Other hemolytic anemias Flashcards
Defects in RBC membrane
Cation permeability
Hereditary Stomacytosis
Hereditary Xerocytosis
Defects in RBC membrane
Cytoskeleton
Herditary Spherocytosis
Hereditary Elliptocytosis
Hereditary Pyropoikolocytosis
Hereditary spherocytosis
- Most common
- Spectrin deficiency (cytoskeleton)
- Problem: Loss of surface area - decreased surface to volume ratio
- Clinical manifestations
1. splenomegaly
2. Jaundice
3. Anemia
Hereditary Spherocytosis
LAB
- Decreased Haptoglobin
- Normal or increased MCHC
- Increased osmotic fragility
- Increased reticuolcytes
- Increased bilirubin (indirect and total)
Hereditary spherocytosis
Morphology + treatment?
Morphology - spherocytes
Treatment - Total or Partial splenecotomy
Cause of hereditary elliptocytosis
defective or deficienct spectrin (cytoskeleton)
- Weakened cytoskeleton cannot go back to original form after shear stress
Clinical subtypes of Elliptocytois
- Common Hereditary Elliptocytosis
- Southeast Asian Ovalocytosis
- Spherocytic Hereditary Elliptocytosis
- Hereitary Pyropoikilocytosis
Hereditary elliptocytosis
severity + Morphology?
Severity - anemia severity varies from asymptomatic to severe between types.
Morphology - Elliptocytes, some HE clinical subtypes exhibit ovalocytes
Hereditary Pyropoikilocytosis
Cause?
Problem?
RARE
Cause - Reduced assembly of spectrin + increased spectrin degradation
Problem - Severely weakened cytoskeleton that cannot go back to original form and may fragment after shear stress.
Hereditary pyropoikilocytosis
symptoms
- severe hemolysis
- Poor growth
- Bone expansion - facial abnormalities
morphology of pyropoikilocytosis
Schistocytes !
Other fragmented cells, spherocytes, elliptocytes, bizarre RBCs
RBCs heat sensitive and can fragment at body temperature (pyro)
Hereditary Stomacytosis (permeability)
Cause?
Problem?
Cause - Deficiency in stomatin - a protein that regulates ion transport across RBC membrane
Problem?
- increased permability to sodium (Na+)
- Na+ influxes into cell
- Water follows and influxes into cell
Hereditary Stomacytosis - Lab findings
High MCV
Low MCHC
Morphology: stomatocytes
Treatment: Splenectomy
Hereditary Xerocytosis
Cause?
Problem?
Cause - unknown, but due to defect in membrane permeability
Problem
- Increased permeability to Potassium (K+)
- K + OUTfluxes from cell
- Water follows outfluxing
- Results in cell dehydration with hemoglobin concentrating in one area
Herditary Xerocytosis Lab findings
High MCHC
Low Osmotic Fragility - more resistant
morphology - Target cells, crenated cells and Xerocytes
Hexose monophosphate pathway
G6PD deficiency
Glycolytic pathway
Pyruvate Kinase Deficiency
Methemoglobin Reductase Pathway
Methemoglobin reductase deficiency
Hexose monophosphate pathway aka phosphogluconate pathway /PPP
- Uses 5-10% of RBC glucose
- Forms NADPH
- NADPH is reduced and forms reduced Glutathionene (GSH)
- GSH protects hemoglobin from oxidative denaturation
G6PD Deficiency
X linked recessive disorder (more prevalent in males)
- Decrease in G6PD
Hgb becomes susceptible to oxidation, followed by denaturation and precipitation
- increased Heinz bodies
In G6PD deficiency ..heinz bodies are
Removed in the spleen, leaving (helmet cells) aka. bite cells
G6PD deficiency, RBC loses deformability ..
tough time getting through microvasculature
- leads to premature destruction in the circulation = intravascular hemolysis
G6PD clinical manifestiations
Majority is asymptomatic
- only 20% of normal G6PD activity is required for normal RBC function
Clinical manifestations occur in states of oxidation:
1. oxidative drugs
2. Infections
3. Ingestion of fava beans
G6PD - Favism
Fava beans contain chemicals that destroy gluthione
Always want to pair with a nice Chianti
G6PD - CBC, Smear, Chemistry
- Decreased Hgb, HCT
1. normocytic, normochromic - Hemoglobinemia
1. Visual hemolysis - Increased reticulocytes
- Increased Bite cells
- Increased Serum indirect bilirubin
- Decreased/absent Haptoglobin
- Increased LDH
G6PD - urine
- hemoglobinuria
- Urine may be darker/black (coke or port wine color)
Due to oxidized RBCs
G6PD - Heinz body prep
Heinz bodies
- wright stain
- supravital stain
Glycolytic pathway aka Embden-Meyerhod Pathway
Non oxidative
Generates 90% of ATP needed by RBCs
Forms 2 net ATP
PK deficiency
Hereditary mutation (different autosomal forms not sex-linked)
- Decreased pyruvate kinase (PK)
- decreased PK leads to decreased ATP generated
- Decreased ATP leads to RBC membrane rigidity and fragility
Rigid RBCs are sequestered by the spleen = extravascular hemolysis
PK deficiency - Clinical Manifestations
Hemolytic anemia can range from mild to severe
- dependent on type of mutation inherited
More pronounced with concurrent infections or other stress states
Severe cases may require lifelong repeated transfusions
Splenectomy may help to increase RBC life span
PK deficiency Lab findings
*CBC + Peripheral smear *
- decreased Hgb and Hct
Accelerated Erythropoiesis
- Polychromasia
- nRBCs
*Chemistry *
- increased serum indirect bilirubin
- decreased/absent haptoglobin
Diagnosis is done using a specialized fluorescent screening test
Importance of methemoglobin reductase pathway
- Important in maintaining heme iron in reduced (Fe2+, ferrous) form
NADH - Methhemoglobin Reductase Deficiency
Autosomal recessive inheritance
Not able to keep iron in reduced form
Leads to increased methemoglobin
- methemoglobinemia
NADH - Methhemoglobin Reductase Deficiency
Main lab finding
Major clinical feature
Treatment
Main lab finding
- Methemoglobinemia
Major clinical feature
- Cyanosis (not able to carry oxygen)
Treatment
- Intravenous Methylene Blue
1. Artifically activates NADH - Methemoglobin reductase system
Paroxysmal Nocturnal hemoglobinuria - PNH
Acquired Intracorpuscular defect - hemolytic anemia
X Linked PIGA mutation in hematopoietic stem cell
- Deficiency in GPI anchor proteins
- ^Decreased GPI anchor proteins = sensitive to complement-mediated hemolysis
Complement enhanced with acidity
Blood pH slightly decreased at night - increased hemolysis
- or with infection, surgery, transfusion
PNH - CBC and differential
Low RBC cpunt, Hgb, Hct
Low WBC - Leukopenia
- decreased Neutrophils - Neutropenia
PNH reticulocyte count
- Increased Reticulocyte count, but not enough to compensate
Can lead to aplastic anemia = bone marrow failure - decreased reticulocyte count
PNH peripheral smear
- Normocytic, normochromic
- occasional increase in macrocytosis and polychromasia
1. due to increased reticulocyte
2. reverse if aplastic anemia is developed
PNH - BM
Erythroid hyperplasia
- responding to chronic hemolysis
- reverse if aplastic anemia is developed
Usually decreased iron
- Leading to development of IDA
PNH - Urinalysis
- Possible dark urine
- Hemoglobinruia
- Hemosiderinuria (iron)
- All due to chronic hemolysis
Ham’s Test (PNH)
RBC incubated at 37 degrees
- acidified to 6.5-7.0
Normal RBC are resitant to acidification
PNH RBCs are sensitive to acidification and lyse from activated complement
Flow cytometry is considered current gold standard
PNH treatment
Bone marrow transplant is curative
Long-term tranfusions for anemia
Monoclonal Ab Treatment - Eculizumab
- Binds C5 - prevents complement mediated hemolysis
Extravascular defects
- Immune hemolytic anemias
- infections
- Exposure to chemicals and toxins
- Exposure to physical agents
- Microangiopathic and macroangiopathic hemolysis
- General system disorders
Extravascular defects
- Immune hemolytic anemias
- infections
- Exposure to chemicals and toxins
- Exposure to physical agents
- Microangiopathic and macroangiopathic hemolysis
- General system disorders
