Normocytic Anemia Disorders

Normocytic anemia

• Def:
  • MCV 80-100
    
  • normal-sized RBCs
• Etiologies:
  • anemia of chronic disease, acute blood loss, hemolysis, volume overload (dilutional drop in Hgb due to pregnancy or parenteral intake)
• Presentation:
  • S: mild malaise and fatigue
    
  • O: facial mask of fatigue (when Hbg < 10), sallow skin, pale mucous membranes, tachycardia, tachypnea at rest; prolonged blanch response in nails
• Diagnosis:
  • CBC: no alternation in RBC indices
    
  • absolute reticulocyte count (normally 0.5-2.5%)
    
  • (reticulocytes are the less mature type of RBCs)

Autoimmune hemolytic anemia

• Def:
  • > Autoantibodies.
    
  • > Normal Hgb Electrophoresis
    
  • > ↑ retics, ↑ indirect bili, ↓ haptoglobin, pos DAT.

Warm AIHA

• Def:
  • IgG antibodies attach to the RBC membrane and cause the immune system to attack and phagocytose in the spleen
• Presentation:
  • Symptoms of anemia
    
  • Jaundice, scleral icterus
    
  • Mild splenomegaly
    
  • Symptoms of precipitating the disorder
• Precipitating factors:
  • Idiopathic
    
  • Presence of other autoimmune disorders
    
  • Lymphoproliferative disorders
    
  • Viral infections
• Diagnosis:
  • DAT-> take patient blood and incubate with coombs reagent; if it is + there will be agglutination
    
• Labs:
  
  • High bili, high LDH, low haptoglobin
    
  • Spherocyte on PBS
• Management:
  • 1st line:
    • Corticosteroids (1st line)
      • prednisone 1-2 mg/kg/day in divided doses
      • taper slowly to prevent a recurrence
    • calcium, vitamin D, folic acid, biphosphonate therapy to prevent osteoporosis
    • Splenectomy
      • effective in 2/3, rarely done in children
    • Immunosuppression or Immunomodulation
    • cyclophosphamide, azathioprine
    • In emergencies, short term IVIG
  • 2nd line:
    • Immunosuppression: rituximab, azathioprine
      
    • RBC Transfusion (some caution, because risk of reaction is very high in these patients)

Cold AIHA

• Def:
  • Relies on IgM which causes agglutination at cold temperatures
• Presentation:
  • SYmptoms of agglutination: acrocyanosis, ulceration
    
  • Exacerbation with exposure to cold
• Precipitating factors:
  • Idiopathic
    
  • Lymphoproliferative
    
  • Mycoplasma infection
    
  • EBV
• Diagnosis:
  • Direct cooms positive for complement
    
  • Red cell agglutination on PBC
• Management:
  • Resistance to treatment
    
  • Avoid cold
    
  • plasmapheresis removes IgM
    
  • Treatment precipitation disorder:
    
    • Transfusion warmed blood, fluids

Hereditary spherocytosis

• Def:
  • ABnormalities of ankyrin, spectrin or other membrane proteins
    AD: 75%
  • > Defect of the cell membrane.
    
  • > Normal Hgb Electrophoresis
    
  • > MCHC usually >36 g/dL. ↑ retics, ↑ osmotic fragility
• Presentation:
  • Vary from completely asymptomatic to severe anemia
• Complications:
  • Folate deficiency
    
  • Jaundice, anemia, splenomegaly
• Diagnosis:
  • Spherocytes
    
  • When actively hemolyzing: high reticulocytes, high indirect bili, high LDH, low haptoglobin
    
  • DAT negative
    
  • Osmotic fragility test: increased susceptibility
• Management:
  • Folate supplementation
    
  • Splenectomy if severe hemolysis

G6PD Deficiency

• Def:
  • Involved in NADPH generation, protects the cells from oxidative damage
    
  • Causes Heinz body and bite cell
    
  • Most common in regions where malaria is endemic (X linked)
• Presentation:
  • Most commonly asymptomatic until exposed to oxidative stress
    
  • Infection, diabetic ketoacidosis, liver failure
    
  • Oxidative drugs (sulfa drugs, antimalarials)
    
  • Fava beans
• Diagnosis:
  • Bite cells on PBS
    
  • High retic, High bili, high LDH, low haptoglobin
    
  • Measurement of G6PD activity
• Management:
  • Avoid oxidative triggers such as dapsone, quinidine, and sulfonamides
  • prevent hemolysis!
    
  • avoid environmental triggers (mothballs)
    
  • treat hemolysis: discontinue oxidant drugs, increase oral/IV fluids, RBC transfusions if necessary
  • screen for G6PD in HIV/AIDs patients and elderly women susceptible to UTIs who may require Bactrim

MAHA

• Def:
  • Damage occurs to the endothelium of small vessels
    
  • Fibrin mesh form, which guillotines RBC as they travel
    
  • RBC membrane reseals but a small amount of hemoglobin leaks out
    
  • Damaged RBC fragment now called schistocyte
• Types of disorders:
  • DIC
    
  • TTP
    
  • HELLP
    
  • Malignant hypertension
• Diagnosis:
  • Elevated LDH, bili
    
  • Increased bili
    
  • Often associated with low platelets
    
  • Schistocytes on PBS
    
  • Other findings depending on etiology
• Management:
  • Depends on the underlying disorder

Sickle Cell Disorders

Sickle cell anemia (SS)

• Def:
  • > Inheritance of sickle cell gene from both parents.
    
  • > Valine substituted for glutamic acid in 6th position of β chain.
    
  • > Hgb Electrophoresis – ≥ 80% S, 1%-20% F, normal A2 , no A
    
  • > Moderate to severe anemia.

Sickle cell trait (AS)

• Def:
  • > Inheritance of sickle cell gene from 1 parent.
    
  • > Hgb Electrophoresis – 50%-65% A, 35%-45% S, normal F, N to slightly ↑ A2
    
  • > No anemia. Important to Dx for genetic counseling.

Hemoglobin C disease (CC)

• Def:
  • > Inheritance of gene for Hgb C from both parents.
    
  • > Lysine substituted for glutamic acid in 6th position of β chain.
    
  • > Hgb Electrophoresis – >90 C, <7% F, no A
    
  • > Mild to moderate anemia.

Hemoglobin C trait (AC)

• Def:
  • > Inheritance of gene for Hgb C from 1 parent.
    
  • > 60%-70% A, 30%-40% C

SC disease (SC)

• Def:
  • > Inheritance of 1 sickle cell gene & 1 Hgb C gene.
    
  • > Hgb Electrophoresis – >S than C, normal to 7% F, no A
    
  • > Mild to moderate anemia.