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健康受试者经静脉和皮下途径给予去氨基-D-精氨酸加压素(DDAVP)后的纤溶和止血反应。

Fibrinolytic and haemostatic responses to desamino-D-arginine vasopressin (DDAVP) administered by intravenous and subcutaneous routes in healthy subjects.

作者信息

MacGregor I R, Roberts E M, Prowse C V, Broomhead A F, Ozolins M, Litka P

机构信息

H. Q. Unit Laboratory, Scottish National Blood Transfusion Service, Edinburgh, UK.

出版信息

Thromb Haemost. 1988 Feb 25;59(1):34-9.

PMID:3129807
Abstract

DDAVP was administered at 0.4 microgram kg-1 intravenous (i.v.) and subcutaneous (s.c.) routes to 6 healthy subjects in a double blind crossover study. Both study treatments were well tolerated. Flushing occurred after both treatments but was more prominent after i.v. than after s.c. DDAVP. Mild transient local discomfort at the s.c. injection site occurred in 5 of 6 subjects. The mean peak factor VIII (FVIII) response was 369% and 247% of baseline after i.v. and s.c. DDAVP respectively and the maximum increase in FVIII occurred earlier with the i.v. route. Changes in FVIII antigen (FVIII:Ag) and von Willebrand factor antigen (vWF:Ag) were also monitored. Tissue-type plasminogen activator (t-PA) activity measured by a chromogenic assay employing soluble fibrin had a median peak value of 2.9 IU ml-1 at 20 min after i.v. and of 1.9 IU ml-1 at 60 min after s.c. DDAVP. t-PA antigen was also measured so that the specific activity of circulating t-PA could be determined. Preinjection median values of 14,650 and 13,700 IU mg-1 increased to peak median values of 236,200 IU mg-1 at 20 min after i.v. and 202,400 IU mg-1 at 60 min after s.c. DDAVP. Plasminogen activator inhibitor (PAI) activity fell following DDAVP and became undetectable in some subjects during the sampling period. The ratio of maximum fibrinolytic response was similar to the ratio of maximum haemostatic responses obtained by two routes of injection. Our results indicate that s.c. DDAVP might successfully replace i.v. DDAVP in several applications such as confirmation of haemostatic or fibrinolytic responsiveness in patient groups; for obtaining FVIII enriched plasma; as well as its obvious potential usefulness in home treatment of haemophilia A and von Willebrand's disease.

摘要

在一项双盲交叉研究中,对6名健康受试者静脉注射(i.v.)和皮下注射(s.c.)0.4微克/千克的去氨加压素(DDAVP)。两种研究治疗方法耐受性良好。两种治疗后均出现面部潮红,但静脉注射后比皮下注射后更明显。6名受试者中有5名在皮下注射部位出现轻度短暂局部不适。静脉注射和皮下注射DDAVP后,平均峰值因子VIII(FVIII)反应分别为基线的369%和247%,FVIII的最大增加在静脉注射途径时出现得更早。还监测了FVIII抗原(FVIII:Ag)和血管性血友病因子抗原(vWF:Ag)的变化。采用可溶性纤维蛋白的显色法测定的组织型纤溶酶原激活剂(t-PA)活性,静脉注射后20分钟的中位数峰值为2.9 IU/ml,皮下注射DDAVP后60分钟为1.9 IU/ml。还测定了t-PA抗原,以便确定循环t-PA的比活性。注射前的中位数分别为14,650和13,700 IU/mg,静脉注射后20分钟增加到峰值中位数236,200 IU/mg,皮下注射DDAVP后60分钟为202,400 IU/mg。去氨加压素给药后纤溶酶原激活剂抑制剂(PAI)活性下降,在采样期间一些受试者中无法检测到。最大纤溶反应的比率与两种注射途径获得的最大止血反应的比率相似。我们的结果表明,皮下注射DDAVP在一些应用中可能成功替代静脉注射DDAVP,如确认患者组的止血或纤溶反应性;获取富含FVIII的血浆;以及在甲型血友病和血管性血友病的家庭治疗中其明显的潜在用途。

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