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Flashcards in Hemolytic Anemia Deck (47):

Hemolytic anemia is RBC destruction resulting in...(2)

Loss of RBC mass

Release of cellular contents


What types of inherited disorders cause hemolytic anemia?

RBC membrane disorders

RBC enzyme deficiencies



What types of acquired disorders cause hemolytic anemia?

  • Autoimmune (antibody mediated) hemolysis
  • Mechanical trauma
  • Infections
  • Chemical disorders
  • Splenic Sequestration


Is hemolysis more common extravascularly or intravascularly?

Extravascularly (Spleen > liver, bone marrow)


What is the difference between extravascular and intravascular autoimmune hemolysis?

Extravascular involves antibodies

Intravascular involves complement


Which types of pathologic hemolysis can be both extravascular and intravascular?

RBC enzyme disorders

Sickle cell anemia


Which types of pathologic hemolsis disorders are only extravascular? Which are only intravascular?

  • Extravascular
    • RBC membrane disorder
    • Thalassemia
  • Intravascular
    • Paroxysmal nocturnal hemoglobinuria
    • Mechanical trauma
    • Malaria


What findings in a laboratory evaluation are associated with hemolysis?

  • Reticulocytosis (increased reticulocytes)
  • Increased LDH, AST, potassium (released cellular content)
  • Bilirubinemia - Unconjugated (indirect) or conjugated (with liver disease)
  • Hemoglobinemia (free hgb in plasa)
  • Decreased haptoglobin (scavenges free hgb)


What test is ordered to check for an autoimmune hemolytic disorder?

DAT (direct antiglobulin test)


Describe hemoglobinuria and hemosiderinuria

  • Hemoglobinuria - Intravascular process (mostly) where Hgb is not scavenged by haptoglobin
  • Hemosiderinuria - Intravascular process (mostly) where  iron deposits in renal epithelium, then shed in urine



What is a false hyperkalemia?

Phlebotomy induced hemolysis


Why is spectrophotometry sometimes faulty in analyzing hemoglobin levels?

Hemoglobin absorbs at measured wavelengths, therefore, many assay produce falsely increased results in the setting of hemolysis


Common symptoms in hemolytic anemia (regardless of etiology)

Anemia (obvi)



Symptoms of anemia are more related to _____ of hemolysis

acuity (compare to baseline levels)


Assuming a starting point at normal hemoglobin levels, describe the symptoms and signs associated with the following changes?

  • <20% hemolysis (>11g/dL hgb):
  • 20-30% hemolysis (10-11g/dL hgb):
  • 30-40% hemolysis (8-9 g/dL hgb):
  • >40% hemolysis (<8 g/dL hgb):

  • <20% hemolysis (>11g/dL hgb):
    • Restlessness
  • 20-30% hemolysis (10-11g/dL hgb):
    • Anxiety, dyspnea with exertion
    • Orthostatic hypotension; tachacardia with exertion
  • 30-40% hemolysis (8-9 g/dL hgb):
    • Syncope
    • Orthostatic hypotension, tachycardia at rest
  • >40% hemolysis (<8 g/dL hgb):
    • Confusion, shock


Indirect bilirubin > 5mg/dL is almost always concurrent with ______ ______

liver disease


What risks are associated with hyperbilirubinemia and at what levels of bilirubin do they occur?

Jaundice (>2.5 mg/dL)

Scleral icterus (>1.7 mg/dL)

Increased risk of bilirubin gallstone (pigmented)


What are some rare complications of hemolytic anemia?

  • Pigment induced kidney injury (tubular obstruction, vasoconstriction)
  • Folate deficiency due to increased utilization
  • Increased risk of venous and arterial thrombosis of atypical sites


What are some clinical features associated with...

  • Extra-medullary hematopoiesis (Thalassemia, hereditary spherocytosis):
  • Beta thalassemia major:
  • Sickle cell anemia:


  • Extra-medullary hematopoiesis (Thalassemia, hereditary spherocytosis):
    • Splenomegaly and hepatomegaly
  • Beta thalassemia major:
    • Skeletal changes related to expansion of marrow - "chipmunk facies"
  • Sickle cell anemia:
    • Asplenia


What are some clinical features of Microangiopathic Hemolytic Anemia?

  • Microvascular infaction causing acute kidney injury
  • Liver disease
  • Abdominal pain
  • Fever
  • Mental status changes
  • Thrombocytopenia
  • Rash
  • Hemorrhagic diarrhea


Hereditary spherocytosis

  • Inheritance:
  • Defect:
  • Lab diagnosis:
  • Unique clinical features:

  • Inheritance: 75% autosomal dominant; 25% sporadic
  • Defect: Defect in ankyrin, band 3, band 4.2 or α/ß-spectrin leads to weakened or absent spectrin causing weakened cytoskeleton
  • Lab diagnosis: Blood smear review
  • Unique clinical features: Splenomegaly - aplastic crises caused by parvovirus


Sickle cell anemia

  • Inheritance:
  • Defect:
  • Lab diagnosis:
  • Unique clinical features:

  • Inheritance: Autosomal
  • Defect: Point mutation in ß-hgb chain (chrms 11)
  • Lab diagnosis: Hgb HPLC to identify HbS
  • Unique clinical features: Pain crises; acute chest syndrome; stroke; asplenia



  • Inheritance:
  • Defect:
  • Lab diagnosis:
  • Unique clinical features:

  • Inheritance: Autosomal
  • Defect: Decreased production of ß or α hgb chains
  • Lab diagnosis: Elevated hgb A2 for beta-thal trait; gene sequencing; smear review
  • Unique clinical features: Secondary hemochromatosis; skeletal deformities (due to marrow expansion)


G6PDH deficiency

  • Inheritance:
  • Defect:
  • Lab diagnosis:
  • Unique clinical features:

  • Inheritance: X-linked
  • Defect: Deficiency in G6PDH enzyme - Deficient RBCs cannot reduce oxidant stresses and accumulate, denature, form precipitated hgb (Heinz bodies) - cause lysis or removed in spleen
  • Lab diagnosis: Blood smear review for bite cells
  • Unique clinical features: Males preferentially affected; hemolysis dependent on inciting oxidant stresses


Paroxysmal Nocturnal Hemoglobinuria

  • Pathophysiology:
  • Lab diagnosis:
  • Unique clinical features:

  • Pathophysiology: Stem cell with deficiency in GPI-linked proteins including the anti-complement proteins CD55 and CD59 on RBCs and WBCs
  • Lab diagnosis: Flow cytometry for CD55 and CD59
  • Unique clinical features: Hypercoagulability (thrombi at unusual sites); may have accentuation of lysis at night


Warm autoimmune hemolytic anemias

  • Pathophysiology:
  • Lab diagnosis:
  • Unique clinical features:

  • Pathophysiology: RBC autoantibodies that react at 37º causing intravascular coating of RBCs and extravascular lysis in spleen
  • Lab diagnosis: Smear review for spherocytes; DAT
  • Unique clinical features: Splenomegaly; seen in association with B-cell lymphoproliferative disorders


Cold autoimmune hemolytic anemia

  • Pathophysiology:
  • Lab diagnosis:
  • Unique clinical features:

  • Pathophysiology: RBC IgM autoantibodies that react at <30º and may lead to extravascular hemolysis in the spleen or liver
  • Lab diagnosis: Smear review for spherocytes; DAT
  • Unique clinical features: Rarely clinically significant; Raynaud phenomenon associated with Mycoplasma infections and EBV infections


Microangiopathic hemolytic anemia

  • Pathophysiology:
  • Lab diagnosis:
  • Unique clinical features:

  • Pathophysiology: Traumatic shearing and subsequent lysis of RBCs due to malfunctioning heart valve or vascular obstruction by microthrombi
  • Lab diagnosis: Smear review for schistocytes; ADAMTS-13 activity; coagulation tests
  • Unique clinical features: DIC; TTP (thrombotic throbocytopenia purpura); Metastatic carcinoma; malignant hypertension



  • Pathophysiology:
  • Lab diagnosis:
  • Unique clinical features:

  • Pathophysiology: Intracellular parasites infect the RBC and cause lysis
  • Lab diagnosis: Smear review (thick and thin); PCR for parasites
  • Unique clinical features: Cyclic fever; cerebral malaria; Blackwater fever


What are spherocytes?

  • Normal sized RBCs with increased hemoglobin concentration
  • Less flexible, trapped in the spleen
  • Shortened life span


What are three causes of spherocytes in the blood?

  • Thermal injury
  • Intrinsic abnormalities
  • Immune hemolysis


What protein most commonly has a defect in Hereditary spherocytosis?

Ankyrin (though most patients have deficiencies in both ankyrin AND spectrin)


How is Hereditary spherocytosis managed?

  • Removal of gallbladders in younger patients
  • Folate supplementation in aplastic crisis
  • Splenectomy: Complete (in adults) and partial (in children < age 6)


Warm-autoantibody type represents ___% of the autoimmune hemolytic anemias



What are some secondary causes of Warm autoantibody type hemolytic anemia?

  • Lymphoproliferative disorders
  • Autoimmune disorders
  • Non-hematopoietic neoplasms (Ovarian cancer)
  • Drugs (methyldopa; cephalosporins)


What are some secondary causes of cold-autoantibody type hemolytic anemias?

  • Postinfectious (Infectious mononucleosis)
  • Lymphoproliferative disorders


What type of immunoglobulin is associated with cold AIHA? What is the mechanism?

  • IgM - RBC agglutination impedes blood flow in superficial distant vessels
  • Igm and complement mediate RBC injury (intravascular hemolysis)


What immune cells are associated with Warm AIHA?

IgG or Complement mediated (extravascular hemolysis)


Blood smear findings in Warm/Cold AIHA?



Agglutinins (Cold)


Acute vs Chronic Cold AIHA?

  • Acute form occurs 2-3 weeks into infectious illness (EBV/Mycoplasma)
  • Chronic form is associated with lymphoproliferative disorders


A G6PDH deficiency results in decreased _______ production and an inability to reduce _______ _______

glutathione; oxidant stressors


What are heinz bodies (in G6PDH deficiency)?

Denatured hemoglobin that directly damages the RBC causing intravascular hemolysis

Heinz bodies are removed in the spleen


What are oxidant stressors in a G6PDH deficiency?


Fava beans

Drugs (Dapsone, sulfonamides, primaquine, nitrofuantoin, quinolones)


What are the differences between the following G6PD variants in terms of hemolysis and population affected?

  • G6PD A (normal):
  • G6PD B (normal):
  • G6PD A-:
  • G6PDMED:

  • G6PD A (normal): No hemolysis; Blacks (20% AA)
  • G6PD B (normal): No hemolysis; All races
  • G6PD A-: Moderate hemolysis; Blacks (11% AA)
  • G6PDMED: Severe hemolysis; Whites
  • G6PDCANTON: Moderate hemolysis; Asian


In G6PD A-, what is the difference between new RBCs and old RBCs due to an unstable enzyme?

100% acitivity in new RBCs

5-15% activity in "old" RBCs (120 day lifespan normally)


How are G6PDH deficiencies screened for today? How are they measured?

NADPH fluorescence

Normal, Deficient (intermediate), and Grossly deficient (Low)

In Males: Low OR Normal (during hemolytic rxns)

In Female carriers: Normal, intermediate, or low dependent (on X-inactivation)


Paroxysmal Nocturnal Hemoglobinuria is an acquired mutation in the ____ gene 

PIGA (X chromosome)