Autoimmune Hemolytic Anemia

Snapshot

• A 57-year-old woman recently moved from Florida to Maine over the summer. She presents in November as a new patient, looking to establish a primary care relationship. She complains that ever since the temperature dropped, she develops painful, numb, blue fingers, and toes. They return back to normal once she warms up indoors. However, this happens every time her fingers and toes are cold. Her nose sometimes turns blue too. On closer questioning, a few weeks ago, she felt fatigued and had a “long cold,” with sore throat and swollen lymph nodes. She shows a photo of her lymph nodes at the time.

Introduction

• Extrinsic hemolytic anemia caused by antibodies
  • type II hypersensitivity
• Epidemiology
  • peak incidence in 50s-80s

Characteristics	Warm Agglutinin (IgG)
Temperature at which antibodies are most reactive to RBC	Body temperature
Chronic vs acute	Chronic
Associated conditions	SLE (most common)CLLDrugs (α-methyldopa and penicillin)
Epidemiology	AIHA (most common)
Mneumonic	Warm weather is GGGreat

Presentation

• Symptoms
  • warm agglutinin disease
    • chronic hemolytic anemia
  • cold agglutinin disease
    • acrocyanosis (different from Raynaud)
      • painful and blue toes/fingers in the cold
      • “colder” parts of the body
    • symptoms resolve upon warming that part of the body
    • acute hemolytic anemia with the cold
• Physical exam
  • splenomegaly
• jaundice

Evaluation

• Two types of Coombs test
  • direct (direct antiglobulin test, DAT)
    • anti-IgG (Coombs reagent) added directly to patient’s RBCs
    • if RBCs coated with Ig (like in warm agglutinin disease), RBCs agglutinate
    • RBC agglutination = + DAT
    • can also use anti-C3 Coombs reagent
  • indirect
    • normal RBCs added to patient serum
    • if serum has anti-IgG, RBCs agglutinate when you add anti-IgG
    • RBC agglutination = + indirect Coombs
  • direct and indirect tells us the same thing, but indirect will tell us that there’s more antibodies

Characteristics	Warm Agglutinin (IgG)	Cold Aglutinin (IgM)
Direct Coombs test results	+ Direct Coombs test with anti-IgG Coombs reagent	+ Direct Coombs test (DAT) with anti-C3 Coombs reagent
Indirect Coombs test results	+ Indirect Coombs test (tests for IgG autoantibodies)	– Indirect Coombs test (tests for IgG autoantibodies, not performed with IgM antibodies)
Other tests	RBCs spontaneously agglutinate at room temperature	Most accurate testCold agglutinin titer
Complement levels	Normal	↓ C3 and C4

• Peripheral blood smear
  • spherocytes (also seen in hereditary spherocytosis)
• Urinalysis
  • hemoglobinuria
• hemosiderinuria

Differential Diagnosis

• Raynaud’s syndrome
• HIT 
• Hereditary spherocytosis 

Treatment

• Warm agglutinin
  • from best initial therapy to further steps in treatment ladder
    • glucocorticoids
    • IVIG
    • splenectomy
    • immunosuppressants
• Cold agglutinin
  • keep extremities warm
  • supportive therapy with folate
  • rituximab
• plasmapheresis for those refractory to rituximab

Prognosis, Prevention, and Complications

• Prognosis
  • mortality rate 10%
  • for most patients, prognosis is good
• Prevention
  • for cold agglutinin disease
    • keep warm
• Complications
  • warm agglutinin
    • lymphoproliferative disease
    • venous thromboembolism
  • cold agglutinin
    • peripheral gangrene