Hemolytic Anemias Flashcards
What makes someone anemic?
Hbg below 11
Hct below 35
3 major causes of anemia
Decreased production of RBC
Increased destruction of RBC
Blood loss
Intravascular anemia
RBCs lyse within the blood vessels
Extravascular anemia
RBCs are destroyed within organs (spleen, liver)
Iron levels in intravascular anemia
Decrease in iron over time
___ are formed in intravascular anemia
Schistocytes
What are common things to see in intravascular anemia?
Hemoglobinuria
Decrease in haptoglobin
Iron levels in extravascular anemia
Iron is stored and recovered
How much Hgb is released into circulation in intravascular anemia?
Large amounts
How much Hgb is released into circulation in extravascular anemia?
Minimal
___ are formed in extravascular anemia
Spherocytes
Why would mean cell volume be increased in hemolysis?
Increased reticulocytes
Haptoglobin levels after inflammation
Increases and can mask changes in haptoglobin
Cause of hereditary spherocytosis
Inherited genetic effect that causes abnormal formation of proteins in RBC membrane
Pathology of hereditary spherocytosis
Abnormally shaped RBCs that are round instead of flexible disks
What does a lack of flexibility of the RBCs cause?
Causes them to get trapped in the spleen
Presentation of hereditary spherocytosis
Varying degrees of anemia
What may cause hereditary spherocytosis to present?
Infection
Treatment for hereditary spherocytosis?
Folic acid supplementation
Blood transfusions
Splenectomy
Why do we want to delay a splenectomy until after the patient is 5 years old?
Want to give the immune system time to mature and develop
Hemoglobin A
Normal adult Hgb
97-99%
aabb
Hemoglobin A2
1-3%
aadd
Hemoglobin F
Fetal hemoglobin
Less than 1%
aagg
What chromosome holds 2 copies of the alpha gene?
16
What chromosome holds 1 copy of the beta gene, delta gene, and gamma gene?
11
Cause of alpha thalassemia
Gene deletion causing reduced alpha chain synthesis
The ___ mutated the gene, the worse the anemia
More
What proportions would you see on a Hgb electrophoresis in alpha thalassemia?
Equal proportions of A, A2, and F
Pathology of alpha thalassemia
Increased number of small, pale RBCs
Why do you have excess B chains in alpha thalassemia?
The beta chains are being produced normally but the alpha chains are not being made to match with them
What will excess beta chains cause?
Damage to RBC membranes causing hemolysis in marrow and splenic vessels
Most common alpha thalassemia patients
Southeast Asia and Chinese
Silent carrier (alpha thalassemia minima)
3 normal and 1 abnormal genes
Alpha thalassemia minor (trait)
2 normal and 2 abnormal genes
Hemoglobin H disease
1 normal and 3 abnormal genes
Results in little to no use for O2 transport
Hydrops fetalis
All 4 genes are abnormal
Results in death of fetus
What type of anemia is alpha thalassemia?
Microcytic, hypochromic
Inclusion bodies
When beta chains precipitate and cause damage to the cells
Peripheral smear of alpha thalassemia
Microcytic, hypochromic
Target cells
Treatment for hemoglobin H disease
Folic acid supplementation
Why should you monitor iron levels in hemoglobin H disease?
It’s extravascular
Cause of beta thalassemia
Gene point mutations causing reduces beta chain synthesis
Pathology of beta thalassemia
Increased number of small, pale RBCs
Why do we see altered proportions of Hb subtypes in the Hb?
They don’t need beta chains for the other types so it will fall back on those other types
Demographics of beta thalassemia patients
Mediterranean
Beta thalassemia minor
1 normal and 1 abnormal gene
Beta thalassemia intermedia (mild)
Requires occasional transfusions
Has mostly HgF
Beta thalassemia major
Has all mutated genes
Has mostly HgF
Is dependent on regular transfusions
Why do we see failure to thrive in beta thalassemia?
Decreased O2
What are exam findings of beta thalassemia?
Chipmunk faces
Why do you see nucleated RBC in beta thalassemia major?
Because bone marrow is pushing out RBC so often and fast
Only definitive treatment for beta thalassemia major
Allogenic bone marrow transplant
Cause of sickle cell anemia
Genetic disorder that causes abnormal substitution of an amino acid in the beta chain
Hemoglobin S
Present in sickle cell anemia
Demographics of sickle cell anemia patients
African Americans
Pathology of sickle cell anemia
Abnormally shaped RBCs causes vaso-occlusive episodes
Vaso-occlusion
Cells stick to the endothelium causing ischemia, pain, and end-organ damage
Triggers of sickle cell anemia flare ups
Hypoxemia
Infection
Exercise
Stress
Abrupt temperature changes
Sickle cell trait vs. sickle cell anemia
Sickle cell trait: only 1 mutation and doesn’t show symptoms
Sickle cell anemia: 2 mutations and clinically present
Why is WBC count elevated in sickle cell anemia?
Increased inflammation from vaso-occlusive episodes
Key sign on peripheral smear that patient has sickle cell anemia
Howell-jolly inclusion body
Sickle cell crisis
Condition in sickle cell anemia in which the sickled cells interfere with oxygen transport, obstruct capillary blood flow, and cause fever and severe pain in the joints and abdomen
What would you see in the extremities of a patient with sickle cell anemia
Non-healing wounds and dactylitis
What would you see in the retinal exam of a patient with sickle cell anemia?
Hemorrhages and cotton wool spots
What would you see on an abdominal exam of a patient with sickle cell anemia?
Hepatomegaly and splenomegaly
Treatment of sickle cell anemia
Avoidance of triggers
Folic acid supplementation
Stem cell transplant
Cause of G6PD deficiency
X-linked recessive genetic trait
Pathology G6PD deficiency
RBCs especially vulnerable to oxidative stress leading to formation of heinz bodies
Demographics of patients with G6PD deficiency
African American males
Why is G6PD deficiency rarely seen in females?
Because it’s X-linked
Presentation of G6PD deficiency
Episodic hemolytic anemia
3 main triggers of G6PD deficiency anemia
Infection
Food
Medications (3 As: antibiotics, Azo, aspirin)
What type of cells would you see on a peripheral smear of someone with a G6PD deficiency?
Bite cells
Blister cells
Reticulocytes
Heinz bodies
G6PD deficiency treatment
Avoid triggers
Folic acid
Why do we not need to monitor iron levels in G6PD deficiency anemia?
It’s episodic
Cause of autoimmune hemolytic anemia
Antibody forms against surface antigens of RBC
Pathology of autoimmune hemolytic anemia
RBCs tagged for destruction by the immune system
In autoimmune hemolytic anemia, splenic macrophages remove portions of RBC membrane leads to ___
Spherocyte formation
Presentation of autoimmune hemolytic anemia
Abrupt, rapid, potentially life-threatening anemia
Diagnostic test for autoimmune hemolytic anemia
Coombs test
Direct Coombs test
Reagent is mixed with patient’s RBC
Indirect Coombs test
Serum is mixed with RBCs and then reagent is added
Treatment for autoimmune hemolytic anemia
Immunosuppression
Transfusions
Why is immunosuppression key in autoimmune hemolytic anemia?
Problem is immune system, not RBC, so unless we suppress the immune system, then the cells will continue to get destroyed, no matter how much RBC are supplemented
Why do you need to type/cross match transfusions for autoimmune hemolytic anemia treatment?
Cells are already getting destroyed so it won’t matter much if the new ones do too. We are just trying to get as many RBCs as possible
Erythroblastosis fetalis
Hemolytic disease of the newborn
Cause of hemolytic disease of the newborn
Maternal IgG to antigens on surface of fetal RBCs
Pathology of hemolytic disease of the newborn
Maternal IgGs to fetal RBCs cross placenta to fetal circulation and bind to fetal RBCs
Classic case of hemolytic disease of the newborn
Rh- mother and Rh+ father have an Rh+ baby
Presentation of hemolytic disease of the newborn
Jaundice
Anemia at birth
Why is the indirect Coombs test on the fetus negative and the mother positive?
Baby: because the baby is not the one making the antibodies
Mother: the mother is the one making antibodies
Why is the direct Coombs test positive on the baby and negative on the mother?
Mother: because the antibodies are not attacking her own RBCs
Baby: the baby’s RBCs are coated in the mother’s antibodies
Hemolytic disease of the newborn treatment
Before birth: transfusion and early delivery
After birth transfusion
RhoGAM
Used to prevent an immune response to Rh positive blood in people with an Rh negative blood type
Cause of paroxysmal nocturnal hemoglobinuria
Acquired genetic defect leading to lysis of RBCs
Pathology of paroxysmal nocturnal hemoglobinuria
RBCs are vulnerable to lysis by complement
Who is paroxysmal nocturnal hemoglobinuria most common in?
Young adults
Presentation of paroxysmal nocturnal hemoglobinuria
Hemoglobinuria present first thing in the morning
Improves throughout the day
Why does hemoglobinuria only occur first thing in the morning in paroxysmal nocturnal hemoglobinuria patients?
Drop in blood pH overnight facilitates hemolysis of RBC
Do you need to monitor iron in paroxysmal nocturnal hemoglobinuria?
Yes, it is intravascular so it may get low
Gold standard diagnostic test for paroxysmal nocturnal hemoglobinuria
Flow cytometry
Treatment for mild paroxysmal nocturnal hemoglobinuria
No treatment needed
Treatment for severe or aplastic paroxysmal nocturnal hemoglobinuria
Stem cell transplant
Treatment for hemolysis or thrombosis paroxysmal nocturnal hemoglobinuria
Monoclonal antibodies
Pathway of anemia due to blood loss
- Hypovolemia
- Fluids are replaced and patient is now anemic
- Recovery - bone marrow attempts to replace lost RBCs
