8/6- Hemolytic Anemia Flashcards
What is hemolytic anemia (broad def)?
What is seen with marrow production? Reticulocyte count?
Anemia caused by a shortened RBC lifespan
- Marrow production is typically normal or increased
- Reticulocyte count is increased
What may cause proliferative anemia?
- Hemolysis
- Blood loss
- Sequestration (big spleen)
What is the normal lifespan of a RBC?
About 120 days
What is the response of bone marrow to accelerated red cell destruction?
Increased production (more than 6-8x)!
What is seen in compensated hemolysis in regards to hematocrit and reticulocytes?
Hematocrit; normal
Reticulocytes: elevated
When does hemolytic anemia occur/what characterizes it?
Hemolytic anemia ensues when RBC survival is shortened to < 30 days
What are the phases of normal RBC senescent destruction?
- Reticuloendothelial Phase
- Transport and Hepatic Phases
- Intestinal Phase
What are processes/steps of normal RBC senescent destruction in the reticuloendothelial phase?
- Macrophages do what?
- What happens to protoporphyrin?
- What happens to CO?
- What happens to Fe?
- What happens to globin chains?
- Macrophages in spleen, liver and bone marrow ingest old RBC (the reticuloendothelial system)
- Protoporphyrin is converted to bilirubin
- Carbon monoxide is generated and expired in lungs
- Iron is stored in macrophages as ferritin and hemosiderin
- Globin chains are hydrolyzed to amino acids, which can be re-utilized
T/F: There is typically some amount of intravascular destruction of normal RBCs
False! There is typically no intravascular destruction of normal red blood cells
What are processes/steps of normal RBC senescent destruction in the transport and hepatic phases?
- Unconjugated bilirubin binds to albumin, is transported to liver (not soluble!)
- Taken up by hepatocytes and conjugated by glucuronyl transferase (soluble!)
What are processes/steps of normal RBC senescent destruction in the intestinal phase?
Conjugated bilirubin excreted into bile is converted by bacteria to stercobilinogen which can be resorbed and excreted in the urine as urobilinogen
Overview (picture) of extravascular hemolysis
Extravascular hemolysis is just an acceleration of the usual pathway for senescent red blood cells
- RBC gobbled up by macrophage
- Globin converted into amino acids
- Heme converted into CO, Fe, and biliverdin
—Iron binds to transferrin
- Biliverdin converted to bilirubin and sent to liver as unconjugated form
- Liver conjugates and sends bilirubin glucuronides to colon (excreted as stercobilinogen?)
- Stercobilinogen sent to kidney and excreted as urobilinogen
What is direct bilirubin a measure of? Soluble or insoluble?
Direct = conjugated (soluble)
Overview (picture) of intravascular hemolysis
- Hemoglobin breaks down into its dimer and binds haptoglobin and is reclaimed in the liver
- Hemoglobin can overwhelm haptoglobin and go to the kidney where it passes into the urine as hemoglobinuria
- Some of the hemoglobin is take up by tubular cells and these cells are eventually sloughed into the urine and can be stained with Perl’s Prussian blue: hemosiderinuria
- Free heme is also generated and this is bound to another protein hemopexin and cleared by the liver
- Intravascular hemolysis results in plasma hemoglobin, hemoglobinuria, hemosiderinuria (if chronic), decreased haptoglobin, and typically increased LDH.
What are the 2 main categories of hyperbilirubinemia?
- Indirect (unconjugated) hyperbilirubinemia (acholuric)
- Direct (conjugated) hyperbilirubinemia
What characterizes indirect (unconjugated) hyperbilirubinemia (acholuric)?
- Elevation of total bilirubin with low direct
- Elevation of total is modest (under 5%)
What are some causes of indirect (unconjugated) hyperbilirubinemia (acholuric)?
- Hemolytic anemia
- Ineffective erythropoiesis
- Resorption of hematomas
- Sometimes hepatocellular disease
- Hereditary (Gilbert’s disease)
What characterizes direct (conjugated) hyperbilirubinemia?
- Elevation of total bilirubin with 50% or more direct
- Can be quite high
What are some causes of direct (conjugated) hyperbilirubinemia?
- Biliary obstruction
- Cholestasis (drugs, sepsis)
- Hepatocellular disease
- Hereditary (Dubin-Johnson)
What is seen in Gilbert’s disease?
- Pts have mild intermittent jaundice (sometimes brought on by stress or dieting)
- Characterized by 70-80% reduction in the glucuronididation activity or uridine diphosphate glucuronosyltransferase isoform 1A1 or UGTA1
Hemolysis causes (direct/indirect) bilirubinemia? Unless?
Hemolysis causes indirect bilirubinemia
- Unless there is co-morbid hepatobiliary disease
What are the 2 classes of hemolytic anemia?
Are they hereditary or acquired?
How are transfused RBCs affected in each?
Intrinsic abnormality
- Hereditary (except PNH- paroxysmal nocturnal hemoglboniuria, which is acquired)
- Transfused RBCs typically have normal lifespan
Extrinsic abnormality
- Acquired
- Includes autoimmunity
- Transfused RBCs have shortened lifespan
What is another method of classifying hemolytic anemia?
By where the RBCs are destroyed
- Intravascular: red cells perish in the bloodstream
- Extravascular: red cells perish in the RE system
Hemolytic anemias can be mostly one or the other or a combination of both
Basic approach to hemolytic anemia?
- Hx and physical
- Review peripheral blood smear
- Reticulocyte count
What is this?
Hereditary elliptocytosis
What is a reticulocyte? What is seen in staining?
Youngest normal circulating RBC
- When a nucleated RBC precursor extrudes the nucleus
- The RNA in residual ribosomes stains supravitally with crisyl violet of methylene blue
What are some congenital causes of hemolysis?
Membrane abnormalities
- Hereditary spherocytosis
- Hereditary elliptocytosis
- Others
Enzymopathies
- G6PD deficiency
- Pyruvate kinase deficiency
- Others
Hemoglobinopathies
- Sickle cell disease
- Thalassemias (also ineffective erythropoiesis)
- Unstable hemoglobins
What is seen here?
Spherocytosis
What is seen here?
HbSS
What is seen here?
Elliptocytosis
What is seen here?
HbSC
What is this?
Pt PBS in hemolytic anemia?
What is the most likely acquired cause of hemolytic anemia associated with this blood smear?
A. Hereditary spherocytosis
B. Cold Agglutinin disease
C. Warm autoimmune hemolytic anemia
D. Microangiopathic hemolytic anemia
E. March hemoglobinuria or foot strike hemolysis
?
Table of typical scenarios in regards to DAT and IAT?
- If DAT is positive, lab will then do an IgG Coombs and a C3 Coombs
- For warm autoimmune hemolytic anemia (IgG): DAT+++, IgG+++, C3 +/-
- For cold agglutinin disease (IgM): DAT+++, IgG-, C3++
What is this?
_**Will see this on test**_
Agglutination
- IgM antibody that agglutinates red cells in the presence of cold
- Indicative of IgM cold agglutinin syndrome
A 19 year old college student presents with fever cough
- Has chest X ray showing a small infiltrate
- Treated as walking pneumonia
- Gets better, but a week or so later
- Becomes fatigued short of breath and
- Has a hemoglobin of 7 and this smear.
Which one of these is most likely:
A. EBV virus infection
B. Mycoplasma
C. Pneumocystis carinii
D. Pneumococcal pneumonia
E. Hemophilus influenzae B
Which one of these is most likely:
A. EBV virus infection
B. Mycoplasma???
C. Pneumocystis carinii
D. Pneumococcal pneumonia
E. Hemophilus influenzae B
What is this?
Microangiopathic hemolytic anemia
- Also note that there are no platelets in this high power field
- Helmets, schizocytes, and spherocytes are seen
- Remember that the spherocyte can be the end stage cell in any hemolytic process—when they predominate we think of HS and AIHA
