Biochemistry
This tetrameric protein consists of two alpha and two beta globins, each with a heme group containing Fe²⁺.
What is hemoglobin (HbA)?
This first-line disease-modifying medication increases HbF, dilutes HbS, and reduces crises, ACS, transfusions, and mortality in SCD patients.
What is hydroxyurea (hydroxycarbamide)?
This is the ASH-recommended standard for approaching SCD patients presenting with pain, prioritizing pain control before evaluating drug-seeking concerns.
What is "treat first, investigate later"?
This crescent-shaped RBC morphology, formed when HbS polymerizes into rigid tactile rods under deoxygenation, is seen on Isaiah's peripheral blood smear.
What are sickle cells (drepanocytes)?
This chromosome contains the HBB gene responsible for β-globin production and the sickle cell mutation.
What is chromosome 11?
This "relaxed" or "R state" conformation of hemoglobin hides the hydrophobic pocket that valine would otherwise bind to.
What is the oxygenated state?
This intervention reduces blood viscosity and is a first-step acute crisis treatment along with opioid analgesia.
What is IV hydration?
This clinician-led initiative, launched by the ABIM Foundation in 2012, aims to reduce unnecessary, potentially harmful medical tests and treatments.
What is Choosing Wisely?
This acute SCD complication involving chest pain, fever, cough, hypoxia, and pulmonary infiltrates is the leading cause of death in adults with SCD.
What is acute chest syndrome?
This inheritance pattern describes SCD — technically codominant at the biochemical level but classically taught as this form.
What is autosomal recessive?
This rightward-shifting phenomenon decreases oxygen affinity to deliver O₂ to tissues when CO₂ rises, pH drops, temperature rises, or 2,3-BPG increases.
What is the Bohr Effect?
This laboratory test involves a single drop of blood
What is a peripheral blood smear?
Because SCD isn't on the differential based on the patient's appearance, patients from these two regions with vaso-occlusive symptoms are often worked up for kidney stones, appendicitis, or musculoskeletal pain instead.
What are South Asian and Middle Eastern populations?
This visible yellow discoloration of the whites of Isaiah's eyes is caused by elevated bilirubin from RBC breakdown.
What is scleral icterus (jaundice)?
This amino acid substitution at position 6 of the β-globin chain, caused by a GAG → GTG DNA change, produces hemoglobin S.
What is glutamic acid → valine?
In hemoglobin, this property means the binding of one oxygen molecule to a subunit increases the affinity of the remaining subunits for oxygen.
What is cooperative binding?
This DNA-based diagnostic method confirms specific mutations in SCD
What is PCR?
This time frame is the ASH-recommended target for administering opioid analgesia after an SCD patient arrives in the ED with a vaso-occlusive crisis.
What is 30–60 minutes?
Isaiah's RBC lifespan is reduced from the normal ~120 days to this range due to sickled cells being mechanically fragile and rapidly cleared by the spleen and liver.
What is 10–20 days?
This evolutionary phenomenon — where HbAS carriers gain ~50–90% protection against severe malaria — explains why the S allele reaches 25–30% frequency in some parts of Africa.
What is heterozygote advantage (balanced polymorphism)?
Mr. Jackson's cousin's Geotype
What is HbSC?
This is the typical starting daily dose of hydroxyurea in SCD, before titration up to maximum tolerated dose.
What is 15–20 mg/kg/day?
This "traditional red flag" for drug-seeking is actually misleading in SCD because opioid tolerance develops from repeated crises.
What is requesting high doses?
Isaiah's total bilirubin is elevated because the liver becomes overwhelmed by this process
What is hemolysis (RBC breakdown)?
These three mechanisms — accelerated clearance of RBCs, impaired feeding of the parasite, and reduced stickiness in the vasculature — collectively explain how HbAS carriers gain protection against this organism.
What is Plasmodium falciparum?