Throughout the process of digestion,
triglycerides are broken down to monoglycerides and fatty acids within the
small intestine. After breakdown, both components are transported through the
intestinal epithelium and resynthesized into triglycerides. The resynthesized
triglycerides enter the intestinal lymph from the basolateral side as small
particles and are referred to as chylomicrons. Chylomicrons then travel by
lymph to be released into venous circulation at the connection of the jugular
and subclavian veins.(1,2)
a high-fat meal, triglyceride and chylomicron concentrations significantly
increase and potentially become as much as 1 to 2% of plasma, causing it to
become turbid. To remove chylomicrons from circulation, lipoprotein lipase
(LPL) is produced in certain tissues, including adipose, skeletal muscle, and
cardiac. When chylomicrons pass through the epithelium of these tissue types,
LPL is released and hydrolyzes the triglycerides into fatty acids and glycerol.
After hydrolysis, fatty acids can be absorbed by various tissues, including
adipose and muscle to be stored for use in energy production (i.e., eventually
ATP production). Remnants of chylomicrons are then rapidly cleared from
is a glycosaminoglycan found endogenously in mast cells or synthesized from
porcine intestinal mucosa mast cells.(3,4) While the primary pharmacological
use of heparin is anticoagulation, another effect of heparin is direct
stimulation of LPL release into plasma from epithelial cells. The increase in LPL
will enhance the body's ability to remove triglycerides, lowering plasma
patients with severe hypertriglyceridemia, heparin can be used to reduce
triglyceride concentrations to levels < 1,000 mg/dL within 72 hours.
Stimulation of LPL peaks approximately 1 hour following administration of
heparin. However, the effect rapidly declines and repeat dosing of heparin
produces LPL concentrations 15 to 35% of the original peak. Additional doses of
heparin can result in continually decreasing concentrations of LPL, thereby
causing a reduction in hydrolysis of chylomicrons. Ultimately, heparin will
deplete LPL at a more rapid pace than new enzyme is synthesized.(6-8)
administration of heparin leads to the absence of sufficient LPL to hydrolyze
chylomicrons, thereby resulting in an inability to remove triglycerides from
plasma. Since the process to synthesize new LPL is slow, the use of heparin may
lead to long-term suppression of LPL and its ability to remove triglycerides
from circulation. As a result, the discontinuation of heparin may lead to a
rebound hypertriglyceridemia until sufficient quantities of LPL can be
our knowledge there are no official dosing guidelines for the use of heparin in
this situation. Based on case reports, heparin was initiated after insufficient
lowering of triglycerides with making the patient NPO (nothing by mouth),
intravenous (IV) fluids, and insulin infusions. Both subcutaneous heparin
and heparin intravenous (IV) infusions have been used, with most requiring IV
heparin infusions to achieve sufficient lowering of triglycerides even if
initially starting with subcutaneous heparin. If heparin is needed
despite other interventions, starting with a standard weight based infusion to
keep the PTT 1.5 - 2 times the upper limit of normal and to achieve
triglyceride levels of at least < 1,000 mg/dL is reasonable, while keeping
in mind that the effectiveness of heparin can decline with continued use.
Lastly, it is most important to treat the underlying cause for the
hypertriglyceridemia as well give consideration to the initiation of a fibric
acid derivative and/or fish oil.
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Saunders Elsevier; 2011. 1120 p.
RL. Pharmacotherapy: A Pathophysiologic Approach. 7th ed. New York, NY:
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JI. Goodman & Gilman's the Pharmacological Basis of Therapeutics.
12th ed. New York, NY: McGraw-Hill; c2011. Chapter 30, Blood coagulation and
anticoagulant, fibrinolytic, and antiplatelet drugs; p. 853-5.
D, Zimmerschied J. Heparin and insulin for hypertriglyceridemia-induced
pancreatitis: a case report. Scien World J. 2009;9:1230-2.
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M, Rassin T, Eisenberg S, et al. Continuous intravenous heparin administration
in humans causes a decrease in serum lipolytic activity and accumulation of
chylomicrons in circulation. J Lipid Res. 1994;35:229-38.
B, Olivecrona G, Olivecrona T, Stegmayr BG. Lipoprotein lipase during
continuous heparin infusion: tissue stores become partially depleted. J Lab
Clin Med. 2001;138(3):206-13.
JD, Mancell J. Hypertriglyceridemia-induced acute pancreatitis treated with
insulin and heparin. Am J Health-Syst Pharm. 2012;69:213-6.
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hypertriglyceridemia in diabetic ketoacidosis. Arch Intern Med.