使用中间纯度的凝血因子VIII-血管性血友病因子浓缩物（海莫莱士）对2型血管性血友病患者进行大手术时的出血预防。

Bleeding prophylaxis for major surgery in patients with type 2 von Willebrand disease with an intermediate purity factor VIII-von Willebrand factor concentrate (Haemate-P).

作者信息

Michiels Jan Jacques, Berneman Zwi N, van der Planken Marc, Schroyens Wilfried, Budde Ulrich, van Vliet Huub H D M

机构信息

Haemostasis and Thrombosis Research, Department of Haematology, Antwerp University Hospital, University of Antwerp, Belgium.

出版信息

Blood Coagul Fibrinolysis. 2004 Jun;15(4):323-30. doi: 10.1097/00001721-200406000-00006.

DOI:10.1097/00001721-200406000-00006

PMID:15166918

Abstract

The parameters to diagnose von Willebrand disease (vWD) include factor VIII coagulant activity (FVIII:C), von Willebrand factor antigen (vWF:Ag), von Willebrand factor ristocetin cofactor activity (vWF:RCo), and von Willebrand factor collagen binding activity (vWF:CB). Type 2 vWD is associated with a moderate bleeding diathesis due to low levels of vWF:RCo and vWF:CB as compared with near normal or normal values for FVIII:C and vWF:Ag. As the factor VIII/von Willebrand factor (vWF) concentrate, Haemate-P, is featured by a vWF:RCo/FVIII:C ratio of about 2.2, the recommended loading dose of 50 U/kg FVIII:C followed by 25 U/kg FVIII:C every 12 h for several days for bleeding prophylaxis in type 2 vWD patients undergoing major surgery demonstrated a predicted significant over-treatment reaching vWF:RCo levels above 2 U/ml. Therefore, we restricted Haemate-P substitution for major surgery to one loading dose of 40-50 U/kg FVIII:C (88-110 U/kg vWF:RCo) followed by 15-20 U/kg FVIII:C (33-44 U/kg vWF:RCo) every 12 h for several days and evaluated this strategy in a prospective pharmacokinetic and efficacy study for bleeding prophylaxis in five type 2 vWD patients. Pre-treatment and peak levels (1 h after Haemate-P loading dose) rose from 0.43-0.66 to 1.5-2.5 U/ml for FVIII:C, from 0.23-0.45 to 1.5-2.5 U/ml for vWF:Ag, from 0.10-< 0.20 to 1.5-2.5 U/ml for vWF:RCo, and from < 0.05-0.10 to 1.0-2.0 U/ml for vWF:CB. Mean in vivo recoveries per transfused IU FVIII:C/kg body weight were 3.2% for FVIII:C, 3.9% for vWF:RCo, and 2.8% for vWF:CB. Mean in vivo recoveries per transfused IU vWF:RCo/kg were 1.45% for FVIII:C, 1.7% for vWF:RCo and 1.25% for vWF:CB. The biological half-life times after transfused Haemate-P were about 12 h for both vWF:RCo and vWF:CB. Based on these pharmacokinetic data, we propose to adapt the loading dose factor VIII/vWF concentrate (Haemate-P) to 60-80 U/kg vWF:RCo followed by 30-40 U/kg vWF:RCo every 12 h for no longer than several days (less than 1 week) for bleeding prophylaxis during major surgery or trauma, and to one loading dose of 40-60 U/kg vWF:RCo for minor surgery, trauma or mucotaneous bleedings in patients with type 2 vWD unresponsive to DDAVP.

摘要

诊断血管性血友病（vWD）的参数包括凝血因子 VIII 促凝活性（FVIII:C）、血管性血友病因子抗原（vWF:Ag）、血管性血友病因子瑞斯托霉素辅因子活性（vWF:RCo）以及血管性血友病因子胶原结合活性（vWF:CB）。2 型 vWD 与中度出血倾向相关，因为与 FVIII:C 和 vWF:Ag 的接近正常或正常水平相比，vWF:RCo 和 vWF:CB 的水平较低。由于凝血因子 VIII/血管性血友病因子（vWF）浓缩物 Haemate-P 的 vWF:RCo/FVIII:C 比值约为 2.2，对于接受大手术的 2 型 vWD 患者，推荐的预防出血的负荷剂量为 50 U/kg FVIII:C，随后每 12 小时给予 25 U/kg FVIII:C，持续数天，这显示出预测的显著过度治疗，使 vWF:RCo 水平超过 2 U/ml。因此，我们将大手术中 Haemate-P 的替代限制为一次负荷剂量 40 - 50 U/kg FVIII:C（88 - 110 U/kg vWF:RCo），随后每 12 小时给予 15 - 20 U/kg FVIII:C（33 - 44 U/kg vWF:RCo），持续数天，并在一项针对 5 例 2 型 vWD 患者预防出血的前瞻性药代动力学和疗效研究中评估了该策略。FVIII:C 的治疗前水平和峰值水平（Haemate-P 负荷剂量后 1 小时）从 0.43 - 0.66 升至 1.5 - 2.5 U/ml，vWF:Ag 从 0.23 - 0.45 升至 1.5 - 2.5 U/ml，vWF:RCo 从 0.10 - <0.20 升至 1.5 - 2.5 U/ml，vWF:CB 从 <0.05 - 0.10 升至 1.0 - 2.0 U/ml。每输注 1 IU FVIII:C/kg 体重的平均体内回收率，FVIII:C 为 3.2%，vWF:RCo 为 3.9%，vWF:CB 为 2.8%。每输注 1 IU vWF:RCo/kg 的平均体内回收率，FVIII:C 为 1.45%，vWF:RCo 为 1.7%，vWF:CB 为 1.25%。输注 Haemate-P 后，vWF:RCo 和 vWF:CB 的生物半衰期均约为 12 小时。基于这些药代动力学数据，我们建议将负荷剂量的凝血因子 VIII/vWF 浓缩物（Haemate-P）调整为 60 - 80 U/kg vWF:RCo，随后每 12 小时给予 30 - 40 U/kg vWF:RCo，持续不超过数天（少于 1 周），用于大手术或创伤期间的出血预防；对于对去氨加压素无反应的 2 型 vWD 患者，小手术、创伤或黏膜出血的负荷剂量为 40 - 60 U/kg vWF:RCo。