Hypertriglyceridaemia, Pancreatitis, and Pregnancy: The need for Plasma Exchange.
H.Beckwith*, C. Kanonidou*, F. Cheng, R.Kadiyala, D. Ashby, N.Duncan, C. Nelson-Piercy, T. Aitman
*Joint first co-authors
Imperial College Healthcare NHS Trust.
A progressive rise in serum triglycerides and cholesterol levels is seen routinely during pregnancy. For patients with primary hypertriglyceridaemia, this rise can cause life-threatening complications including acute pancreatitis, hyperviscosity syndrome and pre-eclampsia, with significant morbidity and mortality to both mother and foetus. Conventional conservative management of gestational hypertriglyceridaemia- dietary restriction, omega-3 fatty acid supplementation, medium chain triglyceride administration, insulin in the presence of hyperglycaemia and even fibrates may be inadequate, and an alternative therapeutic approach- plasma exchange has been reported in the literature1, 2. We describe our first experience of using therapeutic plasma exchange to treat severe hypertriglyceridaemia in pregnancy, challenges faced and lessons learned.
A 25 year old primigravida was initially diagnosed with type 1 hyperlipidaemia aged 11, following repeated hospital admissions with abdominal pain. Initial management was conservative, with serum triglyceride levels ranging from 3- 50mmol/L. Her first episode of pancreatitis occurred aged 20, but she has never had associated hyperglycaemia.
At 20/40 gestation, she developed acute pancreatitis and was admitted under joint care of the lipid and endocrine teams. She was initially treated with dietary restriction, omega-3 fatty acids and one session of Lp (double-filtration) plasmapheresis, but this had minimal effect, reducing her triglycerides from 21 to 18mmol/L. Two weeks later she was reviewed in lipid clinic, again her triglycerides had increased to >35. She was admitted for central tunnel led line insertion and underwent plasma exchange (PEX) with HAS on two consecutive days. Interestingly, she developed pancreatitis after her first PEX with a maximum serum amylase level of 324 IU/L (normal range <90 IU/L) - this was felt to be secondary to prolonged exposure to high triglycerides and not due to PEX itself.
PEX-1 resulted in ~60% reduction in triglycerides (37->11mmol/L).
PEX-2 resulted in a further ~60% reduction (11-> 3.3 mmol/L), with rapid resolution within two hours of completion of PEX of all symptoms of pancreatitis.
Four days after PEX-2 her triglycerides had risen and so she was electively admitted for a further 2 sessions of PEX. A multi-disciplinary meeting was held between Lipid, obstetric, renal and endocrinology medicine specialists to formulate a management plan for the remaining 18 weeks of pregnancy.
She was initially commenced on twice weekly PEX programmes, but with the elevation of plasma lipids typically seen in third trimester, her serum triglyceride levels were consistently above 20mmol/L despite PEX twice a week. It was then decided to increase PEX and she ended up having 5 sessions of PEX per week. It is worth noting that all PEX procedures were very well tolerated. She successfully was induced and delivered a healthy baby boy at 36 weeks.
Severe hypertriglyceridaemia in pregnancy is a challenging condition to manage, with little experience and literature available. The use of therapeutic plasma exchange is emerging as an effective treatment modality with increasing numbers of successful pregnancies reported.
1. Safety of medications: No data currently exists supporting the use of fenofibrate in pregnancy. However, no teratogenicity in humans associated with fibrates has been reported.
2. Risk of line occlusion: High plasma viscosity in hypertriglyceridaemia predisposes to line thrombosis.
3. Insufficient data of use of PEX in pregnancy: No data available with respect to safety of standard PEX line lock (Taurolock Hep 500- contains antibiotics) so line locked with heparin to the dead space of the line.
4. Anaemia- combination of pregnancy and PEX.
5. Repeated PEX with HAS risks depletion of coagulation factors, necessitating regular monitoring of fibrinogen and FFP replacement as required.
6. PEX depletes CCa levels, and normal to high CCa levels necessary throughout pregnancy to prevent risk of pre-eclampsia. Replacement with Calcium gluconate required.
1. Sivakumaran P, Tabak S, Gregory K et al. 2009. Management of familial hypertriglyceridaemia during pregnancy with plasma exchange. J Clin Apheresis 24: 42-46.
2. Crisan L, Steidl E, Rivera-Alsina M. 2008. Acute hyperlipidaemic pancreatitis in pregnancy. Am J Obstet Gynecol 198: e57-e59.