Hemoglobin Disorders Flashcards
Thalassemia definition
genetically heterogeneous conditions resulting from imbalance between amounts of alpha and beta globin chains
What type of mutations occur with alpha chains?
full deletions
What type of mutations occur with beta chains?
point mutations
Beta0 versus Beta+ thalassemias
0 means no beta chains produced and + means some produced still
Beta Thalassemia Major name and genotype
Cooleys anemia B0/B0
symptoms of beta thalassemia major
splenomegaly (can be massive), bone deformities, anemia, and iron overload
How to diagnose beta thalassemia major?
all a4 tetramers
what do alpha 4 tetramers in beta thalassemis major cause?
ineffective erythropoiesis or intramedullary hemolysis, and destruction of produced RBCs
intramedullary hemolysis
destruction of RBC precursors in bone marrow
seen in beta thalassemia major
why splenomegaly in beta thalassemis major?
sequesteration of RBCs that are not functional due to a4 tetramer Hb
why iron overload in beta thalassemia major?
transfusions required and give some iron
iron hyper absorbed in gut too
how to treat beta thalassemia major?
transfusions and chelation of iron
beta thalassemia minor characteristics
heterozygous state with a normal and problematic allele
usually asymptomatic with microcytic RBCs and elevated RBC count
how to spot beta thalassemia minor?
best way is to look for delta or HbA2 in electrophoresis because lack of beta will upregulate production of the delta chain for Hb
cis and trans two gene deletions for alpha thalassemia
which population has which one?
cis is –/aa common in asians
trans is a-/a- common in AA
one gene alpha thalassemia characteristics
asymptomatic, not anemic, normal
very prevalent though
two gene alpha thalassemia characteristics
microcytosis, mild anemia
electrophoresis of adult is normal
Hemoglobin Barts
gamma4 Hb…due to hypoxic enviro and with two alpha thalassemia will make these tetramers
will see on electrophoresis for newborn
Hemoglobin H disease Thalassemia characteristics
a-/–
known to be beta4 tetramers
CBC characteristics of hemglobin H disease
MCV low, Hb low, MCH low, high RDW
What happens to hemoglobin H?
as it ages it turns into heinz body cause it is unstable and it is eaten…bite cell formation….splenomegaly common in hemoglobin H
Hydrops fetalis thalassemia characteristics
a is –/–…so make gamma4 tetramers or hemoglobin Barts
in utero still birth death at 25 weeks
treated by bone marrow transplant or transfusions
hemoglobin C mutation change
6th AA in beta chain changed from glutamate to lysine
hemoglobin C smear findings
target cells and hemoglobin C crystals
Gardos Ion channel in sickle cell disease?
abnormal Hb/membrane interactions activate the channel and lead to cellular dehydration in sickle cell
do sickle cells adhere to endothelial cells regularly? if not what is the risk?
no…creates risk of downstreak ischemia
What is SC sickle disease?
this is when you have a sickle trait and a hemoglobin C trait…heme C causes worse dehydration of cells and leads to worse sickling
Sickle-B0 thalassemia
sickle and B0 thalassemia combined…cannot distinguis from regular SS sickle
Sickle-B+ thalassemia
sickle and B+ thalassemia so a bit milder since you have some normal Hb being made
what happens to sickle cell patient spleen?
it is typically inactive and has infarcted by adulthood
What may be cause of Hb count dropping below sickle cell patients normal anemic level?
parvovirus B19
splenic or hepatic sequestration, acute chest syndrome
why do sickle cell patients have leukocytosis and thromobocytosis?
spleen not there to take them out
thrombocytosis leads to what risk in sickle cell patients?
more venous clots
Splenic sequestration crisis in sickle cell kids
outflow vessels of spleen are blocked with sickle cells and the spleen blows up with blood
have severe anemia and splenomegaly
treat with small transfusion
aplastic crisis in sickle cell patient
parvovirus B19 prevents marrow from production so have rapid anemia
painful crisis in sickle cell patients
vaso occlusion of flow to bones..leads to bone and joint pain
trigger of painful crisis in sickle cell patients
exercise, dehydration, infection, cold, stress, menstruation, surgery, pregnancy
common infections in sickle cell
encapsulated organisms cause of splenectomy
in iron chelation therapy of sickle cell patient, what two organisms can cause problems?
yersinia and vibrio
what organism commonly causes osteomyelitis and septic arthritis in sickle cell?
salmonella
acute chest syndrome in sickle cell definition
hypoxemia, new infiltrate on chest Xray, new fever and chets pain, acute worsening anemia
what two organisms lead to infection commonly causing acute chest syndrome in the sickle cell?
chlamydia and mycoplasma
how can a fat embolism lead to acute chest syndrome in sickle cell?
necrotic bone marrow leads to fat deposits in the lungs…
how to treat acute chest syndrome in sickle cell patient?
need early detection
antibiotics and oxygen
transfusion to lower HbS
pulmonary hypertension in sickle cell patient characteristics
very common, mechanism is unknown, leads to death in 2 years by dyspnea chest pain and hypoxia, no good treatment besides prevention
what is the reason for Stroke in sickle cell patients? what is age of onset?
not artherosclerosis but is due to disordered blood vessels
usually around age 5
how to treat stroke in sickle cell patient?
acutely use exchange transfusions and chronically use regular transfusions to prevent further strokes
how can we prevent strokes in young patients with sickle cell?
doppler of the head will show narrowing of vessels in cranium and can tell doc to give chronic regular transfusions to prevent stroke
simple transfusion
give red blood cells
exchange transfusion in sickle cell
give red blood cells and remove red blood cells to titrte to certain percent of HbS
rule about transfusions in sickle cell
do not let hemoglobin get above 10….one unit raises it by 1
high Hb raises viscosity of blood and increases risk of stroke in sickle cell
what type of transfusion for stroke, acute chest, and pre surgery?
stroke is exchange and others are simple
What are two complications of transfusions in SCD?
iron overload and allo-immunization
what does iron overload cause after a transfusion in SCD? how do you treat it?
organ failure..heart liver and endocrine
chelation
allo-immunization in transfusion for SCD?
african americans have less RBC antigens, so need to give blood without C, E and Kell red cell groups so they do not react
Isothenuria in SCD
cannot concentrate urine because of renal papillary necrosis (no oxygen)
Avascular necrosis in SCD
affects heads of femurs and humeri, shoulder and hip pain
priapism in SCD
occludes outflow of penis…long erections
Hydroxyurea mechanism for SCD treatment
causes switch from beta chain to gamma chain so patient makes more fetal hemoglobin
effects of hydroxyurea on SCD
increases Hb reduces sickle cell pain crises reduces acute chest syndrome prevent pulmonary hypertension reduces mortality
should you give hydroxyurea to pregnant?
NO
side effect of hydroxyurea
bone marrow suppression so need to watch white cell count
