Hemoglobinopathies and Sickle Cell Disease Flashcards
HbA: 97%
HbA2: 2%
HbF: 1%
HbS: 0%
HbC: 0%
Normal
HbA: 92%
HbA2: 5%
HbF: 3%
HbS: 0%
HbC: 0%
Beta-thalassemia trait (A/B+ or A/B0)
HbA: 50%
HbA2: 3%
HbF: 2%
HbS: 45%
HbC: 0%
Sickle Cell Trait
HbA: 0%
HbA2: 2%
HbF: 5%
HbS:93%
HbC: 0%
HbSS
HbA: 0%
HbA2: 15%
HbF: 10%
HbS: 75%
HbC: 0%
HSB0
HbA: 37%
HbA2: 5%
HbF: 2%
HbS: 55%
HbC: 0%
HbSB+
HbA: 0%
HbA2: 2%
HbF: 1%
HbS: 45%
HbC: 42%
HbSC
HbA: 0%
HbA2: 2%
HbF: 3%
HbS: 0%
HbC: 95%
HbCC
HbA: 55%
HbA2: 2%
HbF: 1%
HbS: 0%
HbC: 43%
HbC Trait (AC)
HbA: 0%
HbA2: 2%
HbF: 40%
HbS: 58%
HbC: 0%
HbS/HPHbF
*Hereditary Persistence of HbF
What is Hb Barts?
Total absence of alpha globins in utero, meaning Hb is four gamma globins. It has high oxygen affinity causing hypoxia.
What is Hb H?
(a-/–)
Major absence of alpha globins after birth, meaning four beta globins conglomerate. This leads to hemolysis and ineffective erythropoiesis. It is transfusion dependent.
Genotype, Hb electrophoresis, and clinical manifestation of alpha thalassemia minima
(-a/aa) Clinically silent
Hb electrophoresis is normal
Genotype, Hb electrophoresis, and clinical manifestations of Alpha thalassemia trait?
(a-/a-) or (aa/–)
Clinically mild hypochromic, microcytic anemia
Hb electrophoresis is normal
What’s the difference between deletional Hb H disease and non-deletional?
Non-Deletional (Hb Constant Spring) is much more severe anemia
What’s the difference between B+ and B0 thalassemia?
B+ is reduced expression and B0 is absence of expression
What is the clue on Hb electrophoresis that the answer is Beta thalassemia trait?
HbA2 >3.5%
What are clinical complications of Beta thalassemia major?
Obviously RBC transfusions
Osteoporosis
Splenomegaly
High output heart failure
pHTN
Thrombotic events
Leg ulcers
A patient has transfusion dependent beta thalassemia and significant splenomegaly. What effect would a splenectomy have?
Increase risk of thrombosis, silent cerebral infarcts, pHTN, leg ulcers, infection, and iron endocrinopathies
What is Betibeglogene autotemcel?
Gene therapy for beta thalassemia that works like CAR-T. ~90% achieve transfusion independence
What is exagamglogene autotemcel?
CRISPR gene-editing cell therapy that targets BCL11A to raise HbF levels. 91% transfusion independence
What are indications for chronic RBC transfusions in TDT?
Hgb <7 on 2 occasions, more than 2 years apart or
less severe anemia but symptomatic
What is the goal hb in chronic transfusions for TDT?
9.5-10.5
Hemoglobin E homozygosity has what clinical manifestations?
Asymptomatic, minimal anemia, low MCV
What hemoglobin migrates withA 2 and C in alkaline electrophoresis and migrates with A and A2 in acid on agarose gel?
Hemoglobin E
What hemoglobin migrates like HbS on alkaline electrophoresis and migrates like HbA ona cid electrophoresis
Hemoglobin Lepore
What is the clinical manifestations of Hb Lepore?
Moderate-severe anemia
What clinical manifestation is more common in HbSC disease compared to SCD?
Proliferative retinopathy
What is the phenotype of Sickle cell/alpha thalassemia?
Milder phenotype, milder anemia. Reduced incidence of leg ulcers, but increased incidence of osteonecrosis
What are clinical complications of sickle cell trait?
Not a disease. normal life span. but there are increased risk of renal medullary carcinoma and UTI in pregnancy
When is a RBC transfusion NOT indicated in treatment of sickle cell disease?
Uncomplicated acute pain
Clinical manifestations of acute chest syndrome
Fever and/or respiratory symptoms with new pulmonary infiltrate on CXR
Treatment of Acute chest syndrome?
Simple transfusion for those with Hb >2 below baseline, lobar involvement, hypoxemia, increasing O2 needs. Exchange transfusion for severe
Secondary prevention treatment options for ACS in sickle cell? (2)
Hydroxyurea
Chronic transfusions
What screening test done in children predicts an increased risk of ischemic stroke in SCD?
Abnormal transcranial dopppler
Management of acute ischemic stroke in SCD (2)
Exchange transfusion
Aspirin
2 treatment options for prevention of acute ischemic stroke in SCD?
Chronic transfusions and hydroxyurea
Primary prevention for acute ischemic CVA for children with abnormal transcranial doppler
Chronic transfusions to keep HbS <30% and Hb >9 for 1 year. Can switch to hydrea after 1 year
or hydrea
Clinical manifestation of hyperhemolysis
Pain, marked hemolytic anemia often occurring within 1 week after RBC transfusion. Can be DAT positive or negative, low reticulocyte count
Management of hyperhemolysis
IVIG
Steroids
You see an inpatient with SCD admitted for pain crisis, on opiates. Has splenomegaly but no signs of ACS. After RBC transfusion, spleen shrinks and she is in hypovolemic shock. Diagnosis and management?
Splenic sequestration crisis
RBC transfusion
Splenectomy
painless hematuria or flank pain with hematuria in SCD should make you think of what complication?
Renal papillary necrosis
Patient with SCD presents witha cute protrusion of R eye, pain, lid/orbital edema. Diagnosis and treatment?
Orbital infarction.
IV fluids, pain control, steroids
What is prognostic for patients with SCD and pHTN?
Abnormal TR jet velocity are at increased risk of mortality, should get RHC
Indications (7) for simple RBC transfusion
Symptomatic
Pre-operative
Transient RCA
Splenic sequestration
Hepatic sequestration
Mild ACS
Pain crises
At what hemoglobin level do you not increase above when transfusing a patient with SCD?
10
Goal HbS and Hgb for exchange transfusions
HbS <30%
Hgb >10
Indications for exchange transfusions in SCD (5)?
Acute stroke
ACS
Multiorgan failure
Intrahepatic cholestasis
Ocular vaso-occlusive events
Mechanism of hydroxyurea
Increases HbF production, diluting HbS, vasodilation by NO release, improves RBC hydration, decreasing sickling, decreases adhesiveness of neutrophils
Goal HbF level of hydroxyurea
HbF >20%
Indications for hydroxyurea in SCD (3)
HbSS or HbS/B0 with severe symptoms: (>3 episodes/year, >3 ACS episodes in 2 years, severe or recurrent ACS)
Anemia w Hb <7
Other complications like pHTN like priapism
Mechanism of Voxeletor and clinical result
Small molecule that binds to alpha chains of Hgb and keep it in relaxed state, resulting in increased affinity for oxygen and then an increased Hgb. Has not been proven to result in reduced clinical consequences
Mechanism of action and clinical benefit of Crizanlizumab
IV administered P-selectin antibody that reduces frequency of vaso-occlusive crises
What type of patient with SCD would benefit most from Voxeletor?
Low baseline hemoglobin
What type of patient with SCD would benefit most from Crizanlizumab?
Frequent pain crises despite HU
Mechanism of action of L-glutamine oral powder and clinical effect
Anti-oxidant increasing availability of reduced glutathione, reducing susceptibility to oxidative stress. Found to reduce hospitalizations, fewer days in hospital, fewer ACS episodes
What is goal Hgb prior to surgery for patients with SCD?
Hgb 10 decreases complications
Indications for pre-operative exchange transfusion?
Prior to high-risk surgeries like intracranial CVS, intrathoracic, abdominal surgeries, or prolonged surgeries
What treatments for SCD cannot be given to a pregnant patient?
Hydroxyurea
