COLD AGGLUTININS [Cryoproteins]

1. Definition

a) Serum antibodies that become active at decreased body temperature

b) Produce agglutination or hemolysis (via complement) of r.b.c.

c) Are directed towards antigens on the r.b.c.

2. Characteristics

a) Thermal amplitude

i) Temperature below which the Ab become activated

ii) As temperature drops below this thermal amplitude, the Ab activity increases exponentially

iii) This activity reverses as rewarming occurs

b) Titre

i) High titre of Ab are clinically more significant

c) Complement activation with hemolysis can only occur if the temp is cold enough for agglutination but still warm enough for complement activation

d) Agglutination may or may not be reversible

e) Heparinisation & dilution of blood by CPB circuit offer little/no protection against agglutination

3. Laboratory testing

a) Often see agglutination when doing routine X-matching at room temp

b) Initially screen at 4°C — if negative no further screening required; if positive require to determine thermal amplitude

c) Thermal amplitude measured by subjecting samples to several different temperatures (eg 4°C, 15°C, 22°C & 37°C)

d) — eg, positive results at 4°C & 15°C but negative at 22°C & 37°C indicate a thermal amplitude between 15°C & 37°C

4. Development

a) May be transient associated with viral infections [postpone surgery for several weeks]

b) May be chronic eg not associated with recent viral infection

5. Clinical signs

a) Rarely seen as usually only see agglutination well below body temp

b) Acrocyanosis of digits, tip of nose & ears

6. Signs on CPB

a) Undiagnosed in hypothermic CPB

i) Haemoglobinuria

ii) Intravascular agglutination [more likely due to inadequate heparinisation]

iii) Agglutination in cold blood cardioplegia circuit

iv) May proceed to multiorgan damage due to gangrene from prolonged vascular occlusion with r.b.c. agglutination

7. CPB management

a) Most important technique — use of normothermic or mildly hypothermic CPB at temperatures above the thermal amplitude

b) Warm blood cardioplegia

c) Cold crystalloid cardioplegia

d) Septal temperature monitoring of reduced myocardial temp

e) Warming of fluids, blood etc

f) Warming inspired gases

g) Plasmapheresis with high thermal amplitude patients

h) Use of arterial filters