Ryan K E, Lane D A, Flynn A, Ireland H, Boisclair M, Shepperd J, Curtis J R
Department of Haematology, Charing Cross and Westminster Hospital, Hammersmith, London, UK.
Thromb Haemost. 1992 Nov 10;68(5):563-9.
The therapeutic potential of the glycosaminoglycan (GAG), dermatan sulphate (DS), as an antithrombotic agent in humans has yet to be established. We have performed dose ranging studies of DS to determine its effectiveness as an antithrombotic agent in patients (n = 6-8) undergoing haemodialysis for chronic renal failure. In an initial study, Study 1, i.v. bolus doses of 2-4 mg/kg and 5-6 mg/kg DS were given to patients dialysing with polyacrylonitrile hollow fibre (PAN HF) membranes. In a second crossover study, Study 2, performed using cuprophane hollow fibre (CHF) membranes, i.v. bolus doses of 3 mg/kg and 6 mg/kg DS were compared to a standard unfractionated heparin (UFH) regime that has been shown previously to inhibit fibrin formation. Further infusion studies, Study 3 and Study 4 evaluated the antithrombotic efficacy of an i.v. DS bolus of 3 mg/kg plus an i.v. infusion of DS 0.6 mg kg-1 h-1 and a DS bolus of 5 mg/kg plus an infusion of 1 mg kg-1 h-1 over 5 h, respectively. These studies were compared to standard UFH regimes in a randomised crossover design. Plasma levels of fibrinopeptide A (FPA) and thrombin-antithrombin (TAT) were used as markers of fibrin formation and thrombin generation during dialysis using both membranes. The changes in DS concentration following administration of the different doses were similar in Studies 1 and 2. However, the effectiveness of DS as an anticoagulant appeared to depend markedly on the different dialyser types used in the two studies.(ABSTRACT TRUNCATED AT 250 WORDS)
硫酸皮肤素（DS）作为一种糖胺聚糖（GAG），其在人类体内作为抗血栓形成药物的治疗潜力尚未得到证实。我们进行了DS的剂量范围研究，以确定其在接受慢性肾衰竭血液透析的患者（n = 6 - 8）中作为抗血栓形成药物的有效性。在初步研究（研究1）中，向使用聚丙烯腈中空纤维（PAN HF）膜进行透析的患者静脉推注2 - 4 mg/kg和5 - 6 mg/kg的DS。在第二项交叉研究（研究2）中，使用铜仿中空纤维（CHF）膜，将3 mg/kg和6 mg/kg的DS静脉推注剂量与先前已证明可抑制纤维蛋白形成的标准普通肝素（UFH）方案进行比较。进一步的输注研究（研究3和研究4）分别评估了3 mg/kg的DS静脉推注加0.6 mg kg-1 h-1的DS静脉输注以及5 mg/kg的DS推注加1 mg kg-1 h-1的5小时输注的抗血栓形成效果。这些研究在随机交叉设计中与标准UFH方案进行比较。使用两种膜进行透析期间，血浆纤维蛋白肽A（FPA）和凝血酶 - 抗凝血酶（TAT）水平用作纤维蛋白形成和凝血酶生成的标志物。在研究1和研究2中，给予不同剂量后DS浓度的变化相似。然而，DS作为抗凝剂的有效性似乎明显取决于两项研究中使用的不同透析器类型。（摘要截断于250字）
