Impact of lipoprotein apheresis on thrombotic parameters in patients with refractory angina and raised lipoprotein(a): Findings from a randomized controlled cross-over trial.


Journal

Journal of clinical lipidology
ISSN: 1933-2874
Titre abrégé: J Clin Lipidol
Pays: United States
ID NLM: 101300157

Informations de publication

Date de publication:
Historique:
received: 08 02 2019
revised: 21 06 2019
accepted: 24 06 2019
pubmed: 30 7 2019
medline: 9 7 2020
entrez: 30 7 2019
Statut: ppublish

Résumé

Raised lipoprotein(a) [Lp(a)] is a cardiovascular risk factor common in patients with refractory angina. The apolipoprotein(a) component of Lp(a) exhibits structural homology with plasminogen and can enhance thrombosis and impair fibrinolysis. The objective of the study was to assess the effect of lipoprotein apheresis on markers of thrombosis and fibrinolysis in patients with high Lp(a). In a prospective, single-blind, crossover trial, 20 patients with refractory angina and raised Lp(a) > 50 mg/dL were randomized to three months of weekly lipoprotein apheresis or sham. Blood taken before and after apheresis/sham was assessed using the Global Thrombosis Test, to assess time taken for in vitro thrombus formation (occlusion time) and endogenous fibrinolysis (lysis time), as well as von Willebrand Factor, fibrinogen, D-dimer, thrombin/anti-thrombin III complex, prothrombin fragments 1 + 2, and thrombin generation assays. Lp(a) was significantly reduced by apheresis (100.2 [interquartile range {IQR}, 69.6143.0] vs 24.8 [17.2,34.0] mg/dL, P = .0001) but not by sham (P = .0001 between treatment arms). Apheresis prolonged occlusion time (576 ± 116 s vs 723 ± 142 s, P < .0001) reflecting reduced platelet reactivity and reduced lysis time (1340 [1128, 1682] s vs 847 [685,1302] s, P = .0006) reflecting enhanced fibrinolysis, without corresponding changes with sham. Apheresis, but not sham, reduced von Willebrand Factor (149 [89.0, 164] vs 64.2 [48.5, 89.8] IU/dL, P = .0001), and fibrinogen (3.12 ± 0.68 vs 2.20 ± 0.53 g/L, P < .0001), and increased prothrombin fragments 1 + 2 (158.16 [128.77, 232.09] vs 795.12 [272.55, 1201.00] pmol/L, P = .0006). There was no change in D-dimer, thrombin/anti-thrombin III complex, or thrombin generation assay with apheresis or sham. Lipoprotein apheresis reduces Lp(a) and improves some thrombotic and fibrinolytic parameters in patients with refractory angina.

Sections du résumé

BACKGROUND
Raised lipoprotein(a) [Lp(a)] is a cardiovascular risk factor common in patients with refractory angina. The apolipoprotein(a) component of Lp(a) exhibits structural homology with plasminogen and can enhance thrombosis and impair fibrinolysis.
OBJECTIVES
The objective of the study was to assess the effect of lipoprotein apheresis on markers of thrombosis and fibrinolysis in patients with high Lp(a).
METHODS
In a prospective, single-blind, crossover trial, 20 patients with refractory angina and raised Lp(a) > 50 mg/dL were randomized to three months of weekly lipoprotein apheresis or sham. Blood taken before and after apheresis/sham was assessed using the Global Thrombosis Test, to assess time taken for in vitro thrombus formation (occlusion time) and endogenous fibrinolysis (lysis time), as well as von Willebrand Factor, fibrinogen, D-dimer, thrombin/anti-thrombin III complex, prothrombin fragments 1 + 2, and thrombin generation assays.
RESULTS
Lp(a) was significantly reduced by apheresis (100.2 [interquartile range {IQR}, 69.6143.0] vs 24.8 [17.2,34.0] mg/dL, P = .0001) but not by sham (P = .0001 between treatment arms). Apheresis prolonged occlusion time (576 ± 116 s vs 723 ± 142 s, P < .0001) reflecting reduced platelet reactivity and reduced lysis time (1340 [1128, 1682] s vs 847 [685,1302] s, P = .0006) reflecting enhanced fibrinolysis, without corresponding changes with sham. Apheresis, but not sham, reduced von Willebrand Factor (149 [89.0, 164] vs 64.2 [48.5, 89.8] IU/dL, P = .0001), and fibrinogen (3.12 ± 0.68 vs 2.20 ± 0.53 g/L, P < .0001), and increased prothrombin fragments 1 + 2 (158.16 [128.77, 232.09] vs 795.12 [272.55, 1201.00] pmol/L, P = .0006). There was no change in D-dimer, thrombin/anti-thrombin III complex, or thrombin generation assay with apheresis or sham.
CONCLUSION
Lipoprotein apheresis reduces Lp(a) and improves some thrombotic and fibrinolytic parameters in patients with refractory angina.

Identifiants

pubmed: 31353231
pii: S1933-2874(19)30229-6
doi: 10.1016/j.jacl.2019.06.009
pii:
doi:

Substances chimiques

Biomarkers 0
Lipoproteins 0

Types de publication

Journal Article Randomized Controlled Trial Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

788-796

Subventions

Organisme : British Heart Foundation
ID : FS/12/60/29874
Pays : United Kingdom

Informations de copyright

Copyright © 2019 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Auteurs

Tina Z Khan (TZ)

National Heart and Lung Institute, Imperial College London, London, UK.

Diana A Gorog (DA)

National Heart and Lung Institute, Imperial College London, London, UK.

Deepa J Arachchillage (DJ)

Department of Haematology, Royal Brompton and Imperial College Healthcare NHS Trust and Imperial College London, London, UK.

Josefin Ahnström (J)

Department of Haematology, Royal Brompton and Imperial College Healthcare NHS Trust and Imperial College London, London, UK.

Samantha Rhodes (S)

NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, UK.

Jacqueline Donovan (J)

NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, UK.

Winston Banya (W)

NIHR Cardiovascular Biomedical Research Unit, Royal Brompton Hospital, London, UK.

Alison Pottle (A)

Cardiology Department, Harefield Hospital, Harefield, UK.

Mahmoud Barbir (M)

Cardiology Department, Harefield Hospital, Harefield, UK. Electronic address: M.Barbir@rbht.nhs.uk.

Dudley J Pennell (DJ)

National Heart and Lung Institute, Imperial College London, London, UK.

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Classifications MeSH