Normocytic Anemias with Predominant Extravascular Hemolysis Flashcards
An inherited defect in the RBC cytoskeleton membrane tethering proteins…
Hereditary Spherocytosis
What are the 3 most common cytoskeleton tethering proteins involved in hereditary spherocytosis?
Ankyrin
Spectrin
Band 3
Why does anemia result from hereditary spherocytosis?
Spherocytes are formed due to membrane blebing—this makes the RBCs less able to maneuver through splenic sinusoids, which leads to their destruction by the spleen
What is seen on the blood smear of a patient with hereditary spherocytosis?
Spherocytes with loss of central pallor
With respect to RDW and mean corpuscular hemoglobin concentration (MCHC), how does hereditary spherocytosis affect these values?
Increases both
MCHC—only disease where you’ll see this elevated EXCEPT for autoimmune anemia
What are the two most common clinical findings seen with hereditary spherocytosis?
Splenomegaly
Jaundice with unconjugated bilirubin
Patients with hereditary spherocytosis are at an increased risk of developing _______ due to extravascular hemolysis?
Bilirubin gallstones
Patients with hereditary spherocytosis are at an increased risk of ________ infection to the erythroid precursors, which causes what to occur?
Parvovirus B19—causing aplastic crisis
What test is used to diagnose hereditary spherocytosis?
Osmotic fragility test—reveals increased spherocyte fragility in hypotonic solution
What is the treatment for hereditary spherocytosis?
Splenectomy
Even after splenectomy to treat hereditary spherocytosis, what still remains and what is seen on blood spear?
Spherocytes still remain because spleen is not there to destroy them
Howell-Jolly bodies seen on blood smear due to left over fragments of DNA in RBCs, usually removed by spleen
Autosomal recessive mutation in B chain of hemoglobin—caused by a single amino acid change, glutamic acid→ valine…
Sickle cell anemia
Patients who are carries of sickle cell anemia have protection against________.
Falciparum malaria
What occurs to the RBCs causing them to sickle, in sickle cell anemia?
HbS polymerizes when deoxygenated—causing aggregation of the polymerized HbS→ sickled cells
What 3 things increase the risk of sickling of RBCs in sickle cell anemia?
Hypoxemia
Dehydration
Acidosis
What type of hemoglobin is protective against sickling?
HbF
What drug is given to increase HbF and allowing protection from sickling of cells seen with sickle cell anemia?
Hydroxyurea
Extravascular hemolysis seen with sickle cell anemia involves the reticuloendothelial system removing RBCs with damaged membranes. What are the clinical manifestations seen with this and what are these patients at an increased risk of developing?
Anemia
Jaundice with unconjugated hyperbilirubinemia
Increased risk for bilirubin gallstones
Intravascular hemolysis is seen with sickle cell anemia and is caused by dehydration of damaged membranes of the RBCs. What scavenger is decreased during this process and what appears on blood smears of these patients?
Haptoglobin decreases
Target cells are seen on blood smears
What are the 3 major effects of erythroid hyperplasia seen with sickle cell disease?
1) Expansion of hematopoiesis into the skull and facial bones
2) Extramedullary hematopoiesis with hepatomegaly
3) Risk of aplastic crisis with parvovirus B19 infection to erythroid precursors
Expansion of hematopoiesis into the skull and facial bones are seen with erythroid hyperplasia occurring with sickle cell disease. What are the two clinical findings caused by this expansion?
Skull→ crewcut appearance on XRAY
Facial bone→ chipmunk facies
Swollen hands and feet caused by vaso-occlusive infarcts in bones…
Dactylitis
Patient with sickle cell disease who have extensive sickling are at risk of developing autosplenectomy. This will leave the patient more susceptible to what type of infections?
Infection with encapsulated organisms such as:
- Streptococcus pneumoniae
- Haemophilus influenzae
Also at increased risk of Salmonella paratyphi osteomyelitis
What will be on a blood smear of patients with autosplenectomy caused by sickle cell disease?
Howell-Jolly bodies
A patient with a history of sickle cell anemia presents with chest pain, shortness of breath and lung infiltrates. What is the most likely diagnosis?
Acute chest syndrome caused by vaso-occlusion in pulmonary microcirculation due to the sickled RBCs
Acute chest syndrome is the most common cause of death in _____ patients with sickle cell disease.
Adult
What results from renal papillary necrosis caused by extensive sickling seen with sickle cell disease?
Gross hematuria and proteinuria
Sickle cell trait is caused by the presence of what?
One mutated and one normal B chain–
Why are patient with sickle cell trait most likely to be asymptomatic with no anemia?
Because RBCs with
What are the two distinctive abnormal cells are found on blood smear with sickle cell disease?
Sickle cells and target cells
What screening test is performed that causes HbS cell to sickle in both sickle cell disease and sickle cell trait?
Metabisulfite screen
What test is used to confirm the presence and amount of HbS in sickle cell disease?
Hb electrophoresis
What is the hemoglobin distribution seen with sickle cell disease?
HbS—90%
HbF—8%
HbA2—2%
NO HbA
What is the hemoglobin distribution seen with sickle cell trait?
HbA—50%
HbS—43%
HbA2—2%
An autosomal recessive mutation in the B chain of hemoglobin caused by glutamic acid being replaced by lysine…
Hemoglobin C
How does Hemoglobin C present?
Mild anemia caused by extravascular hemolysis
What are the distinctive cells seen on a blood smear of a patient with Hemoglobin C?
Characteristic HbC crystals seen within RBCs
