Cryoprecipitates are clotting precursors that settle out in particle form when blood is exposed to low temperatures. They contain large amounts of coagulation factor VII, von Willebrand factor, fibronectin, fibrinogen, and coagulation factor XIII. This clotting precipitant may occur more readily if there is an abnormal fibrinogen- fibrin activation. Patients with ischemic heart disease, smokers, those exposed to excessive stress probably have an increased risk of fibrin formation during hypothermic episodes. This intro is actually concerned with possible irreversible oxygenator clotting problems associated with this phenomena.
The activation of the coagulation mechanism by contact with synthetic surfaces is an obstacle when putting a patient on cardiopulmonary bypass (CPB) or other types of extracorporeal circulation. During CPB there is a strong reaction that takes place when rapidly cooling the blood. Platelet activation and aggregation enhance the formation of cold-reactive proteins. Agarwal et al. showed that the incidence of cold- reactive proteins in heart patients ranged from 0.4 to 4 %. The cold-reactive proteins have been broken down into four categories: Donath-Landsteiner antibodies, cold agglutinins, cryoglobulins, and cryofibrinogen. These four categories are further separated into two types. Those that react with red blood cells and those that react with platelets.
Red Blood Cell Reactions: The D-L antibodies and cold agglutinins occur in the sera of healthy patients. The reaction takes place at hypothermic temperatures. The activation of cold agglutinins is of low clinical significance due to the fact that relatively few people are either intentionally or accidentally exposed to hypothermic core temperatures. D-L antibodies show a broader range of temperature reactions however these antibodies are very uncommon in patients tested for heart surgery. These two cold-reactive proteins are can be easily controlled to prohibit oxygenator clotting problems. The cold agglutinin reaction is easily identified and can be reversed when temperatures remain above is reactive amplitude.
Platelet Reactions: The third category of serum protein or antibody reaction is that of cryoglobulins. Cryoglobulins show a weak reaction with platelets that undergoes a reversible precipitation at low temperatures. The fourth category, cryofibrinogens demonstrates a strong reaction with platelets during hypothermic temperatures. Hypothermic CPB activating the intrinsic cascade up to the formation of fibrinogen combined with platelet activation and aggregation has shown significant clots in oxygenators. This phenomena is focused during the time period of rapid cooling. Cryoprecipitation of cryofibrinogen explains the frequent presence of thrombus in heat exchangers with narrow channels, low priming volumes and a high heat exchange coefficients. There is also a suggestion that polycythemic patients could also exacerbate this phenomena. It should also be mentioned that these clotting problems are not a newly discovered phenomena. It is simply more obvious because of advances seen in perfusion equipment technology.
PREVENTIVE MEASURES: At the moment there are no screening tests to effectively predict which patients are predisposed to cryoprecipitation problems, high platelet counts, high serum levels of fibrinogen, and high coagulation factor XII may induce suspicion. It is suggested that perfusionists modify their CPB protocols by: Using albumin in the priming solutions Slow the rate of hypothermic inductions Monitor oxygenator inlet pressures Stop hypothermia and/or rewarm slightly is cryoprecipitation is encountered Vroman effect: the sequential adsorption and displacement of proteins on an artificial surface over time. Using albumin in the priming solution will add another protein displacement step in this sequence to eventually produce stable fibrin.
This Intro was excerpted from AmSECT Today © 1996; The feature article, The Puzzling Case of the Cryoprecipitates, Bearss M.G., Ericson D., Parks P.J., Rice R.
Mark Bearss 3M Health Care Professional Services (800) 262-3304, ext. 6336.
Agarwal S.K., Ghosh P.K., Gupta D., Cardiac surgery and cold-reactive proteins. Ann Thorac Surg. 1995;60:1143-1150