Anemia Flashcards
1
Q
Which type of bilirubinemia would one expect from a hemolytic process?
A
Indirect bilirubinemia
2
Q
How would ferritin be used to determine total body iron levels?
A
Iron is stored in the bone marrow as ferritin. Therefore, ferritin levels typically reflect iron stores. However, ferritin is also an acute phase reactant and does not accurately reflect iron stores if there is ongoing inflammation.
3
Q
If a patient presents with anemia, ice-eating, and lethargy, what underlying process would you suspect is the cause of the anemia?
A
Iron deficiency anemia
4
Q
If a patient presents with anemia and distal paresthesias, what underlying process would you suspect is the cause of the anemia?
A
B12 deficiency anemia
5
Q
If a patient presents with anemia and LUQ pain, what underlying process would you suspect is the cause of the anemia?
A
Hereditary spherocytosis with splenomegaly
6
Q
If a patient presents with anemia and RUQ pain or intolerence of fatty foods, what underlying process would you suspect is the cause of the anemia?
A
Cholelithiasis from chronic hemolysis
7
Q
If a patient presents with anemia, constipation, and cold intolerence, what underlying process would you suspect is the cause of the anemia?
A
Hypothyroidism
8
Q
Which tests are recommended in the initial workup of anemia?
A
The evaluation starts with a CBC, retic count, and examination of the peripheral blood smear.
9
Q
What type of anemia is present in this slide?
A
Iron deficiency anemia. There is thrombocytosis, microcytosis, and hypochromia.
10
Q
What type of anemia is present in this slide?
A
B12 or Folate deficiency with pernicious anemia. Low-power view shows a hypersegmented neutrophil and macrocytosis.
11
Q
List four potential etiologies of microcytic anemia.
A
Iron deficiency anemia, Thalassemias, Sideroblastic anemia, and anemia of chronic disease.
12
Q
List five potential etiologies of normocytic anemia.
A
Acute blood loss, hemolytic anemia, anemia of chronic disease, chronic renal disease, and aplastic anemia.
13
Q
List four potential etiologies of macrocytic anemia.
A
Folate deficiency, B12 deficiency, Drug-related (e.g. valproic acid), and inherited bone marrow failure syndromes.
14
Q
In which type of anemia would one expect the RDW to be increased?
A
Iron deficiency anemia
15
Q
In which type of anemia would one expect the MCHC to be increased?
A
Hereditary spherocytosis
16
Q
Which type of anemia is shown in this slide?
A
Hereditary spherocytosis. Note the lack of central pallor. The normal sized lymphocyte shows that these are microcytic spherocytes.
17
Q
What type of cell is displayed on this slide?
A
Target cells
18
Q
What type of cell is displayed on this slide?
A
Teardrop cells (dacrocytes)
19
Q
What condition should one expect based on the findings in this slide? The arrows are pointing to what type of cell?
A
Uremia. The arrows are pointing to Echinocytes/Burr cells. These are RBCs with regular, short, spiny projections. The membrane changes disappear when the uremia is corrected.
20
Q
What condition should one expect based on the findings in this slide? The arrows are pointing to what type of cells (1) and (2)?
A
This slide shows hepatorenal failure. Burr cells (1) as seen in uremia, and spur cells (2) as seen in hepatic failure.
21
Q
What type of cell is indicated by the arrows in this slide? What condition does its presence usually indicate?
A
Acanthocytes (spur cells). Also some nucleated RBCs. Spur cells are RBCs with multiple irregular projections that vary in length, width, and regularity. The usual cause is hepatic failure.
22
Q
How would one differentiate between Burr cells and Spur cells on a blood smear?
A
Burr cells (echinocytes) are RBCs with regular, short, spiny projections. Spur cells (acanthocytes) are RBCs with multiple irregular projections that vary in length, width, and regularity.
23
Q
What hematologic condition is characterized by the findings on this blood smear?
A
Hereditary elliptocytosis
24
Q
What hematologic condition is characterized by the findings on this blood smear?
A
Sickle Cell Disease
25
What are the blue inclusions indicated by the arrows called? When would you expect to see them on a blood smear?
Howell-Jolly bodies. They are present in patients who have had splenectomies.
26
What is the term for the finding indicated by the arrow in this image?
Basophilic stippling
27
What condition is represented by the findings in this slide?
Burn hemolysis. Hemolytic anemia, nucleated RBC, and spherocytosis.
28
In what three situations would one expect to see schistocytes?
Microangiopathic hemolytic anemia (seen in TTP, HUS, HELLP, DIC, and occasionally vasculitis), severe burns, and valve hemolysis.
29
In what two situations would one expect to see spherocytes?
Autoimmune hemolytic anemia and hereditary spherocytosis
30
In what four conditions would one expect to see target cells?
Significant liver disease, thalassemia syndromes, sickle cell disease type SC, and homozygous hemoglobin C disease.
31
In what condition would one expect to see Burr cells (echinocytes)?
Uremia
32
In what two conditions would one expect to see teardrop cells (dacrocytes)?
Infiltrating bone marrow processes (such as myelofibrosis) and thalassemia
33
In what condition would one expect to see spur cells (acanthocytes)?
Hepatic failure
34
In what condition would one expect to see hypersegmented PMNs?
Megaloblastic anemia (e.g. pernicious anemia/B12 deficiency and folate deficiency)
35
In what two conditions would one expect to see elliptocytes?
Hereditary elliptocytosis and severe iron deficiency anemia
36
In what condition would one expect to see sickled cells?
Sickle Cell Disease (HbSS and HbS β-thalassemia; less common in HbSC)
37
In what condition would one expect to see Howell-Jolly bodies?
Asplenia/functional asplenia
38
In what three conditions would one expect to see basophillic stippling?
Basophilic stippling indicates ineffective erythropoiesis and can be seen in conditions such as: lead poisoning, thalassemia, and pyrimidine 5'-nucleotidase deficiency.
39
In what condition would one expect to see Heinz bodies?
G6PD deficiency
40
What are the three categories of β-thalassemia?
Minor (heterozygous), intermedia (homozygous β+/β+), and major (homozygous β0/β0 or heterozygous β0/β+)
41
What is the significance of elevated HbA2 in the evaluation of microcytic anemia?
An HbA2 \>3.5% is diagnostic for β-thalassemia minor.
42
What is the typical clinical presentation of patients with β-thalassemia minor?
Patients are usually asymptomatic but have a disproportionate degree of microcytosis with no or mild anemia if blood is analyzed.
43
What would be the expected hemoglobin electrophoresis findings in patients with β-thalassemia intermedia?
Decreased production of β-globin leads to increased production of gamma and delta chains. Therefore, HbA2 (α2δ2) and HbF (α2γ2) are increased on electrophoresis.
44
How does β-thalassemia intermedia usually present clinically?
Patients with β-thalassemia intermedia have similar presenatations as those with β-thalassemia major, but milder. They generally do not require transfusions.
45
Why are Heinz bodies present in the RBCs of patients with β-thalassemia major?
In these patients, there is essentially no β-globin production. The remaining, highly insoluble α-globin precipitates into inclusion bodies (Heinz bodies) within the cells.
46
How do patients with β-thalassemia major usually present clinically?
By 6-12 months of age, most infants show pallor, irritability, growth retardation, hepatosplenomegaly, profound anemia, and jaundice. Extramedullary hematopoiesis in the facial bones leads to characteristic changes such as frontal bossing and prominent malar eminences (i.e. "chipmunk facies" in children).
47
What are the typical electrophoresis findings in patients with β-thalassemia major?
Hemoglobin electrophoresis shows almost exclusive HbF.
48
What therapy is required for management of β-thalassemia major and what is the major complication associated with it?
Patients with β-thalassemia major are transfusion dependent and often develop iron overload, which requires chelation therapy.
49
What are the four categories of α-thalassemia, and what differentiates them?
α-thalassemia trait (1 allele affected), α-thalassemia minor (2 alleles affected), HbH disease (3 alleles affected), and hydrops fetalis (4 alleles affected). Each category involves the deletion/dysfunction of 1 or more of the four α-globin alleles, and the more alleles are affected, the worse the clinical presentation.
50
What clinical findings would you expect in a patient with α-thalassemia trait?
These patients are asymptomatic and have no hematologic abnormalities (the "silent carrier").
51
What clinical findings would you expect in a patient with α-thalassemia minor?
These patients are asymptomatic but have a low MCV and may have no or mild anemia.
52
What clinical findings would you expect in a patient with HbH disease?
These patients have moderate-to-severe hemolysis.
53
What clinical findings would you expect in a patient with hydrops fetalis?
These patients die in utero.
54
What is hemoglobin Bart?
Hemoglobin Bart is a type of hemoglobin formed by a tetramer of gamma chains that is found in patients with α-thalassemia. Levels will vary based on which form of thalassemia is present.
55
In what condition and in what circumstance would one expect to see hemoglobin Bart?
Hemoglobin Bart is seen on the newborn screen in patients with α-thalassemia. Higher amounts of Hb Bart correlate with increasing severity of α-thalassemia.
56
Which types of thalassemia may be diagnosed on the newborn screen?
β-thalassemia major is diagnosed on the newborn screen (HbF only), but the other β-thalassemias would not be identified because they show the normal newborn pattern of fetal and adult hemoglobin. α-thalassemia shows up with FA and elevated levels of Hb Bart.
57
What is the most common cause of iron deficiency anemia in the pediatric population?
Inadequate iron intake is the most common cause of iron deficiency anemia and is usually caused by excess intake of cow's milk in infants and young children.
58
List 5 potential GI etiologies of iron deficiency anemia.
GI blood loss from Meckel diverticulum, H. pylori w/ gastric ulcer, hookworm infection, or inflammatory bowel disease. Celiac disease prevents adequate iron absorption.
59
What infection is most commonly responsible for chronic GI blood loss in children worldwide?
Worldwide, hookworm infection (Necator americanus or Ancylostoma duodenale) is the most common cause of chronic GI blood loss.
60
What is the Mentzer index and how is it used diagnostically?
The Mentzer index (MCV/RBC) is ≥ 13 in iron deficiency and \< 13 in thalassemia trait, which is explained by the fact that the RBC count is generally low in iron deficiency but normal or increased in thalassemia trait.
61
How can you use RDW to differentiate iron deficiency anemia from β-thalassemia minor?
The RDW is normal in patients with thalassemia trait but is increased in early iron-deficient patients.
62
What is the most common type of hypoproliferative anemia?
Anemia of chronic disease
63
What is the role of hepcidin in patients with anemia of chronic disease?
Hepcidin blocks iron transport, so when levels are high, iron absorption is low. In ACD, iron stores are normal to high, but the cytokine-mediated production of hepcidin inhibits their use and causes anemia.
64
What is iron refractory iron deficiency anemia?
It is a rare, inherited condition in which children are unresponsive to oral iron and only minimally responsive to IV iron. It is caused by a mutation that increases hepcidin, leading to impaired iron absorption and transport.
65
What is the recommended route, formulation, and dose of iron replacement for children with iron deficiency anemia?
Give oral iron as 3-6 mg/kg of elemental ferrous sulfate per day.
66
How soon would one expect to see results from iron replacement therapy in children with iron deficiency anemia?
Look for reticulocytosis to begin 3-5 days after beginning therapy and peak at 7-10 days. If the retic count does not rise in response to iron therapy, you must consider either nonadherance or an alternate diagnosis.
67
By how much would one expect the hemoglobin to rise in the first month after starting iron replacement therapy in a child with iron deficiency anemia?
Expect the hemoglobin to increase 1-2 g/dL in the first month.
68
When should iron supplementation begin in infants who are exclusively breastfed?
Provide elemental iron supplementation of 1 mg/kg/day for infants who are exclusively breastfed beyond 4 months of age.
69
Why is cow's milk discouraged for infants \< 12 months of age?
To prevent occult GI bleeding.
70
Which animal's milk is low in folate and results in folate deficiency in infants predominantly given this type of milk?
Goat's milk
71
What is the recommended dose of folic acid for treatment of megaloblastic anemia due to folic acid deficiency?
Treat with folic acid at a dose of 1-5 mg daily.
72
What vitamin level should be checked before beginning folate supplementation for megaloblastic anemia due to folate deficiency?
If the patient has concomitant Vitamin B12 deficiency, the use of high-dose folate will correct the RBC problems but worsen the neurologic manifestations of B12 deficiency. Therefore, it is important to check for Vitamin B12 deficiency before treating with folate.
73
How do folate and vitamin B12 deficiencies cause anemia?
Folate and vitamin B12 deficiencies cause slowing of DNA synthesis and delayed maturation of the entire erythrocyte cell line, resulting in large, immature erythrocytes (megaloblasts). There may also be abnormalities of the neutrophils, especially hypersegmentation.
74
List four potential etiologies for the development of folate deficiency.
Folate deficiency can result from inadequate dietary intake, increased metabolic demand (i.e. infancy, pregnancy, lactation), malabsorption, or metabolic interference (e.g. methotrexate, sulfonamide).
75
What is the typical cause of vitamin B12 deficiency in children?
In children, vitamin B12 deficiency occurs most often due to abnormalities in the absorption of B12.
76
Where in the intestinal tract is the vitamin B12-IF complex absorbed?
The vitamin B12-IF complex is absorbed in the terminal ileum.
77
List two risk factors for vitamin B12 deficiency in children.
Small bowel resection and maternal vegan diet in an infant who is exclusively breastfed.
78
What is congenital pernicious anemia?
It is an autosomal recessive disorder characterized by the absence of intrinsic factor, which prevents vitamin B12 from being properly absorbed. Patients with congenital pernicious anemia present before 3 years of age.
79
What is juvenile pernicious anemia?
It is an autoimmune-mediated decrease in gastric intrinsic factor which prevents vitamin B12 from being properly absorbed. It occurs in older children and adolescents and often occurs with other autoimmune conditions.
80
How do you differentiate between the congenital and juvenile forms of pernicious anemia?
Age (\<3 years vs older children). In congenital, gastric histology and acid secretion are normal, whereas in juvenile there is gastric atrophy and decreased secretion of acid and pepsin. Congenital has no autoimmune associations, but juvenile does.
81
Which cause of macrocytic anemia can lead to neurologic problems?
B12 deficiency, in contrast to folate deficiency, leads to neurologic symptoms and eventual irreversible neurologic damage (bilateral paresthesias, decreased proprioception and vibration sense, spastic ataxia, central scotomata, and dementia).
82
What laboratory findings would be expected in patients with pernicious anemia?
Low vitamin B12 levels, the presence of anti-IF antibodies, and high serum methylmalonic acid (MMA).
83
What is the treatment for pernicious anemia?
Parenteral vitamin B12 administration for life.
84
List 5 inherited and one acquired RBC survival defect.
Inherited: hereditary spherocytosis, hereditary elliptocytosis, paroxysmal nocturnal hemoglobinuria, G6PD deficiency, and sickle cell disease. Acquired: immune-mediated hemolytic anemia.
85
In populations of northern European origin, what is the most common congenital hemolytic anemia?
Hereditary spherocytosis
86
What is the underlying defect in hereditary spherocytosis?
HS is due to a structural or functional abnormality of cytoskeletal proteins, spectrin, ankyrin, and, less commonly, band 3 or protein 4.2.
87
What serious complication in the neonatal period can occur due to hereditary spherocytosis?
HS can be a life-threatening cause of hyperbilirubinemia/kernicterus in the neonatal period.
88
If a child with hereditary spherocytosis undergoes splenectomy, what interventions should be performed before and after the procedure to minimize infectious complications long-term?
Prior to splenectomy, administer pneumococcal, haemophilus influenzae, and meningococcal vaccinations to minimize the risk of post-splenectomy sepsis. Post-splenectomy penicillin prophylaxis is also necessary, and urgent medical evaluation is necessary for splenectomized children with fever.
89
What are the two forms of hereditary elliptocytosis?
Common HE (asymptomatic, uniformly elliptical RBCs w/o other abnormalities) and hemolytic HE (causes splenomegaly with mild-to-moderate anemia and hemolysis and has both spherocytes and elliptocytes).
90
What is paroxysmal nocturnal hemoglobinuria?
It is a rare, acquired clonal stem cell disorder caused by a protein deficiency which makes cells more susceptible to complement-mediated lysis.
91
What is the paroxysmal nocturnal hemoglobinuria triad of lab/clinical findings used to help make the diagnosis?
Hemolytic anemia, pancytopenia, and arterial or venous thromboses.
92
What three conditions may be present in association with paroxysmal nocturnal hemoglobinuria?
PNH can appear alone or in association with myelodysplastic syndromes, AML, or aplastic anemia.
93
How is paroxysmal nocturnal hemoglobinuria treated?
Eculizumab (Soliris) blocks complement-mediated lysis and can decrease the need for transfusions. Bone marrow transplant is curative and is indicated for patients with severe refractory pancytopenia or life-threatening thrombosis.
94
List five scenarios which may precipitate a G6PD crisis?
Systemic infection, sulfa drugs, dapsone, primaquine, and fava beans.
95
How do you diagnose G6PD deficiency? Is testing reliable during a hemolytic crisis?
Except during an acute hemolytic crisis (when all the affected RBCs have hemolyzed and the remaining RBCs have normal/near-normal G6PD levels), measurement of G6PD level is diagnostic.
96
What is the genetic defect that results in hemoglobin S?
HbS is caused by a point mutation in the 6th codon of the β-globin gene, which is located on the short arm of chromosome 11. Adenine is replaced by thymidine, which results in valine being encoded instead of glutamic acid. Upon deoxygenation, HbS polymerizes, leading to sickled RBCs.
97
List the four different types of sickle cell disease in decreasing order of severity.
HbSS \> HbSβ0 thalassemia \> HbSC \> HbSβ+
98
What is the average lifespan of a sickle cell?
15-50 days
99
List five vaso-occlusive complications of sickle cell disease.
Pain crisis, acute chest syndrome, splenic sequestration, priapism, and stroke.
100
How do you diagnose sickle cell disease?
In the U.S. SCD is diagnosed through newborn screening programs which use hemoglobin electrophoresis.
101
Which medication has been shown to reduce the acute and chronic complications of sickle cell disease?
Hydroxyurea
102
Which types of bacterial infection result in serious disease in children with sickle cell disease?
Patients with sickle cell disease are at higher risk of infection due to encapsulated organisms (S. pneumoniae, N. meningitidis, and H. influenzae) due to their functional asplenia. They are also at higher risk of infection with Salmonella.
103
At what age is penicillin prophylaxis started in patients with sickle cell disease?
Penicillin ppx is started in infancy since in dramatically decreases invasive pneumococcal infections in children \< 5 years of age with SCD.
104
Which vaccines are recommended in all children with sickle cell disease?
Pneumococcal conjugate and polysaccharide vaccines.
105
What is the most common reason for hospital admission of a patient with sickle cell disease?
Pain (vaso-occlusive) crisis.
106
What is the most common first crisis in children with sickle cell disease?
Dactylitis (symmetric painful swelling of the hands and feet)
107
What would the presence of splenomegaly and thrombocytopenia suggest in a patient with sickle cell disease?
These findings are concerning for acute splenic sequestration.
108
What is the treatment for patients with sickle cell disease who present with acute splenic sequestration?
IV hydration and RBC transfusion. Splenectomy is recommended for children with life-threatening splenic sequestration or recurrent events.
109
What is the recommended management of an acute pain crisis in a patient with sickle cell disease.
IV hydration, NSAIDs, and opioid analgesics.
110
What is acute chest syndrome?
It is defined as the development of a new pulmonary infiltrate with fever, chest pain, tachypnea, and/or hypoxia in a patient with sickle cell disease.
111
What is the most common cause of death for adolescents with sickle cell disease?
Acute chest syndrome is the leading cause of death in adolescents and adults with SCD.
112
What is the recommended management of acute chest syndrome?
Treatment includes respiratory support, hydration, and antibiotics that cover pneumococcus, mycoplasma, and chlamydia. Exchange transfusions may be required for patients who have significant hypoxia and respiratory distress, or who don't improve with appropriate therapy.
113
Which infection causes aplastic crisis in patients with sickle cell disease?
Parvovirus B19, which destroys early red cell precursors in the bone marrow and causes an abrupt cessation of RBC production.
114
In what age range are children with sickle cell disease most likely to have stroke?
Peak incidence is between 5 and 10 years of age.
115
What is the acute treatment for a stroke in a patient with sickle cell disease?
Emergent exchange transfusion, which should be done even before an MRI in patients with concerning physical exam findings.
116
What therapy is used in patients with sickle cell who have had previous strokes to reduce the risk of recurrence?
Patients with SCD who have had a stroke require chronic RBC transfusion therapy to keep the HbS \< 30% to reduce the risk of recurrence.
117
When and how should children with sickle cell disease be screened for stroke?
Starting at 2 years of age, children with SCD should be screened with transcranial doppler ultrasound (TCD). If they have abnormally high TCD velocities, they require chronic RBC transfusions to keep the HbS percentage down.
118
What is priapism? What are the treatment options for priapism with sickle cell disease?
Priapism is a prolonged, painful erection, and it occurs in up to 10% of older boys and adolescents with sickle cell disease. Management includes hydration, pain control, and urgent heme and urology consults. In many cases, aspiration of the corpora cavernosa and irrigation with a dilute solution of epinephrine rapidly alleviates the condition. Rarely, surgical intervention (glans-cavernosum shunt) is indicated.
119
When are people with sickle cell trait at risk for sickle-cell-related complications?
It's rare for people with sickle trait to have any sickle-related complications, except in cases of extreme physical exertion or low oxygen tension (e.g. unpressurized aircraft, high-altitude).
120
What type of cancer is more common in people with sickle cell trait?
Renal cell carcinoma. However, it is still rare enough that screening is unnecessary.
121
What is the genetic defect in Hemoglobin C?
Hemoglobin C occurs because of the substitution of a lysine for the glutamic acid residue in the 6th position of the β-globin chain.
122
What clinical features are found with HbCC and HbC trait?
Homozygotes for HbC have a mild hemolytic anemia and splenomegaly but do not have vaso-occlusive problems. Those with HbC trait have no symptoms and only a large number of target cells as the hematologic manifestation.
123
What is hemoglobin E disease?
Patients homozygous for HbE have mild hemolytic anemia with significant microcytosis, hypochromia, and target cells. Heterozygotes have minimal findings. It is common in populations of south and southeast Asia and Northeast India.
124
How is the direct Coombs test performed?
Antibodies against IgG or C3 are prepared in an animal and then mixed with a patient's blood. A positive test is characterized by agglutination of the patient's RBCs, which means that there is IgG or C3 on the surface of their RBCs.
125
List three possible diseases for which one would want a direct Coombs test?
Autoimmune hemolytic anemia, infectious mononucleosis, and mycoplasma infection (EBV and mycoplasma cause cold-agglutinin disease and will be Coombs negative).
126
How is the indirect Coombs test performed?
Rh- and ABO compatible RBCs are mixed with the patient's serum. A positive test is characterized by agglutination of the RBCs.
127
In what two situations would one want to order an indirect Coombs test?
Incompatible blood match with transfusion and erythroblastosis fetalis.
128
Which (2) pathogens can cause cold agglutinin disease in children?
Mycoplasma and EBV
129
What is paroxysmal cold hemoglobinuria?
It is caused by an IgG antibody which binds to RBCs at low temperatures and causes RBC lysis at warm temperatures. It is common after a viral illness and treatment is supportive.
130
What is the treatment for warm autoimmune hemolytic anemia?
Treat with corticosteroids. If necessary, transfuse with the most compatible RBCs. In refractory cases, splenectomy or immunosuppressive agents may be required.
131
What is isoimmune hemolytic disease of the newborn?
It is a distinctive form of immune hemolytic anemia that presents in infancy due to maternal production of antibodies against RBC antigens that cross the placenta during pregnancy. This can include ABO antibodies or Rh antibodies.
132
List four drugs which can cause hemolysis.
Penicillin, quinine, methyldopa, and certain cephalosporins.
