Ch5 - 5) Normocytic anemia with predominant extravascular hemolysis Flashcards
What are the normocytic anemias with predominant extravascular hemolysis?
1) hereditary spherocytosis 2) Sickle cell anemia 3) Hemoglobin C
What is hereditary spherocytosis?
Inherited defect of RBC cytoskeleton-membrane tethering proteins
What does hereditary spherocytosis most commonly involve?
spectrin, ankyrin, or band 3.1
What is seen in hereditary shperocytosis?
membrane blebs are formed and lost over time
In hereditary spherocytosis what happens due to loss of the membrane?
It renders cells round (spherocytes) instead of disc-shaped.
How does hereditary spherocytosis lead to anemia?
Spherocytes are less able to maneuver through splenic sinusoids and are consumed by splenic macrophages, resulting in anemia.
What do the clinical and laboratory findings for hereditary spherocytosis include?
1) Spherocytes with loss of central pallor, 2) increased RDW and increased mean corpuscular hemoglobin concentration (MCHC) 3) Splenomegaly, jaundice with unconjugated bilirubin, and increased risk for bilirubin gallstones (extravascular hemolysis) 4) Increased risk for aplastic crisis with parvovirus B19 infection of erythroid
How is hereditary spherocytosis diagnosed?
by osmotic fragility test, which reveals increased spherocyte fragility in hypotonic solution
What is the treatment for hereditary spherocytosis?
splenectomy; anemia resolves, but spherocytes persist and Howell Tolly bodies emerge on blood smear
What are Howell Tolly bodies?
fragments of nuclear material in RBCs – appears on blood smear
What is sickle cell anemia?
Autosomal recessive mutation in beta chain of hemoglobin; a single amino acid change replaces normal glutamic acid (hydrophilic) with valine (hydrophobic).
Who carries the gene for sickle cell anemia?
it is carried by 10% of individuals of African descent, likely due to protective role against falciparum malaria.
When does sickle cell disease arise?
When two abnormal beta genes are present; results in >90% HbS in RBCs
What causes the formation of the sickle cell structure?
HbS polymerizes when deoxygenated; polymers aggregate into needle-like structures, resulting in sickle cells
When is there increased risk of sickling?
hypoxemia, dehydration, and acidosis.
Is sickle cell seen at birth?
HbF protects against sickling; high HbF at birth is protective for the first few months of life.
What is the treatment for sickle cell anemia?
hydroxyurea increases levels of HbF
In sickle cell anemia, what happens to cells as it passes through microcirculation?
The cells sickle and de-sickle while passing through the microcirculation, resulting in complications related to RBC membrane damage.
How does sickle cell anemia interact with the reticuloendothelial system?
intravascular hemolysis where the reticuloendothelial system removes RBCs with damaged membranes, leading to anemia, jaundice with unconjugated hyperbilirubinemia, and increased risk for bilirubin gallstones.
How does sickle cell anemia lead to decreased haptoglobin and target cells on blood smear?
Intravascular hemolysis where RBCs with damaged membranes dehydrate, leading to hemolysis with decreased haptoglobin and target cells on blood smear
Massive erythroid hyperplasia ensues in sickle cell anemia resulting in what?
1) Expansion of hematopoiesis into the skull (‘crewcut’ appearance on x-ray) and facial bones (‘chipmunk fades’). 2) Extramedullar hematopoiesis with hepatomegaly 3) Risk of aplastic crisis with parvovirus B19 infection of erythroid precursors
What does irreversible sickling lead to?
complications of vaso-occlusion
What are the complications of vasso-occlusion resulting from irreversible sickling?
1) Dactylitis 2) autosplenectomy 3) acute chest syndrome 4) Pain crisis 5) Renal papillary necrosis
What is dactylitis?
swollen hands and feet due to vaso-occlusive infarcts in bones; common presenting sign in infants
What is autosplenectomy, and what are the consequences?
shrunken, fibrotic spleen. Consequences include: 1) Increased risk of infection with encapsulated organisms such as Streptococcus pneumoniae and Haemophilus influenzae (most common cause of death in children); affected children should be vaccinated by 5 years of age. 2) Increased risk of Salmonella paratyphi osteomyelitis 3) Howell-Jolly bodies on blood smear
What is the most common cause of death in children sickle cell patients?
autosplenectomy
What is acute chest syndrome?
vaso-occlusion in pulmonary microcirculation
What does acute chest syndrome present with?
Presents with chest pain, shortness of breath, and lung infiltrates
Acute chest syndrome is often precipitated by?
Often precipitated by pneumonia
What is the most common cause of death in adult sickle cell patients?
Acute chest syndrome
Renal papillary necrosis results in what?
gross hematuria and proteinuria
What is the sickle cell trait?
It is the presence of one mutated and one normal beta chain;
What does presence of the sickle cell trait results in?
<50% HbS in RBCs (HbA is slightly more efficiently produced than HbS)
How does the sickle cell trait present?
Generally asymptomatic with no anemia; RBCs with < 50%, HbS do not sickle in vivo except in the renal medulla.
When would sickling occur in the sickle cell trait?
Extreme hypoxia and hypertonicity of the medulla cause sickling,
In the sickling trait what happens?
microinfarctions leading to microscopic hematuria and, eventually, decreased ability to concentrate urine,
What are the laboratory findings for the sickle cell trait?
1) Blood smear shows no sickle cells and target cells (unlike sickle cell disease) 2) Metabisulfite screen causes cells with any amount of HbS to sickle; positive in both disease and trait 3) Hb electrophoresis confirms the presence and amount of HbS.
What does Hb electrophoresis show in sickle cell disease?
90% HbS, 8% HbF, 2% HbA2 (no HbA)
What does Hb electrophoresis show in sickle cell trait?
55% HbA, 43% HbS, 2% HbA2
What is hemoglobin C?
Autosomal recessive mulalion in beta chain of hemoglobin
What amino acid is affected in hemoglobin C?
Normal glutamic acid is replaced by lysine
How common is Hemoglobin C?
It is less common than sickle cell disease
What does hemoglobin C present with?
presents with mild anemia due to extravascular hemolysis
In Hemoglobin C what is seen on blood smear?
Characteristic HbC crystals are seen in RBCs on blood smear
