The Alpha and Beta of it all
Take it to the cellular level
It's clinic time
Name that Mutation!
It's a moon! It's a banana! No it's a sickle!
100
One of the Simpsons characters shares a name with this Mutated hemoglobin type. It leads to a complete lack of alpha chains leaving none to pair with gamma chains leading to a severe fetal anemia for the fetus.
For 100 bonus points, what type of thalassemia does this cause?
What is Hemoglobin Barts?
Alpha chains are an integral part of making fetal hemoglobin. It is often fatal before birth without in utero transfusions.
Leads to hydrops faetalis
This is type of alpha thalassemia
100
This type of anemia is associated with crescentic erythrocytes and named so for their shape.
What is Sickle Cell disease?
100
Name three possible acute manifestations of Sickle cell disease (SCD).
Possible answers: infections, aplastic crisis, splenic sequestration, acute pain crisis due to vaso-occlusive pain, CVA, acute chest syndrome, kidney infarction, bone infarction, dactylitis, MI, priapism, VTE
100
This hemoglobin mutation Hb ___ can be inherited homozygously or can be coinherited with a different beta globin variant.
The resulting hemoglobin creates polymers when it is deoxygenated and this leads to hemolysis, vascular occlusion
Hb S
The resulting hemoglobin creates polymers when it is deoxygenated and this leads to hemolysis, vascular occlusion, pain crises, and chronic organ damage.
100
This is the average life expectancy for a patient that has sickle cell disease.
What is ~50 years?
More accurately 52.6 years: Males 49.3 years and females 55 years
200
Alpha thalassemia is characterized by reduced production of ____ chains and accumulation of excess ____ chains.
Both needed for points
Alpha chains and accumulation of excess beta chains
Phenotypic severity increases with the loss of each of the four alpha alleles.
200
Thalassemias are most often associated with this type of anemia? You would expect to find this MCV on a CBC panel.
microcytic anemia
low MCV
200
A 22yo African American female gives birth to a daughter. On newborn screens, her daughter is found to have sickle cell trait.
You explain to her that:
A: her child has two defective alpha chain alleles
B: her child will may suffer from acute pain crises requiring hospitalization for treatment
C: Her child will most likely be asymptomatic and live a normal lifespan
What is C?
Her child will be asymptomatic and live a normal lifespan
Prevalence of sickle cell Trait: African American (7-10%), Sub-Saharan Africa (~30%), Latin America (0.2-6.3%), India (up to 13%), Middle East (0.2-27%), Greece (1.5-7.5%), Caribbean (4-10%)
This is a test part of routine newborn screening and often identified early in the US due to this, however, some immigrants or those who did not undergo routine screening may be unaware of their status.
There is increased risk of very rare life-threatening complications: medullary renal carcinoma, rhabdomyolysis, sudden death with prolonged physical activity, splenic infarction in high altitudes
Individuals are at increased risk of dehydration
Typically, individuals with sickle cell trait have approximately 50 to 60 percent Hb A and 35 to 45 percent Hb S
200
This hemoglobin variant causes mild hemolytic anemia, splenomegaly and jaundice. There is low MCV and it is characterized by hexagon-shaped crystals in red blood cells.
What is hemoglobin C?
200
The most common cause of death in a patient with sickle cell disease is ______ ______ _________. Pt's may experience fever, hypoxemia, wheezing, respiratory distress, chest pain, hypoxemia. Xray may show pulmonary infiltrates. This condition affects about 1/2 of patients that have SCD and cause is often multi-factorial.
What is acute chest syndrome?
Management: may include pain treatment, oxygen, incentive spirometer, transfusions, antibiotics.
Risk is reduced with prophylactic antibiotics and immunizations to decrease risk of infection, hydroxyurea compliance.
300
This type of thalassemia is characterized by inclusions on a BCB prep.
What is Alpha Thalassemia?
The inclusion bodies (aka Heinz bodies) seen in red blood cells are thought to be precipitated subunits of the excess beta chain subunits.
Heinz bodies are also seen in G6PD deficiency, chronic liver disease and NADPH deficiency.
300
This is a blood smear from a patient with Hb H disease. The smear shows microcytic red cells, cell fragments, and target cells. Each is delineated by a type of arrow: arrowhead, dashed arrow or arrow. Which arrow type corresponds to each cellular finding?
What type of thalassemia is associated with this?
arrowhead: target cell
dashed arrow: microcytic red blood cell
arrow: red cell fragments
This is an alpha thalassemia
300
A mother of a 4 month old male patient presents to your office concerned that her child is in pain. Her son has SCD and she states that she thinks he is having a pain crisis.
You correctly advise her that infants are not effected by SCD symptoms for this initial amount of time after birth.
What is 6 months?
300
This alpha thalassemia causing hb variant, Hb ____ has variable presentations. Most often the clinical severity is most similar to thalassemia intermedia, however, some patients become transfusion dependent. They are susceptible to forming Heinz bodies (inclusions) and more severe phenotypic presentations are seen in certain variants including Hb constant spring type.
What is Hb H or hemoglobin H disease?
300
While gene therapy is being explored as potential treatment/cure for SCD, the only known cure is ____ _____ _________.
bone marrow transplant
400
An 8 month old patient who had positive finding on newborn screening is found to have microcytic anemia and and labs show increased levels of hemoglobin A2 which did not occur until after 6 months of age. You see in her chart that she was found to have this type of thalassemia on screening.
Beta thalassemia
400
This hereditary illness is caused by a mutation on chromosome 11 in the hemoglobin Beta gene.
Sickle cell disease
400
Your 11 yo male patient presents to the office for a well visit. He was diagnosed with a hemoglobinopathy when he was about 2 years old. On your exam, you note that he has classic skeletal findings seen in his face that are associated with the condition he has. You see frontal bossing, maxillary expansion, saddle nose, and depressed cranial vault. He reports that another child recently told him that he resembled a chipmunk. You console the child, and then explain that his facial features are most likely due to having _____ _____________ _______.
Beta thalassemia major or intermedia are both acceptable
400
Patients with SCD are at significantly increased risk of infection from these types of bacteria.
Name two such bacteria.
What is encapsulated orgnaisms?
Streptococcus pneumoniae (pneumococcus), neisseria meningitidis (meningococcus), H influenzae
Pts treated with prophylactic PCN and pneumococcal vaccinations
400
Your 18 yo patient with SCDnpresents for follow up in office. he has not had a pain crisis or acute chest syndrome in more than 6 moths. He states that after his most recent painful crisis for which he was in the hospital nearly a week, he understood the importance of taking his prescribed preventive medicine you had prescribed. This medication improves survival and decreases risk of complication for patients with SCD. Name the medication.
Also, this medication has a black box warning. Name either increased risk possible with this medication from the black box warning.
Each part of this question is worth 200 pt
Hydroxyurea (AKA siklos or droxia):antineoplastic agent
clinical response 3-6 months after initiation
This is a selective ribonucleoside diphosphate reductase inhibitor. It holds cells in the G1/S phase of growth
It increases red blood cell hb F levels, RBC water content, and changes the adhesive ability of RBC to endothelium.
When starting therapy, 15mg/kg daily; CBC at baseline then every two weeks. increases should occur at 5/g/kg/day about every 12 weeks as tolerated with goal of 35mg/kg daily
Black Box: May cause severe myelosuppresion and should not be given with decreased bone marrow function. When initia
500
This transfusion dependent anemia was previously known as Colley's anemia or Mediterranean anemia.
These individuals have little to no ___ globin chains production or hb A.
Transfusion dependent beta thalassemia or previously beta thalassemia major
little to no beta globin chains
Symptoms typically manifest between 6months to 12 months of age.
500
Pt's with thalassemia may experience weakness, fatigue, abnormal swelling, slowed growth, iron overload, pallor. This is a disorder of hemoglobin. Hemoglobin plays this important role in the body which is not optimal when there are mutations.
What is transferring oxygen from lungs to the tissues of the body and transferring CO2 from cells to lungs for expulsion from the body?
500
You are meeting with a 23 yo female who has sickle cell disease. She would like to become pregnant and is discussing reproductive planning. Her male partner is negative for hemoglobinopathies on recent testing during preconception counseling. You explain to her possible complications that can occur during pregnancy for which she is at increased risk. Name 3 possible complications.
IUGR, low birth weight, fetal demise, infections, preeclampsia, thromboembolism, acute chest syndrome.
This is considered a high risk pregnancy and patient should also be seeing maternal fetal medicine preferably clinician with SCD expertise. Pt's may require prophylactic transfusions, postpartum anticoagulation
500
A patient is seen in office and found on vitals to have SpO2 85%. You send the patient to the hospital for further evaluation. With further evaluation they are determined to have splenomegaly. They are correctly diagnosed as Hb ____ variant.
What is Hb KOLN?
This is an unstable hemoglobin variant. Effected red blood cells are sequestered in the spleen and patients often have improvement after splenectomy with increased survival of RBCs.
Pt's may also present with darkened urine, jaundice from chronic hemolysis.
500
A 16 yo patient that has sickle cell disease presents for annual wellness visit. She asks you to go through a list from the internet she found to determine which are correct for increasing risk of a sickle cell crisis.
The choices are:
A. Infection E. Eating shellfish
B. Dehydration F. Hemorrhage
C. Low altitudes G. Hypoxia
D. strenuous exercise
You know that there are five correct answers from these choices. 100 points per answer. You correctly tell her: ____, _____, _____, ______, ______ all can increase her risk of sickle cell crisis.
A infection, B dehydration, D strenuous exercise, F hemorrhage, G hypoxia