Inherited Anemias Flashcards
______ is an inherited hemoglobinopathy in which a genetic mutation leads to abnormal hemoglobin
Sickle Cell Disease
Inheritence pattern of sickle cell disease
autosomal recessive; most common in those of african descent
____ black children in the US are born
homozygous for Hgb S (Sickle Cell Disease)
1 in 400
heterozygous for Hgb S
Sickle cell trait
Pathophysiology of sickle cell disease
Hemoglobin S is unstable and will
polymerize in the setting of various stressors, such as hypoxic tissue and acidosis
● This polymerization leads to the
Sickle-shaped RBCs
Sickled cells have difficulty passing through small capillaries, which can lead to ____
blockage and tissue necrosis
Sickled cells are either destroyed in
peripheral circulation or by the spleen,
resulting in _____
Hemolytic Anemia
Free Hgb from hemolysis causes ____
endothelial dysfunction, vascular injury, and pulmonary hypertension
Early S/S sickle cell disease
● Early signs can include delayed growth and development, fevers, and
splenomegaly
○ Recurrent infections start occurring with hyposplenism
When is Hgb F present?
first 6-12 months of life
Babies born with Sickle Cell Disease present with symptoms at about
6-12 months of age when fetal hemoglobin (Hgb F) is replaced by Hgb S
Decreased Hgb S affinity for O2 and endovascular damage can cause
_____
pulmonary hypertension, CHF, etc.
How can multi-organ failure occur in sickle cell disease?
Repeated episodes of vascular occlusion especially affect the heart, lungs, and liver
○ Multisystem organ failure, heart failure, stroke, and osteonecrosis are all possible and common complications
Patients with Sickle Cell Trait do not have clinical disease unless they
are exposed to an episode of ____
significant hypoxia
Clinical management if a patient presents with a sickle cell crisis
○ Hydration (often IV)
○ Generous analgesics
○ Oxygen supplementation
○ Hydroxyurea – reduces the frequency of painful crises, but
has some associated risks
Patients with sickle cell disease should avoid ___ and ____
dehydration and hypoxia
When _____is possible before significant
organ damage, it can cure more than 80% of patients with Sickle Cell
Anemia who have suitable matched donors
allogeneic Bone Marrow Transplant
What should you recommend to patients who are heterozygous carriers (sickle cell trait)
Genetic counseling
With supportive care, average life expectancy for sickle cell disease is now between ____ years of age
40-50
Thalassemias are hereditary disorders characterized by ____
reduction in the synthesis of globin chains (alpha or beta)
Reduced globin chain synthesis causes reduced hemoglobin creation and
a ____ because of defective
hemoglobinization of RBCs
hypochromic microcytic anemia
T/F The inheritance pattern of Thalassemia is not straightforward, being autosomal
dominant for some and recessive for others
T
Thalassemia overall is most common in families from ____
southeast Asia and China, the Mediterranean area, and those of African descent
Alpha-Thalassemia:
Due to complete loss of one or more of the four
copies of the alpha-globin chain gene
Alpha- thalassemia levels
○ Loss of 1 - Silent carrier (asymptomatic)
○ Loss of 2 - Alpha-Thalassemia trait (“minor-thalassemia”)
○ Loss of 3 - “Alpha 3”
■ Severe anemia with signs of hemolysis – requires treatment
○ Loss of 4 - Hydrops fetalis (death in utero)
■ No normal alpha hemoglobin is produced
Alpha-Thalassemias are seen primarily in persons from ______
southeast Asia and
China, and (less commonly) in African and persons of Mediterranean origin
Beta-Thalassemia:
Due to mutation of promoter sequence for beta-globin chain gene
Depending on the type of mutation, the reduced beta-globin
synthesis results in a relative increase in proportions of ____
Hgb A2 and Hgb F compared to Hgb A
Beta-Thalassemia primarily affects persons of ____
Mediterranean origin (such
as Italian, Greek, etc.), and to a lesser extent Asians and African
Signs and Symptoms (for both alpha and beta thalassemia)
● Clinical presentation can vary significantly and depends on the severity of inherited mutations
● In more mild disease, normal symptoms of anemia may be present (may present like IDA)
● In severe disease, as seen with Alpha-3 or Beta-Major, patients can present with severe anemia, hemolysis, jaundice, hepatosplenomegaly, and significant fatigue
Patients with mild disease (Alpha-Thalassemia Trait or
Beta-Thalassemia Minor) require ___
no treatment
Patients with severe thalassemia are generally maintained on a
regular ____
transfusion schedule (every 2-3 weeks)
____ is the treatment of choice for
Beta-Thalassemia Major and the only available cure for these patients
Allogeneic stem cell transplantation
Thalassemia should not be treated with ____
iron
Glucose-6-Phosphate Dehydrogenase is ____
a cytosolic enzyme that
maintains normal cellular levels of another enzyme, NADPH
____ is necessary for
maintaining levels of Glutathione
(GSH)
NADPH
GSH is an important
antioxidant capable of
_____
donating an electron to free
radicals
G6PD Deficiency is an ____ condition
X-Linked Recessive
It is the most common human
enzyme defect
G6PD deficiency
Deficiency of G6PD in RBCs means that the cell cannot handle large
amounts of ____
oxidative stress
If oxidative stress occurs, the RBCs can’t
stabilize oxidants which results in ____
structural damage within the cells
Oxidative damage to the cells results in
either spontaneous RBC rupture or
removal by the spleen, causing
○ Heinz bodies
○ Bite/blister cells
○ Schistocytes
G6PD deficiency results in ____
hemolytic anemia
In situations of oxidative stress, the patient presents with Hemolytic
Anemia with these S/S
○ Fatigue
○ Jaundice
○ Dark urine
Clinical management of G6PD deficiency
● Treatment generally revolves around treating the infection or removing the offending drug/food
○ No G6PD-specific treatment is necessary
● Full recovery occurs within a matter of weeks
● After recovery, the patient should focus on lifelong avoidance of know triggers
