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Anemias Flashcards

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1
Q

What are the Microcytic anemias?

A
  • Iron def
  • ACD
  • Thalassemias
  • Lead poisoning
  • Sideroblastic anemia
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2
Q

What are the Normocytic Nonhemolytic anemias?

A
  • Anemia of chronic dz
  • Aplastic anemia
  • Chronic kidney dz
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3
Q

What are the Normocytic Intrinsic hemolytic anemias?

A
  • Hereditary spherocytosis (RBC mem defect)
  • G6PD, PK (RBC enzyme def)
  • HbC
  • Sickle cell anemia
  • Paroxysmal nocturnal hemoglobinuria
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4
Q

What are the Macrocytic Megaloblastic anemias?

A
  • Folate def
  • B12 def
  • Orotic aciduria
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5
Q

What are the Macrocytic Non-megaloblastic anemias?

A
  • Liver dz
  • Alcoholism
  • Reticulocytosis
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6
Q

What are the Normocytic Extrinsic hemolytic anemias?

A
  • Autoimmune
  • Microangiopathic
  • Macroangiopathic
  • Infections
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7
Q

What is Microcytic hypochromatic anemia?

A

MCV <80fL

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8
Q

What causes iron def anemia?

A

Dec iron d/t chornic bleeding (GI loss, menorrhagia), malnutrition/absorption disorders or inc demand→ dec final step in heme synthesis

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9
Q

What are the findings in Iron def anemia?

A
  • Dec iron
  • Inc TIBC
  • Dec ferritin
  • Microcytosis
  • Hypochromia
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10
Q

What is the triad of Plummer-Vinson synd?

A
  • Iron def anemia
  • Esophageal webs
  • Atrophic glossitis
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11
Q

What is the defect in alpha-thalassemia?

A

Alpha-globulin gene mutations→ dec alpha-globin synthesis

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12
Q

Which deletion is prevalent in Asian pop w/ alpha-thalassemia?

A

Cis deletion

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13
Q

Which deletion is prevalent in African pop w/ alpha-thalassemias?

A

Trans deletion

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14
Q

What are the features of 4 gene deletion alpha thalassemia?

A
  • No alpha globin
  • Excess gamma-globin forms gamma 4 (Hb Barts)
  • Incompatible with life–hydrops fetalis
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15
Q

What are the features of 3 gene deletion alpha thalassemia?

A
  • HbH dz
  • Very little alpha-globin
  • Excess ß-globin forms ß4 (HbH)
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16
Q

What are the features of 1-2 gene deletion alpha thalassemia?

A

No clinically significant anemia

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17
Q

What causes ß-thalassemia?

A

Point mutations in splice sites & promoter sequences→ dec ß-globin synthesis

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18
Q

Which pop is ß-thalassemia prevalent in?

A

Mediterranean

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19
Q

What are the findings in ß-thalasemia minor?

A
  • Heterozygote
  • ß chain underproduced
  • Dx confirmed by inc HbA2 (>3.5%) on electrophoresis
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20
Q

What are the findings in ß-thalassemia major?

A
  • Homozygote
  • ß chain is absent
  • Marrow expansion
  • Inc in HbF (alpha2gamma2)
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21
Q

What does absent ß chain produce?

A

Severe anemia requiring blood transfusion

(2° hemochromatosis)

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22
Q

What are the features of marrow expansion?

A

Skeletal deformities

  • Chipmunk facies
  • “Crew cut” on skull x-ray
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23
Q

What are the features of HbS/ß thalassemia heterozygote?

A

Mild to moderate sickle cell dz depending on amount of ß-globin production

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24
Q

What does lead poisoning lead to?

A
  • Lead inhibits ferrochelatase & ALA dehydratase→ dec heme synthesis
  • Also inhibits rRNA degradation causing RBC’s to reatin aggregates of rRNA (basophilic stippling)
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25
What inc the risk of lead poisioning?
High risk in houses w/ chipped paint
26
What are the sx of lead poisoning?
* Lead lines on gingivae & metaphyses of long bones on x-ray * Encephalopathy & erythrocyte basophilic stippling * Abd colic & sideroblastic anemia * Wrist & foot drop
27
What are Burton's lines?
Lead lines on gingivae
28
What is the 1st line tx for lead poisoning?
Dimercaprol & EDTA
29
What is used for chelation in kids?
Succimer
30
What is the defect in Sideroblastic anemia?
Defect in heme synthesis
31
What is the defect in Hereditary Sideroblastic anemia?
X-linked defect in delta-ALA synthase gene
32
What are the reversible etiologies in Sideroblastic anemia?
Alcohol, led & isoniazid
33
What are the findings in Sideroblastic anemia?
* Ringed sideroblasts (w/ iron-laden mitochondria) * Inc iron * Normal TIBC * Inc ferritin
34
What is the tx for Sideroblastic anemia?
Pyridoxine (B6 cofactor for delta-ALA synthase)
35
What is Megaloblastic anemia?
Impaired DNA synthesis→ maturation of nucleus delayed relative to maturation of cytoplasm Ineffective ereythropoiesis→ pancytopenia
36
What are the etiologies of Folate deficiency?
* Malnutrition * Malabsorption * Antifolates * Inc requirement
37
What are the findings in Folate deficiency?
* Hypersegmented neutrophils * Glossitis * Dec folate * Inc homocysteine but normal methylmalonic acid
38
What are the etiologies of B12 deficiency (cobalamin)?
* Insufficient intake * Malabsorption * Pernicious anemia * *Diphyllobothrium latum* * Proton pump inhibitors
39
What are the findings in B12 def?
* Hypersegmented neutrophils * Glossitis * Dec B12 * Inc homocysteine * Inc methylmalonic acid
40
What causes the neurologic sx in B12 def?
Subacute combined degeneration d/t involvement to B12 in fatty acid pathways & myelin synthesis
41
What are the neurologic sx in B12 def?
* Peripheral neuropathy w/ sensorimotor dysfunction * Posterior columns (vibration/proprioception) * Lateral corticospinal (spasticity) * Dementia
42
What causes Orotic aciduria?
Genetic mutation in enzyme that synthesizes uridine from orotic acid
43
How does Orotic aciduria present?
In children as megaloblastic anemia that cannot be cured by folate or B12
44
What are the findings in Orotic aciduria?
* Hypersegmented neutrophils * Glossitis * Orotic acid in urine
45
What is the tx for Orotic aciduria?
Uridine monophosphate to bypass mutated enzyme
46
What are Nonmegaloblastic macrocytic anemias?
Macrocytic anemia in which DNA synthesis is unimpaired
47
What are the causes of Nonmegaloblastic macrocytic anemia?
* Liver dz * Alcoholism * Reticulocytosis→ Inc MCV * Drugs (5-FU, AZT, hydroxyurea)
48
What are the findings in Nonmegaloblastic macrocytic anemias?
Macrocytosis & BM suppression can occur in the absence of folate/B12 def
49
What are the findings in Intravascular hemolysis?
* Dec haptoglobin * Inc LDH * Hb in urine
50
What are the findings in Extravascular hemolysis?
* Macrophage in splen clears RBC * Inc LDH plus inc UCB which causes jaundice
51
What is Anemia of chronic dz (ACD)?
Inflammation→ inc hepcidin→ dec release of iron from macrophages
52
What is hepcidin?
Released by liver, binds ferroportin on intestinal mucosal cells & macrophages thus inhibiting iron transport
53
What are the findings in ACD?
* Dec iron * Dec TIBC * Inc ferritin * Can become microcytic, hypochromic or nonhemolytic, normocytic
54
What causes Aplastic anemia?
Failure or destruction of myeloid stem cells
55
What are the etiologies of Aplastic anemia?
* Radiation & drugs (benzene, chloramphenicol, alkylating agents, antimetabolites) * Viral agents (B19, EBV, HIV, HCV) * Fanconi's anemia (DNA repair defect) * Idiopathic
56
What are the findings in Aplastic anemia?
* Pancytopenia characterized by severe anemia, leukopenia & thrombocytopenia * Normal cell morphology but hypocellular BM w/ fatty infiltration (dry BM tap)
57
What are the sx of Aplastic anemia?
* Fatigue * Malaise * Pallor * Purpura * Mucosal bleeding * Petechiae * Infection
58
What is the tx for Aplastic anemia?
* Withdrawal of offending agent * Immunosuppressive regimens * Allogenic BM transplantation * RBC & platelet transfusion * G-CSF or GM-CSF
59
What is the anemic affect of Chronic kidney dz?
Dec erythropoietin→ dec hematopoiesis
60
What is the defect in Hereditary spherocytosis?
Defect in proteins interacting w/ RBC membrane skeleton & plasma membrane
61
What does the dec in membrane in hereditary spherocytosis cause?
Small & round RBC's w/ no central pallor→ premature removal of RBCs by spleen
62
What are the findings in Hereditary spherocytosis?
* Splenomegaly * Aplastic crisis (Parvovirus B19 infection) * _Labs_: positive osmotic fragility test, normal to dec MCV w/ abundance of cells, masks microcytia
63
What is the tx of Hereditary spherocytosis?
Splenectomy
64
What is the defect in G6PD deficiency?
X-linked G6PD→ dec glutathione→ inc RBC susceptibility to oxidant stress
65
What happens following oxidant stress in G6PD def?
Hemolytic anemia RBC's primarily destroyed extravascularly
66
What are the findings in G6PD def?
* Back pain * Hemoglobinuria a few days later * _Labs_: blood smear shows RBCs w/ Heinz bodies & bite cells
67
What is the defect in Pyruvate kinase def?
AR defect in pyruvate kinase→ dec ATP→ rigid RBCs
68
What are the findings in Pyruvate kinase def?
Hemolytic anemia in a newborn
69
What is the cause of HbC defect?
Glutamic acid-to-lysine mutation at residue 6 in ß-globin
70
What are the findings in HbC defect?
Pts w/ hbSC (1 of each mutant gene) have milder dz thatn have HbSS pts
71
What is Paroxysmal nocturnal hemoglobinuria?
Inc complement-med RBC lysis (impaired synthesis of GPI anchor or decay-accelerating factor that protect RBC mem from complement)
72
What is the cause of Paroxysmal nocturnal hemoglobinuria?
Acquired mutation in a hematopoietic stem cell
73
What is the triad in Paroxysmal nocturnal hemoglobinuria?
* Hemolytic anemia * Pancytopenia * Venous thrombosis
74
What is shown on labs in paroxysmal nocturnal hemoglobinuria?
CD55/59 neg RBCs on flow cytometry
75
What is the tx of paroxysmal nocturnal hemoglobinuria?
Eculizumab
76
What is the cause of Sickle cell anemia?
HbS point mutation causes a single amino acid replacement in ß chain (substitution of glutamic acid w/ valine) at position 6
77
What is the pathogenesis in Sickle cell anemia?
Low O2 or dehydration precipitates sickling (deoxy HbS polymerizes) which results in anemia & vaso-occlusive dz
78
Why are sickle cell anemia newborns initially asx?
Inc HbF & dec HbS
79
What are heterozygotes w/ sickle cell trait resistance to?
Malaria
80
8% of ___ \_\_\_ carry the HbS trait.
African Americans
81
What are the findings in Sickle cell anemia?
* Sickled cells are crescent-shaped RBCs * "Crew cut" on skull x-ray d/t marrow expansion from in erythropoiesis
82
What are the complications in homozygotes w/ sickle cell dz?
* Aplastic crisis (d/t parvovirus B19) * Autosplenectomy * Splenic sequestration crisis * Salmonella osteomyelitis * Painful crisis * Renal papillary necrosis & microhematuria
83
What does Autosplenectomy inc risk for?
Inc risk of infection w/ encapsulated organisms
84
What are the painful crisis in sickle cell anemia?
* Dacytlitis * Acute chest synd * Avascular necrosis
85
What is the tx for Sickle cell anemia?
Hydroxyurea (inc HbF) & BM transplantation
86
What is Warm agglutinin (IgG) seen in?
Chronic anemia seen in SLE, CLL, or w/ certain drugs
87
What is Cold agglutinin (IgM) seen in?
* Acute anemia triggered by cold * CLL * *Mycoplasma pneumonia* infections * Infectious mononucleosis
88
What are the findings in Autoimmune hemolytic anemia?
Usually Coombs' positive
89
What is Direct coombs' test?
* Anti-Ig Ab added to pt's serum * RBCs agglutinate if RBCs are coated w/ Ig
90
What is Indirect Coombs' test?
Normal RBC's added to pt's serum agglutinate if serum has anti-RBC surface Ig
91
What is the pathogenesis in Microangiopathic anemia?
RBCs are damaged when passing through obstructed or narrowed vessel lumina
92
What disorders are Microangiopathic anemia seen in?
* DIC * TTP-HUS * SLE * Malignant HTN
93
What are the findings in Mircoangiopathic anemia?
Shistocytes (helmet cells) are seen on blood smear d/t mech destruction on RBCs
94
What can cause Macroangiopathic anemia?
Prosthetic heart valves & aortic stenosis may also cause hemolytic anemia 2° to mech destruction
95
What are the findings in Macroangiopathic anemia?
Schistocytes on peripheral blood smear
96
What can infections cause?
Inc destruction of RBCs
97
What are the lab values in Iron def?
* 1° dec serum iron * Inc Transferring or TIBC * Dec Ferritin * Dec % transferrin saturation
98
What are the lab values in Chronic disease?
* Dec serum iron * Dec Transferring or TIBC * 1° Inc Ferritin
99
What are the lab values in Hemo-chromatosis?
* 1° inc in serum iron * Dec in Transferrin or TIBC * Inc Ferritin * Inc % transferrin saturation
100
What are the lab values in Pregnancy/OCP use?
* 1° inc in Transferrin or TIBC * Dec in % transferring saturation
101
What is the function of Transferrin?
Transports iron in blood
102
What is the function of Ferritin?
1° storage protein of body
103
Why does Transferrin or TIBC dec in chronic dz?
Pathogens use ciruclating iron to thrive. Iron is stored w/in the cells of the boyd & prevents pathogens from acquiring iron
104
When is Transferrin production inc?
Pregnancy & OCP use

Hematology & Oncology (7 decks)

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