see also:

• hyperlipidaemia
• https://www.uwhealth.org/cckm/cpg/cardiovascular/related/Very-severe-hypertriglyceidemia---Adult---Inpatient-Emergency-Dept--181115.pdf

• 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)

• 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
    • obesity
    • poorly treated diabetes mellitus
    • excessive ethanol use
    • pregnancy
    • hypothyroidism
    • nephrotic syndrome
    • certain medications
      • beta adrenergic blockers, corticosteroids, oestrogens, progestogens, anabolic steroids, tamoxifen, retinoids such as isotretinoin (Roaccutane), Thiazide diuretics, loop diuretics, anti-psychotic medications, and others
    • occasionally may be due to ApoE2/E2 homozygosis (dysbetalipoproteinemia, type III hyperlipoproteinemia)

• 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.

• triglycerides produced by the liver are carried by very low-density lipoproteins (VLDL) and are also catabolized by lipoprotein lipase.

• 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.

• this is a syndrome that results from hyper-viscosity due to high levels of chylomicrons in the circulation
• it can manifest as:
  • pancreatitis
  • abdominal pain
  • impaired cognition/memory
  • paresthesias
  • hepatosplenomegaly
• in addition:
  • 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.

• supportive Mx of pancreatitis as per usual
• acute reduction of serum TG levels:
  • nil orally to allow clearance of chylomicrons
  • cease any offending medications
  • control hyperglycaemia
  • 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
• long term Mx of hypertriglyceridaemia:
  • fibrates +/- statin
  • increase exercise
  • avoid alcohol
  • weight reduction
  • control diabetes and hypothyroidism if present
  • avoid medications which exacerbate TG levels
  • see hyperlipidaemia