normocytic anemia Flashcards
what is a hypoproliferative anemia and what are the subtypes?
- normocytic anemia with low reticulocyte count
- disease/inflammation (2/3)
- aplastic anemia
- chronic renal failure
- medications
- infections
- leukemias
- myodysplastic syndromes
- marrow infiltrative malignancy
- endocrine
disease/inflammation pathophys
- increased immune activation and release of cytokines
- hepcidin - decreases iron absorption and release of iron from macrophages “functional iron deficiency”
- decreased EPO, erythropoiesis, RBC lifespan
contrast iron deficiency anemia with anemia of chronic disease
in chronic disease, ferritin and transferrin and Tsat are not affected much. marrow stores remain high and there are inflammatory markers
characteristics of aplastic anemia
- diminished hematopoietic precursors due to injury to pluripotent stem cells
- pancytopenia
- empty bone marrow (aplasia)
aplastic anemia involving purely RBCs is called
pure red cell aplasia
causes of aplastic anemia
- primary idiopathic Franconi Anemia (congenital) - secondary drug side effect (anticonvulsants, antibiotics, ASA) chemo radiation benzene viruses - parvo, EB
aplastic anemia diagnosis
- blood smear for pancytopenia
- marrow smear for hypocellularity, high fat content
aplastic anemia usually accompanied by
leukopenia and thrombocytopenia which are more clinically serious
aplastic anemia treatment
- bone marrow transplant
- anti-thymocyte globulin (ATG
- EPO, G-CSF
in chronic kidney disease, at what renal function percentage does anemia usually present?
30%
pathophys of anemia of chronic kidney disease
- decreased renal function means decreased renal cortical cells and decreased EPO
- RBC rigidity may mean shorter lifespan
other causes of hypoproliferative anemia
- drugs - chemo, antibiotics
- infection
- malignancy - tumor into bone marrow
- endocrine - hypothyroidism, panhypopituitarism, low T
what is the first question we ask when we have normocytic anemia and high reticulocyte count?
is there bleeding?
definition of hemolysis
early destruction of red blood cells, usually before 100 days
what are schistocytes and spherocytes and when are they seen?
schistocytes - fragments of destroyed RBCs in circulations
spherocytes - RBCs with damaged membranes that take on a spherical look
both are seen in intravascular hemolysis
explain the diagnostic significance of haptoglobin and hemoglobin in hemolytic anemia
haptoglobin binds free hemoglobin released from lysed RBCs. in severe anemia, the haptoglobin will all be bound so the haptoglobin count will be low. after haptoglobin saturation, the free hemoglobin will cause hemoglobinemia and hemoglobinuria.
hemolytic anemia diagnosis
- anemia with increased reticulocytes should tip you off
- confirmation with increased LDH, increased indirect bilirubin, or decreased haptoglobin
contrast intravascular and extravascular hemolysis
- both will have decreased haptoglobin
- extravascular is more likely to have spherocytes while intravascular is more likely to have schistocytes
- hemoglobinemia and hemoglobinuria are present in intravascular
- extravascular is where most normal RBC breakdown occurs due to senescence.
name some types of normocytic anemia with a high reticulocyte count
- hemorrhage
- hemolytic (various types)
- enzymatic
- membranopathy
- hemoglobinopathy
- infection
pathogenesis of immune mediated hemolytic anemia
- antibodies bind RBCs
- splenic macrophages bind antibodies at FC receptor
- antigen-antibody complex pitted
- RBC reseals as microspherocyte
how do we test for immune mediated HA?
- direct antiglobulin test (DAT)
- direct Coomb’s test
how does a Coomb’s test work?
antihuman antibodies attach to human antibodies on the RBCs of someone with immune mediated HA
what are the two categories of immune mediated HA?
warm and cold
how are warm immune mediated HAs defined and what are the types?
- IgG antibodies binding at body temperature, lysed in spleen
- split into thirds, lymphoproliferative, connective tissue like lupus, idiopathic
treatment for warm immune mediated HA
- treat underlying disease
- steroids/immunosuppressants to decrease antibody binding
- splenectomy?
how are cold immune mediated HAs defined?
- IgM binding to RBCs in cold areas such as nose, fingers, etc.
- can pick up complement on their way back to the circulation, sometimes lyse in circulation but more often in the liver
likely causes of cold immune mediated HAs
- viral or mycoplasma infections
- lymphoma or connective tissue disease
- idiopathic
treatment of cold immune mediated HAs
- treat underlying disease
- preventive (wear gloves, move to warmer climate)
- splenectomy is NOT an option
three mechanisms of drug induced hemolytic anemia
1) hapten - exemplified by penicillin, drug and RBC combined are targeted by antibody
2) innocent bystander - exemplified by quinidine, drug attached to plasma protein lands on RBC surface and combines with antibody that also lands there.
3) membrane incorporation - exemplified by methyldopa, drug becomes part of RBC membrane and elicits antibody response
what are microangiopathic HAs (MAHAs) and what are the three subtypes?
- non-immune intravascular hemolytic processes
- prominent RBC fragmentation (schistocytes)
1) thrombotic thrombocytopenic purport (TTP) - hemolytic uremic syndrome (HUS)
2) DIC
3) malfunctioning heart valves
explain the mechanism behind TTP-HUS MAHA and the treatment
- thrombocytopenia and fragmentation
- associated with ADAMTS13 mutation, HIV, shiga toxin, infections, drugs
- treat with plasmapheresis
explain mechanism of DIC MAHA and treatment
- diffuse coagulation cascade seen during trauma, sepsis, malignancy
- fragmentation due to fibrin strands
- treat underlying problem
explain mechanism of valvular disfunction MAHA
- fragmentation caused by turbulence and shearing forces
two membranopathy HAs
- hereditary spherocytosis, AD
- paroxysmal nocturnal hemoglobinuria (PNH)
indicators of hereditary spherocytosis
- increased bilirubin
- decreased haptoglobin
- increased reticulocytes
- smear with polychromasia and spherocytes
- splenectomy is effective
what test confirms hereditary spherocytosis?
osmotic fragility test
explain PNH mechanism, diagnosis, and treatment
- acquired genetic defect in PIG-A gene
- missing GPI anchor molecule (CD59), become vulnerable to complement mediated destruction and intravascular hemolysis
- episodes of dark urine
- flow cytometry will show lack of GPI/CD59
- treat with transfusion, eculizumab (anti-complement), stem cell transplantation
what is the main enzymopathy related HA?
G6PD deficiency
explain the genetics of G6PD
- on x-chromosome
- males are homozygous. heterozygous women are mosaic, only occurs for females if present in RBCs
explain the two different G6PD deficiency syndromes
- first is from oxidative stress brought on by drugs, infections, diabetic ketoacidosis, fava beans
- second involves on-going hemolysis without a drug stress
what do you see on a G6PD deficiency smear?
Heinz bodies and bite cells
explain the main conceptual difference between hemoglobinopathies and thalassemias
hemoglobinopathies are qualitative while thalassemias are quantitative diseases. hemoglobinopathies are caused by gene mutations while thalassemias are caused by gene deletions.
what is the most important hemoglobinopathy to understand?
sickle cell anemia
what causes sickle cell anemia?
substitution of a valine for glutamic acid as the sixth amino acid on the beta chain gene on chromosome 16
sickle cell trait vs sickle cell disease
trait occurs with one affected chromosome while the disease occurs when both chromosomes are affected
