module 8 study tool
hemoglobinopathies
thalassemia
Hemoglobin diseases
sickle cell anemia
S-beta thalassemia
E
SC
D
C
O
Qualitative defect
quantitative defect
homozygous or heterozygous
It is gene mutation
most common
places it can occur
most common: africa
other places: mediterranean, middle east, india, nepal
chromosome 11 mutation that changed glu->valine
pathophysiology
net negative charge made
deoxyhemoglobin s molecules polymerize
creates the sickle cell shape
anemia
85-38% oxygen saturation
happens in hypoxic, acidotic, hypertonic microenvironment
clinical features
symptoms: hemolytic anemia, Vaso occlusion of microvasculature, infections, acute splenic sequetration
peripheral smear: poik, aniso, polychromasia
5-20% reticulocytes
variety of cells but diagnosis would be the sickle shaped cells
increased: bilirubin, uric acid, lactic dehydrogenase
decreased haptoglobin
diagnosing
Adults: screening solubility test
newborn
prenatal DNA analysis
Hgb electrophoresis
isoelectric focusing
high performance liquid chromatography
alkaline hemoglobin electrophoresis
can only do preventative measures for treatment
prophylactic penicillin
avoid dehydration
PRBC transfusion
pharmacological agents to increase hemoglobin F production
hematopoietic stem cell transplant
hemoglobin crystals (bar of gold)
mainly known in African people
decreased life span of RBC (30-55 days)
joint and abdominal pain
enlarged spleen
the trait is asymptomatic
no treatment
normochromic, normocytic anemia
increased target cells
2-3% reticulocytes
negative solubility test
Definitive Dx by electrophoresis, HPLC, and nucleic acid testing
morphology: microcytic, hypochromic, polychromasia, target cells
both chains are abnormal
creates beta s and beta c chains
no hemoglobin a
both chains are abnormal
codes for beta s and c chains
hemoglobin A is absent
"mild" sickle cell disease
sickling and Hgb C crystals are there
vaso occlusive crises
splenomegaly
normochromic/normocytic anemis
solubility test is positive
in the electrophoresis Hgb s and c move the same amount
F is normal
symptoms
electrophoresis
morphology: target cells
homozygous: mild hemolytic anemia and splenomegaly
heterozygous: asymptomatic
alkaline: moves with C, E, and A2
acidic: moves to A position
morphology: few target cells
symptoms: asymptomatic
electrophoresis
acidic: moves to A
alkaline: moves to a band at s and one at A2
symptoms: asymptomatic
electrophoresis: strong band in HgbC/A2 position
symptoms: splenomegaly
electophoresis: a band at s and one at A2
morphology: Microcytic, hypochromic, nucleated RBCs, Reticulocytes, target cells, polychromasia, & Sickle cells
mild- asymptomatic, severe-anemia, hepatosplenomegaly, infections, gallstones, bone deformities
mutation gets rid of globin chains
beta thalassemia
alpha thalassemis
major (Hgb Barts hydrops fetalis syndroms)
symptoms start at about 6 months
distorts the cell
symptoms: failure to thrive, enlarged spleen, bone fractures, anemia, jaundice, frequent transfusions, diabetes
peripheral smear has: microcytic, hypochromic anemia, nRBCs, precipitates stain with methyl violet stain
lab results
decreased MCV, MCH, MCHC
secondary leukopenia and thrombocytopenia
dark urine
elecrtophoresis
will show deficient beta chain production
in adult: 0% A, 90% F, less than 2.5% A2
treatment: hyper transfusion, iron chelating agents, splenectomy
if left untreated they will die by 20
can have hepatic and cardiac disturbances
Intermedia: it is not well defined but is asymptomatic
has moderate microcytic hypochromic anemia and shows target cells, basophilic stippling and nRBC's
minor
silent
found mainly in asian populations
Hgb H disease
halotype (--/--)
not compatible with life
severe anemia, microcytic, hypochromic, elevated reticulocytes, elevated nRBC's
dangerous for mom and fetus
halotype: (--/-alpha)
Barts produced at birth with y chain production
at 6 months changes to Hgb H
chronic hemolysis/ anemia, splenomegaly, 50% chance of skeletal changes, Hgb=8-10 g/dL, elevated retics, nrbcs, inclusions can be seen with brilliant cresyl blue
electrophoresis
adult: 40% hgb H
infant 25% bart hgb
1 unaffected alpha chain, one deleted
(--/alpha, alpha)
asymptomatic
you can find microcytic, hypochromic anemia, Hgb H inclusions
electrophoresis in newborns shoe 5-6% barts
can be masked by iron deficiency anemia
only 1/4 of the chain genes are missing
asymptomatic
can find borderline low MCV, slight microcytosis
genetic analysis is the only reliable diagnostic tool