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Neutralization by protamine of the heparin activation of antithrombin III in plasma, in vitro, represents an equilibrium reaction in which by mass action heparin remains complexed only in the presence of an excess of protamine. Loss of this excess through enzymatic breakdown of the free protamine leads to instability of the complexes with liberation of the heparin, reestablishing antithrombin activity. This "heparin rebound" can also be produced by an increase in heparin levels or increased amounts of antithrombin III. These phenomena could occur after extracorporeal bypass procedures by an increase in heparin from whatever source or by added antithrombin III, through transfusions of fresh frozen plasma. A larger excess of protamine does not itself act as an anticoagulant but produces large heparin-protamine complexes that can still activate antithrombin III. Such large complexes, formed in vivo, could possibly block the pulmonary microcirculation and cause the acute pulmonary hypertension that has been reported after protamine infusions.

With the observation that bacterial endotoxins alter the blood coagulation system in ~/vo (1), the question was raised as to whether this is a direct or an indirect effect of the toxins on the blood. I n an a t t e m p t to answer this question and to determine the mechanism b y which bacterial endotoxin affects the coagulation system the following in ~itro studies were performed. E(ect of Endotoxin on Whole Blood.-To test the effect of bacterial endotoxins on the coagulation time of whole blood, a modified Lee-White coagulation time in silicone was used. One ml. of human blood was added to each of three tubes containing 0.2 ml. of saline for the control series, and 0.2 ml. of saline containing varying concentrations of Shear's polysaccharide 1 for the tests. Four concentrations of endotoxin were used; i.e., 1, 0.1, 0.01, and 0.005 nag. per 0.2 ml. of sterile saline. The highest dilution (0.005 mg.) was caicuiated to be the concentration per milliliter of blood which would be achieved immediately following the intravenous injection of doses of endotoxin capable of producing the generalized Shwartzman reaction in 1 kg. rabbits. The blood of three individuals was used with all 4 concentrations of Shear's polysaccharide. The time required to achieve a solid dot in the third tube was taken as the coagulation time. The results are presented in Table I and Fig. 1.In amounts as small as 0.005 rag. per ml., Shear's polysaccharide shortens the coagulation time of whole blood approximately 20 per cent. Within the range of amounts of endotoxin used, the shortening of the clotting time was directly proportional to the amount of endotoxin until at levels of 1 mg./ml. it was at least 50 per cent shorter than the control dotting time.T h a t this property of Shear's polysaccharide is shared b y other bacterial endotoxins is shown in experiments illustrated in Table I

A programme for the daily monitoring of Fresh Frozen Plasma (FFP) usage, combined with continuous education in the correct use of FFP, was started at William Beaumont Hospital in 1985. In 2 years, this had resulted in a 77% reduction in FFP usage. An analysis of the type of cases which received FFP, after the major reduction had occurred, from July, 1985 through June, 1989 is presented. During this time 2,612 units were administered to 873 patients, an average of 54 units per month. According to the accepted criteria established by the Hospital Transfusion Committee, 67% of the transfused units on the medical service were deemed indicated, compared with 54% on the surgical service. Most of the FFP was used to treat patients with liver disease, or receiving coumadin, or undergoing coronary bypass surgery. Conditions which will decrease the need for FFP administration are also presented for consideration. The results indicate that a consistent monitoring and education programme can keep blood and blood component usage at a defensible minimum.