Effect of low-dose citrate anticoagulation on the clinical safety and efficacy of direct adsorption of lipoproteins (DALI apheresis) in hypercholesterolemic patients: a prospective controlled clinical trial.

Direct adsorption of lipoproteins (DALI) is the first lipid apheresis system compatible with whole blood with the advantage of a very simple procedure. A mixture of heparin plus citrate (ACD-A) is used for the anticoagulation regimen (AR). A clinical, prospective, controlled crossover study was performed to test the safety and efficacy of low-dose citrate (LDC) anticoagulation in DALI. Five chronic DALI patients suffering from coronary heart disease and hypercholesterolemia underwent 3 DALI sessions each using the LDC anticoagulation regimen (60 IU heparin/kg body weight as initial bolus; 1:40 ACD-A: blood as perfusion). This was compared to 3 sessions per patient with the standard AR (bolus of 20 IU heparin/kg, 1:20 ACD-A as perfusion). Patient blood volumes (1.6; average of 7,040 ml) were treated with 750 ml adsorber gel per session at a blood flow rate of 60 ml/min. Mean LDL and Lp(a) reductions exceeded 60% with both AR. No clinical side effects were observed. Both AR controlled the coagulation well as evidenced by a sufficient prolongation of the partial prothrombin time (PTT) and activated clotting time as well as low thrombin-antithrombin (TAT) formation. Biocompatibility parameters exhibited favorable results (low activation of complement and cells, and only slight formation of C3a, C5a, beta-thromboglobulin, elastase, and TNF-alpha). The asymptomatic bradykinin generation was comparable in both study arms. LDC optimized the ionized calcium levels and pH in the efferent blood postadsorber. LDC anticoagulation was safe and effective, and may further improve the tolerance of DALI apheresis in hypercholesterolemic patients.

Heparin-free DALI LDL-apheresis in hyperlipidemic patients: efficacy, safety and biocompatibility.

BACKGROUND AND AIM OF STUDY: In routine DALI apheresis--the first technique for direct adsorption of lipoproteins from whole blood--heparin plus citrate (ACD-A) is used as anticoagulation regimen. However, recently several publications have warned of heparin-induced thrombocytopenia as a rare but potentially life-threatening complication of heparin administration (HIT type 2). The aim of the present study was therefore to test the efficacy and biocompatibility of DALI using a heparin-free anticoagulation regimen consisting exclusively of citrate. METHODS: Four symptomatic hypercholesterolemic patients on regular DALI apheresis were switched to the heparin-free protocol for two sessions each. Two of the patients were on oral anticoagulation using phenprocoumon. In the weekly sessions, 1.3 patient blood volumes were processed at a blood flow rate of 60 ml/min using ACD-A at a ratio of 1:20 (v/v) during adsorber priming and the session. RESULTS: Clinically, all sessions were essentially uneventful. Uncorrected lipoprotein reductions amounted to 65% for LDL-C, 62% for Lp(a), 53% for VLDL-C, 24% for HDL-C, 17% for triglycerides and 19% for fibrinogen. Cell counts remained virtually constant. No signs of hemolysis or clotting could be detected. Thromboplastin time (Quick) was slightly prolonged and partial thromboplastin time (PTT) moderately elevated in all patients. In contrast, whole blood coagulation time acc. to Lee-White and activated clotting times were increased only in orally anticoagulated patients. Biocompatibility in terms of complement, leukocyte and thrombocyte activation was excellent. Bradykinin activation was moderate peaking at 3038 pg/ml in the efferent line. Systemic thrombin-antithrombin complex (TAT) reflected perfect anticoagulation in orally anticoagulated patients and adequate anticoagulation in the patients without phenprocoumon. CONCLUSION: In this pilot study, heparin-free DALI apheresis was safe and effective and may thus be performed in LDL-apheresis dependent patients who suffer from heparin intolerance.

Evaluation of microparticle leakage during DALI LDL adsorption in a simulated clinical setting.

The aim of the present study was to investigate microparticle (Mp) leakage during simulated LDL-hemoperfusion using 12 DALI 750 adsorbers and the original DALI hardware under conditions strictly comparable to the clinical situation. Thus, the sessions were divided into 4 sections, i.e. priming and preparation of the adsorber followed by treatment (6-7 L at a flow rate of 60 ml/min) and reinfusion. As Mp counts can be performed only in clear, cell-free media, blood was replaced by normal saline in sections 2-4 of the simulated sessions. Mp counts were analysed for > or = 2, > or = 5, > or = 10 and > or = 25 microm particle sizes in the efferent line post adsorber using a standard light blockage method. As there are no official thresholds for particle release in extracorporeal circuits, the limits for infusion of large fluid volumes of 500, 100 (80), 25 and 5 (3) Mp/ml according to the Europäische Arzneimittelbuch, the British and American Pharmacopoeias were used. Mean particle counts for the sections 3 and 4 in which the patient is connected to the efferent line were 19, 7, 2 and 0 Mp/ml and amounted to < 10% of the above mentioned limits. Modifications of the standard simulation procedure by inserting additional pump stops or using different flow rates during the treatment phase slightly increased Mp leakage, but never exceeded the prescribed limits. In summary, no undue particle release could be detected during simulations of the clinical DALI LDL-adsorption procedure.