Hemoglobinopathies Flashcards
What are the genotypes that will produce sickle cell disease?
Hb SS, Hb SC (sickle and crystallizing mutations) and Hb SB-thal
note sickle cell mutation effects B class HbA thalasemias can be some what sheltering
Are there any clinical symptoms for sickle cell trait?
(HbAS) usually has no serious clinical consequences, although serious clinical consequences can occur during intensive training
Deoxygenation of sickle mutant Hb leads to what 3 main cellular changes.
increased K+ influx
increased cell density/dehydration
increased polymerization of Hb
conditions that cause rightward shift of hemoglobin binding curve tend to promote polymerization (decreased pH, increased 1,3 DPG), slowed transit time and endothelial adhesion
Name as many clinical sequalae of sickle cell as possible. (16)
painful episodes pneumococcal disease acute chest syndrome splenic infarction splenic sequestration (acute enlargement entrapping RBC) stroke osteonecrosis priapism retinopathy leg ulcers gallstones renal abnormalities osteopenia nutritional deficiencies placental insufficiency pulmonary HTN dactylitis (occlusive vasculopathy- moya-moya pattern)
Contrast symptoms correlated with higher hemoglobin v. lower hemoglobin.
higher: painful epidsodes, acute chest syndrome, osteonecrosis, proliferative retinopathy
lower: stroke, priapism, leg ulcers
What treatments are currently used for SC patients?
hydroxyurea (changes adhesion and hydration of RBC, promotes fetal hemoglobin etc.)
opiates and hydration for painful crises
pneumococcal vaccination, Abx prophylaxis
retinal surveillance
transfusions for serious manifestations
stem cell transplant
In thalassemia, unbalanced global chain synthesis causes ________ (seen on smear), ineffective erythropoiesis and hemolysis.
microcytosis, a thal will have inclusion bodies of HbH (B tetramers- visible with supravital stain) and B thal will have precipitate of a tetramers
What are Heinz bodies?
an inclusion body that contains denatured hemoglobin, can be result of G6-PD deficiency (classically leading to bite cells) as well as in thalassimias (ie. B4 = HbH)
What are the symptomatic genotypes of a thalassemia ?
aa/a- and aa/– lead to mild microcytosis
a-/– leads to HbH disease
–/– leads to Hydrops fetalis and hemoglobin Bart’s
Characterize the hemaglobin of a patients with Beta thalassemia major.
no beta chain is produced (no HbA - 2a, 2B)
What are the pathologic consequences of Beta thalassemia major?
no HbA is produced
severe microcytic anemia occurs, marrow expands, iron overload (increased absorption and transfusions)
hemolysis, splenomegaly
growth failure and death
What are the key features of thalassemia intermedia on smear?
microcytic anemia with target cells, nucleated RBC and other bizarre red cell forms
What are the features of a thalassemia minor and HgbH ?
microcytosis, hypochromia, varying levels of anisocytosis, poikilocytosis, target cells (HgbH)
Hemoglobin E is associated with which population?
(B mutation)
clinically significant mutation most common in patients of southeast asian decent
A possible treatment for SC patients requiring frequent transfusions, a port may be placed for this type of transfusion.
erythrocytopheresis
Acanthocytes are most commonly associated with which liver malfunction?
due to alteration of membrane lipids, associated with absence of apolipidproteins (severe liver disease)
Which two cellular features are most characteristic of a patient without a spleen
Howell-Jolly Bodies (retained nuclear material)
Pappenheimer Bodies (ribosomal, lysosomal, mitochondrial and iron rich material) ** can indicate iron handling problems and hemoglobinopathies
Large, chunky, squarish cells that are more polygonal in shape appear in response to crystallization of hemoglobin, what is the corresponding genotype?
Bc
What are likely features of a smear from a SC patient besides sickle cells?
Howell-Jolly bodies if spleen has been infarcted
nucleated RBC due to reticulocytosis
and target cels
Presence of target cells is significant for what underlying pathology?
inappropriate defective globin chain synthesis
Discuss the RBC, MCV and RDW of a thalassemia, B thalassemia and Fe deficiency
a thal: high RBC, low MCV, low RDW (typically minimal anemia)
B thal: high RBC, low MCV, low RDW (basophilic stippiling is common)
Fe deficiency: low MCV, low RBC, high RDW
In which conditions would you expect to find basophilic stippling?
disorder or defective hemoglobin synthesis (thalassemia and lead poisoning), can also be found in normal individuals
Slightly elevated A2 should make you at least consider which hemoglobinopathy?
B thalasemmia depending on the degree of elevation either major or minor
How would you expect iron studies to change in a patient with B thalassemia trait?
no change
