Cold Blood (short Tweetorial)
#Goodman_heme

3 confusing diseases

1. Cold agglutinin disease
2. Cryoglobulinemia
3. Paroxysmal cold hemoglobinuria

Two of these disease are seen often on both the heme consult service and boards.

Cold Agglutinin Disease

Hemolytic anemia precipitated by cold
Monoclonal IgM binds RBCs (I antigen), agglutination, and fixes complement in cold->hemolysis
DAT+ for C3 and - for IgG
Associated with IgM gammopathies/LPL
Polyclonal form after Mycoplasma infection
Rx = Rituximab

Cryoglobulinemia = precipitate at cold temp

I:
MPGN, palpable purpura
Monoclonal IgG/IgM
LPL, MGUS, myeloma, CLL

II:
Meltzer's triad = palpable purpura, arthralgias, weakness
Mononeuritis multiplex
Monoclonal IgM + polyclonal IgG
HCV, HIV

III:
Polyclonal IgM+IgG
Autoimmune dz

Paroxysmal cold hemoglobinuria

Cold polyclonal IgG (Donath Landsteiner Ab)
Unlike cold-reacting IgM, no RBC agglutination
But able to fix 1st 2 components of complement in cold
Antibody dissociates at warmer temps
Complement cascade completed on rewarming and hemolysis occurs

Paroxysmal cold hemoglobinuria

Polyclonal IgG specific to P antigen of RBC
DAT positive (anti-C3)
Associated with secondary or tertiary syphilis
Clinical manifestations: Dark urine after exposure to cold