Treatment of Homozygous and Double Heterozygous Familial Hypercholesterolemia Children with LDL-Apheresis

Stefanutti, Claudia; Vivenzio, A.; Colombo, Cinzia; Giacomo, Silvia Di; Mazzarella, B.; Berni, Andrea; Nigri, A; Koga, Nobuhiko

doi:10.1177/039139889501800210

Cited by 20 publications

(8 citation statements)

References 10 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, some symptoms such as shivering, nausea, vertigo (5) or a vasovagal reaction (10) suggested a reaction to bradykinin. Hypochromic anemia has been observed in some studies (4,10), but was not found in our children. The problems of hypovolemia and hypotension were present in the youngest children and could be easily treated by plasma expenders (8).…”

Section: Discussioncontrasting

confidence: 65%

“…The youngest child treated by LDL apheresis was 3.5 years old (8), as in our series. The most frequently used method was adsorption by DSC (4,5,8–11), but other procedures were also used: heparin‐induced lipoprotein precipitation (HELP) (7), immunoadsorption (12), direct adsorption by DALI (13), and even non‐specific methods such as plasma exchange (6). Although weekly sessions are more efficient (10), fortnightly sessions were often performed.…”

Section: Discussionmentioning

confidence: 99%

“…Most patients had coronary lesions before treatment (5,6,12) and this constituted the reason for starting LDL apheresis. In some cases there were no coronary lesions before treatment and repeated investigations were normal (4,7) over a follow up of 3–8 years. In only one report the atherosclerotic lesions in the aorta worsened during the treatment period (10).…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Low‐density Lipoprotein Apheresis in Children With Familial Hypercholesterolemia: Follow‐up to 21 Years

Palcoux¹,

Atassi-Dumont

Lefevre³

et al. 2008

Ther Apher Dial

View full text Add to dashboard Cite

Twenty-seven patients (14 girls, 13 boys) affected by familial hypercholesterolemia who had begun low-density lipoprotein (LDL) apheresis treatment before the age of 15 were studied. The median age at diagnosis was 4 years and the blood LDL cholesterol level was 704 +/- 163 mg/dL. Screening was performed for homozygous or double heterozygous mutations of the LDL cholesterol receptor gene and mutations were found in 24 of the patients. The mean age at the beginning of treatment was 8.5 years and the mean length of follow up was 12.6 years. The two main procedures used were direct adsorption of lipoproteins and dextran sulfate cellulose adsorption. Nine patients experienced anaphylactic reactions due to bradykinin and six had to have their treatment changed. The LDL cholesterol level before the session was lowered by 45 +/- 11% of the value at diagnosis. The LDL cholesterol reduction in a session was 72 +/- 10%. Tendinous xanthomas disappeared or diminished dramatically in 62% of the children. In 22 patients no cardiovascular event occurred during LDL apheresis treatment. Three had angina pectoris; two others had surgical management of aortic stenosis, but no clinical manifestations. Seven children had normal cardiovascular pictures while on treatment. Eleven had abnormalities of the aortic root or coronary arteries, which in six cases had appeared before treatment; the other five children did not undergo prior cardiac evaluation. In five children the abnormalities appeared during treatment. Based on these data, LDL-apheresis can be recommended for the treatment of homozygous familial hypercholesterolemia, even in young children, with good efficiency on biological parameters, cutaneous lesions and cardiovascular events.

show abstract

Section: Discussioncontrasting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Low‐density Lipoprotein Apheresis in Children With Familial Hypercholesterolemia: Follow‐up to 21 Years

Palcoux¹,

Atassi-Dumont

Lefevre³

et al. 2008

Ther Apher Dial

View full text Add to dashboard Cite

show abstract

“…Patients were treated only by LDL-apheresis. All patients were subjected to consecutive coronary angiography to moni-LDL oxidation and GSH content after LDL-apheresis [14][15][16][17]. The study included two types of FH patients : (1) patients receiving fortnightly LDL-apheresis treatment (ON patients ; n l 9) ; and (2) patients receiving their first LDL-apheresis treatment (OFF patients ; n l 5).…”

Section: Subjectsmentioning

confidence: 99%

Acute and long-term effects of low-density lipoprotein (LDL)-apheresis on oxidative damage to LDL and reducing capacity of erythrocytes in patients with severe familial hypercholesterolaemia

STEFANUTTI¹,

Giacomo²,

Vivenzio³

et al. 2001

Clinical Science

Self Cite

View full text Add to dashboard Cite

Several studies have suggested that the oxidative modification of low-density lipoprotein (LDL) could play a key role in the early stages of atherosclerosis. The susceptibility of LDL to oxidation has been found to be greater in patients with coronary heart disease. Familial hypercholesterolaemia (FH) is a powerful clinical model in which to study the predictive role of LDL in atherogenesis. LDL-apheresis is a treatment that is able to decrease lipid levels in plasma. This study was aimed at investigating the reducing capacity of erythrocytes and the in vitro susceptibility to oxidation of LDL isolated from patients with homozygous, heterozygous and double-heterozygous FH, who were treated fortnightly with LDL-apheresis or left untreated. In 14 FH patients, at baseline and after a cycle of treatment, the susceptibility of LDL to oxidative modification was analysed by studying the kinetics of conjugate diene formation. Plasma hydroperoxides, polyunsaturated fatty acid content, LDL electrophoretic mobility on agarose, the titre of auto-antibodies against oxidized LDL and serum paraoxonase activity were also measured. Furthermore, in order to evaluate a potential relationship between LDL oxidation and redox status, erythrocyte GSH and ATP levels were determined in FH patients treated regularly or never treated previously by LDL-apheresis. Unlike in the control group, the oxidative status of LDL in all FH patients was modified by LDL-apheresis, as revealed by the higher negative charge and the increase in levels of hydroperoxides and antibodies against oxidized LDL in the plasma. Our findings suggest both an acute effect and a long-term effect of LDL-apheresis in FH patients treated with dextran sulphate cellulose apheresis. The acute effect of LDL-apheresis on the susceptibility to oxidation of plasma and LDL was demonstrated by significant decreases in plasma hydroperoxide content, total LDL concentration and polyunsaturated fatty acid content. The increased resistance of LDL to oxidation was shown by prolongation of the lag time (P<0.05) in samples after a single cycle of treatment. The long-term effect of LDL-apheresis was demonstrated by the comparable values for lag phases (obtained from the kinetics of conjugate diene formation) in patients under active treatment and controls. Compared with healthy controls and untreated patients, the erythrocyte GSH content was significantly higher (P

show abstract

“…The extracorporeal volume of plasma and the flow rate required generally restrict the use of plasmapheresis to larger children and adults, but it is possible with appropriate equipment to use plasmapheresis in smaller children. 53 Creating arteriovenous fistulae best attains reliable vascular access for weekly to fortnightly treatment schedules. Excessive shunting of blood may be a cardiovascular stress and necessitated fistula closure in one of our patients.…”

Section: Managementmentioning

confidence: 99%

Homozygous Familial Hypercholesterolemia and Its Management

Marais

Firth

Blom

2004

Seminars in Vascular Medicine

View full text Add to dashboard Cite

Mutations in the low-density lipoprotein (LDL) receptor gene cause familial hypercholesterolemia. In homozygous familial hypercholesterolemia, both genes for the LDL- receptor are mutated and LDL levels are markedly elevated. High-density lipoprotein cholesterol concentration is often reduced and lipoprotein(a) levels are high when corrected for apolipoprotein(a) isoforms. Cutaneous and tendinous xanthomata develop in childhood and are the most common reason for initial presentation. The diagnosis can be confirmed by analysis of LDL-receptor genes or studies of LDL receptor function in cultured cells. Severe aortic and coronary atherosclerosis usually occurs within the first or second decades of life. Left ventricular outflow tract obstruction may be at the level of the aortic valve or the supravalvar aorta. Treatment for the hyperlipidemia is with plasmapheresis, high-dose statins, and ezetimibe. Liver transplantation reverses the metabolic defect but requires chronic immunosupression, and rejection may still occur. Liver transplantation is indicated if cardiac transplantation becomes necessary. Portocaval shunt may still play a role in patients with coronary artery disease who do not have access to plasmapheresis. Gene therapy is currently not practicable but is being actively developed.

show abstract

Treatment of Homozygous and Double Heterozygous Familial Hypercholesterolemia Children with LDL-Apheresis

Cited by 20 publications

References 10 publications

Low‐density Lipoprotein Apheresis in Children With Familial Hypercholesterolemia: Follow‐up to 21 Years

Low‐density Lipoprotein Apheresis in Children With Familial Hypercholesterolemia: Follow‐up to 21 Years

Acute and long-term effects of low-density lipoprotein (LDL)-apheresis on oxidative damage to LDL and reducing capacity of erythrocytes in patients with severe familial hypercholesterolaemia

Homozygous Familial Hypercholesterolemia and Its Management

Contact Info

Product

Resources

About