The release of histaminase activity in plasma after small intravenous doses of heparin was studied in 85 normal subjects and in patients. In normal subjects, plasma histaminase activity (basal level, 1.7 ± 0.1 U/ml, mean ± SEM) increased 1.6 ± 0.2 U/ml after 10 U of heparin/kg, 8.5 ± 2.4 U/ml after 20 U/kg, and 33 ± 4.9 U/ml after 75 U/kg. The extent of the increase varied widely among individuals but in a particular individual the response was constant and dose dependent. Histaminase activity rose to peak levels within 7 to 15 min and then declined exponentially with a half life of 40 to 120 min. This pattern of response was also observed in 2 patients with the histaminase producing tumor, medullary carcinoma of the thyroid. A significantly reduced response was observed in 14 patients with type I hyperlipoproteinemia, a disorder in which high plasma triglyceride levels are associated with low postheparin plasma lipolytic activity. After 10 U heparin/kg, plasma histamine activity increased 0.5 ± 0.2 U/ml and after 75 U heparin/kg, 10.9 ± 5.6 U/ml. In 27 patients with other types of hyperlipoproteinemia in whom post heparin lipolytic activity was normal, the increase (2.4 ± 0.6 U/ml) in plasma histaminase activity after 10 U heparin/kg was not significantly different from that of normal subjects. The reduced response of the plasma histaminase activity to heparin in patients with type I hyperlipoproteinemia did not appear to be due to the presence of lipemia or to an inhibitor of the enzyme in plasma. These findings suggest that many patients with type I hyperlipoproteinemia may have deficient release of both lipolytic and histaminase activities into plasma after heparin administration.
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