Test 4 (Units 16-17) Flashcards by Gabrielle Baldwin

Define the overall type of defect found in Megaloblastic Anemia.

Impaired DNA synthesis leading to less cell division and therefore bigger, oval shaped RBCs

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Describe RBC development with Vitamin B12 and folate deficiency including mechanism and cell changes in megaloblastic transformation.

-Ineffective erythropoiesis  Increased apoptosis and cell lysis
Remaining cells are large, immature nucleus
-For DNA, thymine can’t be made, so uridine is used can’t replicatess breaksfragmented DNA
-Normal RNA development
-Asynchrony between nucleus and cytoplasm
-Sometimes pancytopenia

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Describe systemic manifestations Vitamin B12 and folate deficiency.

Systemic: Fatigue, Weakness, SOB
Gastritis, nausea, constipation
Glossitis

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B12 Deficiency: Specific manifestations

Neuro: Memory loss, numbness, tingling and loss of balance

- Neuropsych: personality changes, psychosis

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B12 Deficiency: Causes

Impaired absorption
Inadequate intake
Increased need

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B12 Deficiency: Absorption

Food protein—B12 Stomach: haptocorrin—B12  Small intestine: Intrinsic factor—B12 Enterocyte: Transcobalamin—B12 Circulation

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B12 Deficiency: Testing

Homocysteine inc
Serum B12 dec
Methylmalonic acid inc
Antibodies to intrinsic and parietal cells (pernicious anemia)
D. latum (Competition)

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B12 Deficiency: Impaired absorption causes

Failure to Separate 
Lack of intrinsic factor 
Malabsorption
Inherited errors
Competition

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B12 Deficiency: Impaired absorption; Failure to Separate

-From food protein: Need acidic environment
in stomach for separation; “food cobalmin
(B12 malabsorption”
-From haptocorrin: Pancreatic enzymes help
separation in SI

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B12 Deficiency: Impaired absorption; Lack of intrinsic factor

-Autoimmune diseases: pernicious anemia
Lymphocytes attack parietal cells
Parietal cells normally make IF and HCl
-Destruction of parietal cells: H pylori infection
Or Gastrectomy
-Hereditary deficiency

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B12 Deficiency: Impaired absorption; Competition

-Diphyllobothrium latum splits B12 from IF
-Blind loops: areas of SI that become over-
grown with bacteria

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Folate Deficiency: Specific manifestations

-Depression, peripheral neuropathy, psychosis, neural tube defects (if during pregnancy)

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Folate Deficiency: Causes

Inadequate intake
Increased need
Impaired absorption (small intestine issues like Celiac)
Impaired use of folate (some drug like anti-epileptic)
Excessive loss of folate (dialysis-need for supplements)

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Folate Deficiency: Testing

Homocysteine inc

Serum folate dec

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Hematologic abnormalities of megaloblastic anemia in Peripheral Blood and Bone Marrow

3 Main findings:

1) Large ovalocytes
2) Teardrops
3) Hypersegmented neutrophils (1st finding)

Note: Retics will NOT increase so we will not see polychromasia (b/c there’s a problem with replication)

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Megaloblastic anemia test results:

Hypercellular marrow but Pancytopenia
Increased Normal Decreased
MCV 100-15-, avg 120 MCHC N (normochromatic) H+H dec
MCH inc Retics N or dec Retics N or dec
RDW inc

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Outline a sequential approach to the differential diagnosis of macrocytic anemias

If homocysteine is high Check B12 and folate
If B12 is lowCheck methylmalonic acid, if its high Confirm achlorhydria
if pos,test for antibodies to intrinsic & parietal cellsPernicious anemia
if neg, check for D. latum in stool analysis
If folate is lowgive folic acid supplement and monitor response
Retics should increase within a week
H+H should increase within 3 weeks
Everything should be back to normal within 3-6 weeks

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Acquired aplastic anemia: Etiology

-70% idiopathic
-10-15% Secondary
Dose Dependent
Idiosyncratic
Viruses
Miscellaneous

Higher rates in Asia
Ages 15-25, >60

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Acquired aplastic anemia: Pathophysiologic mechanisms

-Quantitative or qualitative deficiency HSC
-Inc growth factor, EPO, TPO, CSF
signals to make cells but BM can’t
-Direct damage to stem cells
-Immune damage to stem cells
-Unknown
-Shortened telomers in 1/3, no response to IST

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Acquired aplastic anemia: Specific clinical findings

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Asymptomaticsevere
Low RBC: pallor, fatigue, weakness
Low WBC: infection
Low Plt: Bleeding and bruising 
NO hepatospenomegaly

Acquired aplastic anemia: Specific lab findings

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Low hgb
Low plt
MCV N or inc
Dec retics
RBCs normal but some macrocytes

Acquired aplastic anemia: Secondary: Miscellaneous

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PNH (Paroxysmol Nocturnal Hgb)
- Autoimmune diseases
- Very rarely, pregnancy

Acquired aplastic anemia: Secondary: Miscellaneous

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PNH (Paroxysmol Nocturnal Hgb)
- Autoimmune diseases
- Very rarely, pregnancy

Acquired aplastic anemia: Specific treatment /prognosis

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Removal of causative agent if Dose dependent
Plt or RBC transfusion
Antibiotic and antifungal prophylaxis
IST
BM transplant
10 year survival: children 85%, adults 55%
For IST, increased risk of other hematologic problems developing in future

Inherited aplastic anemia: Etiology and examples

- Early onset because its genetic - May have physical malformations Franconi Anemia Dyskeratosis Congenita Shwachman-Bodian-Diamond Syndrome

Franconi Anemia: etiology

-Inc Ashkenazi, S.African Africaners -Most common, but still very rare -Mostly autosomal recessive deletion/ mutation

Dyskeratosis Congenita: etiology

- Very rare | - Dominant and recessive mutations

Shwachman-Bodian-Diamond Syndrome: etiology

- Very rare | - Autosomal recessive mutation

Franconi Anemia: Pathophysiologic mechanisms

- Chromosome breakage | - Accelerated shortening of telomeres

Franconi Anemia: Specific Clinical Findings

- 2/3 have skeletal abnormalities - Short stature - Hyperpigmentation - Most symptomatic at 5-10 - High risk for solid tumors

Franconi Anemia: Specific Lab Findings

-Similar to acquired, plts dec first, increase in Hemoglobin F and a- fetoprotein -Abnormal chromosomal fragility

Dyskeratosis Congenita: Specific Clinical Findings

- Abnormal skin pigmentation - Dystrophic nails - Oral leukoplasia - Multisystem abnormalities - 40% risk cancer by 40

Shwachman-Bodian-Diamond Syndrome: Specific Clinical Findings

``` -Decreased pancreatic enzyme secretions pancreatic insufficiency; symptoms in early infancy -Neutropenia, immune dysfunction; risk of infection and sepsis -Delayed bone maturation -50% short stature ```

Dyskeratosis Congenita: Specific Clinical Findings

- Abnormal skin pigmentation - Dystrophic nails - Oral leukoplasia - Multisystem abnormalities - 40% risk cancer by 40

Shwachman-Bodian-Diamond Syndrome: Specific Lab Findings

-Neutropenia -Decreased RBCs and Plts in 50% -Pancreatic insufficiency: increase of fat in feces-72 hour fecal fat test

Shwachman-Bodian-Diamond Syndrome: Specific Lab Findings

-Neutropenia -Decreased RBCs and Plts in 50% -Pancreatic insufficiency: increase of fat in feces-72 hour fecal fat test

Franconi Anemia: Specific treatment /prognosis

->90% BM failure by 40 -1/3 hematologic malignancy by 14 -1/4 solid tumors by 26 -Squamous cell carcinoma -Liver, brain kidney cancer -Death by 20 is common -Treatment: supportive hormones, BMT Secondary malignancy risk stays

Dyskeratosis Congenita: Specific treatment /prognosis

-60-70% death due to BM failure -10-15% pulmonary disease -Median survival : 42 -BMT not optimal due to vascular complications and pulmonary fibrosis

Shwachman-Bodian-Diamond Syndrome: Specific treatment /prognosis

- Transfusion - G-CSF for neutropenia - Pancreatic enzyme replacement - Increased risk of AML and MDS - BMT

pure red cell aplasia: Types

Acquired or Diamond-Blackfan Anemia

acquired pure red cell aplasia: clinical features

- Acute or chronic - Idiopathic or autoimmune - Secondary to underlying condition - Transient erythroblastopenia

acquired pure red cell aplasia: lab findings

- Selective and severe decrease in RBC precursors - Severe anemia - Decreased retics - Normal WBC and plt

acquired pure red cell aplasia: treatment

- If secondary, treat underlying condition or IST if not responsive - If TEC, RBC transfusion

Diamond-Blackfan Anemia: clinical features

- Congenital - Early infancy - Short stature, craniofacial dysmorphism, neck and thumb malformations - Mutations on genes coding for ribosomal proteins

Diamond-Blackfan Anemia: lab findings

- Macrocytes | - Severely low hgb

Diamond-Blackfan Anemia: treatment

- RBC transfusion - Corticosteroid therapy - BMT

congenital dyserythropoietic anemias: clinical features

- Refractory-difficult to treat - Ineffective erythropoiesis - Mild to moderate anemia - Symptoms: childhood and adolescence - Secondary hemosiderosis - jaundice and splenomegaly

congenital dyserythropoietic anemias: lab findings

- Hypercellular BM | - Iron overload

Aplastic anemia: general lab findings

- Pancytopenia - Dec retics - Hypocellular BM - HSC depletion

Test 4 (Units 16-17) Flashcards

(49 cards)