acute severe and very severe hypertriglyceridemia causes cause chylomicronemia syndrome and is the 3rd most common cause of pancreatitis and should be suspected when obvious lipaemia is present on venipuncture blood specimens
generally defined as serum TG levels exceeding 1000mg/dL (“very severe”) or 500-999mg/dL (“severe”)1)
almost all patients with very severe elevations in triglycerides have primary and secondary contributors
plasma triglycerides level reflects the concentration of triglyceride-carrying lipoproteins (mainly VLDL and chylomicrons)
Aetiology
young children may have genetic causes which usually present in infancy such as:
lipoprotein lipase (LPL) deficiency
apolipoprotein (Apo) C-II deficiency
adults:
high fatty meal in patients with predisposition to impaired lipid metabolism
occasionally may be due to ApoE2/E2 homozygosis (dysbetalipoproteinemia, type III hyperlipoproteinemia)
Physiology
exogenous pathway
dietary triglycerides (fats) are assembled in the intestinal wall into chylomicrons which enter the venous circulation.
lipoprotein lipase on the luminal surface of the capillary endothelial cells hydrolyze triglycerides in the core of the chylomicrons into free fatty acids and glycerol which can be used as energy sources or for gluconeogenesis.
endogenous pathway
triglycerides produced by the liver are carried by very low-density lipoproteins (VLDL) and are also catabolized by lipoprotein lipase.
pathophysiology of severe hypertriglyceridaemia
In severe and very severe hypertriglyceridemia, the lipoprotein lipase catabolism system is saturated.
Thus after a fatty meal, when a patient’s TG level is already above 500 mg/dL, the TG level can significantly increase.
Chylomicronaemia syndrome
this is a syndrome that results from hyper-viscosity due to high levels of chylomicrons in the circulation
the patient may have eruptive xanthomas which are skin manifestations of very severe triglycerides elevations due to trapping of triglycerides in cutaneous histiocytes and are yellow papules mainly on extensor surfaces and the buttocks
lipemia retinalis (pallor of the optic fundus where the retinal veins and arteries appear white or creamy) also may be present.
those with type III hyperlipoproteinemia can have striate xanthomata of the palms tuberoeruptive xanthoma.
Clinical Mx of pancreatitis due to acute severe hypertriglyceridemia
aggressive insulin Rx may help, especially in diabetics
heparin is NOT recommended in pancreatitis due to bleeding risk
fibrates are 1st choice for lowering TG but have slow onset of action
Fenofibrate (160 mg/day) or micronized fenofibrate (200 mg/day) should be started if therapy is not contraindicated, patient’s creatinine clearance >30 ml/min, and liver enzymes are acceptable (i.e., AST/ALT <2.5x ULN).2)
Omega-3-FA have an immediate onset of action with no significant side effects
medium-chain triglycerides (MCT) also have an immediate onset of action with no significant side effects
plasmapheresis may need to be considered
indicated in medical emergencies such as hypertriglyceridemic pancreatitis if TG levels are excessively elevated (TG > 1,000 mg/dL). 3)
NB. Patients on ACE inhibitors (ACE-I) who are treated with plasmapheresis can uncommonly develop neurochemical hypotension that may be severe and life threatening. Defer for at least 24hrs after last dose ACE although proceed with caution earlier if more urgent need such as evidence of SIRS
Patient probably should not be discharged until the serum triglycerides are under 500 mg/dL and patient is clinically stable