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Lipoprotein Apheresis
Gilbert Thompson Imperial College
Hammersmith Hospital London
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Rationale for lipoprotein apheresis
• To prevent the development, arrest progression or
induce regression of atherosclerosis by long-term
lowering of plasma levels of cholesterol-rich lipoproteins
in hyperlipidaemic subjects refractory to drug therapy.
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LDL particle
22 nm
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Lipoprotein apheresis methods
Unselective removal from plasma • Plasma exchange
Selective removal from plasma • Differential filtration • Adsorption • Precipitation
Selective removal from blood • Adsorption
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Double filtration system (L.I.N.C.)
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Dextran sulphate adsorption (Kaneka)
Plasma Whole blood
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Direct Adsorption of Lipoproteins (DALI) system (Fresenius)
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Heparin Extracorporeal LDL Precipitation (HELP) system (Braun)
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Parameters of lipoprotein apheresis
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HEART UK indications for lipoprotein apheresis (Atherosclerosis 2008;198:247-55)
• Homozygous Familial Hypercholesterolaemia (FH) • Heterozygous FH with progressive CAD refractory to statins • Patients with Lp(a) > 600 mg/l and progressive CAD despite
maximal drug therapy
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Homozygous familial hypercholesterolaemia
• Planar xanthomas in early childhood
• Atheroma of aortic root before puberty
• Serum cholesterol 15 -30 mmol/l from birth
• Sudden death in adolescence or early adulthood
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Apheresing homozygote, aged 6 (1989)
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Serum cholesterol before and during 8 yrs of lipoprotein apheresis in homozygous FH child
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Tendon xanthoma before & after 6 years of apheresis
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Cumulative impact of apheresis & drug therapy in homozygous FH
0
5
10
15
20
25
LDL-C mmol/l
Untreated Apheresis Apheresis + Atorvastatin 80 mg
Apheresis + Atorvastatin 80 mg + Ezetimibe 10 mg
-70% - 45%
- 17%
- 8%
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Efficacy of lomitapide in FH homozygotes (n=29) (Cuchel et al, 2012)
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Lipoprotein apheresis in an FH heterozygote
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Frequency of coronary angiographic change in FH trials of ≥ 2 years duration
0
50
100
Controls Drugs Aph + Drugs
Regression
No change
Progression
n = 89 n = 150 n = 114
Perc
ent o
f Pat
ient
s
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Fibrosed lesion after 6½ years of apheresis
Cholesterol-rich coronary atheromatous plaque
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Lipoprotein (a)
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Effects of weekly apheresis on Lp(a) levels and major adverse coronary events (MACE) (Jaeger et al, 2009)
Reduction in MACE rate similar whether LDL-C < 2.6 or > 2.6 mmol/l
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Lipoprotein apheresis in 3 lipid centres in the UK: Cardiff, Hammersmith & Harefield
(March, 2013)
Category Number/Frequency
Patients 48
Procedures 105/month
Homozygous FH 23%
Heterozygous FH (statin-refractory) 73%
HyperLp(a)aemia 4%
Longest duration 23 years
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NHSBT Specialist Therapeutic Services (STS)
• STS centres in England : North-West (Manchester & Liverpool) Sheffield Leeds Bristol Oxford
• STS performed 3,800 procedures in 2011-2012 Lipoprotein apheresis 4% (≈ 13/ month)
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Hypertriglyceridaemic acute pancreatitis
Serum triglycerides > 10 mmol/l AND
clinical evidence of incipient acute pancreatitis
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Summary
• Lipoprotein apheresis involves the extracorporeal removal of low density lipoprotein and lipoprotein (a) particles from whole blood or plasma by adsorption, precipitation or differential filtration.
• Used weekly on a long term basis it provides safe and effective treatment of patients at high risk of premature cardiovascular disease (CVD) from inherited increases in those atherogenic lipoproteins.
• The procedure is first-line therapy for homozygous familial hypercholesterolaemia (FH) and is increasingly used to treat patients with CVD due to statin-refractory heterozygous FH or raised levels of lipoprotein (a).
• Lipoprotein apheresis or plasma exchange may also be used to prevent acute pancreatitis in patients with severe hyper-triglyceridaemia.
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