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November 1, 1974Journal of Clinical Investigation439 citationsOpen Access

Selective Measurement of Two Lipase Activities in Postheparin Plasma from Normal Subjects and Patients with Hyperlipoproteinemia

RKRonald M. KraussRLRobert I. LevyDFDonald S. Fredrickson

Key Result

Protamine-inactivated lipase activity was markedly reduced in 12 patients with hyperchylomicronemia (including familial type I) compared to normal subjects, while protamine-resistant lipase was generally normal.

Study Design

Type

Cross-Sectional (n=180)

Structured PICO

Does selective measurement of protamine-inactivated and protamine-resistant lipase activities in postheparin plasma distinguish between hepatic and extra-hepatic lipases in normal subjects and patients with hyperlipoproteinemia?

P
Population
180 subjects, including 100 healthy volunteers and 80 patients with various forms of hyperlipoproteinemia or hypothyroidism, evaluated for postheparin plasma lipase activities.
E
Exposure
Intravenous administration of sodium heparin (standard dose 10 U/kg, up to 100 U/kg in special studies) followed by in vitro assay of postheparin plasma with and without protamine sulfate to selectively measure lipase activities.
C
Comparator
Normal subjects compared to patients with various hyperlipoproteinemias and hypothyroidism.
O
Outcome
Protamine-inactivated lipase activity (lipoprotein lipase of extrahepatic origin) and protamine-resistant lipase activity (hepatic lipase) in postheparin plasma.surrogate

Selective measurement of postheparin lipase activities using protamine sulfate distinguishes between hepatic and extra-hepatic lipases, revealing specific extra-hepatic lipoprotein lipase deficiencies in patients with familial type I hyperlipoproteinemia.

Main Result

p-value: p=<0.001

Limitations

  • Small sample sizes in specific patient subgroups
  • Ascertainment was not complete in all families for genetic documentation

Abstract

An assay has been developed for specific measurement of two different lipase activities in postheparin plasma. Lipoprotein lipase, derived from extrahepatic sources, is measured as protamine-inactivated lipase activity; hepatic lipase activity is protamine-resistant under the conditions of this assay. In 100 normal subjects, both enzyme activities were noted to be related to age and sex. Protamine-resistant lipase, which comprised 46-95% of the total activity, was highest in men over 18. Protamine-inactivated lipase activity was greatest in younger males and was age-correlated in women, doubling between the second and sixth decades. In 12 patients with hyperchylomicronemia, including five previously shown to have familial type I hyperlipoproteinemia, protamine-inactivated lipase activity was markedly reduced, whereas protamine-resistant lipase was below normal in only 1. The results were not due to lack of plasma activator, presence of plasma inhibitor, or diet, and the deficiency was not overcome by increasing the provoking dose of heparin from 10 U to 75 U/kg. Mean values for both lipase activities were not reduced in 32 other patients with hyperchylomicronemia, nine with "floating beta" lipoproteins (type III hyperlipoproteinemia), and 23 with hyperprebetalipoproteinemia (type IV). Mean protamine-resistant lipase activity was below normal in a group of four women with hypothyroidism, in whom protamine-inactivated lipase was not reduced. Both of the lipase activities were capable of hydrolyzing lipid in very low-density lipoproteins, but the relative rate of hydrolysis of chylomicrons by protamine-resistant lipase was markedly limited. These results indicate the importance of distinguishing between lipases of hepatic and extra-hepatic origin in the measurement of postheparin lipolytic activity.

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Cite This Study

Krauss et al. (1974) conducted a cross-sectional in Hyperlipoproteinemia (n=180). Hyperchylomicronemia (Type I) vs. Normal subjects was evaluated on Protamine-inactivated (extrahepatic) lipase activity (p=<0.001). Protamine-inactivated lipase activity was markedly reduced in 12 patients with hyperchylomicronemia (including familial type I) compared to normal subjects, while protamine-resistant lipase was generally normal.

synapsesocial.com/papers/6a1ff4a435281a23f90dafc9https://doi.org/10.1172/jci107855
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