Exam 4 - Anemia Part II Flashcards
What can cause a falsely elevated MCV?
- Large number of reticulocytes
- RBC clumping mimicking larger RBC
What deficiencies cause macrocytic anemia?
B12 and folate deficiencies
What causes reticulocytosis?
Hemorrhage and hemolysis
What is the average daily requirement of folate? What about in pregnancy?
- average is 200-400 micrograms daily
- when pregnant, breast feeding, or trying to conceive recommended about is 400-800
What is the etiology of folate deficiency?
Alcoholism, hemodialysis, elderly, anticonvulsant therapy, malabsorption, and hemolytic anemias
What can a deficiency of folic acid in pregnancy lead to?
Neural tube defects
What is considered low serum folate?
Less than 150 ng/mL
In folic acid deficiency, is homocysteine, serum methylmalmonic acid (MMA), or both elevated?
Homocysteine is elevated. MMA is normal
In B12 deficiency, is homocysteine, serum methylmalmonic acid, or both elevated?
Both are elevated
What will you see on a peripheral smear in folic acid deficiency?
Macro-ovalocytes, hypersegmented neutrophils
What is the treatment for folic acid deficiency?
- Treat underlying cause
- replacement therapy with 1g PO daily
- Rule out B12 deficiency
What is the most common cause of B12 deficiency?
Inability to absorb
What is the only source of B12 for the body?
The diet, present in all animal products
What is the daily B12 requirement?
1-2 micrograms
How does B12 get absorbed?
It binds to intrinsic factor (IF) in the stomach, released from IF in the ileum where it is absorbed, and then stored in the liver.
What are the common causes of B12 deficiency?
- Pernicious Anemia (most common)
- Decreased intake (vegan diet)
- Medications. (Metformin, H2 antagonists, PPIs)
- Malabsorption (elderly)
What is Pernicious Anemia?
An immune disorder that causes the destruction of gastric parietal cells that release intrinsic factor (B12 cannot be absorbed)
What are the common symptoms with B12 Deficiency?
- glossitis, GI symptoms
- Ataxia
- Paresthesias
- Confusion
- Defective myelin synthesis in the CNS
**these neuro symptoms are reversible IF it is treated within 6 months
What is an MCV of greater than 115 almost always indicative of?
Folate or B12 deficiency
What will you see on a peripheral smear with B12 deficiency?
- Hypersegmented neutrophils
- Anisocytosis
- Macro-ovalocytes
What is the treatment for B12 deficiency?
- Parenteral B12 (daily IM/SQ injections of 1000micrograms for 1 wee, then weekly for one month, the monthly for life)
- Treat reversible causes
- Monitor K+ with treatment
Why is it EXTREMELY important to differentiate between folate and B12 deficiency?
-Folate replacement will correct the abnormal labs in a B12 deficiency. But if B12 is not also replaced, the patient may develop serious and irreversible neurological damage called subacute combined degeneration of the spinal cord.
What is the normal lifespan for RBCs?
120 days
Bone marrow can compensate for shortened RBC life up until when?
20 days
What are the common symptoms with hemolytic anemia?
- Typical anemia symptoms
- Jaundice if hemolysis is fast enough
- gallstones
- dark urine
Anemia with increased reticulocyte count, polychromasia, increased unconjugated bilirubin, and increased serum lactate dehydrogenase is seen in what kind of anemia?
Hemolytic anemia
What will you seen in a peripheral smear of hemolytic anemia?
- Immature RBCs, nucleated RBCs
- Schistocytes (fragmented RBCs)
What are the tests that can help distinguish between hemolytic anemia?
Direct antiglobin (Coombs) test and DAT
What is extravascular hemolysis?
Destruction of the RBCs in the reticuloendothelial system
Is serum haptoglobin in intravascular hemolysis increased or decreased? Why?
Decreased. It binds to hemoglobin released from lysed RBCs and this decreases the free haptoglobin
What is G6PD?
An enzyme that is essential for ensuring the normal lifespan of RBCs by protecting against oxidative stress
What will you see on peripheral smear in a G6 PD deficiency?
- Bite cells
- Heinz bodies
What is the treatment for G6PD deficiency?
- Hemolytic episodes are self limited as red cells are replaced
- Oxidative drugs should be avoided
What are the main causes of oxidative stress is a G6 PD deficient individual?
- Drugs
- Infections
- Fava beans
What is hereditary spherocystosis?
An autosomal dominant disorders with mild hemolytic anemia.
-Caused from an intrinsic defect in the RBC membrane/cytoskeleton
What happens to the RBCs in a patient in hereditary spherocytosis?
- RBCs maintain a normal MCV, but a smaller surface area so they have a dense and globular appearance and lack central pallor.
- They are poorly deformable, get trapped in the splenic sinusoids, and then phagocytized.
What are the common symptoms seen in Hereditary spherocytosis?
- Often asymptomatic
- Mild jaundice or sclera icterus
- Gallstones
- splenomegaly
- Chronic hemolysis creates need for increased folate
What is the test for hereditary spherocytosis?
- Osmotic fragility test: RBCs demonstrate increased hemolysis on exposure to hypotonic fluid due to RBC membrane defect
- Coombs is negative
What is the treatment of choice for severe hereditary spherocytosis?
Splenectomy
What is sickle cell disease?
A hereditary disorder of hemoglobin structure transmitted though an autosomal recessive gene.
What is the most common feature of sickle cell disease?
Pain crisis
What are the life threatening features of sickle cell anemia?
Hemolytic or aplastic crises
What is the best test to confirm diagnosis of sickle cell?
Hub electrophoresis reveals Hb S
What does a peripheral smear of sickle cell show?
A few sickled RBCs, nucleated RBCs, target cells, Howell Jolly bodies and thrombocytosis
What is the treatment of sickle cell?
- Avoid precipitating factors
- Analgestics, fluids, oxygen
- RBC transfusion if needed
- Hydroxyurea to decrease incidence of painful crises
- Bone marrow transplant
What causes Autoimmune hemolytic anemia (AIHA)?
Autoantibodies that adhere to the surface of RBCs and induce hemolysis by fixing complement and damaging the cell membrane. RBCs with antigen-antibody complex are phagocytized by macrophages and spherocytes are formed which are destroyed by the spleen.
What are the two types of antibodies associated with AIHA?
- IgM: “cold” agglutinins, generally more acute
- IgG: “warm agglutinins, attacks RBCs at normal body temp
What are patients with AIHA at higher risk for?
Venous thromboembolism
What are the symptoms associated with AIHA?
- Typical anemia symptoms
- Fever, fatigue, weakness
- Lymphadenopathy
- Hemoglobinurea
- Acrocyanosis
What diagnostic test is positive with AIHA?
Positive Coombs test (DAT)
How is cold AIHA treated in children?
It usually is not treated in children because it is normally viral and self limited
How is warm AIHA treated?
- Corticosteroids are first line
- Rituximab: antibody that targets B cell lymphocytes
- Splenectomy
- Immunosuppressants
How is cold AIHA treated in adults?
- Avoid cold exposure
- Rituxumab
- Plasmapheresis if refractory
What is intravascular hemolysis?
Destruction of RBCs within the blood stream
What is paroxysmal nocturnal hemoglobinurea?
-Rare acquired stem cell mutation, complement mediated RBC lysis
What are the symptoms of paroxysmal nocturnal hemoglobinurea?
- Hemolytic anemia
- Dark cola colored urine at night and morning with clearing during the day
- venous thrombosis of large vessels
- Pancytopenia
How is Paroxysmal nocturnal hemoglobinurea diagnosed?
- Flow cytometry
- osmotic fragility test
- Coombs negative
How is paroxysmal nocturnal hemoglobinurea treated?
- Monoclonal antibody against complement C5
- Steroids
- Stem cell transplant
What is the treatment for hemolysis?
- Identify and treat the underlying cause
- corticosteroids
- splenectomy
- Folic acid supplementation
What is aplastic anemia?
An acquired abnormality of hematopoietic stem cells. May be total, or selective for RBCs, WBCs, or platelets
What are the common causes of aplastic anemia?
- Over 50% are idiopathic
- 20% due to drug or chemical exposure
- 10% viral illness
What is the hallmark feature of aplastic anemia?
Pancytopenia
What is the treatment of aplastic anemia?
- Identify cause and eliminate it if possible
- hematology Referral
- transfusions PRN
- Bone marrow transplant is the preferred treatment.
