Therapeutic plasma exchange as a novel treatment for severe intrahepatic cholestasis of pregnancy: Case series and mechanism of action

Caroline Ovadia, Anita Lövgren-Sandblom, Lindsey A. Edwards, Jacqueline Langedijk, Victoria Geenes, Jenny Chambers, Floria Cheng, Louise Clarke, Shahina Begum, Muna Noori, Charles Pusey, Radhika Padmagirison, Sangita Agarwal, James Peerless, Kate Cheesman, Michael Heneghan, Ronald Oude Elferink, Vishal C. Patel, Hanns Ulrich Marschall, Catherine Williamson*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

Abstract

Introduction: Intrahepatic cholestasis of pregnancy is characterised by pruritus and elevated serum bile acids. The pruritus can be severe, and pharmacological options achieve inconsistent symptomatic improvement. Raised bile acids are linearly associated with adverse fetal outcomes, with existing management of limited benefit. We hypothesised that therapeutic plasma exchange removes pruritogens and lowers total bile acid concentrations, and improves symptoms and biochemical abnormalities in severe cases that have not responded to other treatments. Methods: Four women with severe pruritus and hypercholanemia were managed with therapeutic plasma exchange. Serial blood biochemistry and visual analogue scores of itch severity were obtained. Blood and waste plasma samples were collected before and after exchange; individual bile acids and sulfated progesterone metabolites were measured with HPLC-MS, autotaxin activity and cytokine profiles with enzymatic methods. Results were analysed using segmental linear regression to describe longitudinal trends, and ratio t tests. Results: Total bile acids and visual analogue itch scores demonstrated trends to transiently improve following plasma exchange, with temporary symptomatic benefit reported. Individual bile acids (excluding the drug ursodeoxycholic acid), and the sulfated metabolites of progesterone reduced following exchange (P =.03 and P =.04, respectively), whilst analysis of waste plasma demonstrated removal of autotaxin and cytokines. Conclusions: Therapeutic plasma exchange can lower potentially harmful bile acids and improve itch, likely secondary to the demonstrated removal of pruritogens. However, the limited current experience and potential complications, along with minimal sustained symptomatic benefit, restrict its current use to women with the most severe disease for whom other treatment options have been exhausted.

Original languageEnglish
Pages (from-to)638-644
Number of pages7
JournalJournal of Clinical Apheresis
Volume33
Issue number6
Early online date15 Oct 2018
DOIs
Publication statusPublished - Dec 2018

Keywords

  • autotaxin
  • bile acids
  • cytokine
  • obstetric cholestasis
  • progesterone sulfate
  • pruritus

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