Cryofibrinogen: formation and inhibition in heparinized plasma

¹ Parke, Davis and Company, Ann Arbor, and Anemia Research Laboratory, Harper Hospital, Detroit, Michigan

Cold precipitable proteins (cryoglobulins, cryofibrinogen, and heparin-precipitable fractions) have presented a considerable problem to the clinician in treatment of patients who are discovered to have such fractions and to the cardiac surgeon who is confronted with clogged filters in heart surgery with hypothermia. When heparin, 0.04 mg/ml blood, is added as an anticoagulant, fibrin threads or clots may be observed in the red cell mass. The plasma of such blood, when exposed to temperatures of 5 C for 16 hr will show two precipitable fractions, one of which is soluble at 37 C whereas the other is not. As the heparin concentration is increased, there is a serial disappearance of each fraction. The heat-soluble fraction is the last to disappear, and this occurs when the heparin concentration reaches 3.0 mg/ml blood. Normal blood similarly treated with sodium oxalate or sodium citrate shows no cold precipitation. Normal plasma, after addition of thrombin, shows both cold-precipitable fractions. Twelve patients who had varying amounts of cryofibrinogen were studied by employing a modification of the thromboplastin generation test. Eight of the twelve patients showed a hypercoagulable state.