The Effect of Intravenously Administered Fat on the Coagulation Mechanism

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Abstract
The effect of long-term infusion (fifteen bottles or more) of fat emulsions (Lipomul) on the clotting mechanisms was studied in eleven subjects. Increased prothrombin consumption (measured by the TAMe synthetic substrate assay) and tendency for a shortened clotting time usually followed each infusion. Plasma prothrombin levels (TAMe) fell slightly following infusions. In eight patients prothrombin was determined before infusion at weekly intervals by the former method. In seven of these eight subjects prothrombin levels fell gradually particularly as the infusions were continued beyond fifteen days. This trend progressed despite discontinuance of therapy. In two patients on long-term therapy a hemorrhagic syndrome developed associated with a long bleeding time, depression of prothrombin, factors v and vii (one patient) and impaired prothrombin consumption. In addition, one patient demonstrated a factor ix and/or x defect as well as abnormalities in fibrinogen conversion; an acquired thrombasthesia was also demonstrated in this patient. These observations led to more intensive studies of patients receiving twelve bottles of Lipomul. Two types of determinations were performed; studies before infusion on days 1 (control), 6 and 12 and similarly timed studies at the termination of the infusions to detect the immediate effects of the emulsion. Following the infusions, a shortening of the clotting and viper venom times was noted, as well as an increase in platelet adhesiveness and a slight fall in prothrombin (TAMe assay). These changes were transient in nature when therapy was limited to twelve bottles. The only persistent change noted before infusion was a slight but statistically significant prolongation of the one-stage prothrombin time. Platelet function using the thromboplastin generation screening test (TGST) was assayed with a variety of preparations. Intact platelets derived from the patients’ plasma before and after infusion were tested in their parent plasma samples. With this method, abnormalities were observed prior to the infusion by the twelfth day of therapy in two of ten subjects. Pooled frozen platelets derived from normal donors were tested in eleven paired “nonlipemic” and “lipemic” plasma samples obtained from patients receiving Lipomul. Abnormalities in the TGST were noted in three of eleven instances prior to the infusions on the sixth day of therapy, with the defect persisting through the twelfth day. When these platelet preparations were utilized with “lipemic” plasmas, abnormalities were noted in five of eleven instances on the fourth day of therapy and in eight of eleven by the twelfth day. The patients’ platelets derived from paired “nonlipemic” and “lipemic” samples were frozen and subsequently tested in their parent plasma samples, as well as in “nonlipemic” plasmas derived from normal subjects. Frozen platelets derived from “lipemic” plasmas, functioned abnormally in both their parent plasma samples and in “nonlipemic” plasmas obtained from normal subjects. Progressive deterioration in function, with continuation of therapy, was not noted in this small series. Gross abnormalities were noted in the TGST when platelet substitute was used. Such abnormalities were observed prior to the infusion by the twelfth day of therapy in three of six instances. The infusion of the fat corrected the defect, suggesting that in this particular system the fat itself had furnished thromboplastic activity. The transient and moderate nature of these various changes in the clotting mechanisms indicate the relative safety of therapy with twelve bottles of the emulsion. They may, however, represent the prelude to the gross abnormalities observed with more prolonged therapy.