5.5 Normocytic Anemias with Extravascular Hemolysis Flashcards
What is the underlying cause of Hereditary Spherocytosis?
Inherited defect in the RBC cytoskeleton-membrane tethering proteins
Most commonly involving ankyrin, spectrin, Band 3.1
Loss of these allows blebs to form in the membrane that are removed by the spleen and this eventually turns the RBC into a sphere-like shape
These cannot maneuver as well through the spleen and are eventually destroyed leading to anemia
What cells are infected by parvovirus B19?
Erythroid precursors
What are the clinical and lab findings in spherocytosis?
Spherocytes: loss of central pallor
Increased RDW: as RBC’s are chopped up by macrophages, their sizes are going to vary
Increased MCHC: smaller cells have increased concentration of Hb, one of only conditions to have this
Splenomegaly: from macrophage hypertrophy from eating RBC’s
Jaundice: from the increased breakdown of RBC’s, (unconjugated)
Increased risk of bilirubin gallstones
Increased risk of aplastic crisis from B19 virus infection on erythroid precursors
How is spherocytosis diagnosed?
Osmotic fragility test: normal RBC’s can handle a little increase in pressure in cell because they have room to swell, spherocytes do not have room to swell and therefore are prone to burst much easier than a normal cell
How is spherocytosis treated? What is the outcome?
Splenectomy
Anemia resolves, but the spherocytes persist as they are still processed by other components of the reticuloendothelial system
Howell-Jolly bodies emerge on smear (fragments of nuclear material in RBC’s) these are usually removed by the spleen
What is a Howell-Jolly body?
Remnant of nuclear material in an RBC
Usually removed by the spleen, so will show up on smear in patients who do not have a spleen or otherwise have splenic dysfunction
What are the three conditions that cause normocytic anemia with extravascular hemolysis?
Extravascular hemolysis seems to be caused by structural abnormalities in the RBC, so think Spherocytosis and Sickle Cell anemia
Also include hemoglobin C
Explain the genetics of sickle cell anemia
Autosomal Recessive mutation in the Beta chain of Hb
Disease when both beta globin genes are mutated
Mutation is single non-conservative missense that changes glutamic acid (hydrophilic) to valine (hydrophobic)
Gene carried by 10% of Africans
Protective against malaria falciparum
What causes and prevents sickling in sickle cell anemia?
Cause: hypoxemia, dehydration, acidosis
Prevents: HbF protects against sickling, treatment with hydroxyurea increases these levels and can be helpful
Why don’t sickle cell patients present with disease until around 6 months of age?
HbF is protective against sickling for the first few months of life
In sickle cell anemia, the cells sickle continuously and damage the RBC membrane. What are the effects of this?
1) Extravascular hemolysis: reticuloendothelial system removes RBC’s causing anemia, jaundice, and gallstones
2) Intravascular hemolysis: RBC’s with damaged membranes dehydrate leading to decreased haptoglobin and target cells
3) Massive erythroid hyperplasia: hematopoiesis in skull (crewcut appearance) and facial bones (chipmunk facies), hepatomegaly, aplastic crisis with parvovirus B19
What 2 diseases cause massive erythroid hyperplasia leading to crewcut appearance on x-ray and chipmunk facies?
beta-thalassemia major
sickle cell anemia
Which anemias have target cells?
sickle cell anemia
beta-thalassemia minor
What is the most common presenting Sx in sickle cell anemia?
Dactylitis: swollen hands and feet due to vaso0occlusive infarcts in bones
What are the complications of the extensive sickling in sickle cell anemia that leads to vaso-occlusion?
Dactylitis Autosplenectomy Acute chest syndrome Pain crisis Renal papillary necrosis
What is the most common cause of death in kids with sickle cell anemia?
Autosplenectomy puts the kids at risk for infection by encapsulated organisms like S. pneumo and H flu
This is the most common cause of death
Should be vaccinated by 5 years of age
They are also at risk for Salmonella paratyphi osteomyelitis
What is the most common cause of death in adults with sickle cell anemia?
Acute chest syndrome:
Vaso-occlusion in pulmonary circulation
Presents with chest pain, sob, lung infiltrates
Often precipitated by pneumonia
How does vaso-occlusion in sickle cell anemia affect the kidney?
Causes Renal Papillary Necrosis resulting in gross hematuria and proteinuria
What is sickle cell trait? Features of the disease?
Presence of only one mutated Beta globin gene
Generally asymptomatic with no anemia because cells with less than 50% HbS generally don’t sickle in vivo except in the renal medulla
Sickling in the renal medulla happens because of extreme hypoxia and hypertonicity in the region
Microinfarctions in the renal medulla lead to microscopic hematuria at first, followed by an eventual decreased ability to concentrate urine
Lab findings in both sickle cell disease and trait
Sickle cells and target cells only seen in the disease and not in the trait
Metabisulfite screen causes cells with any HbS to sickle so + in both cases
Hb electrophoresis confirms presence of HbS
Disease: 90% HbS, 8% HbF, 2% HbA2, No HbA
Trait: 55% HbA, 43% HbS, 2% HbA2
(notice the huge difference in that trait has mostly HbA and disease has none)
Hemoglobin C
Autosomal Recessive mutation in beta chain of Hb
Glutamic acid traded out for Lysine (HbC has LyCine)
Mild anemia, extravascular hemolysis
HbC crystals on blood smear
