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)

After 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 circulation.(1,2)

Heparin 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 concentrations.(2,5,6)

In 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)

Continued 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 resynthesized.(7,9)

To 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.

References:

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