Frey J L, Muro G J, McDougall C G, Dean B L, Jahnke H K
Barrow Neurological Institute, Phoenix, AZ, USA.
Stroke. 1999 Mar;30(3):489-94. doi: 10.1161/01.str.30.3.489.
We chose to evaluate the safety and efficacy of combined intrathrombus rtPA and intravenous heparin in cerebral venous thrombosis (CVT).
We treated 12 patients with symptoms of 1 to 40 days' duration (eg, headache, somnolence, focal deficits, seizures, and nausea and vomiting). Pretreatment MRI disclosed subtle hemorrhagic venous infarction in 4 patients, obvious hemorrhagic infarction in 2, small parenchymal hemorrhage from recent pallidotomy in 1, and no focal lesion in 5. Magnetic resonance venography and contrast venography identified thrombi in the superior sagittal sinus (SSS) in 3 patients; transverse/sigmoid sinus (TS/SS) in 2; SSS and both TS/SS in 1; SSS and 1 TS/SS in 5; and SSS, 1 TS/SS, and straight sinus in 1 patient. A loading dose of rtPA was instilled throughout the clot at 1 mg/cm, followed by continuous intrathrombus infusion at 1 to 2 mg/h. Intravenous heparin was infused concomitantly.
Flow was restored completely in 6 patients and partially in 3, with a mean rtPA dose of 46 mg (range, 23 to 128 mg) at a mean time of 29 hours (range, 13 to 77 hours). Symptoms improved in these 9 patients concomitantly with flow restoration. Flow could not be restored in 3 patients. In 1 of them, treatment was stopped when little progress had been made, and fibrinogen level dropped to 118 mg/dL. In the other 2 patients, hemorrhagic worsening occurred, and treatment was abbreviated after initial rtPA dosing. In 1 of these, the hematoma was evacuated.
Our experience with intrathrombus rtPA in conjunction with intravenous heparin in patients with CVT is encouraging. This therapy should probably be regarded as unsafe in patients with obvious hemorrhage. Time to restore flow may be faster than with urokinase (an average of 71 hours has been reported for 29 documented patients). Further evaluation of rtPA with heparin in CVT is warranted.
我们选择评估联合应用血栓内rtPA与静脉肝素治疗脑静脉血栓形成（CVT）的安全性和有效性。
我们治疗了12例病程为1至40天（如头痛、嗜睡、局灶性神经功能缺损、癫痫发作以及恶心和呕吐）的患者。治疗前MRI显示，4例患者有轻微出血性静脉梗死，2例有明显出血性梗死，1例因近期苍白球切开术有小的脑实质出血，5例无局灶性病变。磁共振静脉造影和静脉造影显示，3例患者上矢状窦（SSS）有血栓；2例横窦/乙状窦（TS/SS）有血栓；1例SSS及双侧TS/SS有血栓；5例SSS及1个TS/SS有血栓；1例患者SSS、1个TS/SS及直窦有血栓。以1mg/cm的剂量在整个血栓内注入rtPA负荷量，随后以1至2mg/h的速度持续进行血栓内输注。同时静脉输注肝素。
6例患者血流完全恢复，3例部分恢复，rtPA平均剂量为46mg（范围23至128mg），平均时间为29小时（范围13至77小时）。这9例患者的症状随着血流恢复而改善。3例患者血流未能恢复。其中1例在进展甚微时停止治疗，纤维蛋白原水平降至118mg/dL。另外2例患者出现出血性恶化，在初始rtPA给药后缩短了治疗时间。其中1例进行了血肿清除。
我们应用血栓内rtPA联合静脉肝素治疗CVT患者的经验令人鼓舞。对于有明显出血的患者，这种治疗可能被视为不安全。恢复血流的时间可能比使用尿激酶更快（29例有记录的患者平均报告时间为71小时）。有必要对CVT患者应用rtPA联合肝素进行进一步评估。
