Hemoglobinopathies Flashcards
Usually with beta thal trait, one allele is normal and the other is ___
B+
How would you treat a stroke in someone with sickle cell disease?
Exchange transfusion; Transfuse children in order to PREVENT the stroke
Should you supplement iron in a patient with beta thal major?
NEVER
How do you treat acute chest syndrome?
Antibiotics, oxygen, simple or exchange transfusion to lower the HbS concentration
Target cells and what other unique type of findings are on a blood smear of someone with Hb C disease?
Hb C crystal
1/3 of patients with sickle cell will have had a ____ ____ by the time they are 30
Venous clot
a-/–; 3 alpha deletion
Hemoglobin H disease
Hydrops fetalis alpha globin genotype
–/–
Sickle cells are sticky and tend to attached to _____ cells
Endothelial
With an infant with Cooley’s Anemia, will it be symptomatic at birth?
No, because has not switched from the gamma to beta gene yet; symptoms emerge after ~ 6 mo
HbSB+ is milder/worse than HbSS
Milder
What is the most common cause of death in patients with sickle cell disease?
Acute chest syndrome
People with iron overload due to hyper absorption in the gut are more susceptible to infection with ____ spp., ____ and should avoid eating raw _____
Vibrio, mucor, shellfish
Iron overload may cause ____, ____, and endocrine failure
heart, liver
HbC substitution switches glu to __
lys at 6th aa
HbS substitution switches glu to __
val at 6th aa
Hb Bart’s
gamma4 tetramers in newborns; seen in alpha thal
In an adult, one unit of blood raises the Hb level by __
1
In a patient with sickle cell anemia with an acute drop in baseline Hb, should look for infection of what virus?
Parvovirus B19
Adult sickle cell patients do or do not have a spleen
Do not; it has infarcted
SE Asians have which alpha thalassemia?
aa/–
Splenic sequestration crisis
When a child has sickle cells sequestered in the outflow of the spleen that causes splenomegaly, increased drop in Hb and very low BP
Patients with sickle cell anemia and sickle cell trait are at an increased risk for ____ clots
Venous
HbC leads to increased
Cellular dehydration
In a newborn who has alpha thal, what will the gel electrophoresis be like?
It will be abnormal due to the production of gamma4 tetramers (Hb Bart’s)
The _____ ion channel is activated abnormally in sickle cell disease and that leads to ____ _______
Gardos; cellular dehydration
What are some respiratory complications in sickle cell disease?
Acute chest syndrome and pulmonary hypertension
How do you treat iron overload?
Iron chelation therapy
In patients with sickle cell anemia, when the Hb falls below the baseline, should look for what causes?
- Infection with parvovirus B19
- Splenic or hepatic sequestration
- Acute chest syndrome
If someone has beta thal trait, what are some lab findings?
- very microcytic, so low MCV (~70)
- high RBC
- normal RDW
As soon as you find out someone has beta thal major, what are the steps to take?
Transfusion and iron chelation therapy
What are the effects of hydroxyurea?
- Increases baseline Hb values
- Reduces the number of sickle crises
- Reduces episodes of acute chest syndrome
- Prevents pulmonary hypertension
- Saves lives
What is the most common crisis that occurs in sickle cell patients?
Painful (vaso-occlusive) crisis
Aplastic crisis
Parvovirus B19 leads to bone marrow suppression that leads to rapid development of anemia
In B-thalassemia major, alpha globin tetramers are formed and they produce _____ bodies and cause destruction of red cells in periphery and in the marrow
Heinz
Give 2 units of blood to someone with Hb of 6 means they should then have Hb of __
8
What is the cause of stroke in children with sickle cell disease?
NOT atherosclerosis; Due to disordered blood vessels
In sickle cell patients, sepsis may occur from _____ organisms and if undergoing iron chelation therapy are at increased risk of infection with ____ or Vibrio organisms
encapsulated; Yersinia
Other complications in sickle cell disease
- Renal
- Leg ulcers
- Avascular necrosis (AVN)
- Priapism (can lead to permanent erectile dysfunction)
How does hydroxyurea work?
Increases amount of HbF and that decreases the concentration of HbS
In thalassemias, you generally have full deletions of ___ genes or point mutations in ____ genes
alpha; beta
On gel electrophoresis, which Hb is the most positive and which is the most negative
Pos: HbF
Neg: HbA
Beta thalassemias are mainly seen in what part of the world?
Mediterraneans
aa/a-; one alpha deletion is typically _____
asymptomatic
Who can never take hydroxyurea?
Pregnant women
Children with beta thal major either die from iron-overload causing organ failure or _____ ____
overwhelming anemia
B-thalassemias are most common in southern _____
Europe; Greece and Italy
T/F; you can only give a patient with acute chest syndrome an exchange transfusion
False
Pulmonary hypertension occurs in about ___ of sickle cell diseased adults
1/3
What is an effective oral treatment for sickle cell?
Hydroxyurea
Beta thal major and Hemoglobin H disease create what kind of tetramers, respectively?
Alpha4 and Beta4
A patient presents with new infiltrates on CXR and an O2 sat of 82%. How would you treat them?
With antibiotics, oxygen, simple or exchange transfusion
How could you diagnose Beta thalassemias major?
Gel with alpha tetramers present and absence or marked deficiency in HbA
Triggers of painful crisis
- Exercise
- Dehydration
- Infection
- Cold
- Stress
- Menstruation
- Surgery/trauma
- Pregnancy
EDICSMSP; “ED is Complaining of Some Major Sickle Pain”
HbSC= sickle cell _____
disease
Side effect of hydroxyurea
Bone marrow suppression
Children with sickle cell anemia need to be on ______ prophylaxis bc their ____ is dysfunctional
Penicillin; spleen
What is an exchange transfusion?
Put in a catheter and take out old red cells and then replace with new red cells over and over again and titrate to a certain percentage of HbS
What is the predominant chain formed in place of the alpha chain in hydrops fetalis?
Hb Bart’s; gamma4 tetramer
The degree of ____ chain excess determines the severity of a thalassemia
Alpha
What is the only current cure for sickle cell disease?
Bone marrow transplant
What are the 2 complications in transfusing someone with sickle cell disease?
- Iron overload
- Allo-immunization
Main etiologies of acute chest syndrome
- Infection- especially with atypical organisms such as chlamydia or mycoplasma
- Fat embolism from necrotic bone marrow
What blood groups should be avoided in transfusions for African Americans?
C,E, Kell
Autosplenectomy from splenic infarct occurs in sickle cell patients and that leads to increased susceptibility to _______ organsims
encapsulated
In children, rapid and extensive trapping of RBCs in the ____ cause massive enlargement, profound anemia (steep drop in Hb) and hypovolemic shock
spleen
African Americans tend to have which alpha thal?
a-/a-
Sickle cell disease is one of the most frequent causes of pulmonary ________
Hypertension; blood cannot get from the heart to the lungs
aa/– and a-/a-; two gene deletions have ____ anemia and are microcytic with a ___ of around 70
mild; MCV
Alpha tetramers are unstable and lead to intramedullary hemolysis and what else?
Destruction of produced RBCs
What is a simple transfusion?
Giving red cells
HbSS = sickle cell _____
anemia
How would you treat hydrops fetalis?
Intrauterine exchange transfusion and bone marrow transplant
What is the median age for stroke in children with sickle cell disease?
5 years old
Where is the pain during a painful crisis in sickle cell anemia?
Bones and large joints
Sickle cell anemia is a problem of production/destruction
Destruction –> hemolysis
Other possible etiologies of acute chest syndrome
- Sequestration of sickle cells
- Pulmonary infarction
- Hypoventilation from rib infarct, narcotic administration
- Pulmonary edema
Cooley’s Anemia has what arrangement of B-globin genes?
B0/B0; most severe
How do you treat a painful crisis?
Treat the underlying infection if necessary, treat the pain, supplement O2, folate supplement, fluids is dehydrated (watch for pulmonary edema)
Symptoms of Beta thalassemia major may include:
- Anemia
- Splenomegaly
- Bone deformities
- Iron overload associated symptoms (bronze skin, liver failure, endocrine failure)
Hemoglobin H=
B4 tetramers; these form Heinz bodies and cause hemolysis
Patients with this condition are functionally apslenic and more susceptible to infections with encapsulated organisms
Sickle cell anemia
What are 3 common sickle cell crises
- Splenic sequestration crisis
- Aplastic crisis
- Painful (vaso-occlusive) crisis
**SAP
In sickle cell anemia, the cells eventually may become irreversibly _____ and obstruct small blood vessels
sickled
Definition of acute chest syndrome
- Hypoxemia
- New infiltrates on CXR
- New fever, chest pain, dyspnea, or cough
With a stroke, what type of transfusion must be used?
Exchange
______ can worsen acute chest syndrome
Pneumonia
When transfusing, the Hb value should not get about __
10
Hemoglobin H disease will have what kind of cells present on the smear that is produced from Heinz bodies?
Bite cells
In an adult who has alpha thal, what will the gel electrophoresis be like?
It will be normal
HbSC genotype of sickle cell disease causes more intracellular _______ and worsening sickling
dehydration
What is the order of gene switching at the Beta-like globin gene locus?
Gamma –> Delta –> Beta
Salmonella ______ is unique to what disease?
Osteomyelitis; Sickle cell
In a gel electrophoresis of a patient with beta thal trait, there will be an increase in which band?
HbA2 bc there is an upregulation of the delta chain in the absence of the beta chain
