Hematology 2- B12, Folic Acid, Aplastic Anemia 10/21/16 Flashcards
What type of cytic anemia with B12, Folic Acid, and Aplastic Anemia?
Macrocytic anemia
MCV over 100 and below 115 is…
Macrocytic
MCV over 115 is…
Megaloblastic
After determining PT has macrocytic anemia what to check next?
Reticulocyte count high or low
What does reticulocyte count check?
Gives idea as to bone marrow function. High is due to high output and pushing immature cells out=reticulocytosis
What is reticulocytosis?
Increase in reticulocytes (immature RBCs)
Normal Reticulocyte count range?
2.0-3.0
If Macrocytic and low Reticulocyte count then what to check? (Hint: 2 things)
Check if Hypersegmented Neutrophils and MCV above or below 115.
If Macrocytic, low Reticulocyte, Hypersegmented Neutrophils, and MCV above 115?
B12 or Folate deficiency
If Macrocytic, low Reticulocyte, no Hypersegmented Neutrophils, and MCV below 115? (Hint: If not d/t meds or liver, thyroid, DS)
Probable myelodysplasia
What causes Macrocytic Anemia?
Abnormal DNA metabolism, shift to immature cells when anemic and pushing out immature cells too early, bone marrow disorder, lipid abnormalities, unknown dz
If Megaloblastic MCV above 115 two common causes?
B12 or Folate deficiency
If Macrocytic MCV above 100 common causes?
Reticulocytosis, alcoholism, liver dz, hypothyroid, meds, aplasic anemia
What stains blue in reticulocytosis?
RNA
B12 or Folate deficiency has MCV above what? High or low Reticulocyte count?
MCV over 115 (Megaloblastic). Low Reticulocyte.
Myelodysplasia MCV, Ret count, segmented?
MCV above 100 macrocytic, low ret count, not hypersegmented neutrophils.
90% of alcoholics have an MCV between what and what?
100-110
Alcoholic Macrocytic anemia resolves after how long of not drinking?
2-4 months
Alcoholics are commonly deficient in what even if taking supplements and will still be macrocytic?
Folic acid deficient
Macrocytic and hypothyroidism do to what?
Unknown. Check liver function, thyroid function, and vitamin deficiency.
What is the cause of medication-induced macrocytic anemia?
Combo antiretroviral therapy for HIV. Inhibition of various pathways. Hydroxyurea for sickel cell dz.
Myelodysplastic Syndromes due to issues of what? Causes inappropriately low response of what?
Issues of bone marrow itself. Inappropriately low reticulocyte response.
Aplastic Anemia is failure of what?
Bone marrow failure
What happens to all 3 cell lines in Aplastic Anemia?
Very low. Peripheral Pancytopenia.
Which 3 cell lines are low in Aplastic Anemia?
Platelets, RBCs, WBCs
Epi of Aplastic Anemia?
2-4 M/yr in US. 2-3x higher in East Asia. Men and women equally.
Distribution of Aplastic Anemia?
Biphasic. 10-25, over 60 years.
What are the two “phases” of injury to pluripotent stem cells in Aplastic Anemia?
- Damage to stem cells from viruses/drugs/chemo/radiation/toxins
- Autoimmune response against stem cells
Both cause pancytopenia!
What is the major cause of autoimmune Aplastic Anemia?
Idiopathic
Which two drugs are major causes of acquired Aplastic Anemia?
Chloramphenicol and Sulfonamides
What is Fanconi Anemia?
Defect in DNA repair pathway. Cause congenital Aplastic Anemia.
What is Dyskeratosis congenita?
Defect in maintenance of hematopoietic stem cell
telomere length maintenance. Cause congenital Aplastic Anemia.
What are the 4 steps in Aplastic Anemia?
- Inciting event
- Aberrant immune response
- Destruction of hematopoietic stem cells
- Clinical disease
After destruction of hematopoietic stem cells how long until pancytopenia seen? Which cells die first?
Weeks to month. WBCs die first, so infection seen first.
Aplastic Anemia clinical presentation?
- Weakness and fatigue
- Cardiopulmonary compromise
- Progressive anemia
- Mucosal and skin bleeding
- Infection
What is common cause of death in Aplastic Anemia?
Invasive fungal infection
Profound neutropenia causes…?
Recurrent infections
Thrombocytipenia causes….?
Mucosal hemorrhage
Aplastic Anemia causes what in premenopausal women?
Increased menstural flow
Is PE for Aplastic Anemia helpful?
Not very
What 2 most common PE findings in Aplastic Anemia?
Pallor, Pepechiae
What 3 things should NOT be seen in Aplastic Anemia?
- Hepatosplenomegaly
- Lymphadenopathy
- Bone tenderness
CBC shows what in Aplastic Anemia?
Pancytopenia. Anemia can be severe.
Are abnormal cells present in Aplastic Anemia?
NO!
Reticulocyte Count/Index in Aplastic Anemia?
Decreased
Diagnostic criteria for Moderate Aplastic Anemia?
- Bone marrow cellularity below 30%
- Absence of severe cytopenia
- Depression of at least two of three blood elements below normal
Diagnostic criteria for Severe Aplastic Anemia (sAA)?
- Bone marrow biopsy 25% below normal, OR
- BM bx 50% below norm with less than 30% hematopoietic AND very low reticulocyte, neutrophil, or platelet count
Diagnostic criteria for Very Severe Aplastic Anemia (vsAA)?
- sAA criteria met
- Absolute neutrophil count (ANC) below 200
3 essentials for Aplastic Anemia dx?
- Pancytopenia
- No abnormal hematopoietic cells circulating or in BM
- Hypocellular bone marrow
Tx for mild to moderate Aplastic Anemia?
- Supportive
- EPO or darbeopoetin
- Myeloid growth factors
- Transfusions
- Abx or antifungals
Tx for severe Aplastic Anemia?
Under 20=Bone marrow t/p
Under 50=Immunosuppressive therapy
Aplastic Anemia IST suggested regimen?
Horse antithymocyte globulin(ATG) plus cyclosporin A (CsA)
Untreated Aplastic Anemia 1 year mortality rate?
70% mortality rate
Severe Aplastic Anemia (sAA) survival rates if correctly treated?
80-90%
What is most common cause of congenital Aplastic Anemia?
Fanconi Anemia
Eti of Fanconi Anemia?
Autosomal recessive disorder->defect in DNA repair pathway. Increased incidents of malignancies.
Presentation of Fanconi Anemia
Congenital abnormalities: fused digits
Fanconi Anemia tx?
Allogeneic hematopoietic cell transplant
MCV of B12 and Folate deficiencies?
110-115. Megaloblastic.
What is B12 involved in what can cause neurological issues?
Myelin production
Megaloblastic anemia is when MCV is above what? What do RBCs look like?
MCV above 110. Macroovalocytic RBCs w/segmented neutrophils.
Megaloblastic anemia and bone marrow?
- Erythroid hyperplasia
- Megaloblastic morphology
Most common causes of Megaloblastic anemia?
- Faulty food intake/being a vegan
- Preggers
Pernicious Anemia epi?
1:7500, over 40 y/o.
How long are B12 stores?
3 years
What produces Intrinsic Factor? Job?
Parietal cells in stomach. Absorbs B12 in terminal ileum.
Where is B12 and IF absorbed?
Terminal ileum
B12 cofactor for what 2 important functions?
- Myelin synthesis
2. Nucleic acid synthesis
Pernicious Anemia eti?
Autoimmune. Antibodies destroy parietal cells, causing atrophic gastritis, and neutralizing IF.
Pernicious Anemia causes higher risk for what?
Gi/gastric cancers. Endoscopy when diagnosed, monitor for occult blood.