体外循环对血小板计数及释放反应的影响

目的：探讨体外循环（ＣＰＢ）对血小板计数及血小板释放反应的影响。方法：２０例ＣＰＢ患者分别于转流前、转流３０分、鱼精蛋白中和肝素后１０分及术后２、１２和２４小时进行血小板计数（ＢＰＣ）、血小板表面α颗粒膜蛋白（ＧＭＰ－１４０）、血小板β球蛋白（β－ＴＧ）、血小板第４因子（ＰＥ４）及５－羟色胺（５－ＨＴ）的测定，并统计术后显著出血的例数。结果：ＢＰＣ在转流期间显著下降，但仍高于５０×１０＾９／Ｌ。Ｇ     

抑肽酶抑制体外循环期间血小板激活反应

为研究体外循环期间抑肽酶对血小板激活的抑制，将４０例心脏手术病人随机分为对照组和观察组。观察组加抑肽酶于预充液中，取围术期５个时段检测血小板计数（ＰＴＣ）、血栓烷Ｂ２（ＴＸＢ２）、血小板表面α颗粒膜蛋白（ＧＭＰ１４０）、β血小板球蛋白（βＴＧ）、血小板第４因子（ＰＦ４）、５羟色胺（５ＨＴ）、术后出血量。结果表明对照组ＰＴＣ明显下降，ＴＸＢ２、ＧＭＰ１４０、βＴＧ、ＰＦ４、５ＨＴ均显著升高；观察组以上各项指标及术后出血量均较对照组明显好转（Ｐ＜０．０５或Ｐ＜０．０１）。作者认为，抑肽酶通过抗纤溶等作用可抑制体外循环期间血小板的激活，减少术后出血量。     

止血芳酸对体外循环心脏手术中血小板功能的保护作用

目的：研究止血芳酸（ＰＡＭＢＡ）对体外循环心肺转流（ＣＰＢ）心脏手术中血小板功能的保护作用。方法：２２例择期心脏瓣膜置换术患者，随分为两组，观察组于麻醉后切片前经中心静脉给予给予ＰＡＭＢＡ ２０ｍｇ／ｋｇ（其中的４００ｍｇ预充体外循环机内），对照组不给药。在ＣＰＢ前、ＣＰＢ后３０分钟、ＣＰＢ结束、鱼精蛋白中和肝素后２０分钟四个时点检测血小板计数、血小板聚集功能和血小板膜糖蛋白ＧＰＩｂ和ＧＰⅡｂ／Ⅲ     

体外循环中止血芳酸对血小板的保护作用

目的：探讨止血芳酸在体外循环中对血小板的保护作用及其临床意义。方法：测定止血芳酸组和对照组血小板数量、出血量和输血量,及体外循环前后血浆α－颗粒膜蛋白（ＧＭＰ－１４０）,血栓烷Ｂ２（ＴＸＢ２）和６－酮－前列腺素Ｆ１a(6-k-PGF1a）的浓度变化。结果,体外循环术后血小板计数组明显高于对照组,出血量明显少于对照组。ＧＭＰ－１４０、ＴＸＢ２上升幅度小于对照组,二者相比差异显著（Ｐ＜０．０５）。结论：止血芳酸在体外循环术中可以起到保护血小板,减少术后出血的作用。     

体外循环对血小板花生四烯酸代谢的影响

选择２２例心脏瓣膜置换术患者，观察在体外循环（ＣＰＢ）中血小板的功能及花生四烯酸（ＡＡ）代谢改变。结果显示：ＣＰＢ中血小板计数、血小板聚集功能及粘附功能均显著下降，而血小板胞浆游离［Ｃａ２＋］及膜磷脂酶Ａ２（ＰＬＡ２）、环氧化酶（ＣＬＯ）活性均显著升高，停机时血小板聚集功能及粘附功能均与术后失血量呈显著负相关，而胞浆游离［Ｃａ２＋］ｉ及膜ＰＬＡ２活性则与术后失血量呈显著正相关。表明ＣＰＢ对血小板胞浆游离［Ｃａ３＋］及膜ＰＬＡ２活性的影响是血小板功能失调及术后非外科性失血的重要原因。     

体外循环中小剂量抑肽酶对血栓素及血小板功能与结构的作用

体外循环中小剂量抑肽酶对血栓素及血小板功能与结构的作用李建华＊孙继领＊高小环＊王京庆＊王红卫＊表１两组血小板计数聚集功能粘附功能ＴＸＢ２ＰＧＦ１α及ＴＸＡ２／ＰＧＦ１α变化（ｘ±ｓ）组别麻醉后ＣＰＢ１０ｍｉｎＣＢＰ４０ｍｉｎ术终术后２ｈ术后１２ｈ术后...     

抑肽酶对血小板膜糖蛋白功能影响的实验研究

目的 研究体外循环期间抑肽酶对血小板保护作用的分子学机制。方法 ２０例健康供血者的静脉血注入含枸橼酸或肝素的试管中,用流式细胞术检测抑肽酶对血小板膜糖蛋白ＧＰⅡｂ－Ⅲａ受体及Ｐ－选择素表达的影响。结果 抑肽酶在５０～２００Ｕ／ｍｌ时可减少ＡＤＰ和凝血酶受体激活肽６激活的血小板膜糖蛋白ＧＰⅡｂ－Ⅲａ受体的表达（Ｐ〈０．０５）,但对Ｐ－选择素表达无影响。结论 抑肽酶减少激动剂诱导的活化血小板膜糖蛋白Ｇ     

小剂量抑肽酶在体外循环中保护血小板作用及减少术后出血

为评估小剂量抑肽酶（１．５×１０６ＫＩＵ）对血小板功能的保护及止血作用，用药组（Ａ组ｎ＝２０）体外循环（ＣＰＢ）预充液中一次性加抑肽酶，对照组（Ｂ组ｎ＝２０）加入同容积生理盐水。检测结果Ａ组较Ｂ组血小板计数、血小板聚集率均增高；血栓烷Ｂ２下降；ＡＣＴ延长但中和效果佳；术中止血时间缩短；术后失血量和输血量明显降低。结论：小剂量抑肽酶减轻血小板膜受体在ＣＰＢ中的损害、增强其聚集功能、减轻血小板数量下降；抑肽酶与肝素有协同作用并竞争性抑制肝素对血小板功能抑制；明显减少手术后失血和输血量。     

抑肽酶在心肺转流术中对肺损伤的保护

目的 探讨心肺转流术（ｃａｒｄｉｏｐｕｌｍｏｎａｒｙ ｂｙｐａｓｓ,ＣＰＢ）导致肺缺血－再灌注损伤,抑肽酶对肺损伤保护的作用。方法 将２４例心内直视手术的患者随机分为对照组和实验组,每组１２例,实验组给予抑肽酶处理。检测ＣＰＢ前后左、右心房血中性粒细胞和血小板计数,围手术期各时段桡动脉血浆中内皮素、血栓素Ｂ２、６－酮－前列腺素Ｆ１α和呼吸指数的变化。结果 对照组ＣＰＢ后左、右心房血中血小板和中性粒细胞计数差异有显著性（Ｐ〈０．０５）;实验组ＣＰＢ前后则差异无显著性;内皮素、血栓素Ｂ２、呼吸指数在ＣＰＢ中、ＣＰＢ后两组比较均差异有显著性（Ｐ〈０．０１）。结论 ＣＰＢ致肺损伤,血小板和中性粒细胞在肺内聚集,内皮素、血栓素Ｂ２、６－酮－前列腺素Ｆ１α在其病理过程中起重要作用。抑肽酶能通过干预这些因素而达到保护肺功能的     

肾移植患者血小板活化指标测定的临床研究

为探讨移植肾排斥反应与血小板活化指标的关系，应用抗人活化血小板ＧＭＰ－１４０（α－颗粒膜蛋白）特异单克隆抗体Ｓｚ－５１（苏州－５１），检测６８例肾移植患者外周血血小板表面及血浆ＧＭＰ－１４０含量；同时采用放射免疫法测定血浆ＴｘＢ２（血栓烷Ｂ２）含量。术后肾功能正常者ＧＭＰ－１４０及ＴｘＢ２略有升高；发生急慢性排斥反应时两者均显著升高（Ｐ＜０．００１），排斥逆转或移植肾切除后逐渐下降。发生环孢素中毒者其含量无明显变化（Ｐ＞０．０５）。提示移植肾排斥与体内血小板活化有关，活化指标ＧＭＰ－１４０、ＴｘＢ２检测对早期诊断肾移植后排斥反应及环孢素中毒具有一定的临床价值，是监测移植肾排斥反应的一个较灵敏的生物学指标。     

The GP IIb/IIIa inhibitor abciximab (ReoPro) decreases activation and interaction of platelets and leukocytes during in vitro cardiopulmonary bypass simulation.

OBJECTIVE: Cardiopulmonary bypass (CPB) induces a systemic inflammatory response and increases expression of the platelet activation marker P-selectin which mediates binding of platelets to leukocytes. Inhibition of the platelet GP IIb/IIIa receptor during CPB has been shown to protect platelets without increasing bleeding complications and is assumed to reduce the inflammatory response. The aim of this study was to investigate the effect of the GP IIb/IIIa inhibitor abciximab (ReoPro) on the function and interaction of platelets and leukocytes during experimental CPB. METHODS: Heparinized (3 U/ml) fresh whole blood of healthy volunteers was treated before continuous in vitro circulation in a well established CPB model with 3.2 microg/ml abciximab (n=6) or left untreated as control (n=6). Measurements were made before (baseline) and after 30 and 60 min of circulation and comprised: percentage of platelets expressing P-selectin and percentage of platelet-bound leukocytes (flow cytometry), release of the leukocyte activation marker PMN-elastase (ELISA), and platelet and leukocyte counts. RESULTS: Abciximab almost completely prevented a CPB-induced increase of platelet P-selectin and platelet-leukocyte binding after 30 and 60 min of circulation, and significantly inhibited release of PMN-elastase after 30 min of circulation. Furthermore, abciximab significantly inhibited a CPB-induced decrease of platelet and leukocyte counts. CONCLUSIONS: Abciximab inhibits CPB-induced activation, interaction and consumption of platelets and leukocytes in vitro. GP IIb/IIIa inhibition should be considered as a promising approach not only to conserve platelet function but also to inhibit pro-inflammatory events during CPB in vivo.     

Platelet function during cardiac surgery and cardiopulmonary bypass with low-dose aprotinin.

OBJECTIVE: To determine whether two low-dose regimens of aprotinin influence platelet function. DESIGN: Prospective, randomized, single-blinded trial. SETTING: University teaching hospital performing 600 cardiac operations per year. PARTICIPANTS: Fifty-nine patients scheduled for cardiac surgery undergoing cardiopulmonary bypass (CPB) of expected duration of 60 minutes or more. INTERVENTIONS: Patients were randomized into three groups. Group C (control) included 21 patients who did not receive aprotinin. In group A2, 17 patients received 14,286 kallikrein inhibitor units (KIU)/kg (2 mg/kg) of aprotinin before surgery, followed by a continuous infusion of 7,143 KIU/kg/h (1 mg/kg/h) until the end of surgery. In group A4, 19 patients received 28,572 KIU/kg (4 mg/kg) of aprotinin before surgery, followed by the same infusion. MEASUREMENTS AND MAIN RESULTS: Postoperative bleeding and transfusion requirements were significantly less in group A4. Changes in platelet number and function were similar in the three groups. Platelet aggregation was assessed in four periods: before CPB (T1), post-CPB (T2), and 2 hours (T3) and 4 hours (T4) after CPB. Platelet aggregation induced by adenosine diphosphate, 1 and 2 micromol/L; ristocetin, 1 mg/mL; and arachadonic acid (AA), 1.4 mmol/L, decreased at T2 (p < 0.001) in all groups, and for the ristocetin and AA groups, remained at less than baseline values at T3 and T4. In five patients from each group, platelet receptors for glycoprotein IIb-IIIa (GPIIb-IIIa) and expression of platelet activation markers, guanosine monophosphate 140 (GMP-140) and lysosomal protein, were measured by flow cytometry before and after CPB. Modifications in the expression of GPIIb-IIIa were always modest and without statistical significance. Platelet activation markers, GMP-140 or lysosomal protein, nearly doubled from baseline to post-CPB only in the A4 group, whereas they remained stable in both other groups (statistically not significant). CONCLUSION: The two regimens of aprotinin, both considered low dosage, did not exert a protective effect on platelet function. Neither dose produced changes in platelet GPIIb-IIIa or platelet activation markers. However, bleeding and transfusion needs were decreased.     

Management of heparin resistance during cardiopulmonary bypass: the effect of five different anticoagulation strategies on hemostatic activation

OBJECTIVE: Attenuation of hemostatic activation is a central goal during CPB. However, this poses a problem in patients insensitive to heparin. The present investigation was performed to assess different strategies of managing patients with heparin resistance during CPB. DESIGN: A randomized, prospective clinical investigation. SETTING: A major European heart center. PARTICIPANTS: Five groups with 20 patients each were investigated. INTERVENTIONS: The groups were handled as follows: (1). maintenance of a target ACT, (2). maintenance of the target unfractionated heparin (UFH) level and supplementation of a UFH level-based strategy with (3). AT III, (4). the direct thrombin inhibitor r-hirudin, or (5). the short-acting platelet glycoprotein (GP) IIb/IIIa antagonist tirofiban. Platelet count and generation of contact factor XIIa, thrombin, and soluble fibrin were assessed. Samples were obtained before CPB and after CPB before protamine infusion. MEASUREMENTS AND MAIN RESULTS: There were no differences observed in the generation of factor XIIa. The UFH-based strategy and supplementation with AT III, r-hirudin, and tirofiban resulted in significantly reduced (p < 0.05) thrombin generation compared with ACT management. A significant reduction of fibrin formation was seen only in patients who received AT III, r-hirudin, or tirofiban supplementation to the UFH. The administration of tirofiban resulted in a significant preservation of the platelet count compared with the other groups. There were no significant differences in the postoperative blood loss. CONCLUSIONS: Activation of hemostasis during CPB in heparin-resistant patients most likely has to be attributed to stimulation of the tissue factor pathway. Even the sole use of high concentrations of UFH does not effectively inhibit this activation. Therefore, in these patients anticoagulation during CPB with UFH should be supplemented with either AT III, a short-acting direct thrombin inhibitor, or a short-acting platelet glycoprotein IIb/IIIa antagonist.     

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.     

Platelet activation and aggregation during cardiopulmonary bypass.

Increases in plasma concentrations of platelet granule products such as platelet factor 4 and beta-thromboglobulin during cardiopulmonary bypass suggest that platelets are activated during extracorporeal circulation. Subsequent circulation of these activated platelets may be responsible for the ubiquitous platelet dysfunction associated with cardiopulmonary bypass. Using flow cytometry and a monoclonal antibody directed against an alpha-granule membrane protein, granule membrane protein 140 (GMP-140), which is expressed on the platelet surface membrane after activation, we directly measured the percentage of circulating activated platelets in 41 patients before, during, and after cardiopulmonary bypass. In addition, we compared the GMP-140 expression with platelet aggregation in response to adenosine diphosphate (ADP). Cardiopulmonary bypass produced a significant increase in the percentage of GMP-140-positive platelets persisting in the circulation; the percentage peaked at a mean of 29% (range 10-58%) before separation from extracorporeal circulation. A significant percentage of these activated platelets continued to circulate in the early postoperative period. Simultaneous measurement of platelet aggregation in response to ADP demonstrated an aggregation defect that had a time course distinct from platelet activation and whose magnitude did not correlate with the degree of platelet activation in individual patients. We conclude that cardiopulmonary bypass causes a complex constellation of platelet defects, which include alpha-granule release, prolonged circulation of activated, "spent" platelets, and impaired platelet aggregation.     

止血芳酸对体外循环心脏手术中血小板膜糖蛋白受体GP1b的保护作用

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Modulation of platelet surface adhesion receptors during cardiopulmonary bypass.

Alterations in platelet receptors critical to adhesion may play a role in the pathogenesis of the qualitative platelet defect associated with cardiopulmonary bypass. Using flow cytometry, we measured changes in the following platelet surface adhesive proteins: the von Willebrand factor receptor, glycoprotein Ib; the fibrinogen receptor, glycoprotein IIb/IIIa; the thrombospondin receptor, glycoprotein IV; the adhesive glycoprotein granule membrane protein 140, whose expression also reflects platelet activation and alpha-granule release; and, as a control, the nonreceptor protein HLA, A,B,C. Glycoprotein Ib decreased during cardiopulmonary bypass (P less than 0.05) and reached a nadir at 72% (P less than 0.05) of its baseline value at 2-4 h after bypass. This decrease correlated (r = 0.76) with the magnitude of platelet activation (alpha-granule release) in any given patient, but even platelets that were not activated demonstrated a decrease in glycoprotein Ib expression. Glycoprotein IIb/IIIa also decreased in both the activated (47% of baseline, P less than 0.01) and unactivated (63% of baseline, P less than 0.01) subsets of platelets at the end of cardiopulmonary bypass. Glycoprotein IV and HLA A,B,C did not decrease, but instead increased 2-4 h after cardiopulmonary bypass (P less than 0.05). We conclude that cardiopulmonary bypass produces selective decreases in surface glycoproteins Ib and IIb/IIIa as well as in platelet activation; that these two alterations are temporally but not necessarily mechanistically linked; and that these changes have the potential to adversely affect platelet function.     

体外循环期间血小板膜糖蛋白的定量研究及临床意义

目的　探讨体外循环 (CPB)对血小板膜糖蛋白的影响。方法　用流式细胞术对 40例先天性心脏病房、室间隔缺损患者在 CPB下行心内修补术时的血小板膜糖蛋白 CD41 a、CD42 b、CD6 2 p和CD6 3的含量免疫荧光定量测定 ,同时与本组患者和健康供血者试管内血小板膜糖蛋白进行比较。结果　在 CPB中血小板总数明显下降 ,从术前值的 (310± 91)× 10 3/ m l降至术后值的 (181± 44 )× 10 3/ml,CD41 a无明显变化 ,CD42 b明显降低 (P<0 .0 5 ) ,CD6 2 p和 CD6 3明显增加 (P<0 .0 5 )。本组和健康供血者的试管内血小板膜糖蛋白 CD41 a、CD42 b、CD6 2 p和 CD6 3均呈平行变化。结论　 CPB期间既有粘附凝集功能下降 ,也有粘附凝集功能增强的血小板膜糖蛋白 ,而凝血机制缺陷的原因可能与血小板总数下降、低温及肝素的后续作用有关。     

Emergency coronary artery bypass surgery in the era of glycoprotein IIb/IIIa receptor antagonist use

The use of intravenous glycoprotein (GP) IIb/IIIa platelet receptor antagonists in the management of patients with acute coronary syndrome or those undergoing percutaneous coronary intervention (PCI) has become increasingly common in recent years. There are three GP IIb/IIIa receptor antagonists currently available for clinical use. Patients on GP IIb/IIIa receptor antagonists who require emergency surgical revascularization may be at increased risk for excessive peri- and postoperative bleeding. The duration of action of eptifibatide and tirofiban are short because they bind reversibly to the GP IIb/IIIa receptor and have a short half-life. Therefore, within a relatively short time after discontinuation of these agents, surgery can be performed with little or no increased risk of bleeding and without the need for additional hemostatic measures. Abciximab has a short plasma half-life but a long duration of action due to its high-affinity binding of GP IIb/IIIa receptors. Early retrospective studies demonstrated a higher incidence of major bleeding and requirement for blood transfusion, especially in those undergoing surgery within 12 hours of the discontinuation of abciximab. However, platelet transfusion has been shown to successfully reduce the incidence of these complications. The current evidence therefore indicates that, with appropriate measures, urgent surgical revascularization can be safely performed in patients who have received a GP IIb/IIIa receptor antagonist with little added risk. The benefits of these agents in the treatment of patients with an acute coronary syndrome or undergoing PCI are not obviated by the need for emergency bypass surgery.