Normocytic Anemias Flashcards
1
Q
How does anemia present? How do we test for anemia? How are the anemias classified?
A
- anemia presents as hypoxia; weakness, fatigue, dyspnea, pale conjunctiva, headache, light-headedness (can present as angina/claudication in patients with CAD and atherosclerosis)
- tested for with Hb, hematocrit, and RBC count
- anemia is a Hb less than 13.5 g/dL in males (less than 12.5 in females)
- classified based on mean corpuscular volume (MCV): microcytic is less than 80, normocytic is between 80 and 100, macrocytic is greater than 100
2
Q
What is normocytic anemia? What are the general causes of this type of anemia?
A
- normocytic anemia is characterized by a normal MCV (80-100)
- it is caused either by increased peripheral destruction/hemolysis (this can be either intravascular or extravascular hemolysis) or by an underproduction of RBCs
3
Q
What is the reticulocyte count? What do reticulocytes look like? What is the normal value? What is the significance of this value?
A
- the reticulocyte count (RC) is the percent of RBCs that are young/new RBCs that have recently been released by the bone marrow (reticulocytes are slightly larger than normal RBCs and have a bluish cytoplasm because of some residual RNA)
- normal RC is 1-2%; it will increase to be greater than 3% in the setting of anemia and with a functional BM
- therefore, in the setting of a normocytic anemia, a value greater than 3% indicates that the issue is due to peripheral destruction (because the BM is functional); a value less than 3% indicates the issue is due to underproduction
4
Q
Why do we need to correct the reticulocyte count? How do we do this?
A
- any anemia will falsely raise the RC, as the ratio of reticulocytes to RBCs will increase since the number of RBCs is lowered in anemia
- correct RC by multiplying the initial value by hematocrit/45*
- *45 is the normal hematocrit value
5
Q
What’s happening in extravascular hemolysis? What findings will characterize an anemia due to this mechanism?
A
- extravascular hemolysis is via the RES (the reticuloendothelial system): macrophages in the spleen, liver, and lymph nodes
- the RES breaks down RBCs back into their basic constituents (unconjugated bilirubin will increase)
- findings: anemia, splenomegaly, jaundice, bilirubin gallstones, marrow hyperplasia, corrected RC greater than 3%
6
Q
What’s happening in intravascular hemolysis? What findings will characterize an anemia due to this mechanism?
A
- intravascular hemolysis is the destruction of RBCs in the
actual vessels, leading to Hb directly leaking into the blood - findings: anemia, hemoglobinemia, hemoglobinuria, decreased free haptoglobin*, hemosiderinuria (this occurs a few days after the onset, renal tubular cells absorb the iron and become hemosiderin-laden; when they slough off, hemosiderinuria will result)
- *haptoglobin is a scavenger molecule that rapidly binds to free Hb in order to save it (it really only saves a very small amount)
7
Q
What are the major causes of predominantly extravascular hemolysis resulting in normocytic anemia?
A
- hereditary spherocytosis: increased RES (reticuloendothelial system) clearance of small spherocytes
- sickle cell anemia: cycles of sickling and de-sickling damage RBCs, leading to increased RES clearance
- hemoglobin C: abnormality increases RES clearance
- immune hemolytic anemia (IgG-mediated; IgM-mediated is mainly via intravascular hemolysis): RES clearance of IgG bound RBCs
8
Q
What are the major causes of predominantly intravascular hemolysis resulting in normocytic anemia?
A
- paroxysmal nocturnal hemoglobinuria: complement-mediated damage to RBCs, platelets, monocytes, granulocytes
- G6PD deficiency: damage via oxidative stress
- immune hemolytic anemia (IgM-mediated; IgG-mediated is actually mainly via extravascular hemolysis)
- microangiopathic hemolytic anemia: microthrombi shear RBCs as they pass through vasculature
- malaria: life cycle of organism ruptures RBCs
9
Q
What are the major causes of normocytic anemia via underproduction?
A
- renal failure: no EPO
- parvovirus B19 infection: halts erythropoiesis by infecting erythroid progenitor cells
- aplastic anemia: damage to hematopoietic stem cells
- myeloproliferative processes: BM replaced with nonfunctional tissue (i.e. metastatic cancer)
10
Q
What is hereditary spherocytosis? What’s the pathophysiology driving this disorder? What is the key finding on blood smear?
A
- (anemia mainly due to extravascular hemolysis)
- hereditary spherocytosis is an inherited defect of the RBC’s cytoskeleton-membrane tethering proteins such as spectrin, ankyrin, and band 3.1
- the resulting instability yields blebbing of the membrane; the blebs are removed by the spleen; this results in the loss of the normal RBC’s bi-concave shape, resulting in spherocytes (this is the key finding on blood smear)
- eventually, the RBCs will shrink enough to trigger their complete elimination by the spleen (this causes the anemia; the spherocytes themselves are not the issue!)
11
Q
What findings are associated with hereditary spherocytosis?
A
- normocytic anemia
- spherocytes with a loss of the normal central pallor (because the bi-concave shape is lost)
- increased RDW (RBC distribution width; older cells are smaller because they have lost more membrane)
- increased MCHC (mean corpuscular Hb concentration)
- splenomegaly, jaundice, bilirubin gallstones (because it is mainly extravascular hemolysis)
- increased risk of crisis with parvovirus B19 infection
12
Q
How do we diagnose hereditary spherocytosis? How do we treat it?
A
- Dx with an osmotic fragility test: spherocytes have increased fragility in hypotonic solution compared to normal RBCs
- treat with splenectomy (note that this will resolve the anemia, but not the spherocytes because the liver and lymph nodes will still remove the membrane blebs); splenectomies result in the presence of Howell-Jolly bodies on blood smear
13
Q
What is a Howell-Jolly body?
A
- Howell-Jolly bodies are seen on blood smear in patients with a splenectomy or a non-functional spleen
- these are RBCs with some nuclear fragments still remaining; usually, the spleen removes these fragments
14
Q
What is sickle cell anemia? What mutation is involved and what results? What’s the pathophysiology of this anemia? What precipitates the pathophysiology?
A
- (anemia mainly due to extravascular hemolysis)
- sickle cell anemia is an autosomal recessive mutation in Hb’s beta chain; the normal glutamic acid (which is hydrophilic) is replaced by valine (which is hydrophobic)
- the disease requires 2 abnormal genes, which results in more than 90% of RBCs having the abnormal Hb (HbS)
- HbS has a propensity to polymerize*, resulting in the RBC to develop a needle-like shape (these are the sickle cells)
- the constant cycling of sickling and de-sickling damages the RBC’s membrane, and the spleen then eliminates these cells
- *HbS polymerizes when it is deoxygenated; thus risk for a precipitating event increases with hypoxemia, dehydration, and acidosis
15
Q
What findings are associated with sickle cell disease? When do these findings typically present? Why?
A
- normocytic anemia
- presence of sickle cells
- splenomegaly, jaundice, bilirubin gallstones (because it is mainly extravascular hemolysis)
- decreased free haptoglobin, hemoglobinemia, hemoglobinuria presence of target cells (because occasionally, the RBCs lyse intravascularly as well)
- massive erythroid hyperplasia may occur as well (hematopoiesis in skull/”crew cut” and facial bones/chipmunk facies, extra medullary hematopoiesis)
- increased risk of crisis with parvovirus B19 infection
- symptoms develop at around 6 months of age because HbF is protective
