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94 Cards in this Set
- Front
- Back
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What are the clinical features of hereditary spherocytosis?
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Chronic hemolysis
Jaundice Splenomegaly |
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What is the inheritance pattern of hereditary spherocytosis?
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Most show autosomal dominant inheritance
1/4 show autosomal recessive or other forms of inheritance |
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What defects are associated with hereditary spherocytosis?
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Band 3
Protein 4.2 Spectrin Ankyrin |
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How is hereditary spherocytosis treated?
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Splenectomy
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What is the most common RBC disorder in persons of Northern European descent?
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Hereditary spherocytosis
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What are patients with hereditary spehrocytosis at the risk of developing?
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Pigmented gallstones
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Which chronic hemolytic disorder is not associated with splenomegaly?
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Sickle cell disease
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What are the characteristic lab findings of hereditary spherocytosis?
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Increased MCHC
Spherocytes on peripheral blood that are typically smaller than normal RBCs Elevated reticulocyte count Elevated lactate dehydrogenase (due to extravascular hemolysis) Elevated bilirubin (due to extravascular hemolysis) |
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Which tests can be used to diagnose hereditary spherocytosis?
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Osmotic fragility test
Autohemolysis test |
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Describe the osmotic fragility test in hereditary spherocytosis
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The RBCs of the patient are incubated in incrementally hypotonic NaCL solution with the degree of hemolysis measured
Spherocytes hemolyze more readily in hypotonic saline than normal cells |
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Is the osmotic fragility test specific for hereditary spherocytosis?
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No, it just identifies the presence of spherocytes in general from any cause
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Describe the autohemolysis test used in hereditary spherocytosis?
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The RBCs of the patient are incubated at 37 degrees Celsius for 48 hours and hemolysis is measured
HS cells autohemolyze more readily than normal, but hemolysis can decrease if it is incubated with excess glucose |
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How is immune-mediated hemolysis differentiated from hereditary spherocytosis?
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A direct antiglobulin test (DAT) and low MCV would be seen in immune-mediated hemolysis, unlike in hereditary spherocytosis
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What number of circulating elliptocyes are needed to define hereditary elliptocytosis?
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>25%
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What is the inheritance pattern of hereditary elliptocytosis?
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Autosomal dominant
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What defect is seen in hereditary elliptocytosis?
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Defective spectrin tetramers
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What conditions other than hereditary elliptocytosis are associated with elliptocytes, usually <25%?
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Iron deficiency anemia
Megaloblastic anema Myelodysplasia Myelophthisis |
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What are the three types of hereditary elliptocytosis?
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Common
Spherocytic Stomatocytic |
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What are the characteristics of the common type of hereditary elliptocytosis?
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Seen mostly in African-Americans
Heterozygotes have mild to moderate anemia whereas homozygotes have moderate to severe anemia Most common form of hereditary elliptocytosis |
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What are the characteristics of the spherocytic type of hereditary elliptocytosis?
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Results when there is heterozygosity for HS and HE
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What are the characteristics of the stomatocytic type of hereditary elliptocytosis?
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Also called Southeast Asian ovalocytosis because it is commonly found in Malaysia
Due to band 3 protein defect Confers protection against P vivax malaria |
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Which type of hereditary elliptocytosis confers protection against P vivax malaria?
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Stomatocytic type
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What is hereditary pyropoikilocytosis?
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A variant of common hereditary elliptocytosis that is characterized by unusual sensitivity of red cells to heat
In vitro incubation at 45 degrees Celsius leads to hemolysis whereas normal RBCs can withstand up to 49 degrees Celsius |
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When is hereditary pyropoikilocytosis typically seen?
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Neonates with common hereditary elliptocytosis
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What is the inheritance pattern of hereditary stomatocytosis?
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Autosomal dominant
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What are the 2 types of hereditary stomatocytosis?
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Hydrocytotic
Xerocytotic |
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Is there hydrocytotic or xerocytotic type of hereditary stomatocytosis more severe?
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Hydrocytotic
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In which chronic hemolytic disease is a splenectomy not recommended?
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Hereditary stomatocytosis
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Why is a splenectomy avoided in patients with hereditary stomatocytosis?
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There is a tendency toward thrombosis following splenectomy in these patients
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What characterestic Rh findings is associated with hereditary stomatocytosis?
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Rh null red cell phenotype
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What are the characteristics of hydrocytotic type of hereditary stomatocytosis?
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More severe form in which the RBCs take on extra water
Significant stomatocytosis, macrocytosis, low MCHC (24-30%), and moderate to severe anemia Associated with decreased Stomatin protein |
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What are the characteristics of xerocytotic type of hereditary stomatocytosis?
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Less severe form in which the RBCs lose water
Normocytic RBCs, few stomatocytes, spiculated dessicocytes, and target cells as wellas increased MCHC and mild anemia |
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Where has the gene responsible for xerocytotic type of hereditary stomatocytosis been mapped?
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16q23-q24
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Which RBCs have more G6PD?
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Reticulocytes
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What is the role of G6PD?
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Produces NADPH, which maintains glutathione and other proteins in RBCs in the reduced state when they are subjected to oxidant stress
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What inclusion occurs when hemoglobin becomes oxidized?
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Heinz bodies
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What can cause oxidant stress in patients with G6PD deficiency?
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Medications
Fava beans Infection |
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What is the inheritance pattern of G6PD deficiency?
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X-linked recessive
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What are the two main types of G6PD deficiency?
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Mediterranean
African |
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Which type of G6PD deficiency is more evere and why?
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Mediterranean, because even young red cells are depleted of G6PD; steady state G6PD is around 10% of normal
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What are the characteristics of the African type of G6PD deficiency?
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More commonly seen in this country
Young red cells maintain adequate G6PD Steady state G6PD activity is 20-60% |
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Why would G6PD levels appear to be normal in a patient with G6PD deficinecy?
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In the days following a hemolytic crisis, the surviving red cells are those with normal G6PD activity because the ones with decreased activity are the ones that were destroyed, and the patient is actively releasing reticulocytes, which have more G6PD; this gives a falsely normal result
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When is the best time to test a patient for G6PD deficiency?
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>3 months after a hemolytic crisis
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What can be seen in the peripheral smear of patients with G6PD deficiency following oxidant exposure?
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Poikilocytosis
Spherocytosis Heinz bodies Bite cells Blister cells |
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What stains can be used to visualize Heinz bodies?
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Methyl violet
Crystal violet Brilliant cresyl blue |
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What two tests can be used to test for G6PD deficiency?
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Ascorbate cyanide test
Fluorescent spot test |
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How does the ascorbate cyanide test for G6PD deficiency work?
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Ascorbate cyanide is added to the patient's RBCs; G6PD deficient red cells are more sensitive to hemolysis under these conditions than normal cells
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How does the fluorescent spot test for G6PD deficiency work?
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The patient's RBCs are incubated with NADP and G6P, and the production of NADPH is measured (it fluoresces)
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What is the inheritance pattern of pyruvate kinase deficiency?
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Autosomal recessive
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What are the causes of acquired pyruvate kinase deficiency?
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Myelodysplastic syndrome
Acute myeloid leukemia |
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What biochemical pathway is interuppted in pyruvate kinase deficiency?
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The rate limiting step of the glycolysis pathway (Embden-Meyerhoff), which is the main generator of ATP; thus, ATP is depleted, there is an impairment in ion pumps, red cell dehydration, and hemolysis occur
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What is the classic peripheral smear finding in pyruvate kinase deficiency?
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Echinocytes (dessicocytes), which are more prominent after splenectomy
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What tests are used in the diagnosis of pyruvate kinase deficiency?
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Autohemolysis test
Fluorescent spot test |
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What is the result of the autohemolysis test in pyruvate kinase deficiency, and how does it differentiate from hereditary spherocytosis?
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The autohemolysis test is positive, it normalizes with the addition of ATP
However, unlike hereditary spherocytosis, it does not incubate with NADH |
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What is the result of the fluorescent spot test in patients with pyruvate kinase deficiency?
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Red cells are incubated with NADH (which fluoresces) to check for conversion to NAD (which does not)
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What is the most common type of congenital dyserythropoietic anemia?
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CDA type II
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What are the characteristics of congenital dyserythropoietic anemia?
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Multinucleate erythroid precursors
Positive acidified serum |
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What is the inheritance pattern of congenital dyserythropoietic anemia?
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Autosomal recessive
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What antigen is commonly present on the RBCs of patients with congenital dyserythropoietic anemia?
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i antigen
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Describe the positive acidified (Ham) test in congenital dyserythropoietic anemia
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Lysis in CDA type II is observed in heterologous serum only because 1/3 of normal individuals have an antibody against the abnormal red cell antigen found in CDA type II
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What is the difference between the positive acidified serum (Ham) test in CDA type II versus paroxysmal nocturnal hemoglobinuria (PNH)?
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Lysis occurs in CDA type II only in heterologous serum whereas it occurs both in autologous and heterologous serum of patients with PNH
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Is paroxysmal nocturnal hemoglobinuria inherited or acquired?
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Acquired
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What causes paroxysmal nocturnal hemoglobinuria?
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Decreased glycosyl phosphatidyl inositol (GPI) anchors, which normally functions to attach an array of proteins to the cell surface
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What gene is responsible for paroxysmal nocturnal hemoglobinuria?
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PIG-A gene located on the X chromosome
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What is the clinical description of PNH?
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Episodic hemolysis at night
Chronic normocytic, normochromic anemia Can develop with transient thrombopenia and leukopenia with time |
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What conditions can develop with longstanding PNH?
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Aplastic anemia
Acute myelogenous leukemia |
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What laboratory findings are associated with PNH?
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Decreased decay-accelerating factor (DAF, CD55)
Decreased membrane inhibitor of reactive lysis (MIRL, CD59) Decreased acetylcholinesterase (AchE) Decreased CD16 Decreased CD48 |
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What tests can be used in the diagnosis of PNH?
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Flow cytometry (demonstrates CD59 and CD55)
Leukocyte alkaline phosphatase (LAP).....decreased Sucrose hemolysis test Acidified serum (Ham) test |
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How is the sucrose hemolysis test for PNH performed and what are the results?
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RBCs are incubated in serum and isotonic sucrose, which promotes complement binding
There is more hemolysis compared to control RBCs |
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How is the acidified serum (Ham) test for PNH performed and what are the results?
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RBCs are incubated in heterologous and homologous serum that has been acidified, which activates complement)
There is more hemolysis in both types of sera (as oppossed to congenital dyserythropoietic anemia, which is only positive in heterologous serum)compared to control RBCs |
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What defines sideroblastic anemia?
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Anemia
Ringed sideroblasts in bone marrow aspirate |
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What are the findings of sideroblastic anemia on peripheral blood?
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Hypochromic anemia
Microcytic (inherited forms) Macrocytic (acquired forms) Basophilic stippling Pappenheimer bodies |
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What is the classic laboratory finding of sideroblastic anemia that is found on hematology histograms?
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Bimodal red cell volume distribution
There is also low MCV and high RDW |
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What findings are present in the bone marrow of sideroblastic anemia?
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Ringed sideroblasts
Increased iron stores Erythroid hyperplasia Dyserythropoiesis (sometimes) |
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What chemistry findings are seen with sideroblastic anemia?
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Increased serum iron
Increased transferrin percent saturation Increased ferritin High LDH (due to hemolysis due to ineffective erythropoiesis) Decreased haptoglobin (due to hemolysis due to ineffective erythropoiesis) |
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What are some causes of acquired sideroblastic anemia?
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Myelodysplasia (refractory anemia with ringed sideroblasts)
Medications (Isoniazid, chloramphenicol, etc) Alcohol Irradiation Copper deficiency Pearson syndrome (sideroblastic anemia with pancreatic insufficiency) |
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What causes most cases of acquired sideroblastic anemia?
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Myelodysplasia (refractory anemia with ringed sideroblasts)
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What percentage of the bone marrow must have ringed sideroblasts in sideroblastic anemia?
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>15%
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What typically causes the inherited forms of sideroblastic anemia?
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ALAS2, which is found in the X chromosome
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What drug can be used to overcome inhereited sideroblastic anemias?
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Pyridoxine (B6)
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Which type of sideroblastic anemia is particularly prone to iron overload due to increased iron stores?
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Inherited sideroblastic anemia
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What are causes of acquired pure red cell aplasia?
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Parvovirus B19
Thymoma Collagen vascular disease Lymphoproliferative disorders of large granular lymphocytes Medications (erythropoietin) |
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What is the cause of congenital pure red cell aplasia?
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Blackfan-Diamond syndrome
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What does parvovirus B19 infect?
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Progenitor erythroid cells, causing a maturation arrest at the pronormoblast stage
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How long does parvovirus B19 infection typically last?
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2 weeks
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What bone marrow findings are seen with parvovirus B19 infection?
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Numerous giant pronormoblasts
Decreased mature forms of erythryocytes Viral nuclear inclusions within the pronormoblasts |
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What is the typical cause of acquired pure red cell aplasia in adults?
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Thymoma
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Which type of thymoma is particularly associated with acquired pure red cell aplasia?
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Spindle cell/medullary type
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What is Blackfan-Diamond syndrome?
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Congenital pure red cell aplasia typicaly diagnosed before the age of 5 years with low to absent erythroid precursors
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What blood antigen is found in the RBCs of patients with Blackfan-Diamond syndrome?
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i antigen
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What laboratory finding is present on hemoglobin electrophroesis of patients with Blackfan-Diamond syndrome?
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Hb F
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What is the treatment for Blackfan-Diamond syndrome?
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Corticosteroids (75% respond)
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What is transient erythrocytopenia of childhood (TEC)?
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A self-limiting disorder seen in patients 1-4 years of age characterized by a temporary arrest in erythropoiesis that is thought to be caused by parvovirus B19 infection
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What findings can be found on the peripheral blood smear of patients with erythrocytopenia of childhood?
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Reticulocytopenia
Normochromic, normocytic anemia Thrombocytosis |
