Hypoproliferative Anemia Flashcards

1
Q

What are the characteristic lab findings of hypoproliferative anemias?

A

Anemia and low reticulocyte count in lab

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2
Q

What are the types of hypocellular bone marrow/hypercellular bone marrow?

A

Hypocellular bone marrows

  • Stem cell disorders
  • Drugs/Treatments

Hypercellular bone marrows

  • infiltration
  • Ineffective erythropoiesis
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3
Q

What should the differential for pancytopenia be?

A

Stem cell disorders – Aplastic anemia, PNH
Ineffective hematopoiesis – MDS, Megaloblastic anemia
Marrow infiltration – Leukemia/lymphoma, metastatic carcinoma, myelofibrosis
Splenic sequestration – Massive splenomegaly
Drugs/Treatments – Immunosuppressants, Chemotherapy/radiation, other medications

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4
Q

What is associated with hypersplenism?

A

Variable cytopenias – Estimated that 1/3 of platelets are stored in spleen

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5
Q

What are the major steps involved in the folate pathway?

A

Purine synthesis

Conversion of dUMP to dTMP

One carbon for S-adenosylmethionine

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6
Q

How is folate activated? What is it inhibited by?

A

Takes folate which is activated to THF via DHF reductase

Two step
Inhibited by MTX

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7
Q

What does thymidylate synthetase do?
What inhibits it?
What does it require?

A

Conversion of dUMP to dTMP

Inhibited by 5-FU derivative FdUMP

Requires THF

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8
Q

What are potential etiologies of megaloblastic anemia?

A

DHF reductase deficiency via MTX
Thymidylate synthetase deficiency – 5FU
Folate deficiency
Vitamin B12 deficiency

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9
Q

What is the prurpose of the folate one-carbon?
What is it required for?

A

Purine synthesis
Required for thymidylate synthetase for conversion of dUMP to dTMP for DNA synthesis
Synthesis of methionine for SAM

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10
Q

What is 5-Adenosylmethionine used for?

A

Methyl donation via methyl transferases

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11
Q

What does methionine synthetase require?

A

Requires methyl THF and Vitamin B12

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12
Q

What is Vitamin B12 bound to and how is it taken and transferred?

A

Bound to food
Released in stomach by HCl and pepsin
Binds mainly to R-protein but some to IF
In duodenum, R-protein degraded releasing Vitamin B12
Vitamin B12 binds intrinsic factor
Complex binds IF receptor
Vitamin B12 transferred to transcobalamin

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13
Q

What are the causes of vitamin B12 deficiency?

A

Impaired absorption
IF deficiency
Ileal resection
Pancreatic insufficiency

Increased requirement (Pregnancy)
Decreased intake (strict vegans)
Tapeworm – Diphyllobothrium latum
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14
Q

What are the clinical manifestations of Vitamin B12?

A

Megaloblastic anemia, pernicious anemia

Subacute combined degeneration
Dorsal and lateral tract demyelination
Parasthesias
Spastic paraparesis
Sensory ataxia

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15
Q

What is pernicious anemia? What is its etiology?

A

Secondary B12 def to IF abnormalities
Most frequent cause of B12 deficiency
Autoantibodies against IF – Required for diagnosis

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16
Q

What are the lab values of vitamin B12?

A

Low vitamin B12 levels
Low reticulocyte count
Auto-antibodies to IF or parietal cells (if pernicious anemia)
Elevated methylmalonic acid

17
Q

What are the causes of folate deficiency?

A

Decreased intake – Alcoholism, poverty
Increased requirements – Growth, pregnancy, high cell turnover: hemolytic anemias, leukemias
Defective absorption – Jejunal resection or malabsorption
Folic acid antagonists

18
Q

What are the clinical manifestations of folate deficiency?

A

Megaloblastic anemia

Neural tube defects
300,000 children/year
Spina bifida occulta – Anencephaly
Importance of supplementation

19
Q

What is the therapy for megaloblastic anemia?

A

Vitamin B12 or folate supplementation
Oral vs IM injection

Do not treat vitamin B12 deficiency with folate
Anemia will reverse
Neurological manifestations will not

20
Q

What are the diagnostics for megaloblastic anemia in PB and BM?

A

PB
Hypersegmented neutrophils – 5 or more lobes
Macrocytic anemia with oval macrocytes
Anisopoikilocytosis

BM – Not needed for diagnosis
Hypercellularity
Giant bands
Nuclear to cytoplasmic dyssynchrony (megaloblastic change) in erythroids, granulocytes

21
Q

What is the functional role of iron?
Where is iron stored?

A

Component of heme (80%)
Component of myoglobin, cytochromes, catalases (20%)

Liver, spleen, marrow
Hemosiderin: Breakdown of ferritin
Ferritin

22
Q

What is the epidemiology for iron deficency?

A

Most common worldwide nutritional disorder
4-5 billion people worldwide
2 billion with IDA
Infants, children, and women are most susceptible

23
Q

What are the clinical outcomes for iron deficient?

A

Iron Deficient Anemia (IDA)
Impaired cognition, work capacity
Immune deficiency

24
Q

What are the causes for iron deficiency?

A

Dietary lack, i.e. milk-fed infants

Impaired absorption (duodenum)

Increased requirement

Chronic blood loss
GI source (>50 y/o)
Menstrual bleeding

25
Q

What transporter moves heme iron?
What transporter moves non-heme iron?
What is mucosal ferritin ?

A

Heme iron transporter

Reduced by duodenal cytochrome B – Vitamin C to ferrous iron (Fe2+)
Dication metal transporter – DMT-1

Huge complex
4500 molecules of iron per ferritin

26
Q

What is the ferroportin transporter regulated by?
What kind of iron does it require?

A

Regulated by Hepcidin – Liver feedback of iron and inhibits Ferroportin 1

Must be ferrous

27
Q

What oxidizes the iron?
What moves iron to the cells?
How can iron be lost?

A

Hephaestin oxidizes to 3+
Binds transferrin to moves it to cells
Iron can be lost via shedding of the GI epithelial cells

28
Q

What is the serum ferritin study?
What is the difficulty with using ferritin?

A

Most sensitive assay for iron deficiency anemia

Ferritin has a high sensitivity and specificity for IDA when a cut-off equal to 30 microg/L is used
<12 is diagnostic of IDA

Ferritin is an acute phase reactant (increases during inflammation) making its usage during a chronic inflammatory process more cloudy

29
Q

What is the use of serum iron study?

A

Not sensitive or specific
Many metabolic variations affect level

30
Q

What is the total iron binding capacity study?

A

Essentially equivalent to a transferrin concentration
Normally 30% of transferrin is saturated with iron
Qualitatively opposite of serum ferritin levels

31
Q

What is the defintion of percent iron saturation?

A

Serum iron/TIBC

32
Q

What are the two bone marrow studies?

A

Storage iron: Macrophages within particles

Sideroblastic iron: Within eryhtroid precursors

33
Q

What is anemia of a chronic disease??

A

Most common anemia in hospitalized patients
Mild to moderate

34
Q

What are the clinical associations of anemia of chronic disease?

A

Chronic infections
Immune dysfunction disorders
Neoplastic disorders

35
Q

What is the mechanism of anemia of chronic disease?
What is the diagnostic criteria?
What is the treatment for it?

A

Mechanism: Block in transport of irons from macrophages into erythroid precursors mediated by hepcidin (inverse relationship)
Diagnosis

Mild normocytic (80%) or microcytic (20%) anemia
Without significant anisopoikilocytosis
Iron studies

Treatment

Treat underlying disorder

EPO or iron therapy

36
Q

What is the anemia of renal failure?
What medical treatment is associated with it?
What cellular finding is associated with it?
What is the treatment?

A

Decreased EPO production due to kidney damage
Hemodialysis blood loss also contributes
Hypoplastic erythroids
Tx: EPO

37
Q

What is pure red cell aplasia?
What is the cause?

A

Selective absence of marrow erythroid precursors (differs from aplastic anemia which involves all 3 myeloid lineages)

Difficult to identify etiology in many cases
Seen in association with
Thymic hyperplasia or thymomas (excision may be curative)
Autoimmune disorders
Drugs
Large granular lymphocytic leukemia

38
Q

What is myelophistic anemia?
What kind of plastic state is it?
What cellular finding is associated with it?

A

Anemia secondary to marrow infiltration by metastatic carcinoma
Leukoeryhtroblastic reaction
Tear drop cells