Cold Agglutinins => Autoimmune hemolytic anemia (AIHA) occurring around 28-31°C -> Typically IgM auto antibodies directed against red blood cells, causing clumping (agglutination) of RBCs (i.e Mycoplasma pneumoniae, CMV, EBV, infectious mononucleosis, varicella zoster virus, HIV, lymphoma, CLL, Waldenström’s)

Cryoglobulins =>  Insoluble immunoglobulins (also IgM/IgG) that precipitate out of serum in cold temperatures and re-dissolve upon rewarming (i.e Hepatitis C, Multiple Myeloma, lymphoma, CLL, sarcoidosis, SLE, RA) 

TYPE 1 CRYOGLOBULINS
Monoclonal IgM. Think Myeloma/ Lymphoma. Hypervisocity, Raynauds. Digital ischemia
TYPE 2 CRYOGLOBULINS
Monoclonal IgM, Poly IgG. Think Infections/ Hepatitis C. Fatigue, Mylagia, Purpura 
TYPE 3 CRYOGLOBULINS
Poly IgM, Poly IgG. Think autoimmune (i.e Sjogrens).  
TESTS
ANA, ENA, RF (elevated in 2/3) and C3 and C4 (typically low) 

REFERENCES

  1. CHAPTER 126: Rheumatology in the ICU. Scott Vogelgesang; Vijay Raveendran Pottathil; John A. Robinson. Principles of Critical Care, 4e
  2. Chapter 41. Hematologic Emergencies. MK Strecker-McGraw, MD; Wilson Mark Andrew, MD. CURRENT Diagnosis & Treatment Emergency Medicine, 7e

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