Perioperative use of tirofiban hydrochloride (Aggrastat) does not increase surgical bleeding after emergency or urgent coronary artery bypass grafting

Bizzarri, Federico; Scolletta, Sabino; Tucci, Enrico; Lucidi, M.; Davoli, Giuseppe; Toscano, Thomas; Neri, Eugénio; Muzzi, Luigi; Frati, Giacomo

doi:10.1067/mtc.2001.117838

Cited by 94 publications

(52 citation statements)

References 13 publications

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“…The few studies that did, have not noted excessive post-operative bleeding after treatment with tirofiban [14]. In most studies however, patients with emergency CABG and prior use of tirofiban showed no enhanced or even reduced bleeding rates [15].…”

Section: Bleeding Complications-the Evidencementioning

confidence: 97%

Tirofiban and emergency coronary surgery

Shanmugam

2005

European Journal of Cardio-Thoracic Surgery

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The final common pathway of platelet aggregation leading to coronary thrombosis involves cross-linking of platelet receptor glycoprotein IIb-IIIa by primarily fibrinogen. Glycoprotein IIb-IIIa antagonists are being increasingly used as adjunctive therapy during percutaneous coronary intevention, and have shown to reduce the risk of death and myocardial infarction. However, a proportion of these patients continue to remain ischemic and present for emergency coronary grafting. The profound platelet inhibition in these patients enhances the already heightened risk of post-operative bleeding. With the recent approval of tirofiban for patients with acute coronary syndromes, the number of patients receiving tirofiban who subsequently undergo coronary artery bypass grafting is expected to increase substantially. Little clinical data exist, on patients who require immediate coronary artery grafting after receiving tirofiban. This article reviews the evidence for bleeding following tirofiban, discusses the relevant mechanism of action and pharmacodynamics, and analyses the strategies available in patients who need emergency coronary artery grafting after tirofiban.

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Section: Bleeding Complications-the Evidencementioning

confidence: 97%

Tirofiban and emergency coronary surgery

Shanmugam

2005

European Journal of Cardio-Thoracic Surgery

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“…26 Also, biochemical markers show less activation of the hemostatic and inflammatory system. 61 However, despite these initial promising reports about the effects of GPIIb/IIIa blockers during cardiac surgery, 26,62,63 the currently available agents, particularly abciximab, are too long-acting to provide controllable platelet inhibition that is restricted to the time period of the actual surgical intervention and thus are feared to result in bleeding complications after the surgical procedure. 59,60,64 -67 Overall, because of the dichotomy of antithrombotic (antiischemic) and antihemostatic effects of the currently clinically available antiplatelet drugs, strong evidence for the overall benefit of platelet inhibition in CABG has not been demonstrated.…”

Section: Topcic Et Almentioning

confidence: 99%

An Activation-Specific Platelet Inhibitor That Can Be Turned On/Off by Medically Used Hypothermia

Topcic

Kim

Holien

et al. 2011

ATVB

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Objective-Therapeutic hypothermia is successfully used, for example, in cardiac surgery to protect organs from ischemia.Cardiosurgical procedures, especially in combination with extracorporeal circulation, and hypothermia itself are potentially prothrombotic. Despite the obvious need, the long half-life of antiplatelet drugs and thus the risk of postoperative bleedings have restricted their use in cardiac surgery. We describe here the design and testing of a unique recombinant hypothermia-controlled antiplatelet fusion protein with the aim of providing increased safety of hypothermia, as well as cardiac surgery. Methods and Results-An elastin-mimetic polypeptide was fused to an activation-specific glycoprotein (GP) IIb/IIIablocking single-chain antibody. In silico modeling illustrated the sterical hindrance of a ␤-spiral conformation of elastin-mimetic polypeptide preventing the single-chain antibody from inhibiting GPIIb/IIIa at 37°C. Circular dichroism spectra demonstrated reverse temperature transition, and flow cytometry showed binding to and blocking of GPIIb/IIIa at hypothermic body temperature (Յ32°C) but not at normal body temperature. In vivo thrombosis in mice was selectively inhibited at hypothermia but not at 37°C. Conclusion-This is the first description of a broadly applicable pharmacological strategy by which the activity of a potential drug can be controlled by temperature. In particular, this drug steerability may provide substantial benefits for antiplatelet therapy. Key Words: antibodies Ⅲ antiplatelet drugs Ⅲ platelet receptor blockers Ⅲ thrombosis Ⅲ hypothermia A ntithrombotic treatment is one of the most often used medical therapies, with major benefits for patients. 1 However, the side effects associated with antithrombotic therapy can cause severe and even life-threatening complications. 2,3 Antiplatelet drugs are particularly troublesome because of their long half-life and the lack of effective antidotes. 4 In cardiac surgery, especially when combined with extracorporeal circulation, platelet inhibition could be of major benefit. 5 However, because postoperative bleeding complications with long-acting antiplatelet drugs are feared, therapeutic platelet inhibition is preferentially avoided. We describe here a novel pharmacological strategy that uses hypothermia to tightly control and thus allow broadening of the application of platelet inhibition and potentially reducing bleeding complications. See accompanying article on page 1949Therapeutic hypothermia is already widely used to reduce oxygen requirements and to protect organs from ischemia. 6 In cardiac surgery, hypothermia is typically established temporarily with the heart-lung machine during coronary artery bypass grafting (CABG), 7,8 whereas deep hypothermic circulatory arrest is an integral component of surgery for congenital heart disease 9 and is used in adult patients for the repair of thoracic aortic dissections, 10 as well as in neurosurgical operations for the treatment of cerebral aneurysm. 11 However, therapeutic hypothe...

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“…In respect to protein IIb/ IIIa inhibitors, the surgeries were scheduled for 12 hours after drug cessation, which could have influenced our results. BIZZAARRI et al [23] did not identify differences in the postoperative bleeding in patients who had taken tirofiban as little as two hours before emergency surgery. Unfractioned or low molecular weight heparin, at any time in the preoperative period, did not influence the bleeding.…”

Section: Commentsmentioning

confidence: 99%

Fatores de risco de sangramento no pós-operatório de cirurgia cardíaca em pacientes adultos

Miana¹,

Atik²,

Moreira³

et al. 2004

Rev Bras Cir Cardiovasc

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Objective: To determine predictors of postoperative bleeding after cardiac surgery, in order to focus on preventive measures for high-risk populations.Methods: From October 2001 to March 2002, 411 consecutive adult cardiac surgery patients were prospectively studied, with the exception of those submitted to heart transplantation. In order to determine risk factors for postoperative bleeding, 20 preoperative, 17 operative and 6 postoperative variables were analyzed using univariate methods and multiple linear regression.Results: Operative procedures included coronary artery bypass grafting in 227 (55.2%) patients, valvar operations in 198 (48.2%), aortic surgery in 25 (6.1%) and combined procedures in 60 (14.6%). Cardiopulmonary bypass was used in 335 (81.5%) patients and anti-fibrinolysis agents in 148 (36%). The thirty-day mortality rate was 5.6% (23 patients). Mean 24-hour postoperative blood loss was 610 ± 500 mL (range 10-4900). Re-exploration for bleeding was required in 15 (3.7%) patients. Independent predictors of postoperative bleeding were emergency operations (p=0.049), postoperative metabolic acidosis (p=0.001), preoperative thrombocytopenia (p=0.034) and prolonged cardiopulmonary bypass (p=0.021).Conclusions: When possible, preoperative stabilization and correction of coagulation disturbances should be achieved in patients requiring urgent or emergent surgery and in those with thrombocytopenia. The duration of cardiopulmonary bypass should be minimized as long as this is practical. Postoperative metabolic acidosis must be actively corrected, especially the main determining causes. Descriptors

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Perioperative use of tirofiban hydrochloride (Aggrastat) does not increase surgical bleeding after emergency or urgent coronary artery bypass grafting

Cited by 94 publications

References 13 publications

Tirofiban and emergency coronary surgery

Tirofiban and emergency coronary surgery

An Activation-Specific Platelet Inhibitor That Can Be Turned On/Off by Medically Used Hypothermia

Fatores de risco de sangramento no pós-operatório de cirurgia cardíaca em pacientes adultos

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