Journal of Internal MedicineVolume 238, Issue 6 p. 559-560 Effects of low-density lipoprotein apheresis (dextran sulphate adsorption method) on bleeding tendency in treatment patients Claes-Henrik Florén MD, PhD, Corresponding Author Claes-Henrik Florén MD, PhD Departments of Internal Medicine and Coagulation Disorders, Malmö University Hospital, Malmö, SwedenDepartment of Internal Medicine, Malmö University Hospital, S-205 02 Malmö, SwedenSearch for more papers by this authorE. Berntorp, E. Berntorp Departments of Internal Medicine and Coagulation Disorders, Malmö University Hospital, Malmö, SwedenSearch for more papers by this authorK.-E. Hagstam, K.-E. Hagstam Departments of Internal Medicine and Coagulation Disorders, Malmö University Hospital, Malmö, SwedenSearch for more papers by this author Claes-Henrik Florén MD, PhD, Corresponding Author Claes-Henrik Florén MD, PhD Departments of Internal Medicine and Coagulation Disorders, Malmö University Hospital, Malmö, SwedenDepartment of Internal Medicine, Malmö University Hospital, S-205 02 Malmö, SwedenSearch for more papers by this authorE. Berntorp, E. Berntorp Departments of Internal Medicine and Coagulation Disorders, Malmö University Hospital, Malmö, SwedenSearch for more papers by this authorK.-E. Hagstam, K.-E. Hagstam Departments of Internal Medicine and Coagulation Disorders, Malmö University Hospital, Malmö, SwedenSearch for more papers by this author First published: December 1995 https://doi.org/10.1111/j.1365-2796.1995.tb01239.xAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume238, Issue6December 1995Pages 559-560 RelatedInformation

To determine the acute and long-term effects of low density lipoprotein (LDL) reduction on cholesterol biosynthesis, we studied changes in the cholesterol precursors mevalonic acid (MVA) and lathosterol in patients with heterozygous familial hypercholesterolemia undergoing LDL-apheresis. Long-term LDL-apheresis in eight patients resulted in slight but insignificant increases in plasma MVA levels and lathosterol/cholesterol (L/C) ratios over 18 months. In short-term studies, six patients not on drugs and six patients treated with lovastatin or pravastatin had blood taken immediately before and after LDL-apheresis, and afterwards on days 1, 2, 3, 5, and 7. Plasma L/C ratios and MVA concentration did not change significantly on the first day after LDL-apheresis in those not on statin therapy (1.11 +/- 0.08 vs. 1.40 +/- 0.18, and 9.2 +/- 1.3 vs. 9.1 +/- 0.6 ng/ml, respectively) but increased in the statin-treated group (from 0.78 +/- 0.09 to 1.55 +/- 0.21, P = 0.003 and from 5.0 +/- 0.7 to 11.0 +/- 1.6 ng/ml, P = 0.008, respectively). There was no clear correlation between the changes in either of these precursors and the extent of reduction of total cholesterol by LDL-apheresis, but there was a strong inverse correlation with the post-apheresis LDL-cholesterol level (r = -0.77, P = 0.002 for L/C ratio; r = -0.75, P = 0.003 for MVA). Post-apheresis changes in L/C ratio and MVA were mutually correlated (r = 0.68. P = 0.01). We conclude that LDL-apheresis stimulates cholesterol biosynthesis transiently despite concomitant therapy with an HMG-CoA reductase inhibitor, the degree of stimulation being inversely related to the level to which the LDL-cholesterol was reduced.

Two low-density lipoprotein (LDL) apheresis methods allowing a specific extracorporeal removal of atherogenic lipoproteins from plasma were compared concerning their efficacy and safety in the long-term therapy of severe familial hypercholesterolemia. Five patients were treated with immunoadsorption (IMA) at weekly intervals over 3 years each, and three patients received weekly therapy with dextran sulfate cellulose adsorption (DSA) for up to 2 years. The mean plasma volume processed per session to decrease total cholesterol to a target level of 100-150 mg/dl at the end of LDL apheresis was significantly lower in DSA than in IMA: 143% vs. 180% of the individual plasma volume. Both LDL apheresis procedures achieved a mean acute reduction of plasma LDL cholesterol by more than 70%. The average interval concentrations of plasma LDL cholesterol obtained without concomitant lipid-lowering medication were 151 +/- 26 mg/dl compared to 351 +/- 65 mg/dl at baseline in the IMA-treated patients and 139 +/- 18 mg/dl compared to 359 +/- 48 mg/dl at baseline in the DSA-treated patients. Two patients from the DSA group died after 2 years of study participation due to a stroke and a sudden cardiac death several days after the last plasma therapy. Treatment-related side effects were infrequent. Long-term therapy with IMA and DSA was associated with symptomatic improvement of coronary artery disease and mobilization of tissue cholesterol deposits. Analysis of coronary angiograms after 3 years of weekly LDL apheresis with IMA revealed in five patients nearly identical atherosclerotic lesions without definite regression or progression.

OBJECTIVE:Immunoadsorption (IMA) and dextran sulfate adsorption (DSA) are two methods for selective extracorporeal elimination of low-density lipoproteins which are known as LDL apheresis. Their influence on haemostasis until now is widely unknown.DESIGN:The effects of both LDL apheresis procedures on the coagulation and fibrinolytic systems were compared amongst five patients treated with IMA and four patients who received a DSA therapy.SUBJECTS:All patients with severe heterozygous familial hypercholesterolaemia were participants in a long-term LDL apheresis programme with treatments every 1-2 weeks.INTERVENTION:Combined anticoagulation with heparin and citrate in IMA, and also heparin exclusively in DSA were used for the extracorporeal circulation.MEASURES:Blood samples were taken immediately before and after a single LDL apheresis and five times during the weekly interval until the next therapy.RESULTS:DSA had a significantly greater effect on standard clotting tests than IMA at the end of plasma therapy despite identical dosages of heparin. DSA caused a considerable reduction of the coagulation factors V, VIII:C, vWF:Ag, XI, XII, and prekallikrein by 48-99% at the end of apheresis treatment whereas only factor VIII:C showed a marked decrease of 72% after IMA. All abnormalities of the global coagulation tests and of most clotting factors were restored 1 day after treatment in both procedures followed by a moderate rebound phenomenon of single coagulation factors during the next few days in IMA-treated patients.CONCLUSION:DSA exerts a more profound effect on the coagulation system than IMA by a substantial co-elimination of various clotting factors in addition to the desired removal of atherogenic lipoproteins.

As an open controlled randomized trial of 10 patients with primary hypercholesterolemia, lipid-lowering efficacy and clinical tolerance of the hydrophilic HMG-CoA reductase inhibitor pravastatin and of the bile acid-binding resin colestyramine were compared during a monotherapy over 16 weeks and a combined therapy over 8 more weeks. Colestyramine was administered at a constant dosage of 8 g b.i.d. and pravastatin was successively given over 8 weeks each at a dosage of 10 mg b.i.d. and 20 mg b.i.d. Average reductions of total cholesterol and LDL cholesterol with colestyramine were 16% and 22%, with low-dose pravastatin were 19% and 27% and with high-dose pravastatin were 25% and 33%. The combination of pravastatin 20 mg b.i.d. and colestyramine 8 g b.i.d. resulted in an additive decrease of both lipid parameters by 34% and 38%. Over the whole study period and particularly with the higher dosage, pravastatin was significantly more effective than colestyramine in lowering total and LDL cholesterol. Colestyramine was associated with a variable increase of triglycerides whereas pravastatin led to a moderate reduction of triglycerides by 20% which remained unaffected under combined treatment. Both agents increased HDL cholesterol only to a minor extent.

Extracorporeal procedures for selective removal of low‐density lipoproteins have become a promising new approach for treatment of severe familial hypercholesterolemia. We tested efficacy and safety of a new LDL apheresis system by using two dextran sulfate cellulose adsorbents (Liposorber LA 15TM from Kanegafuchi) under the control of an automatic column‐regenerating unit for continuous alternate adsorption and desorption. Plasma was taken from a continuous‐flow blood cell separator (model IBM/Cobe 2997) allowing an extracorporeal circuit from one cubital vein to another. A 57‐year‐old male with drug‐resistant heterozygous familial hypercholesterolemia accompanied by moderate hypertriglyceridemia and severe coronary artery disease has been treated every 2 weeks for 3 months so far. Treatment of 4–5 liters of plasma resulted in a mean decrease of total cholesterol from 355 to 111 mg/dl (9.20 to 2.88 mmol/l), of LDL cholesterol from 272 to 49 mg/dl (7.05 to 1.53 mmol/l), and of apolipoprotein B from 175 to 44 mg/dl. HDL cholesterol, apolipoprotein A‐I, and other plasma proteins did not substantially change apart from hemodilution. No side effects were seen. This new technique of LDL apheresis represents a very effective and safe method for treatment of drug‐resistant familial hypercholesterolemia without or with concomitant hypertri‐lyceridemia.