vitamin-k-semiquinone-radical and Hypertriglyceridemia

Intravenous lipid emulsions (IVLEs) are an essential component of parenteral nutrition. With the recent incorporation of new lipid emulsions into the Canadian and American market, the clinician responsible for prescribing these lipids should be educated regarding the different fatty acid (FA) profiles of these lipids, as well as their metabolic and functional effects.. New IVLEs contain a mix of soybean oil and olive oil, or a mix of soybean oil, coconut oil, olive oil and fish oil. These new lipid emulsions provide less essential fatty acids (FAs) (linoleic and alpha linolenic acids) than in pure soybean oil, yet incorporation of fish oil into an IVLE may decrease the amount of essential FAs required. Fish oil is a treatment for hypertriglyceridemia, and therefore, IVLEs that include fish oil may decrease serum triglycerides. Historical perspective is that fish oil can be associated with increased bleeding time. Evidence suggests that there is no association between fish oil and increased bleeding in patients, even those who are using anticoagulants. New IVLEs provide less vitamin K than soybean oil alone. Patients, or the parenteral nutrition solutions that include these new IVLEs should be supplemented with vitamin K.. Canadian and American Guidelines for IVLEs were based on soybean oil. Current practice should be tailored to which IVLE is being prescribed.

Topics: alpha-Linolenic Acid; Blood Coagulation; Canada; Coconut Oil; Fat Emulsions, Intravenous; Fish Oils; Humans; Hypertriglyceridemia; Linoleic Acid; Olive Oil; Parenteral Nutrition; Soybean Oil; United States; Vitamin K

To review the current state of the science regarding intravenous fat emulsions (IVFEs), with an emphasis on their safety profile.. Articles were identified via a search of the MEDLINE database, including publications from 1979 to December 2009, using a search string that included the terms parenteral nutrition, lipid emulsion, fat emulsion, IVFE, safety, adverse effect, neonate intralipid, and terms describing a range of specific adverse events (AEs) such as pancreatitis.. We selected articles that allowed us to compare the results of clinical trials involving delivery of medications via IVFEs with the historical use and effects of IVFEs in parenteral nutrition, with an emphasis on AEs. We focused on 2 drugs in current use that are administered intravenously in lipid emulsions: propofol and clevidipine.. Clearance of the fat particles in IVFEs is mediated by the enzyme lipoprotein lipase. AEs are more likely if the rate or duration of IVFE administration exceeds the enzyme's clearance capacity. AEs are also more likely after administration of a 10% IVFE formulation than a 20% formulation, because the higher concentration of free phospholipid in the 10% formulation interferes with lipoprotein lipase activity. AEs can be reduced by administering IVFEs at a dosage < or = 2.5 g/kg/day and at a rate < or = 0.11 g/kg/h. The anesthetic agent propofol, which is formulated in a 10% IVFE, has been used clinically for 25 years. Typical AEs associated with propofol use include infection, high plasma triglyceride concentrations, and pancreatitis. Recent clinical trials involving clevidipine, which is formulated in a 20% IVFE, have demonstrated a low rate of lipid-related AEs.. The results of this review demonstrate that IVFEs are well tolerated when administered in accordance with guideline recommendations.

Topics: Anticoagulants; Antidotes; Bacteria; Drug Delivery Systems; Drug Interactions; Drug Overdose; Fat Emulsions, Intravenous; Humans; Hypertriglyceridemia; Immune System; Infant, Newborn; Infant, Premature; Infant, Small for Gestational Age; Liver Function Tests; Pancreatitis; Parenteral Nutrition; Respiratory Function Tests; Vitamin K

It has been demonstrated that the surface of large VLDL Sf 100-400 can bind both prothrombin and Factor X(Xa) and that on VLDL Factor Xa can convert prothrombin to thrombin, which degrades apo B and apo E. It has been reported also that the VLDL kinetically supports the conversion of prothrombin to thrombin. The binding of vitamin K-dependent proteins to phospholipid is partially Ca2+-dependent and probably involves their Gla residues. The complex of VLDL, prothrombin, Factor Xa, and Ca2+ lacks only Factor Va, a lipid associating, non-Gla residue containing 330 kd protein, to complete the "prothrombinase complex." Factor V (Va) is found at very low concentrations in the circulation, but is localized on platelets, monocytes, and the endothelium. VLDL can bind both to monocytes and to the endothelium, for example, through both receptor and non-receptor pathways. When carrying this complement of the prothrombinase complex, this subpopulation of VLDL, in the presence of Factor Va on cell surfaces, could conceivably upset the local balance of pro- and anticoagulant activities. Thus, directly or indirectly the increased triglyceride levels, reflected in increased VLDL in patients, may alter this balance, and thereby produce a "hypercoagulable state." This is a simplistic view of the potential role of VLDL in the interplay of cells, coagulation proteins, and the regulatory systems involved in vivo. To realize the degree of complexity that we may need to address, we need only look at the work of Booyse et al in this issue of Seminars, in which they demonstrate that hypertriglyceridemic VLDL, in contrast to normal VLDL, do not support the early release of t-PA from endothelial cells, an antifibrinolytic event.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Calcium-Binding Proteins; Factor X; Glycoproteins; Humans; Hypertriglyceridemia; Lipoproteins, VLDL; Protein Binding; Prothrombin; Vitamin K

Vitamin K antagonists (VKA) are the first cause of iatrogenic mortality in France. Therefore, it is crucial to monitor these treatments with the International Normalized Ratio (INR) determination, which can be altered by several plasma elements. We report a patient who presented a serious bleeding event while under VKA treatment related to INR determination difficulties due to a high hypertriglyceridemia. We suggest some solutions (fasting and mechanic method in INR determination) in order to improve the control of the VKA treatment for patients with hypertriglyceridemia.

Topics: Female; Hemorrhage; Humans; Hypertriglyceridemia; International Normalized Ratio; Middle Aged; Vitamin K

To investigate the relationship among lipids, coagulation and thrombosis in the absence of atherosclerosis, spontaneous or dietary-induced hyperlipidemic (FHL) rats were studied. FHL showed higher levels of coagulation factors VII, IX, X, VIII and XII and a shortening of the occlusion time (OT) of an artificial arterial prosthesis as compared with normolipidemic (FNL) animals. Damage of abdominal aorta of FHL was followed by increased fibrin deposition in the vascular intima as compared to FNL. After 5 months of cholesterol-rich diet FNL showed increased cholesterol, triglycerides and factor II, VII, IX, X, XII levels. A significant shortening of the OT and increased fibrin deposition was also observed. Two-month diet withdrawal restored the initial condition. Warfarin treatment, at a dose decreasing vitamin K-dependent factor to levels found in FNL, prolonged the OT and reduced fibrin deposition, without modifying F XII or changing lipid profile. An increase in the activated form of F VII was observed. In contrast, no difference was found in F VII clearance. High lipid levels favour the process of thrombus formation by increasing the activation of vitamin K-dependent coagulation factors. Low-dose warfarin treatment reverts the prothrombotic effect of hyperlipidemia.

Topics: Administration, Oral; Animals; Anticoagulants; Aorta, Abdominal; Aortic Diseases; Blood Coagulation Factors; Blood Vessel Prosthesis; Cholesterol, Dietary; Diet, Atherogenic; Disease Models, Animal; Enzyme Activation; Factor VII; Hypercholesterolemia; Hyperlipidemias; Hypertriglyceridemia; Postoperative Complications; Rats; Rats, Inbred Strains; Rats, Sprague-Dawley; Thrombophilia; Thrombosis; Vitamin K; Warfarin