BL Hassell lecture review Flashcards
(34 cards)
Name hemoglobinopathies that have structural variants with abnormal function?
Hb S and Hb C
Name hemoglobinopathies that have structural variants with decreased production of globin chains?
a thal and b thal
Name hemoglobinopathies that have structural variants with decreased synthesis?
Hb E
What are the normal percentages of adult hemoglobins (Hb A, A2, and F)?
A - 95 %, A2 - 3.5%, F - <2.0%
Define Sickle cell disease.
Hemoglobinopathy with two abnormal Beta genes in which one contains the sickle cell mutation.
Name the different Sickle cell diseases (in order of severity).
Hb S S = Hb S Bo thal; Hb S C; Hb S B+thal; Hb S A (trait). Not sure where to place Hb SE Hb SD, but be aware of their existence.
Which physiological conditions promote sickling?
dec O2, inc K+, dehydration,
Where are sickle cells most likely to manifest in the vasculature?
Post-capillary venules
How do the sickle cells affect the carrier (4 things)?
Decreased ability to supply oxygen to tissues, abnormal cell adhesion to endothelium, direct damage to endothelium, abnormal vasoregulation.
What other cell lines may be affected in sickle cell disease?
WBCs (elevation)
Describe the ways to test for sickle cell disease (4 things).
Sickle solubility test (not reliable in distinguishing different types of sickling genotypes), hemoglobin separation (only gives % of types of Hb in sample as a whole). Isoelectric focusing and HPLC can give a better idea of percent of each type.
Describe the hematologic (CBC and smear) findings of sickle cell disease.
CBC: NORMOCYTIC ANEMIA - Dec RBC, increased retics and robust retic response, inc WBC, inc platelets, inc LDH, inc bili, inc AST. Smear: sickle cells, cell fragments, polychromasia, Howell-Jolly bodies, nucleated RBCs
Describe the organ level findings of sickle cell disease.
May see hepatosplenomegaly, overwhelming infections, infarctions and dead tissue in lungs, brain, retinas, kidneys, intestines, avascular necrosis of head of the femur, ulcers, pain, priapism.
Which organ are uncommonly involved in sickle cell disease?
Heart and liver, although injury to these tissues is not impossible.
Describe the mechanism of vascular injury in sickle cell disease.
The sickle cells may cause vascular injury due to shape and stickiness. The damage to endothelial cells results in tissue hypoxia, cytokine release, decrease in NO release, and vasoconstriction. These things all result in further damage to endothelial cells by sickle cells.
Describe treatments for sickle cell disease
Supply adequate oxygen and improve hydration, treat any infections with antibiotics, give arginine to enhance vasodilation, may need to do blood transfusion, may need to give hydroxyurea, may need to do bone marrow transplant
Name the risks of transfusion therapy.
Iron overload, alloimmunization (transfusion reactions), infection
Describe the pathophysiology of thalassemia.
Primarily causes decreased synthesis of a or b globin chain. This leads to free chains that bind to RBC membrane (precipitation as Heintz bodies), cause membrane injury, cause decreased membrane stability.
Describe the hematologic findings of a thal.
MICROCYTIC ANEMIA - inc RBC, dec MCV, dec MCH, inc RDW, robust reticulocyte response, inc bili, inc LDH, inc AST. Smear: target cells, hypochromia, microcytosis
Describe the organ level findings of a thal.
Possible spelomegaly, cholelithiasis, and cholecystitis.
What are the possible genotypes of a thal syndrome?
-1 a, -2 a, -3 a (aka Hb H), -4 a (hydrops fetalis)
Which races are tend to be associated with thals? (important for classic USMLE questions)
Mediterranean, african, and asian
How can we diagnose thals?
Hematologic findings (microcytosis, anemia), hemoglobin electrophoresis, diagnosis of exclusion (microcytosis without iron deficiency)
Which thalassemia will not show up in examination of electrophoresis?
A thal. All hemoglobin contains a globin. The decrease in each type of hemoglobin will therefore be proportional in a thal disease.
