Flashcards in Hematopathology Deck (120)
What genes are implicated in hereditary spherocytosis?
SLC4A1 (band 3)
*Mostly autosomal dominant inheritance
What hematological parameters are affected by hereditary spherocytosis?
MCHC is increased
Osmotic fragility is increased
Increased reticulocytes (low level hemolysis)
What genes are implicated in hereditary elliptocytosis?
Mutations in the alpha-spectrin chain (SPTB)
In what conditions can elliptocytes be seen?
Iron deficiency, B12 deficiency, folate deficiency, myelophthisis
Hereditary elliptocytosis - At least 25% of circulating red cells
What are the subtypes of hereditary elliptocytosis?
Hereditary pyropoikilocytosis (sensitivity of red cells to heat)
Spherocytic type (compound heterozygote with hereditary spherocytosis)
Stomatocytic type (SE asia, protects against P. Vivax)
2 types: Severe hydrocytotic (macrocytotic, severe hemolysis) and xerocytotic (normocytic RBCs, mild)
Associated with Rh-null phenotype.
What are the clinical features of G6PD deficiency?
Mostly affects African-american (protective against P Falciparum) and mediterraneans. X-linked (affects men).
Exposure to oxidant stress (sulfa drugs, infection, fava beans) precipitates severe hemolysis.
What are the morphologic features seen in G6PD deficiency?
Bite cells and blister cells
Heinz bodies (need supravital dyes to observe)
How is G6PD deficiency diagnosed?
Fluorescent spot test: Measure NADPH production
*Must wait 3mo after resolution of a hemolytic crisis to test.
What are the clinical features of pyruvate kinase deficiency?
Expressed in Northern European and Amish patients.
Loss of the last enzyme in glycolysis, which impairs RBC ATP supplies >> chronic hemolysis.
What are the morphologic and diagnostic features of pyruvate kinase deficiency?
Peripheral smear shows many echinocytes.
Diagnose with fluorescent spot test for NADH >> NAD conversion. Other tests; Quantitative PK assay, antihemolysis test...
Pyrimidine 5' nucleotidase deficiency
Loss of enzyme that normally degrades reticulocyte RNA. Results in basophilic stippling which can cause hemolysis.
What are the globin chain compositions of the following hemoglobins?
Hb Gower 1 and 2
HbA: a2b2 (major adult hemoglobin)
HbA2: a2d2 (minor adult hemoglobin)
HbF: a2y2 (major late fetal hemoglobin)
Hb Gower 1: z2e2 (major early fetal hemoglobin)
Hb Gower 2: a2e2 (minor early fetal hemoglobin)
What is the abnormality that drives HbS formation? What is the consequence for the cell?
E6V (glu>val) mutation of beta-globin gene results in abnormal polymerization when deoxygenated. RBCs have shortened survival of 17 days.
What crises affect patients with sickle cell disease?
Aplastic crisis - Parvovirus B19
Splenic sequestration - Viral infections
Hyperhemolysis - Associated with G6PD def
Acute chest syndrome
How is sickledex testing performed?
Add metabisulfate or dithionate to a red cell lysate; oxygen tension will decrease and precipitate sickling, making the sample cloudy.
How does HbSC compare to HbSS disease?
Less severe clinical manifestations but with about as much avascular necrosis of bone or proliferative retinopathy.
What abnormality drives HbC formation? What is the consequence?
E6K mutation of beta-globin gene (same site as HbS). Results in hexagonal/rod-shaped crystals of precipitated hemoglobin and mild hemolytic anemia.
What abnormality drives HbE formation? Where is it seen and how is it detected?
E26K mutation of beta-globin gene. Seen in southeast asia and is #2 most common variant hemoglobin. CBC findings resemble thalassemia, note that HbE elutes on HPLC at same time as HbA2.
Hemoglobin D (Punjab, Los Angeles)
Driven by E121Q beta-globin mutation
Clinically silent, HbD migrates with HbS on alkaline gel and with HbA on acid gels.
Variant hemoglobin that results from fusion of delta and beta genes. Observed in mediterranean populations.
Migrates with HbS, but is present in low levels (15%)
Hemoglobin constant spring (HbCS)
Mutation in alpha-globin stop codon, producing long unstable transcript. Seen in Southeast Asia.
Can result in HbH disease if in association with other alpha-globin gene abnormalities.
What factors drive the oxygen dissociation curve RIGHTward?
Increase temperature (fever)
What is HbH composed of? Hb Barts?
HbH - Beta-globin tetramer (seen in severe alpha-thalassemia)
Hb Barts - Gamma globin tetramer (seen in utero in severe alpha-thalassemia, incompatible with life)
What is methemoglobinemia? How is it formed?
Hemoglobin that has Fe3+ instead of usual ferrous iron (Fe2+). Blood appears chocolate-brown.
Can be caused by hereditary conditions or acquired from drug/chemical exposures.
How is methemoglobin detected?
Cannot rely on pulse oximetry or arterial blood gas analyzers. Use methemoglobin method (cyanide).
How is methemoglobinemia treated, and in what settings is methemoglobin advantageous?
Treated with methylene blue (reduces Fe3+ to Fe2+). Methemoglobin has a high affinity for cyanide, so generating methemoglobin using nitrites is done for treatment of cyanide poisoning.
Variant hemoglobin formed by oxidation of Hb in presence of sulfur.
Precipitates into Heinz bodies. Increases after exposure to sulfonamides.
How is carboxyhemoglobin normally formed? How is it pathogenic?
Besides environmental exposures, COHb is made from normal breakdown of heme as well as hepatic metabolism of dichloromethane (methylene chloride).
Has extremely high oxygen affinity; does not unload oxygen effectively and competes with other hemoglobin for oxygen.