Ortel T L, Mercer M C, Thames E H, Moore K D, Lawson J H
Department of Medicine, Division of Hematology, Duke University Medical Center, Durham, North Carolina 27710, USA.
Ann Surg. 2001 Jan;233(1):88-96. doi: 10.1097/00000658-200101000-00014.
To determine prospectively the immunologic response and adverse clinical events in surgical patients exposed to bovine thrombin during cardiac surgical procedures.
Topical bovine thrombin is used extensively as a hemostatic agent during cardiovascular surgery. Antibodies developing after exposure to bovine thrombin have been anecdotally associated with hemorrhagic complications.
One hundred fifty-one patients undergoing cardiac surgical procedures were prospectively recruited for this study before surgical exposure with topical bovine thrombin. Immunoassays were used to determine antibody levels against both bovine and human coagulation proteins before and after exposure to bovine thrombin. Alterations in coagulation assay parameters and adverse clinical events were followed in all patients enrolled in the study.
Baseline elevated antibody levels to one or more bovine coagulation proteins were observed most frequently in patients with a prior history of a surgical procedure during which bovine thrombin is frequently used. More than 95% of patients developed a seropositive response to bovine coagulation proteins, and 51% manifested elevated antibody levels to the corresponding human coagulation proteins after bovine thrombin exposure. Postoperative coagulation abnormalities were more common in patients with antibodies to human coagulation proteins. Patients with multiple elevated antibody levels to bovine proteins before surgery were more likely to sustain an adverse clinical outcome after surgery. Using a logistic regression model, the adjusted odds ratio for sustaining an adverse event with multiple elevated antibody levels to bovine proteins before surgery was 5.40.
Bovine thrombin preparations are highly immunogenic and appear to be associated with an increased risk for adverse clinical outcomes during subsequent surgical procedures. The clinical safety of these commonly used preparations needs to be reassessed, and reexposure to these agents should likely be avoided.
前瞻性地确定心脏手术过程中接触牛凝血酶的外科患者的免疫反应和不良临床事件。
局部应用牛凝血酶在心血管手术中被广泛用作止血剂。接触牛凝血酶后产生的抗体与出血并发症有轶事关联。
151例接受心脏手术的患者在手术暴露于局部牛凝血酶之前被前瞻性纳入本研究。免疫测定用于确定接触牛凝血酶前后针对牛和人凝血蛋白的抗体水平。对所有纳入研究的患者随访凝血测定参数的变化和不良临床事件。
在既往有经常使用牛凝血酶的手术史的患者中，最常观察到基线时针对一种或多种牛凝血蛋白的抗体水平升高。超过95%的患者对牛凝血蛋白产生血清学阳性反应，51%的患者在接触牛凝血酶后针对相应的人凝血蛋白的抗体水平升高。术后凝血异常在针对人凝血蛋白有抗体的患者中更常见。术前针对牛蛋白有多种抗体水平升高的患者术后更有可能出现不良临床结局。使用逻辑回归模型，术前针对牛蛋白有多种抗体水平升高的患者发生不良事件的调整比值比为5.40。
牛凝血酶制剂具有高度免疫原性，似乎与后续手术过程中不良临床结局风险增加有关。这些常用制剂的临床安全性需要重新评估，并且可能应避免再次接触这些制剂。
