Background: Severe hypertriglyceridemia (HTG) is associated with major complications such as acute or relapsing pancreatitis (AP) and atherosclerotic cardiovascular disease (ASCVD). Rapid elimination of triglyceride (TG)-rich lipoproteins (LP) with double filtration plasmapheresis (DFPP) without need for substitution has been found to be effective for the acute, short-term treatment of HTG-induced AP. Data on the long-term use of DFPP to prevent HTG-associated complications are scarce. Objectives: To evaluate the use and efficacy of regular DFPP treatment in clinical practice for preventing recurrence of HTG-associated complications in thera-py refractory patients. Methods: Retrospective multicenter study in patients with severe symptomatic drug and diet refractory HTG with regular DFPP treatment. Patients’ incidence of HTG-associated pancreatic or cardiovascular complications was compared before treatment and with regular DFPP treatment. Results: Ten patients (3 female) were identified with baseline maximal TG concentrations of 2,587–28,090 mg/dL (median 5,487 mg/dL; interquartile range [IQR] 4,340–12,636). The mean observation period was 3.9 ± 3.4 years before and 3.8 ± 3.0 years after commencement of DFPP. In 5 patients, severe HTG was related to chylomicronemia, 2 patients had familial partial lipodystrophy Dunnigan, and 1 patient had additional LP(a)-hyperlipoproteinemia. The main HTG-associated complication was recurrent AP in 8 patients, including 1 patient treated during pregnancy. Two patients presented severe progressive ASCVD. With long-term DFPP treatment, the annual rate of HTG-associa-ted pancreatic or cardiovascular complications declined from median 1.4 (IQR 0.7–2.6) to 0 (IQR 0.0–0.4; p < 0.005). The absolute number of events was reduced by 77%. In 6 patients (60%) episodes of AP did not occur, nor was progression of ASCVD detected clinically or by routine imaging techniques. DFPP was effective in the elimination of TG-rich LP from plasma, and was safe and well-tolerated. Conclusion: Long-term, regular DFPP treatment resulted in stabilization of patients with severe HTG and related recurrent AP or progression of ASCVD, who were refractory to conventional dietary and drug therapy.

Hegele RA, Ginsberg HN, Chapman MJ, Nordestgaard BG, Kuivenhoven JA, Averna M, et al.; European Atherosclerosis Society Consensus Panel. The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. Lancet Diabetes Endocrinol. 2014 Aug;2(8):655–66.
Nordestgaard BG. Triglyceride-rich lipoproteins and atherosclerotic cardiovascular disease. Circ Res. 2016 Feb;118(4):547–63.
Nordestgaard BG, Benn M, Schnohr P, Tybjaerg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA. 2007 Jul;298(3):299–308.
Ference BA, Kastelein JJ, Ray KK, Ginsberg HN, Chapman MJ, Packard CJ, et al. Association of triglyceride-lowering LPL variants and LDl-C-lowering LDLR variants with risk of coronary heart disease. JAMA. 2019 Jan;321(4):364–73.
Adiamah A, Psaltis E, Crook M, Lobo DN. A systematic review of the epidemiology, pathophysiology and current management of hyperlipidaemic pancreatitis. Clin Nutr. 2018 Dec;37(6 Pt A):1810–22.
Basar R, Uzum AK, Canbaz B, Dogansen SC, Kalayoglu-Besisik S, Altay-Dadin S, et al. Therapeutic apheresis for severe hypertriglyceridemia in pregnancy. Arch Gynecol Obstet. 2013 May;287(5):839–43.
Schettler V, De Grot K, Fassbender C, Grützmacher P, Heigl F, Julius U. Standard der Therapeutischen Apherese 2019 der Deutschen Gesellschaft für Nephrologie e.V. in Zusammenarbeit mit der Gesellschaft für pädiatrische Nephrologie. [Standard of therapeutic apheresis 2019 of the German Societies for Nephrology and paediatric Nephrology]. Available from:
Padmanabhan A, Connelly-Smith L, Aqui N, Balogun RA, Klingel R, Meyer E, et al. Guidelines on the use of therapeutic apheresis in clinical practice – evidence-based approach from the writing committee of the American society for apheresis: the eight special issue. J Clin Apher. 2019 Jun;34(3):171–354.
Costantini N, Mameli A, Marongiu F. Plasmapheresis for preventing complication of hypertriglyceridemia: A case report and review of literature. Am J Ther. 2016 Jan-Feb;23(1):e288–91.
Saleh MA, Mansoor E, Cooper GS. Case of familial hyperlipoproteinemia type III hypertriglyceridemia induced acute pancreatitis: role for outpatient apheresis maintenance therapy. World J Gastroenterol. 2017 Oct;23(40):7332–6.
Stefanutti C, Di Giacomo S, Vivenzio A, Labbadia G, Mazza F, D’Alessandri G, et al. Therapeutic plasma exchange in patients with severe hypertriglyceridemia: a multicenter study. Artif Organs. 2009 Dec;33(12):1096–102.
Piolot A, Nadler F, Cavallero E, Coquard JL, Jacotot B. Prevention of recurrent acute pancreatitis in patients with severe hypertriglyceridemia: value of regular plasmapheresis. Pancreas. 1996 Jul;13(1):96–9.
Schaap-Fogler M, Schurr D, Schaap T, Leitersdorf E, Rund D. Long-term plasma exchange for severe refractory hypertriglyceridemia: a decade of experience demonstrates safety and efficacy. J Clin Apher. 2009;24(6):254–8.
Moulin P, Dufour R, Averna M, Arca M, Cefalù AB, Noto D, et al. Identification and diagnosis of patients with familial chylomicronaemia syndrome (FCS): expert panel recommendations and proposal of an “FCS score”. Atherosclerosis. 2018 Aug;275:265–72.
Langlois MR, Chapman MJ, Cobbaert C, Mora S, Remaley AT, Ros E, et al.; European Atherosclerosis Society (EAS) and the ­European Federation of Clinical Chemistry and Laboratory Medicine (EFLM) Joint Consensus Initiative. Quantifying atherogenic lipoproteins: current and future challenges in the era of personalized medicine and very low concentrations of LDL cholesterol. A consensus statement from EAS and EFLM. Clin Chem. 2018 Jul;64(7):1006–33.
Mach F, Baigent C, Catapano AL, Koskinas KC, Casula M, Badimon L, et al. ESC/EAS guidelines for the management of dyslipidemias: lipid modification to reduce cardiovascular risk. Eur Heart J. 2020 Jan;41(1):111–88.
Rawla P, Sunkara T, Thandra KC, Gaduputi V. Hypertriglyceridemia-induced pancreatitis: updated review of current treatment and preventive strategies. Clin J Gastroenterol. 2018 Dec;11(6):441–8.
Achard JM, Westeel PF, Moriniere P, Lalau JD, de Cagny B, Fournier A. Pancreatitis related to severe acute hypertriglyceridemia during pregnancy: treatment with lipoprotein apheresis. Intensive Care Med. 1991;17(4):236–7.
Click B, Ketchum AM, Turner R, Whitcomb DC, Papachristou GI, Yadav D. The role of apheresis in hypertriglyceridemia-induced acute pancreatitis: A systematic review. Pancreatology. 2015 Jul-Aug;15(4):313–20.
Galán Carrillo I, Demelo-Rodriguez P, Rodríguez Ferrero ML, Anaya F. Double filtration plasmapheresis in the treatment of pancreatitis due to severe hypertriglyceridemia. J Clin Lipidol. 2015 Sep-Oct;9(5):698–702.
Gavva C, Sarode R, Agrawal D, Burner J. Therapeutic plasma exchange for hypertriglyceridemia induced pancreatitis: A rapid and practical approach. Transfus Apheresis Sci. 2016 Feb;54(1):99–102.
Gubensek J, Buturovic-Ponikvar J, Romozi K, Ponikvar R. Factors affecting outcome in acute hypertriglyceridemic pancreatitis treated with plasma exchange: an observational cohort study. PLoS One. 2014 Jul;9(7):e102748.
Huang C, Liu J, Lu Y, Fan J, Wang X, Liu J, et al. Clinical features and treatment of hypertriglyceridemia-induced acute pancreatitis during pregnancy: A retrospective study. J Clin Apher. 2016 Dec;31(6):571–8.
Kadikoylu G, Yavasoglu I, Bolaman Z. Plasma exchange in severe hypertriglyceridemia – a clinical study. Transfus Apher Sci. 2006 Jun;34(3):253–7.
Kandemir A, Coşkun A, Yavaşoğlu İ, Bolaman Z, Ünübol M, Yaşa MH, et al. Therapeutic plasma exchange for hypertriglyceridemia induced acut pancreatitis: the 33 cases experience from a tertiary reference center in Turkey. Turk J Gastroenterol. 2018 Nov;29(6):676–83.
Kandemir A, Coşkun A. Treatment of hypertriglyceridemia-induced acute pancreatitis with therapeutic plasma exchange in 2 pregnant patients. J Obstet Gynaecol. 2019 Jul;39(5):702–4.
Yeh JH, Chen JH, Chiu HC. Plasmapheresis for hyperlipidemic pancreatitis. J Clin Apher. 2003;18(4):181–5.
Zeitler H, Balta Z, Klein B, Strassburg CP. Extracorporeal treatment in severe hypertriglyceridemia-induced pancreatitis. Ther Apher Dial. 2015 Aug;19(4):405–10.
Chang CT, Tsai TY, Liao HY, Chang CM, Jheng JS, Huang WH, et al. Double filtration plasma apheresis shortens hospital admission duration of patients with severe hypertriglyceridemia-associated acute pancreatitis. Pancreas. 2016 Apr;45(4):606–12.
Klingel R, Fassbender C, Fassbender T, Erdtracht B, Berrouschot J. Rheopheresis: rheologic, functional, and structural aspects. Ther Apher. 2000 Oct;4(5):348–57.
Ewald N, Kloer HU. Severe hypertriglyceridemia: an indication for apheresis? Atheroscler Suppl. 2009 Dec;10(5):49–52.
Esparza MI, Li X, Adams-Huet B, Vasandani C, Vora A, Das SR, et al. Very severe hypertriglyceridemia in a large US county health care system: associated conditions and management. J Endocr Soc. 2019 May;3(8):1595–607.
Wang SH, Chou YC, Shangkuan WC, Wei KY, Pan YH, Lin HC. Relationship between plasma triglyceride level and severity of hypertriglyceridemic pancreatitis. PLoS One. 2016 Oct;11(10):e0163984.
Neumann CL, Schulz EG, Hagenah GC, Platzer U, Wieland E, Schettler V. Lipoprotein apheresis–more than just cholesterol reduction? Atheroscler Suppl. 2013 Jan;14(1):29–32.
Roeseler E, Julius U, Heigl F, Spitthoever R, Heutling D, Breitenberger P, et al.; Pro(a)LiFe-Study Group. Lipoprotein apheresis for lipoprotein(a)-associated cardiovascular disease. prospective 5 years of follow-up and apolipoprotein(a) characterization. Arterioscler Thromb Vasc Biol. 2016 Sep;36(9):2019–27.
Witztum JL, Gaudet D, Freedman SD, Alexander VJ, Digenio A, Williams KR, et al. Volanesoren and triglyceride levels in familial chylomicronemia syndrome. N Engl J Med. 2019 Aug;381(6):531–42.
Hovland A, Hardersen R, Nielsen EW, Mollnes TE, Lappegård KT. Hematologic and hemostatic changes induced by different columns during LDL apheresis. J Clin Apher. 2010;25(5):294–300.
Michalova R, Mankova A, Vnucak M, Mikulova S, Nehaj F, Raslova K, et al. Therapeutic plasma exchange in secondary prevention of acute pancreatitis in pregnant patient with familial hyperchylomicronemia. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub. 2019 Feb;163(1):90–4.
Sivakumaran P, Tabak SW, Gregory K, Pepkowitz SH, Klapper EB. Management of familial hypertriglyceridemia during pregnancy with plasma exchange. J Clin Apher. 2009;24(1):42–6.
Toth PP, Philip S, Hull M, Granowitz C. Hypertriglyceridemia is associated with an increased risk of peripheral arterial revascularization in high-risk statin-treated patients: A large administrative retrospective analysis. Clin Cardiol. 2019 Oct;42(10):908–13.
Brown RJ, Araujo-Vilar D, Cheung PT, Dunger D, Garg A, Jack M, et al. The diagnosis and management of lipodystrophy syndromes: a multi-society practice guideline. J Clin Endocrinol Metab. 2016 Dec;101(12):4500–11.
Bolan C, Oral EA, Gorden P, Taylor S, Leitman SF. Intensive, long-term plasma exchange therapy for severe hypertriglyceridemia in acquired generalized lipoatrophy. J Clin Endocrinol Metab. 2002 Jan;87(1):380–4.
Lightbourne M, Brown RJ. Genetics of Lipodystrophy. Endocrinol Metab Clin North Am. 2017 Jun;46(2):539–54.
Hegele RA. Premature atherosclerosis associated with monogenic insulin resistance. Circulation. 2001 May;103(18):2225–9.
Álvarez M, Luis-Hidalgo M, Bracho MA, Blanquer A, Larrea L, Villalba J, et al. Transmission of human immunodeficiency virus Type-1 by fresh-frozen plasma treated with methylene blue and light. Transfusion. 2016 Apr;56(4):831–6.
Hewitt PE, Ijaz S, Brailsford SR, Brett R, Dicks S, Haywood B, et al. Hepatitis E virus in blood components: a prevalence and transmission study in southeast England. Lancet. 2014 Nov;384(9956):1766–73.
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.