Severe Hypertriglyceridemia in Pregnancy

May 12,2000
Hon-Mei Cheng

Case Report ( x , 1016-0143)

A 33-year-old woman gravida II para I at 23 weeks of gestation was admitted to
our hospital with abdominal pain and vomiting. Notable physical findings at the time of
admission included BP 105/57 mmHg, BT 36.5 C, PR 94/min, RR 20/min, epigastric
tenderness and a normal gravid uterus, there was no eruptive xanthomas present.
Abdominal ultrasonography showed swelling of pancreatic head and body, c/w acute
edematous pancreatitis and fatty liver. Laboratory tests with abnormal results included
those for lipase, 3870 U/L; amylase 2658 IU/L; leukocyte count, 10300/uL; serum
calcium 8.7 mg/dl; blood sugar 138 mg/dl; and lipemia. Lipid profiles were evaluated
later with triglyceride, 578 mg/dl; total cholesterol, 328 mg/dl; HDL-C, 46.6 mg/dl;
LDL-C, 201 mg/dl. Lipid electorphoresis showed fractions of alpha 27.9% (19-52),
prebeta 45.6% (4-35), beta 22.7% (36-62), chylomicron 3.8% (0-2). The clinical
course was improved after treatment with intravenous fluids and fasting, then a low fat
diet, she was discharged 4 days after. But one week later, patient was readmitted due
to recurrent pancreatitis with hypertriglyceridemia. (1518 mg/dl)
Traced her medical history, hyperlipidemia had been told when age of 18 y/o.
During the previous pregnancy, intermittent abdominal pain was noted after the second
trimester, she was treated as peptic ulcer disease while seeking medical attention. She
received a complete physical check-up 5 years ago, hyperlipidemia with triglyceride
681 mg/dl and total cholesterol 93 mg/dl was noted. Thyroid function test was normal.
She was referred to our OPD and took Lopid 2# bid for a while. There was no history
of alcohol abuse, no family history of hyperlipidemia.
Discussion:
- Severe hypertriglyceridemia causing pancreatitis is a rare complication of pregnancy.
Plasma triglyceride levels normally rise in pregnancy, due mainly to an estrogen-related
increase in hepatic production of TG-rich lipoproteins and to a decrease in endothelial
lipoprotein lipase (LPL) activity.
- In the presence of a preexisting abnormality of triglyceride metabolism, pregnancyassociated hypertriglyceridemia can be complicated maternal death due to severe
pancreatitis, especially if the condition has gone unrecognized.
-Treatment for pregnancy-associated hypertriglyceridemia has focussed on the
reduction of plasma chylomicron levels through the institution of a very low-fat diet (<
10% of total calories as fat) given with protein and vitamin supplementation.
- Long-term compliance with fat-restricted diets is poor because these diets are
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unpalatable and difficult to maintain. An additional concern in the pregnant patient is

the adequacy of total caloric intake to maintain fetal growth. Essential fatty acid and
essential amino acid content must also be ensured through the use of supplements if
severe restrictions are implemented. Also, displacement of fat by carbohydrates to
maintain an isocaloric diet can paradoxically increase endogenous TG production.
- Severe plasma TG elevation refractory to outpatient management requires
interruption of oral intake along with intravenous administration of a 5% dextrose in
water solution for several days until plasma TG levels fall below a predetermined
threshold.
- In very severe cases, TPN or lipoprotein apheresis may be required. The theoretical
metabolic advantages of TPN must be weighed against the risks of complications from
central venous catheter placement, such as hemorrhage, infection, phlebitis, and
pneumothorax.
- Several investigators have also examined the utility of plasma exchange in rapidly
lowering plasma TG levels in refractory cases of pregnancy-associated
hypertriglyceridemia. However, it is not clear that there is sustained benefit over
several months using this treatment.
- Administration of intravenous heparin release LPL from its endothelial binding sites
into the circulation and is used clinically to assess LPL activity. Intravenous heparin has
also been show to acutely lower plasma TG levels. Heparin does not cross the bloodplacenta barrier, so it is the preferred anticoagulant during pregnancy.
- Weintraub et al found that sustained intravenous heparin administration in 12 male
and 5 non-pregnancy female patients resulted in a decrease in plasma lipolytic activity.
They hypothesized that the decrease in plasma lipolytic activity occurred as a result of
depletion of LPL and hepatic lipase due to continuous release from endothelial sites.
- The use of heparin in pregnancy may be complicated by thrombocytopenia, elevation
of liver enzymes, and osteoporosis with long-tern use. There is also a potential for
vertical transmission of anti-heparin antibodies generated in the pathogenesis of
thrombocytopenia from mother to fetus through transplacental transfer. The
hemorrhagic complications of intravenous heparin may be avoided by regular
monitoring of partial thromboplastin times and careful timing of reversal of
anticoagulation before induction of labor.
- In patients with a preexisting impairment of LPL activity, pregnancy can worsen the
biochemical phenotype and exhibit the classical clinical signs of chylomicronemia
during pregnancy, such as lipemia retinalis, hepatosplenomegaly, eruptive xanthomas,
abdominal pain and acute pancreatitis.
- The LPL gene appears on chromosome 8, spans 35kb, has 10 exons and codes for
474 amino acids in a functional enzyme. More than 25 different mutations in the LPL
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gene have been identified that result in a completely catalytically inactive LPL protein.
- Homozygous LPL deficiency is a rare autosomal recessive disorder, and its frequency
is estimated to be one per million. The prevalence of heterozygous LPL deficiency is
calculated to be one in 500 individuals based on the frequency of homozygous LPL
deficiency.

References:
1. Identification of homozygous lipoprotein lipase gene mutation in a woman with
recurrent aggravation of hypertriglyceridemia induced by pregnancy. J Int Med
1998;243:317-312.
2. Acute pancreatitis in pregnancy. Acta Obstet Gynecol Scand 1995;74:607-610.
3. Hyperlipidemia and pancreatitis during pregnancy in two sisters with a mutation in
the lipoprotein lipase gene. Annals Int Med 1996;124:425-428.
4. Successful outcome in severe pregnancy-associated hyperlipemia: A case report
and literature review. Amer J Med Scien 1994;309:213-218.
5. Drug treatment of lipid disorders. NEJM 1999;341:498-511.
6. Therapeutic plasma exchange. NEJM 1984:310:762-771.
7. Lipoprotein lipase. NEJM 1989;320:1060-1068.
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8. Disorders of lipoprotein metabolism . Harrisons chapter 341.