Normocytic anemias Flashcards
Normal reticulocytes count
1-2%
How should bone marrow properly respond to anemia?
Increase reticulocyte count >3%
How to correct reticulocyte count
RC x (Hematocrit/45)
Clinical findings and lab findings of extravascular hemolysis
Anemia with spenomegaly
Jaundice (due to unconjugated bilirubin)
Increased risk for bilirubin gallstones
Marrow hyperplasia and corrected reticulocyte count >3%
Clinical findings and lab findings of intravascular hemolysis
Hemoglobinemia
Hemoglobinuria
Hemosiderinuria
Decreased serum haptoglobin (free haptoglobin binds Hb)
What causes hereditary spherocytosis?
inherited defect of cytoskeleton-membrane tethering proteins most commonly ankyrin, spectrin or band 3
Pathophys of hereditary spherocytosis?
membrane blebs form and are lost over time leading to loss of membrane and spherocyte formation
Sperocytes are less able to maneuver through splenic sinusoid and are consumed by spenic macrophages results in anemia
clinical and lab findings of hereditary spherocytosis
spherocytes
Increased RDW and MCHC
Splenomegaly, jaundice with unconjugated bilirubin, increased risk for bilirubin gallstones
Increased risk for aplastic crisis
Diagnosis of hereditary spherocytosis
osmotic fragility test
Treatment and subsequent findings of hereditary spherocytosis
Splenectomy - resolves anemia
Spherocytes will persists and Howell-Jolly bodies will emerge
pathophys of sickle cell anemia
Autosomal recessive mutation in Beta chain of hemoglobin - glutamic acid –> valine
HbS polymerizes when deoxygenated; polymers aggregate into sickle cells.
When does sickling occur?
hypoxemia, dehydration, acidosis
treatment of sickle cell
hydroxyurea
RBC membrane damage from sickling and recycling leads to what type of hemolysis?
BOTH extravascular and intravascular
Clinical findings of sickle cell
Massive erythroid hyperplasia – crewcut xray of skull, chipmunk facies
Hepatomegaly from intramedullary hematopoiesis
Risk of aplastic crisis with parvovirus
Complications of extensive sickling in sickle cell disease
vaso-occlusion - dactylitis
Autosplenectomy - fibrotic spleen, increases risk of infection from encapsulated organisms
increased risk of salmonella paratyphi
Acute chest syndrome - vasoocclusion in pulmonary microcirculation
Pain crisis
Renal papillary necrosis
Most common cause of death in adult patients with sickle cell anemia
Acute chest syndrome
Blood findings in sickle cell trait
<50% HbS in RBCs, about 55% HbA, 2% HbA2
No sickle cells on blood smear
Positive metabisulfite screen
What is a metabisulfite screen?
A test used to identify cells with any amount of HbS - cells with any amount will sickle - positive in both disease and trait
What is hemoglobin C?
mutation in Beta chain of hemoglobin - glutaminic acid replaced with lysine
Inheritance pattern of hemoglobin C?
autosomal recessive
Presentation of hemoglobin C
mild anemia due to extravascular hemolysic
Blood smear findings of hemoglobin C
HbC crystals
Paraxysmal nocturnal hemoglobinuria pathophys
AQUIRED defect in myeloid stem cells causing loss of GPI, thus cells are susceptible to complement mediated damage leading to intravascular hemolysis
Normal function of GPI
Ancors DAF to the surface of cells which prevents complement activation
Why does intravascular hemolysis occur at nighttime with paroxysmal nocturnal hemoglobinuria?
Blood becomes mildly acidotic due to shallow breathing
Blood findings in intravascular hemolysis
hemoglobinuria and hemoglobinemia
hemosiderinuria days later
Screening test for Paraxysmal nocturnal hemoglobinuria
sucrose test
Confirmatory test for Paraxysmal nocturnal hemoglobinuria
Acidfied serum test or flow cytometry to detect lack of DAF (CD55)
Main cause of death in paraxysmal nocturnal hemoglobinuria
thrombosis of hepatic, portal or cerebral veins (destroyed platelets release contents leading to thrombosis)
Complications of paraxysmal nocturnal hemoglobinuria
Iron deficiency anemia and AML
G6PD Deficiency inheritance pattern
X-linked
G6PD pathophys
reduced half life of G6PD results in decreased NADPH and thus decreased reduced glutathione –> oxidative injury and intravascular hemolysis
What are the variants of G6PD deficiency?
African variant- mildly reduced half life of G6PD leads to mild intravascular hemolysis with oxidative stress
Mediterranean variant - markedly reduced half life of G6PD leading to marked intravascular hemolysis with oxidative stress
What findings will you seen on histology of someone with G6PD deficiency?
heinz bodies(precipitated Hb) and bite cells
Presentation of G6PD deficiency
back pain and hemoglobinuria hours after exposure to oxidative stress
Diagnosis of G6PD deficiency ?
Heinz preparation (special stain) and enzyme study - must be performed weeks after episode (since effected cells will all be lysed during episode so only normal cells will be left)
Immune hemolytic anemia pathophys
Antibodies produced against RBCs
IgG - extravascular hemolysis
IgM - intravascular hemolysis
IgG mediated immune hemolytic anemia pathophys
IgG binds RBcs in warmer temps (central body) leading to consumption by splenic macrophages
What is igG mediated immune hemolytic anemia associated with?
SLE
CLL
certain drugs
treatment of igG mediated immune hemolytic anemia
cessation of offending agent, IVIG, steroids, if necessary a splenectomy
igM mediated immune hemolytic anemia pathophys
igM binds RBCs and fixes complement in colder temps (extremities) –> RBCs inactive complement but the residual C3b causes opsonization and consumption by splenic macrophages
Excessive complement activation may lead to intravascular hemolysis
what is igM mediated immune hemolytic anemia associated with?
Mycoplasma pneumonia and infectious mononucleosis
Direct coombs test
Confirms presence of antibody or complement coated RBCs
Indirect coombs test
confirms presence of antibodies in patients serum
What does parvovirus B19 infect?
progenitor red cells — halts erythropoiesis
What will a biopsy revel in aplastic anemia?
Empty, fatty bone marrow
What is myelophthisic process?
pathologic process that replaces bone barrow (eg metastatic cancer)
Impairs hematopoiesis -> pancytopenia
