Wendler T, Lennertz A, Heinemann O, Duhr C, Samtleben W, Bosch T
Department of Internal Medicine I, Klinikum Grosshadern, University of Munich, Germany.
Int J Artif Organs. 2000 Oct;23(10):710-7.
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.
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.
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.
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.
在常规直接脂蛋白吸附术（DALI）——从全血中直接吸附脂蛋白的首个技术——中，肝素加枸橼酸盐（ACD - A）被用作抗凝方案。然而，最近有几篇文献警告称肝素诱导的血小板减少症是肝素给药罕见但可能危及生命的并发症（2型肝素诱导的血小板减少症，HIT）。因此，本研究的目的是测试仅使用枸橼酸盐的无肝素抗凝方案进行DALI的疗效和生物相容性。
4例接受常规DALI治疗的有症状高胆固醇血症患者，每人转换为无肝素方案进行两个疗程的治疗。其中2例患者正在口服苯丙香豆素进行抗凝治疗。在每周的疗程中，以60 ml/min的血流速度处理1.3倍患者血容量，在吸附器预充和疗程中使用比例为1:20（v/v）的ACD - A。
临床上，所有疗程基本顺利。未校正的脂蛋白降低情况如下：低密度脂蛋白胆固醇（LDL - C）降低65%，脂蛋白（a）[Lp(a)]降低62%，极低密度脂蛋白胆固醇（VLDL - C）降低53%，高密度脂蛋白胆固醇（HDL - C）降低24%，甘油三酯降低17%，纤维蛋白原降低19%。血细胞计数基本保持不变。未检测到溶血或凝血迹象。所有患者的凝血酶原时间（Quick）略有延长，部分凝血活酶时间（PTT）中度升高。相比之下，仅口服抗凝治疗的患者按照Lee - White法测定的全血凝固时间和活化凝血时间增加。在补体、白细胞和血小板活化方面的生物相容性良好。缓激肽活化程度中等，在流出管路中峰值为3038 pg/ml。系统性凝血酶 - 抗凝血酶复合物（TAT）在口服抗凝治疗的患者中反映出完美的抗凝效果，在未服用苯丙香豆素的患者中反映出足够的抗凝效果。
在这项初步研究中，无肝素DALI治疗是安全有效的，因此可在对肝素不耐受的依赖低密度脂蛋白吸附治疗的患者中进行。
