Cryoglobulins are immunoglobulins that precipitate at temperatures below 37 c and redissolve above 37 c.  They are identified in the laboratory by storing clotted blood at 4 c for 7 days and looking for a precipitate. 

There are 3 types of cryoglobulinaemia:
  • Type 1 cryoglobulinaemia 
    • Monoclonal, usually IgM 
    • Accounts for 10-15% of cases of cryoglobulinaemia
    • Associated with 
      • Multiple myeloma 
      • Waldenstroms macroglobulinaemia 
      • CLL 
    • Features of type 1 cryoglobulinaemia include 
      • Raynaud’s 
      • Acrocyanosis 
      • Gangrene 

  • Type 2 and Type 3 cryoglobulinaemia = mixed cryoglobulinaemias 
    • Type 2 is mono and poly clonal while type 3 is polyclonal only 
    • Type 2 is the commonest, accounting for 50-60% of all cases of cryoglobulinaemia 
    • The IgM of mixed cryoglobulinaemia typically has rheumatoid factor activity 
    • Features include 
      • ‘Classic triad’ 
        • Purpura 
        • Arthralgia 
        • Weakness 
      • Widespread vasculitis 
      • Ulcers 
      • Peripheral neuropathy 
      • Membranoproliferative glomerulonephritis 
    • Associated with 
      • Hepatitis C (most common association)
      • HIV 
      • Sjogren’s syndrome 
    • Mixed cryoglobulinaemia may be complicated by 

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