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

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Title: Therapeutic plasma exchange as a novel treatment for severe intrahepatic cholestasis of pregnancy: Case series and mechanism of action
Authors: Ovadia, C
Lovgren-Sandblom, A
Edwards, LA
Langedijk, J
Geenes, V
Chambers, J
Cheng, F
Clarke, L
Begum, S
Noori, M
Pusey, C
Padmagirison, R
Agarwal, S
Peerless, J
Cheesman, K
Heneghan, M
Elferink, RO
Patel, VC
Marschall, H-U
Williamson, C
Item Type: Journal Article
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.
Issue Date: 1-Dec-2018
Date of Acceptance: 30-Jul-2018
URI: http://hdl.handle.net/10044/1/64737
DOI: https://dx.doi.org/10.1002/jca.21654
ISSN: 1098-1101
Publisher: Wiley
Start Page: 638
End Page: 644
Journal / Book Title: Journal of Clinical Apheresis
Volume: 33
Issue: 6
Copyright Statement: © 2018 Wiley Periodicals, Inc. This is the pre-peer reviewed version of the following article, which has been published in final form at https://onlinelibrary.wiley.com/doi/full/10.1002/jca.21654
Keywords: Science & Technology
Life Sciences & Biomedicine
Hematology
autotaxin
bile acids
cytokine
obstetric cholestasis
progesterone sulfate
pruritus
URSODEOXYCHOLIC ACID
PROGESTERONE METABOLITES
BILE
PRURITUS
AUTOTAXIN
PLASMAPHERESIS
CYTOKINES
CELLS
WOMEN
TRIAL
1103 Clinical Sciences
Cardiovascular System & Hematology
Publication Status: Published
Online Publication Date: 2018-10-15
Appears in Collections:Department of Medicine (up to 2019)