Hemoglobinopathies Flashcards
Describe the pathophysiology of thalassemia
Decreased production of alpha and beta globins leads to imbalance of globins
Excess globins precipitate and damage RBC membrane leading to ineffective erythropoesis.
This causes:
1. Anemia
2. Bone marrow expansion
3. Extramedullary hematopoesis
4. Increased intestinal iron absorption
Hemoglobin E
glu to lys change on position 26 of B chain
E trait - microcytic, targets
E disease - mild microcytic anemia, target
EB+ - beta thal minor to NTDT
EB0 - NTDT or TDT
When to initiate chelation?
What are chelation targets?
When:
- 150-200ml/kg transfused
- LIC >5-7
- Ferritin 1000
Targets:
- ferritin between 1500-2000
- LIC < 7
- T2* > 20ms
List 4 indications for DNA testing for hemoglobinopathy. For what hemoglobinopathies is DNA testing available?
Alpha thal
High-affinity hemoglobins
Unstable hemoglobins
Pregnancy counselling
Indications for chronic transfusion
Severe anemia
Growth failure
Extramedullary haematopoesis
Improve quality of life
in sickle trait patients what is the expected amount of HbS?
35-45% HbS
what vessels in the brain are commonly associated with acute stroke in SS disease?
large arteries in the circle of willis, usually distal internal carotid artery, middle cerebral and anterior cerebral artery
for an SS patient with neurologic symptoms, what is the first step in management?
a CT with no contrast-this will detect any hemorrhage, but may not be positive for an acute infarction for 6h
what is the required treatment for an SS patient with stroke?
exchange transfusion to reduce HbS level to less than 30%
what TCD values suggest a chronic transfusion program should be started?
When ACA velocity is >200, or if there’s silent infarcts and or cerebral blood vessel stenosis seen on MRI
when should a child with priapism be seen in the ER
if lasting for >2hrs
when is the highest prevalence of splenic sequestration?
between ages of 5 months-24months
what is the management of splenic sequestration crisis?
- normal saline bolus
- RBC transfusion, do in small aliquots, because of the autotransfusion phenomenon that happens (spleen releases trapped RBCs)
- pain management
when should splenectomy be considered in children with splenic sequestration?
if there’s history of one major event or 2 minor splenic sequestrations
for children <2yrs chronic transfusion therapy can be considered to postpone splenectomy
in SS disease and SC disease by what age does the spleen involute?
by 6mths in SS
by 4yrs in SC
what does the electrophoresis show in SS disease and SC disease?
SS: 80-96% S and 2-20% F
SC: 50-55% S and 45-50% C, and some F
what is the electrophoresis in AS?
35-35% S and 55-60% A
what is the electrophoresis in Sbeta thal0
and Sbeta thal+
Sbeta thal0: 50-85% S, 2-30% F, >3.5% A2
Sbeta thal+: 50-80% S 10-30% A, 0-20% F and <3.5% A2
for HPFH what %HbF would you expect on hemoglobin electrophoresis?
15-35% HbF
what is the most common antigen that alloimmunization occurs with in SS patients?
kell-26%
Rh-24%
C-16%
How does HU work?
it causes upregulation of HbF , inside the red cell HbF interferes with polymerization of HbS, reducing the propensity of sickling
HU also causes:
increased red cell hydration
decreases the expression of red cell adhesion mlcs
increases NO production
lowers the WBC, reticulocytes and platelets
what are the side effects of HU?
myelosuppression skin and nail pigment changes headache hair loss (Rarely) GI upset
what are the amounts of HbA2 and HbF in the following types of thalassemia? Beta+thal Beta0thal deltabeta thal HPFH
Beta+thal-A2 increased, HbF normal to slightly increased
Beta0thal-A2 increased, HbF normal to slightly increased
deltabeta thal-HbA2 normal, HbF increased 5-15%
HPFH-HbA2 normal, HbF increased 15-30%
what are the 3 iron chelators on the market?
Deferoxamine (desferral)
Deferiprone (ferriprox)
Deferasirox (exjade and jadenu)
what side effects are associated with Deferasirox?
GI upset
rash
renal injury
elevations in LFTs
what side effects are associated with Deferiprone?
GI upset
LFT elevations
agranulocytosis
arthralgias
patients being treated with desferoxamine are at risk of what specific bacterial infection?
yersinia enterocolitica
what is Hb Barts?
tetramer of gamma chains (3-8% in trait, 25-50% in HbH disease), seen in newborns, and means they have some form of alpha thal. This is because they aren’t producing enough alpha to bind to gamma, and in turn they all form tetramers
what is HbH?
seen in children/adults, its a tetramer of beta chains. See this when you have alpha thal (3 gene deletions), not enough is being produced so the lonely beta chains bind tetramers together. HbH is 5-10% on electrophoresis, is a fast band
what is the normal adult amount of HbF?
0-2%
what is the adult normal amount of HbA2
2-3%
for beta thal trait what percentages of HbF and HbA2 do you expect?
HbF: 1-10% (normal or increased)
HbA2: 3-10% (increased)
for iron deficiency anemia what percentages of HbF and HbA2 do you expect?
HbF normal 0-2%
HbA2: 0-2.5% normal or low (this mimicks alpha thal trait or could mask beta thal trait)
what is HbE?
a hemoglobin variant, its point mutation causes the exposure of a cryptic splice site which when properly spliced leads to production of HbE and when improperly spliced leads to the gene not being translated and reduced globin output
3 major factors affecting transplant success
- inadequate chelation
- hepatomegaly
- portal fibrosis
Which complication is more common in SC than SS?
retinopathy
