6.5.2 Hemolytic Anemia

Question 1

You suspect hemolytic anemia in your patient who presents with Hgb 6.3, recent fatigue, and increased __________________________, or evidence of _________________________________.

Answer 1

• You suspect hemolytic anemia in your patient who presents with Hgb 6.3, recent fatigue, and:
  
  • increased reticulocyte count without evidence of bleeding or after correction of iron/nutritional deficiency, or
  • evidence of RBC destruction with increased LDH and bilirubin, decreased haptoglobin, and alteration in RBC shape on peripheral smear

Question 2

Name the 5 categories of etiologies for hemolytic anemia

Answer 2

• Intracorpuscular vs extracorpuscular defects
• Inherited vs acquired defects
• Acute vs chronic
• Immune vs non-immune destruction
• Intravascular vs extravascular

Question 3

Describe the following:

• Intracorpuscular etiology of hemolytic anemia
• Mostly inherited or acquired?
• 5 main types of intracorpuscular causes

Answer 3

• Intracorpuscular etiology of hemolytic anemia
  
  • Defects in the RBC itself that result in lysis
• Mostly inhereited
• Types of intracorpuscular causes
  
  • Enzyme deficiencies
    
    • G6PD or pyruvate kinase deficiency
      
      • affect metabolic capacity including transport and recovery
  • Hemoglobinopathies
    
    • Sickle cell disease
    • Thalassemia
  • Membrane defects
    
    • Hereditary spherocytosis, elliptocytosis, tomatocytosis
      
      • Alterations in RBC shape or membrane function
  • Paroxysmal nocturnal hemoglobinuria
    
    • Acquired
  • Alpha thalassemia
    
    • Acquired d/t myelodysplasia

Question 4

Describe the following:

• Extracorpuscular etiology of hemolytic anemia
• Mostly inherited or acquired?
• 7 main causes of extracorpuscular HA

Answer 4

• Extracorpuscular etiology of hemolytic anemia
  
  • Normal RBCs destroyed by mechanical, immunologic, infectious, or metabolic alterations
• Mostly acquired
• 7 main causes of extracorpuscular HA
  
  • Antibodies directed at RBC membrane
    
    • Autoimmune / alloimmune
    • Transfusion rxn (acute/delayed)
    • Drug-induced
  • Mechanical stress
    
    • Valve disease
    • Device implants
    • Platelet microthrombi in TTP/HUS/DITMA
    • DIC: intravascular fibrin stranding
    • Thermal burns
  • Hypersplenism
    
    • Causes trapping and destruction
  • Infection
  • Hereditary TTP
  • Oxidant agents on metabolic defect
  • Central toxins, venom, copper poisoning (Wilson’s dz)

Question 5

Your patient has an immune mediated hemolytic anemia. How is this caused?

How will you identify it?

Answer 5

• Immune mediated
  
  • RBC destruction caused by antigen-antibody complexes and/or
  • Complement proteins (membrane attack complexes)
• Direct or Indirect Coombs test
  
  • Can detect presence of immune complexes directed against RBC globulins
• Causes
  
  • Autoimmune hemolytic anemia, drug-induced hemolysis, hemolytic transfusion reaction, cold agglutinins dz

Question 6

Describe the following:

• Intravascular etiology of hemolytic anemia
• Examples of causes
• Signs/Dx
• Consequences

Answer 6

• Intravascular etiology of hemolytic anemia
  
  • Occurs within the circulation, when there is significant membrane structural damage or when the RES is overwhelmed
• Examples of causes
  
  • Trauma, shear stress
  • Thermal burns
  • Complement induced lysis
  • Toxins
  • Thrombotic microangiopathies
  • Acute txfn rxn
  • Rh immune globulin (used for tx ITP)
• Signs/Dx
  
  • Free serum hgb or heme (products of hemolysis directly into bloodstream)
  • Urinary hemoglobin, heme, hemodiserin
  • Dark urine
  • Oxyhemoglobin pink-tinged blood
  • Mehemoglobin dark-tinged blood
• Consequences
  
  • AKI, DIC, increased risk of thrombosis d/t free Hgb or heme

Question 7

Describe the following:

• Extravascular etiology of hemolytic anemia
• RES
• Consequences

Answer 7

• Extravascular etiology of hemolytic anemia
  
  • Occurs via macrophages within the reticuloendothelial system
• RES
  
  • Liver, spleen, bone marrow, lymph nodes
• Consequences
  
  • Damaged RBCs
  • RBCs coated in complement
  • Alterations in RBC shape or reduced malleability (spherocytosis, sickle cells)

Question 8

Your patient has an anemia with elevated retics, and no clear source of bleeding or dietary deficiency. How will you proceed with dx workup?

Answer 8

• Treatment first if life-threatening anemia
  
  • Transfusion for severe symptomatic anemia
  • Plasmapheresis for TTP
  • Hydration/diuresis for acute transfusion reaction
• H & P
  
  • Onset of sx
  • Recent transfusion? Last 4 wks (delayed onset?)
  • New medication - esp if G6PD deficiency is suspected
  • Hx of hemolytic anemia or fam hx of anemia
  • Splenomegaly, hepatomegaly
  • Presence of jaundice or scleral icterus
  • Dark urine
• Lab tests
  
  • If NO obvious cause based on presentation and initial symptoms:
    
    • Start with direct antiglobin test (Coombs test)
    • Will test for IgG or complement attached to RBC, will help distinguish btwn immune and non-immune mediated hemolysis
  • Hgb, reticulocytes
  • Lactate dehydrogenase (up)
  • Haptoglobin (down)
  • Increased unconjugated bilirubin
  • Peripheral blood sphere
    
    • Schistocytes, likely TMA
    • Sphero, ellipto, stomatocytes: Inherited RBC dysmorphology
    • Sickle cells or thalassemia
• Other causes
  
  • Direct parasitization (malaria, babesiosis, bartonellosis, leishmaniasis)
    
    • Malaria can also cause hypersplenism causing an additional extravascular hemolysis
  • Bactrerial infxn (clostridium, Haem B)
  • Liver disease > splenomegaly d/t portal htn > RBC membrane alteration in target cells, spur cells, burr cells, stomatocytes
  • Renal dz > fragmentation in microvasculature, uremic plasma, hemodialysis