Hemoglobinopathies Flashcards
most common causes of inherited hemoglobin disorders
DNA deletions or point mutations
what is a quantitative hemoglobin disorder
thalassemia
what is a qualitative hemoglobin disorder
hemoglobinopathy
normal fetal hemoglobin made of?
2 alpha chains and 2 gamma chains
normal adult hemoglobin made of
2 alpha chains and 2 beta chains
in thalassemia what is the balance of alpha and beta chains
alpha thalassemia- excess beta
beta thalassemia- excess alpha
pathophysiology of thalassemia
excess globins precipitate and damage the RBC membrane, ineffective erythropoiesis
outcomes of thalassemia
anemia, bone marrow expansion, extramedullary hematopoiesis, increased intestinal iron absorption
Sickle cell and thalassemia protects from what disease?
malaria
silent carrier in thalassemia
one deletion of the functional gene
What is alpha-thalassemia trait
two deletions of functional genes ( cis- more common in Asian pops or trans more common in African pop)
HbH disease
3 deletions of functional genes
hydrops fetalis
4 deletions of functional genes- incompatible with life
alpha thalassemia trait definition
reduced alpha globin chain synthesis due to 2-gene deletion- causes an excess amount of gamma globin at birth, or beta globin as an adult
best time to identify alpha thalassemia
in newborns- excess gamma globin and fast band production makes it more identifiable with testing. For adults, try to track newborn screen.
Heinz bodies
detects protein precipitates, denatured proteins. Test is
not commonly used due to common false negatives
treatment for hydrop fetalis
if caught in utero- can do transfusion support.
then stem cell transplantation to treat after birth.
beta thalassemia
beta-0- producing no beta globin
beta+ produces little beta globin
B-thalassemia major
homozygous
severe anemia
requires life-long RBC transfusion
B-thalassemia intermedia
mild anemia
occasional transfusions required
B-thalassemia trait
heterozygous
asymptomatic
confused with iron deficiency- suspect if patient does not respond to iron therapy
phenotypes for b thalassemia
mild
moderate
severe
B+ B+
Bo B+
Bo Bo
beta thalassemia trait under the microscope
unbalanced a:b chains
elevated A2
elevated Hb F
microcyctic anemia
treatment of beta thalassemia intermedia
hydroxyurea- increase in fetal hemoglobin production.
watch iron absorption- can be increased
outcomes of thalassemia major/erythropoiesis
expansion of marrow cavities, extramedullary hematopoiesis, splenic destruction of RBC, hypersplenism, growth failure
treatments for thalassemia major
hypertransfusion every 2-4 weeks
splenectomy (in non-transfusion dependent)
stem cell transplant to cure
treat iron overload with chelation
iron overload cause
RBC trasfusions
no body mechanism to get rid of excess iron
intake of 1 gm/month in chronic transfusion patients
iron overload complications
pericarditis, arrhythmias, cardia failure
fibrosis, cirrhosis, hepatic failure, cancer
diabeter, growth failure, infertility
how to test for iron overload
serum ferritin, liver biopsy, MRI
treatment of iron overload
chelation (deferasirox or deferoxamine)- start treatment early to prevent iron overload rather than trying to reduce amount of iron in the body if possible.
phlebotomy- regularly remove blood to reduce amount of iron in the blood
sickle cell disease definition
group of blood disorders containing HbS
is sickle cell dominant or recessive?
autosomal recessive
sickle cell pathophysiology
single point mutation on the beta chain
Adenine to Thymine at position 6 of the beta globin.
changes RBC shape (stiff due to deoxygenation)
blood flow obstruction leads to ischemia
epidemiology of sickle cell
in US- 8%
1/400 births
3,000,000 with trait and 100,000 with disease
globally more than 400,000 births per year
how does sickle cell trait protect against malaria
lower transmission
reduced parasitemia
decreased mortality
how is sickle cell diagnosed in the US?
all newborns tested with dried blood spots
most common disease found by newborn screening
newborn screening results
FA
normal
newborn screening results
FAS
sickle cell trait
newborn screening results
FS
sickle cell anemia
newborn screening results
FSA
sickle B+ thalassemia
newborn screening results
F
thalassemia major
newborn screening results
FA
fast band- alpha thalassemia trait
risks for sickle cell trait
hematuria
renal medullary carcinoma
sudden death during prolonged, strenuous physical activity
hyphema
increased occular pressure, loss of vision
those with sickle cell need referral to a specialist to prevent loss of vision
clinical manifestations of sickle cell disease
functional asplenia, pneumococcal infection
hemolysis (partially compensated- increased reticulocytes)
acute vaso-occlusive events (painful)
organ damage
most common cause of death for sickle cell disease patients
organ damage- spleen, kidneys, lung, brain, eyes, hips
how to prevent sepsis in newborns with sickle cell disease
prophylactic therapy with oral penicillin by 3 months
penicillin regimen for sepsis prophylaxis with sickle cell
125mg BID- until age 3
250mg BID- until age 5
usually has to be refridgerated and picked up every 2 weeks from the pharmacy- difficult to get patients to be compliant
why stop prophylaxis at age 5
immunizations with HiB, prevnar, pneumovax, meningovax, no evidence of sepsis prevention beyond age 5
what temperature is considered a medical emergency for patients with sickle cell disease?
38.5 or greater
what to order in a SCD patient with fever
labs- blood cultures, cbc with retic, UA
chest x-ray
type and cross-match if increased pallor or splenomegaly or resp/neuro symptoms
treatment of sepsis in SCD patients
IV broad spectrum antibiotics
most common manifestation of SCD
acute vaso-occlusive pain- occurs as early as 6 months
painful events with SCD
sudden onset in extremities, back , and sternum/ribs
dactylitis/ hand-foot syndrome
treatment of painful events
NSAIDs and opioids
fluids and hydration
early pain control
warning signs with SCD pain
respiratory distress, chest pain- acute chest syndrome fever- infection weakness- stroke lethargy- splenic sequestration abdominal pain/jaundice- cholelithiasis
symptoms of acute splenic sequestation
tender splenomegaly, worsened anemia, increased retics, platelets less than 150,000, LUQ pain, SOB, vomiting
typical age of onset of acute splenic sequestation
6 months to 3 years
treatment of splenic sequestration
RBC transfusions
careful not to overshoot
recurrence rate of splenic sequestration
50%
acute chest syndrome signs/symptoms
+/-fever, dyspnea, pain, hypoxia, increased WBC, pleural effusion, fat embolism, atelectasis, sickling and intra-pulmonary sequestration
acute chest syndrome treatment
admission antimicrobial treatment- ceftriaxone, azithromycin, levofloxacin O2 bronchodilators IV fluids transfusions
avascular necrosis (AVN)
osteonecrosis in limited circulation areas
femoral head most common
AVN treatment
NSAIDs, PT, hip replacement
SCD and renal manifestations
hyposthenuria
renal infarction
progression to renal failure and proteinuria
priapism
prolonged, painful erection
40% of men with SCD
blood flow is obstructed
priapism treatment
analgesics and hydration
aspiration if greater than 4 hours
vasodilators can prevent attacks, but do not treat
sickle retinopathy
vitreal hemorrhage and retinal detachment
causes vision loss
seen in HbSC > HbSS
leg ulcers and SCD
5-10% of people > age 10 have healing problems
incidence of stroke with SCD
11% by age 20
24% by age 45
stroke symptoms
hemiparesis (weakness as opposed to pain) visual/language dysfunction seizures headaches altered sensation altered mental status
treatment of stroke with SCD
transfusion immediately
CT
IV fluids
MRI (can wait a few days)
stroke recurrence with SCD
47-93% without treatment
treat with blood transfusions every 3-4 weeks
10-20% still experience recurrence with treatment
stroke prevention in SCD
transcranial doppler (TCD) ultrasonography screening if > 200 cm/sec- abnormal, requires transfusions
indications for simple transfusions
splenic sequestration transient aplastic crisis anaemia acute chest syndrome pre-ops
indications for chronic transfusions
clinical stroke
abnormal TCD (>200 cm/sec)
multisystem organ failure
