11.5: Anemia II Flashcards
3 broad types of anemia?
- Blood loss
- Hemolytic
- Diminished erythropoesis
What are thalassemias?
- Group of genetic disorders characterized by lack / decreased production of alpha or beta globin chain of hemoglobin A
- Hemoglobin A is 95% of hemoglobin in adults and is made of two alpha and two beta chains
What are alpha, beta plus, and beta zero thalassemia?
- Alpha: decrease alpha globin chain
- Beta zero: absent beta globin chain
- Beta plus: Deficient beta globin chain
Consequences of thalassemias?
- Low intracellular hemoglobin: hypochromic: pale cells
- Relative excess of other chain = toxicity
How many alpha globin alleles?
- 4
- Varying degrees of thalassemia depending on how many missing
1. Silent carrier
2. Mild anemia: blacks and asians
3. HbH disease: Sever anemia
4. Hydrops fetalis: relatively fatal
What is HbH?
- 3 of 4 alpha globin alleles missing
- relatively sever anemia
What is Hydrops fetalis?
- Zero alpha alleles
- Very deadly
- Intrauterine transfusions necessary
- HSC transplant can cure on birth
How many beta alleles?
- 2
- Beta plus and zero thalassemia
What is thalassemia major?
- Severe beta thalassemia w/ reliance on transfusions
- Marrow expands to compensate = bone deformities
- Hepatosplenomegaly
- Transfusions lead to deposition of Fe, cardiac failure
- Expansion of marrow skull: not normal
What is thalassemia minor?
- Clinical term for patients with asymptomatic, mild, or absent microcytic anemia with some RBC abnormalities
- Need to distinguish from Fe deficiency
Where are RCBs produced?
- Long bones in adults
- Live are spleen as well in KIDS
- Marrow will expand in skull in thalassemia major to try to compensate
How to distinguish Diminished Fe from Thalassemia minor?
Hemoglobin electrophoresis: normal if Fe deficiency
Fe studies: abnormal in Fe deficiency
Increase in Hgb A2
When in increase in Hgb A2 seen?
- Beta thalassemias
- Hgb A2 is alpha and delta chain, no beta
What is only acquired, intrinsic abnormality of RBCs?
PNH
What happens in PNH?
- Mutation in GPI anchor preventing GPI-anchored proteins from attaching to RBC membrane
- Stem cell disorder
What are GPI proteins involved in?
- Inactivating the complement pathway
- GP 55 and 59 are most important
- Hemolysis occurs if you cannot inactivate complement pathway
Clinical findings in PNH?
- Intravascular hemolysis
- Paroxysmal and nocturnal in 25%
- Infections
- Portal vein thrombosis
- Occasional evolution to aplastic anemia or acute leukemia
What can cause extrinsic anemias?
- Antibody mediated
- Mechanical trauma
- Infections
- Chemical injuries
- Sequestration
2 most common examples of external trauma to RBCs?
- Anemia due to prosthetic valves
- Anemia due to small vessel narrowing and fibrin deposition
- AKA microangiopathic hemolytic anemia
What can cause microangiopathic hemolytic anemia?
- TTP: thrombotic thrombocytopenic purpura
- HUS: Hemolytic urea syndrome
- DIC
* **Schistocytes in peripheral blood from fibrin deposition in vessels in all 3 cases
What are Schistocytes in peripheral blood indicative of??
Microangiopathic hemolytic anemia
What can cause Fe deficiency anemia?
- Chronic blood loss: Most common, usually in GI
- Malabsorption
- High iron demand in pregnancy
- Low dietary intake
What happens in Fe anemia/
- Stored Fe depleted
- Marrow Fe depleted
- Serum Fe decreases
- INCREASED total Fe binding capacity (TIBC)
Why is TIBC high in Fe anemia?
- Measuring proteins ability to transport Fe
- Since Fe is low, there are lots of proteins willing to move Fe and lots of spare capacity
Presentation of Fe anemia?
- Low serum Fe
- Hgb decreases
- RBCs become small
- Spoon shaped nails
- Smooth tongue
- Intestinal malabsorption
What is expensed central pallor of RBC indicative of?
Fe deficient anemia: normally only middle is white
What are megaloblastic anemias?
- B12 or folate deficiency
- Deficient DNA synthesis disturbing proliferation of Erythroblasts leading to their enlargement
- Enlargement due to abnormal division
- Nuclei are immature and cytoplasm is mature
What are erythroblasts?
RBC precursors
What are megaloblasts? Macrocytes?
Megaloblasts: Enlarged RBC precursors
Macrocytes: Enlarged RBCs
**Seen in megaloblastic anemia
When is B12 deficiency seen?
- Decreased intake: vegetarians
2. Low absorption: IF deficiency, fish tapeworm
What is IF important in?
“Intrinsic factor”
- B12 absorption
What is pernicious anemia?
- B12 deficiency secondary to gastritis with failure to produce IF
Where is IF produced?
- Parietal cells in the stomach
- Necessary for B12 absorption in ileum
- Mal Production of IF is autoimmune disorder
What is B12 important in?
- Essential cofactor for methionine synthase
- Deficiency decreases THF availability
- THF donates carbon unit for DNA synthesis
- **This leads to anemia
Clinical findings in B12 deficiency?
- Megaloblastic anemia
- Leukopenia with hypersegmented granulocytes
- Thrombocytopenia
- Atrophic glossitis
- Chronic gastritis
- Subate combined degeneration in CNS
* **Affects areas where DNA synth. is important as cells are always being produced such as marrow and GI
What is subacute combined degeneration?
- Spastic paraparesis
- Sensory ataxia
- Lower limb paresthesias
Difference between folate and B12 deficiencies?
Folate does not show CNS abnormalities
Can folate admin treat B12 deficiency?
- Yes but it WILL NOT treat CNS abnormalities
Most common anemia in hospital patients?
- Anemia of chronic disease
- Hepcidin is seen at high levels in all these ptns.
What is hepcidin?
- Key protein in anemia of chronic disease
- High levels block transfer of Fe from macs to erythroid precursors
- In marrow macs give Fe to RBC precursors, hepcidin stops this at high levels
Findings in anemia of chronic disease?
. High ferritin
- Microcytic anemia with low serum Fe
- Decreased TIBC
- Increased marrow Fe stores
What causes aplastic anemia?
- Failure of suppression of stem cells
- Leads to anemia
- Granulocytopenia
- Thrombocytopenia
- Pancytopenia
What is pancytopenia?
Decrease in RBC, WBC, and platelets
Causes of aplastic anemia?
- Idiopathic
- Irradiation
- Drugs
- Virus
- Defect in marrow cells
- Suppression of marrow cells by T cells
Appearance of marrow in aplastic anemia?
Hypocellular with increased fat and small foci of lymphocytes and plasma cells
How can you treat aplastic anemia?
- HSC implant
