1)warm antibody type
(2)cold agglutinin type
(3)cold hemolysin
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80. Immunohemolytic AnemiaImmunohemolytic Anemia
(1) warm antibody type
- 80 to 90% of autoimmune hemolytic anemia
- lg G antibody
- coating RBC with anti-Rh Ab and complement
- RBCs are ultimately destroyed by splenic macrophages
clinical:- intermittent hemolysis
- moderate splenomegaly
- unpredictable clinical course
etiology:
a. idiopathic disease
b. secondary disorder
- lymphoma (lymphocytic lymphoma)
- leukemia (chronic lymphocytic leukemia)
- autoimmune disorders (SLE, collagen vascular diseases)
- viral infections
- drugs:penicillin, cephalosporin (hapten)
α-methyldopa (autoantibody)
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81. Immunohemolytic AnemiaImmunohemolytic Anemia
(2) cold agglutinin type
- 10 to 20% of autoimmune hemolytic anemia
- Ig M type antibody
- complement-coated RBC will be removed by liver Kupffer cells
etiology:
a. acute: - mycoplasma
- infectious mononucleosis
b. chronic: - idiopathic
- lymphoma
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82. Immunohemolytic AnemiaImmunohemolytic Anemia
(3) cold hemolysis
paroxysmal cold hemoglobinuria
- caused by IgG bind to RBCs at low temp and fix complement
- acute intermittent massive hemolysis after exposure to cold
- complement dependent hemolysis
- caused by IgG against P blood group antigen
- IgG-Ab (Donath-Landsteiner Ab) binds to RBC and fix
complement at cold temp and then complement activation
when temp is elevated.
mostly seen after infection:mycoplasmal pneumonia
measles
mumps
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83. Drug-Mediated InjuryDrug-Mediated Injury
(1)autoantibody induction
α-methyldopa ¾ Ig G antibody
(2)immune complex formation (drug-Ab complex)
quinidine ¾ Ig M complex
® complement-mediated lysis
(3)hapten formation (drug-RBC membrane protein complex)
penicillin
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84. Aplastic AnemiaAplastic Anemia
- pancytopenia characterized by
(1) anemia
(2) neutropenia
(3) thrombocytopenia
- failure or suppression of multipotent myeloid stem cells causes
inadequate production or release of the differentiated cell lines
Etiology:
- 65% idiopathic
- chemicals/drugs
(benzene, chloramphenicol, alkylating agents, antimetabolite)
- whole body irradiation
- viral hepatitis
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85. Aplastic AnemiaAplastic Anemia
Pathology: markedly hypoplastic bone marrow
Clinical:- may occur at any age
- variable initial manifestations
(depending on the affected cell line)
- no splenomegaly
- normocytic and normochromic RBCs
- no reticulocytosis
Dx: bone marrow biopsy
hypocellular due to stem cell failure
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86. Megaloblastic AnemiaMegaloblastic Anemia
A group of disorders characterized by a reduced
rate of DNA synthesis
The dyssynchrony in nuclear (DNA) and
cytoplasmic (RNA) development is the
morphologic hallmark of this type of disorder,
since RNA synthesis, RNA processing and
protein synthesis are unaffected.
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87. Vitamin B12 / Folate DeficiencyVitamin B12 / Folate Deficiency
Vitamin B12 (cobalamin) -- a vital ingredient for DNA
synthesis and Krebs cycle
Methylcobalamin
a coenzyme for tetrahydrofolate (FH4)
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88. Vitamin B12 AbsorptionVitamin B12 Absorption
Vit B12: absorbed in ileum
(with intrinsic factor)
Intrinsic factor
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89. Vitamin B12 / Folate DeficiencyVitamin B12 / Folate Deficiency
Lab:
Blood:- macro-ovalocytes, giant hypersegmented PMNs
(no giant platelets)
- pancytopenia
- elevated MCV
- anisocytosis
- poikilocytosis
BM: - hyperplastic
- ¯ myeloid : erythroid ratio
- megaloblasts
- giant metamyelocytes
- autohemolysis (→ ↑ serum bilirubin, ↑ LDH)
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90. Vitamin B12 DeficiencyVitamin B12 Deficiency
etiology:
ii.dietary deficiency ---- rare
•strict vegetarians)
iii.decreased absorption
1)decreased intrinsic factor
•gastrectomy
•pernicious anemia
2)pancreatic insufficiency
3)intestinal malabsorption
•parasites (fish tapeworm [Diphyllobothrium latum])
•bacteria (blind-loop syndrome)
•ileal Crohn’s disease
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91. Vitamin B12 DeficiencyVitamin B12 Deficiency
Sx:
2)weakness ← anemia (megaloblastic anemia)
3)sore (“beefy”) tongue ← generalized epithelial atrophy
4)demyelination of spinal cord (posterior and lateral portions)
(subacute combined spinal degeneration)
•loss of vibration and position senses ← posterior tracts loss
•arm and leg dystaxia ← dorsal spinocerebellar tracts loss
•spastic paralysis ← corticospinal tracts loss
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92. Vitamin B12 DeficiencyVitamin B12 Deficiency
Lab:
2.low serum B12 level
3.increased serum homocysteine
4.increased methylmalonic acid in urine
Dx:Schilling test
oral radioactive B12 → 2 hrs later → parenteral large flushing
dose of non-labeled B12 → measure urine for radioactive B12
nl: >7% of radio-labeled B12 excreted in 24-hr urine
abnormal (lacking IF): less than 7% of B12 excreted
Tx:intramuscular vitamin B12
→ increase in reticulocytes in 5 days
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93. folate deficiencyfolate deficiency
etiology:
ii.dietary deficiency (folate def. takes only months to develop)
•“tea and toast” diet (elderly individuals)
•chronic alcoholics
iii.decreased absorption
•intestinal malabsorption (folate is absorbed in upper intestine)
iv.increased requirement
•pregnancy (folate def in pregnancy → neural tube defects)
•infancy
v.folate antagonists
•chemotherapy (i.e. methotrexate)
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94. folate deficiencyfolate deficiency
Sx:
•megaloblastic anemia
•no neurologic degeneration
Lab:
6.low serum folate level
7.increased serum homocysteine
Tx:folate
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95. Iron Deficiency AnemiaIron Deficiency Anemia
Iron:absorbed in duodenum
When iron loss exceeds its intake for a long time, iron
storage decreases and insufficient amount of iron is
available for hemoglobin production
Iron deficiency anemia develops in sequence of stages:
1. Iron Depletion
2. Iron Deficient Erythropoiesis
3. Iron Deficiency Anemia
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96. Iron Deficiency AnemiaIron Deficiency Anemia
Clinical:
- general fatigue
- SOB
- spoon nails (koilonychia)
- smooth, sore tongue
- epithelial atrophy
- pica (eating unusual things [e.g., dirt])
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97. Iron Deficiency AnemiaIron Deficiency Anemia
Lab:
Blood:- normochromic-normocytic
® microcytosis, anisocytosis, poikilocytosis,
hypochromia
- decreased reticulocytes
- low MCV
- relatively low Hgb, Hct
Marrow:no iron storage
normoblastic hyperplasia
® smaller normoblast with deficient Hgb
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98. Iron Deficiency AnemiaIron Deficiency Anemia
Serum iron (nl = 50-160 mg/dL) : low
Serum iron-binding capacity (nl = 250-400 mg/L) : increased
% saturation of TIBC (nl = 20-55%) : <15%
Serum ferritin (nl = 12-300 mg/L) : low
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99. sideroblastic anemiasideroblastic anemia
•due to altered production of heme
(defect in protoporphyrin production)
•associated with ring sideroblasts in bone marrow
•peripheral blood:may show dismorphic RBCs
•lab:increasedserum iron
ferritin
free erythrocyte protoporphyrin (FEP)
% saturation of TIBC
decreasedTIBC
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100. Sideroblastic AnemiaSideroblastic Anemia
a heterogeneous group of disorders associated with
various defects in the porphyrin biosynthetic pathway
porphyrn biosynthesis defects
diminished heme synthesis
increased cellular iron uptake
characterized by the association of anemia with
presence of ringed sideroblast (a normoblast
containing excessive deposits of iron within
mitochondria) in bone marrow
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101. Sideroblastic AnemiaSideroblastic Anemia
Sub-types:
Hereditary Sideroblastic Anemias
hereditary sex-linked
inheritance undetermined
Acquired Sideroblastic Anemias
primary (idiopathic) sideroblastic anemia
secondary (drug- or toxin-induced) sideroblastic anemia
anti TB drugs (isoniazid, cycloserine, pyrazinamide)
lead poisoning
chloramphenicol
ethanol
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102. Sideroblastic AnemiaSideroblastic Anemia
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103. Sideroblastic AnemiaSideroblastic Anemia
clinical:characterized by hypochromic, often microcytic, red
cells in the blood usually mixed with normochromic
cells
hypochromic anemia
hyperferremia
increased transferrin saturation
Lab: serum iron: increased
TIBC: decreased
% saturation: greatly elevated
bone marrow:- markedly increased iron storage
- erythroid hyperplasia
- increased sideroblasts
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104. anemia work-upanemia work-up
M:Hb<13.5Hct<41
F:Hb<12 Hct<36
[check MCV]
MCV <80 = microcytic
•Fe deficiency
•thalassemia
•anemia of chronic disease
•sideroblastic anemia
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105. anemia work-upanemia work-up
MCV >100 = macrocytic
•megaloblastic anemia
•VitB12 deficiency
•folate deficiency
•alcoholic liver disease
MCV 80-100 = normocytic
[chech reticulocyte count]
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106. anemia work-upanemia work-up
low reticulocyte:
- marrow failure - leukemia/metastasis
- aplastic anemia- renal failure
-myelofibrosis - anemia of chronic disease
high reticulocyte:
-sickle cell anemia- autoimmune hemolytic anemia
-G6PD deficiency - hereditary sphelocytosis
-paroxysmal nocturnal hemoglobiuria
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