Goldhaber S Z, Meyerovitz M F, Green D, Vogelzang R L, Citrin P, Heit J, Sobel M, Wheeler H B, Plante D, Kim H
Cardiovascular Division, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Am J Med. 1990 Mar;88(3):235-40. doi: 10.1016/0002-9343(90)90148-7.
To compare the efficacy and safety of recombinant human tissue-type plasminogen activator (rt-PA, supplied as Activase) with heparin alone or rt-PA plus heparin in the treatment of venographically documented proximal deep venous thrombosis (DVT) of the leg.
Sixty-four patients underwent 65 randomizations to rt-PA alone (n = 36), rt-PA plus heparin (n = 17), or heparin alone (n = 12) in a prospective, multicenter, randomized, open-label trial, with efficacy assessed by a radiology panel unaware of treatment assignment. Patients randomly assigned to rt-PA received 0.05 mg/kg/hour for 24 hours via a peripheral vein, with a maximum dose of 150 mg. All patients then received heparin and warfarin for the remainder of the hospitalization. Follow-up venography was performed 24 to 36 hours after initiation of therapy.
Complete or more than 50% lysis occurred in 10 (28%) patients treated with rt-PA, five (29%) patients with rt-PA plus heparin, and no patient treated with heparin. No lysis occurred in 16 (44%) patients treated with rt-PA plus heparin, and 10 (83%) patients who received heparin alone (p = 0.04). There was one major complication, a nonfatal intracranial hemorrhage in a patient who received rt-PA alone. At 7 to 10 days after initiation of treatment, the level of serum glutamic oxaloacetic transaminase nearly doubled among all patients, including those assigned to receive heparin alone.
(1) rt-PA and rt-PA plus heparin cause more clot lysis than heparin alone; (2) the addition of heparin to rt-PA does not improve the lysis rate; (3) DVT treated with heparin is commonly associated with a rise in the transaminase level; (4) heparin does not increase the risk of bleeding from rt-PA therapy; and (5) alternative dosing regimens and modes of administration of rt-PA should be investigated to improve further its efficacy and safety in the treatment of acute DVT.
比较重组人组织型纤溶酶原激活剂（rt - PA，商品名为阿替普酶）单独使用、rt - PA联合肝素与单纯肝素治疗经静脉造影证实的腿部近端深静脉血栓形成（DVT）的疗效和安全性。
在一项前瞻性、多中心、随机、开放标签试验中，64例患者接受了65次随机分组，分别为单独使用rt - PA（n = 36）、rt - PA联合肝素（n = 17）或单纯肝素（n = 12）治疗，疗效由不知治疗分配情况的放射科小组评估。随机分配接受rt - PA治疗的患者通过外周静脉以0.05 mg/kg/小时的剂量给药24小时，最大剂量为150 mg。所有患者随后在住院期间的剩余时间接受肝素和华法林治疗。在治疗开始后24至36小时进行随访静脉造影。
接受rt - PA治疗的10例（28%）患者、接受rt - PA联合肝素治疗的5例（29%）患者出现了完全溶解或超过50%的溶解，而接受单纯肝素治疗的患者无溶解情况。接受rt - PA联合肝素治疗的16例（44%）患者和接受单纯肝素治疗的10例（83%）患者未出现溶解（p = 0.04）。发生了1例主要并发症，为1例单独接受rt - PA治疗的患者出现非致命性颅内出血。在治疗开始后7至10天，所有患者（包括那些分配接受单纯肝素治疗的患者）的血清谷氨酸草酰乙酸转氨酶水平几乎翻倍。
（1）rt - PA及rt - PA联合肝素比单纯肝素能引起更多的血栓溶解；（2）在rt - PA基础上加用肝素并不能提高溶解率；（3）肝素治疗的DVT通常与转氨酶水平升高有关；（4）肝素不会增加rt - PA治疗引起的出血风险；（5）应研究rt - PA的替代给药方案和给药方式，以进一步提高其治疗急性DVT的疗效和安全性。
