Wk 1 Hemoglobinopathies Flashcards
When is an urgent blood transfusion required for patients w/ iron deficiency anemia?
- pregnant female w/ Hb <7mg/dL to prevent fetal M&M
- patients w/ severe anemia, Hb <7mg/dL or 8-10 mg/dL for those w/ acute coronary syndrome
How does iron deficiency anemia classically present?
- decreased Hb
- microcytic, hypochromatic RBCs
- decreased iron stores
What groups are at a higher physiologic risk for iron deficiency?
- breastfed infants w/o iron supplementation
- toddlers & young children w/ high intake of cow’s milk
- female adolescents in growth spurt
- pregnant females
What are 3 other common causes of iron deficiency?
- dietary insufficiency
- malabsorption
- acute or chronic blood loss
What signs might be seen in iron deficiency w/o anemia?
neurocognitive symptoms
How is iron deficiency anemia defined by labs?
- Hb level lower than 2 SD below mean
- MCV <80fL (a late finding)
- elevated RBC distribution width
- decreased reticulocyte count
- decreased ferritin (lower than 15 ng/mL is single, most highly suggestive result)
- decreased serum iron
- increased TIBC
- decreased transferrin
Signs and symptoms of any anemia and specifically iron deficiency
- reflect hypoxic functioning: fatigue, dyspnea, headache
- infants & toddlers - irritability, lethargy, feeding difficulties
- iron - pagophagia
- may be asymptomatic
What is a typical iron supplement?
ferrous sulfate: 60-120 mg/day, kids 3-6 mg/kg/day
What other diseases might cause iron malabsorption?
- celiac disease
- H. pylori colonization
- IBD
What is a commonality of Sickle Cell Disease and Thalassemias?
Both have increased RBC destruction (hemolysis)
What is the major defect in Sickle Cell Disease?
Structurally abnormal globins
What is the major defect in Thalassemias?
Deficient globin synthesis
What is Sickle Cell Disease caused by?
Hereditary hemoglobinopathy caused by a point mutation in beta-globin -> polymerization of deoxygenated hemoglobin
What happens in Sickle Cell Disease?
Red cell distortion, hemolytic anemia, microvascular obstruction, and ischemic tissue damage
What hemoglobins are in adult, fetal, and sickle cell disease?
Adult: HbA
Fetal: HbF
Sickle Cell Disease: HbS
What characterizes HbS?
Missense mutation in the beta-globin gene. Charged glutamate residue replaced w/ hydrophobic valine (G->V)
What is the term for heterozygous HbS?
Sickle cell trait, mostly asymptomatic
How many individuals in the US are homozygous for the sickle mutation?
70-100k
- almost all Hb in the red cell is HbS (alpha2, beta^2)
How did HbS arise?
It has risen independently in at least 6 areas in Africa where malaria is endemic. Parasite densities are lower in infected, heterozygous HbAS children and they are much less likely to have severe disease or to die
What 2 ideas could explain the benefit of HbS for malaria?
- Intracellular parasites consume O2, which decreases pH. Both promote sickling of AS red cells, which may be cleared faster by splenic and hepatic phagocytes faster, decreased parasite load.
- Sickling impairs formation of membrane knobs containing a PRO made by the parasite called PfEMP-1 that may -> adhesion of infected red cells to endothelium and may have role in cerebral malaria
What other diseases might protect against malaria?
G6PD deficiency and thalassemia
How might G6PD deficiency and thalassemia protect against malaria?
By increasing clearance and decreasing adherence of infected red cells
What causes the major pathologic manifestations of SCD?
HbS molecules stack into polymers when deoxygenated -> cytosol becomes viscous gel -> sickle shape
What variables affect the rate and degree of sickling?
- interaction of HbS w/ other types of Hb (HbC, HbSC, HbF)
- Mean Cell Hemoglobin Concentration (MCHC): increases w/ dehydration of cells -> sickling. Decreased MCHC condition decrease disease severity
- Intracellular pH: decrease pH -> reduced O2 affinity of Hb -> increased fraction of deoxygenated HbS -> greater sickling
- Red cell transit time through microvascular beds: sluggish blood flow and inflammation -> sickling and occlusion
- Exposure to hypoxia