Emergency coronary artery bypass graft surgery in abciximab-treated patients

BACKGROUND: Although the platelet antiaggregant abciximab is frequently used with percutaneous coronary interventions, results of emergency coronary artery bypass graft operations in patients recently treated with abciximab are poorly characterized. METHODS: During a 29-month period, 12 patients required emergency coronary artery bypass grafting within 12 hours (mean, 1.9 hours) of abciximab therapy. Our full standard heparin dose regimen was used (mean heparin dose, 53,000 U per patient). Each patient received a single platelet transfusion dose after protamine administration, and further blood products were transfused as necessary. Clinical outcome and transfusion requirements were compared with predicted results based on risk-adjusted historical patients. RESULTS: No patients died and none were returned to the operating room for coagulopathy-related bleeding. Per patient transfusion requirements were as follows: red blood cells, 3.6 units; apheresis platelets, 1.4 units; and fresh frozen plasma, 1.5 units. As compared with predicted values, there was no excessive incidence of mortality, stroke, or red blood cell transfusion requirements. CONCLUSIONS: Emergency coronary artery bypass graft operations using full-dose heparin can be performed successfully in acutely ischemic abciximab-treated patients. Prophylactic transfusion of platelets after protamine administration appears to be useful.     

急诊冠状动脉搭桥术

目的探讨急诊冠状动脉搭桥(CABG)术的手术指征及外科处理要点,提高手术成功率.方法1999年1月至2001年5月18例急诊CABG病人中男15例,女3例.年龄40.0～71.5岁,平均(61.7±8.5)岁.术前急性心肌梗死(AMI)8例[7例直接行冠状动脉造影(冠造)及经皮腔内冠状动脉成形术(PTCA);1例溶栓失败,急诊行冠状动脉造影及PTCA],冠造均提示三支血管病变,急性心肌梗死到急诊CABG手术时间平均(9.4±6.3)?h;不稳定心绞痛不能控制7例;冠状动脉造影术及PTCA时右冠状动脉撕裂、急性心包压塞及室颤各1例.术前放置主动脉气囊反搏泵(IABP)13例.17例在体外循环下行急诊CABG术,平均体外循环时间(78.5±25.2)?min,平均阻断时间(65.3±23.6)?min;平均每例搭桥(3.4±1.1)支;1例小切口行不停跳搭桥.采用左内乳动脉桥14例、右内乳动脉桥1例、桡动脉桥6例.结果1例术中死亡,1例术后死于低心输出量综合征.余16例随访2～25个月,无死亡;亦无明显心绞痛及心肌缺血表现.结论急诊CABG是挽救不能控制的急性心肌缺血的有效方法之一,及时正确的抢救方法是保证手术成功的关键.     

Efficacy of FK633, an ultra-short acting glycoprotein IIb/IIIa antagonist on platelet preservation during and after cardiopulmonary bypass.

OBJECTIVE: Temporary pharmacologic inhibition of platelet function during and after cardiopulmonary bypass (CPB) (platelet anesthesia) is an attractive strategy for preserving platelets during CPB. We examined the efficacy of FK633, an ultra-short acting glycoprotein IIb/IIIa antagonist. METHODS: The study was carried out in six mongrel dogs that received an intravenous bolus of 0.1 mg/kg of FK633 at the time of administration of heparin (group F), and six control dogs (group C). All animals underwent 60 min of normothermic CPB followed by a 2-h observation period. Blood samples for platelet count, platelet aggregation to adenosine diphosphate and parameters concerning the coagulation system were obtained at eight time points. Hemodynamics, bleeding time, and postoperative blood loss were assessed serially. Scanning electron micrograph of the oxygenator's membrane was investigated. RESULTS: FK633 significantly protected platelet number (group F, 59+/-10% versus group C, 38+/-15% of the pre-CPB value; P < 0.01), and inhibited platelet aggregation to adenosine diphosphate (group F, 13+/-12% versus group C, 35+/-9% of the pre-CPB value; P < 0.01) during CPB. Postoperative blood loss did not significantly differ between the two groups, but there was a tendency of less bleeding in group F (group F, 73+/-23 ml versus group C, 111+/-44 ml; P = 0.09). In group F, scanning electron micrograph of the oxygenator's membrane showed that its surface was free from platelets. There were no significant differences between the groups in hemodynamics. CONCLUSIONS: An ultra-short acting glycoprotein IIb/IIIa antagonist, FK633, is effective in preventing both platelet aggregation and thrombocytopenia during CPB, and may be effective for minimizing postoperative bleeding.     

Emergency coronary artery bypass surgery after failed percutaneous transluminal coronary angioplasty

Coronary complications caused by percutaneous transluminal coronary angioplasty (PTCA) may necessitate emergency coronary artery bypass grafting (CABG). In 1994-1998, 132 patients (1.5% of the patients registered in the Danish PTCA registry) underwent CABG within 24 h because of angioplasty complications. We reviewed the files of 86 patients who had emergency operations within 6 h and found that 35% suffered from 1-vessel disease. Fifty-eight percent were taken directly to the operating room from the cardiovascular laboratory, and 13% were given preoperative cardiovascular resuscitation. The vessels most frequently injured were the right coronary artery and the left anterior descending branch (LAD). The patients received a mean of 2.4 coronary bypasses each. Forty-three percent of the patients with lesions of the left main coronary artery and/or the LAD received a vein graft to the LAD. A perioperative Q-wave myocardial infarction developed in 51% of the patients. The in-hospital mortality rate was 12%. These results are inferior to those obtained after elective surgery. Local cardiothoracic backup is vital when PTCA is performed in an unselected patient group.     

Effect of platelet glycoprotein IIb/IIIa receptor antagonist on survival of epigastric island flaps in rats with total venous occlusions.

We evaluated the effect of tirofiban hydrochloride on the survival of epigastric island flaps in rats that had had all the veins occluded. Male Wistar Albino rats were randomly assigned to control (treated with sterile saline) and experimental (treated with tirofiban hydrochloride 1 mg/kg intravenously) groups. An epigastric island skin flap 3x6 cm was raised in each rat. All veins that drained the flap were ligated to give total venous occlusion. Blood flow was recorded by laser Doppler preoperatively (baseline), immediately after the flap had been sutured back to its original position (acute) and on postoperative days 1 and 3. The degree of necrosis was evaluated on day 3. Mean percentage necrosis and minimum laser Doppler values were compared in the two groups. Total necrosis was evident on day 1 in the control group and on day 3 in the experimental group. Macroscopic evidence was confirmed by histopathological examination. There were appreciable differences in blood flow and in the necrotic area of the flap in the experimental group compared with the control group on both days 1 and 3. Tirofiban hydrochloride might be effective in this flap model.     

Pharmacologic platelet anesthesia by glycoprotein IIb/IIIa complex antagonist and argatroban during in vitro extracorporeal circulation

OBJECTIVE: Contact between blood and the synthetic surfaces of a cardiopulmonary bypass circuit leads to platelet activation, and resultant platelet dysfunction contributes to postoperative bleeding. We compared the effects of various platelet inhibitors on preservation of platelet function during simulated cardiopulmonary bypass circulation. METHODS: Fresh human blood was recirculated in an in vitro cardiopulmonary bypass model circuit. We measured various platelet activation markers including expressions of PAC-1 and P-selectin, annexin V binding, and microparticle formations by means of whole-blood flow cytometry. RESULTS: Two types of glycoprotein IIb/IIIa complex antagonists, peptide-mimetic FK633 and abciximab and prostaglandin E(1), significantly prevented platelet loss and the increase in binding of PAC-1, an antibody specific for fibrinogen receptor on activated platelets, during extracorporeal circulation of heparinized blood. These antagonists significantly suppressed but did not abolish P-selectin expression, annexin V binding, and microparticle formation. Anti-von Willebrand factor monoclonal antibody and aurin tricarboxylic acid (an inhibitor of glycoprotein Ib) had no effect on platelet activation during simulated cardiopulmonary bypass circulation. These data suggest that inhibition of fibrinogen binding glycoprotein IIb/IIIa complex is partly effective in attenuating platelet activation in a heparinized cardiopulmonary bypass model circuit. The direct thrombin inhibitor argatroban prevented platelet loss and expression of P-selectin significantly more than did heparin. A combination of FK633 with argatroban as a substitute for heparin further prevented platelet loss and platelet secretion during simulated cardiopulmonary bypass circulation, although the inhibition of microparticle formation was less. CONCLUSION: The inhibition of both platelet adhesion and thrombin may be effective to preserve platelet number and function during cardiopulmonary bypass circulation.     

The glycoprotein IIb/IIIa antagonist c7E3 inhibits platelet aggregation in the presence of heparin-associated antibodies

Purpose: Heparin-associated antibodies (HAAb), in the presence of heparin, can cause platelet activation and aggregation. The purpose of this study was to assess whether a platelet glycoprotein (GP) IIb/IIIa receptor antagonist, c7E3, would inhibit platelet aggregation in the presence of HAAb. If aggregation is inhibited by c7E3, enzyme-linked immunosorbent assays (ELISA) would be done to determine whether c7E3 interfered with the binding of heparin and the HAAb.Methods: HAAb-positive plasmas from 21 patients (determined by platelet aggregation assays) were studied. Normal donor platelet-rich plasmas (PRP) were incubated (1 minute) with either saline solution or 3 μg/ml of c7E3. Platelet-poor plasma from patients with HAAb and one of three sources of heparin (25 μl, 10 U/ml; porcine heparin, bovine heparin, and low molecular weight heparin [enoxaparin]) were added to the PRP mixture. Aggregation was determined using a platelet aggregometer by measuring time to aggregation, the slope of the aggregation curve, and the percent change in optical density.Results: Platelet aggregation occured in 100%, 100%, and 95% of the saline solution incubations exposed to porcine heparin, bovine heparin, and enoxaparin, respectively. Incubation with c7E3 caused 100% inhibition of platelet aggregation in plasma exposed to porcine heparin, bovine heparin, and enoxaparin. The optical density curves obtained from the ELISA, which were dependent on the binding of HAAb to heparin, were not significantly different when c7E3 was compared to buffer alone.Conclusions: The GP IIb/IIIa receptor antagonist, c7E3, inhibits HAAb-induced platelet aggregation via a mechanism that does not appear to interfere with the binding between heparin and HAAb. Clinical trials are warranted to assess whether GP IIb/IIIa antagonists may allow patients with HAAb to safely receive heparin. (J Vasc Surg 1997;25:124-30.)     

Platelet glycoprotein IIb/IIIa receptor antagonist (abciximab) inhibited platelet activation and promoted skin flap survival after ischemia/reperfusion injury

BACKGROUND: Evidence has shown that platelets play an important role in the pathogenesis of flap failure. Employing a rat inferior epigastric artery skin flap as a flap reperfusion injury model, we investigated whether platelet activation was involved in the skin flap failure and whether administration of abciximab (ReoPro, chimeric 7E3 Fab) could decrease platelet activation/aggregation and promote flap survival. METHODS: Normal saline and abciximab (0.06 mg/kg; 0.2 mg/kg; 1 mg/kg) were injected intravenously into skin flaps 30 min before reperfusion and 1 h after reperfusion (each subgroup n = 6). Platelet activation as demonstrated by P-selectin (CD62P) was analyzed by flow cytometry. P-selectin expression on flap vessels was detected by immunohistochemical staining. Platelet aggregation was induced with adenosine diphosphate (ADP). Laser Doppler flowmetry monitored tissue perfusion. The surviving area was evaluated 7 days postoperatively. RESULTS: CD62P progressively increased after reperfusion. The peak CD62P occurred after reperfusion for 12 h. Immunohistochemical staining showed CD62P significantly deposited on the endothelium after reperfusion. Administration of abciximab (1 mg/kg) effectively improved flap survival rate (P = 0.003), significantly decreased ADP-induced platelet aggregation (P < 0.001), and suppressed CD62P expression on blood platelets (P = 0.002) and its deposition on the flap vessels. CONCLUSION: Abciximab promotion of skin flap survival is due to blocked platelet activation/aggregation and decreased activated-platelet deposition on the vascular endothelium. Thus, administration of a platelet glycoprotein IIb/IIIa receptor antagonist such as abciximab may save the skin flap from reperfusion injury after a long period of ischemia.     

Assessment of prosthetic vascular graft thrombogenicity using the technetium-99m labeled glycoprotein IIb/IIIa receptor antagonist DMP444 in a dog model

INTRODUCTION: Prosthetic graft patency greatly depends on graft thrombogenicity. The concept of graft thrombogenicity is poorly understood and difficult to measure or quantify. In a study we tested the experimental radiopharmaceutical DMP444 and developed a suitable dog model. This agent is a radiolabelled ((99m)Technetium) glycoprotein IIb/IIIa receptor antagonist with a high affinity for activated platelets. It binds to platelets that are intimately involved in thrombus formation. The agent does not affect thrombocyte function, when used in a dose necessary for imaging. DMP444 does not require platelet harvesting and processing. Early imaging of thrombocyte aggregation sites such as vascular prostheses is possible within 4 hours after injection. MATERIAL AND METHODS: Adult Beagle dogs weighing 12-15 kg were used for the experiments. In 16 dogs a prosthetic patch was sewn onto the abdominal aorta (Bovine pericard: n=4, Dacron: n=6, Human Umbilical Vein: n=6). Imaging cycles after injection of (99m)Technetium-labelled DMP444 were performed on days 1, 7, 14 and 28 after surgery. RESULTS: We noticed differences in thrombus formation on the tested graft materials. The bovine pericard patches (n=4) showed a relatively high rate of thrombocyte aggregation. In the Dacron patches (n=6) aggregation was not seen. In 1 of 6 cases of human umbilical vein patches a measurable focal aggregation was recorded. CONCLUSION: The method outlined in this study is a relatively simple and reproducable method to visualize thrombocyte aggregation.