Flashcards in 11.5: Anemia II Deck (46):
3 broad types of anemia?
1. Blood loss
3. 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?
1. Alpha: decrease alpha globin chain
2. Beta zero: absent beta globin chain
3. 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?
- 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?
- Beta plus and zero thalassemia
What is thalassemia major?
- Severe beta thalassemia w/ reliance on transfusions
- Marrow expands to compensate = bone deformities
- 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?
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?
1. Intravascular hemolysis
2. Paroxysmal and nocturnal in 25%
4. Portal vein thrombosis
5. Occasional evolution to aplastic anemia or acute leukemia
What can cause extrinsic anemias?
1. Antibody mediated
2. Mechanical trauma
4. Chemical injuries
2 most common examples of external trauma to RBCs?
1. Anemia due to prosthetic valves
2. Anemia due to small vessel narrowing and fibrin deposition
- AKA microangiopathic hemolytic anemia
What can cause microangiopathic hemolytic anemia?
1. TTP: thrombotic thrombocytopenic purpura
2. HUS: Hemolytic urea syndrome
***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?
1. Chronic blood loss: Most common, usually in GI
3. High iron demand in pregnancy
4. Low dietary intake
What happens in Fe anemia/
1. Stored Fe depleted
2. Marrow Fe depleted
3. Serum Fe decreases
4. 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?
What are megaloblasts? Macrocytes?
Megaloblasts: Enlarged RBC precursors
Macrocytes: Enlarged RBCs
****Seen in megaloblastic anemia
When is B12 deficiency seen?
1. Decreased intake: vegetarians
2. Low absorption: IF deficiency, fish tapeworm
What is IF important in?
- 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?
1. Megaloblastic anemia
2. Leukopenia with hypersegmented granulocytes
4. Atrophic glossitis
5. Chronic gastritis
6. 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?
1. Spastic paraparesis
2. Sensory ataxia
3. 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
What is pancytopenia?
Decrease in RBC, WBC, and platelets
Causes of aplastic anemia?
5. Defect in marrow cells
6. 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