A phase 2 prospective, randomized, double-blind trial comparing the effects of tranexamic acid with ecallantide on blood loss from high-risk cardiac surgery with cardiopulmonary bypass (CONSERV-2 Trial)

Bokesch, Paula M.; Szabo, Gábor; Wojdyga, Ryszard; Grocott, Hilary P.; Smith, Peter K.; Mazer, C. David; Vetticaden, Santosh; Wheeler, Alistair; Levy, Jerrold H.

doi:10.1016/j.jtcvs.2011.06.001

Cited by 34 publications

(35 citation statements)

References 19 publications

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“…37,38 Similarly, other plasma kallikrein inhibitors have also shown to have antithrombotic properties in vitro or in animal models of venous and arterial thrombosis ( Table 1). [37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55] These studies provide strong evidence that although components of the plasma KKS are dispensable for normal hemostasis, they play a central role in pathological thrombus formation.…”

Section: Plasma Kallikrein: Synthesis Structure and Functionsmentioning

confidence: 99%

“…115 The CONSERV-2 was a prospective, double-blind, randomized phase 2 trial comparing ecallantide and tranexamic acid (high and low dose) in 242 patients undergoing cardiac surgery using CPB. 54 Like BART, this trial was also terminated early due to a significantly higher 30-day mortality in the ecallantide group (12%) than in the tranexamic acid groups (4%), P < 0.041. Furthermore, ecallantide was less effective in reducing perioperative blood loss than tranexamic acid.…”

Section: Cardiac Surgery and Cardiopulmonary Bypassmentioning

confidence: 99%

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Plasma Kallikrein Inhibitors in Cardiovascular Disease

Kolte

Shariat‐Madar

2016

Cardiology in Review

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Plasma prekallikrein is the liver-derived precursor of the trypsin-like serine protease plasma kallikrein, and circulates in plasma bound to high molecular weight kininogen. Plasma prekallikrein is activated to plasma kallikrein by activated factor XII or prolylcarboxypeptidase. Plasma kallikrein regulates the activity of multiple proteolytic cascades in the cardiovascular system such as the intrinsic pathway of coagulation, the kallikrein-kinin system, the fibrinolytic system, the renin-angiotensin system, and the complement pathways. As such, plasma kallikrein plays a central role in the pathogenesis of thrombosis, inflammation, and blood pressure regulation. Under physiological conditions, plasma kallikrein serves as a cardioprotective enzyme. However, its increased plasma concentration or hyperactivity perpetuates cardiovascular disease (CVD). In this article, we review the biochemistry and cell biology of plasma kallikrein and summarize data from preclinical and clinical studies that have established important functions of this serine protease in CVD states. Finally, we propose plasma kallikrein inhibitors as a novel class of drugs with potential therapeutic applications in the treatment of CVDs.

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Section: Plasma Kallikrein: Synthesis Structure and Functionsmentioning

confidence: 99%

Section: Cardiac Surgery and Cardiopulmonary Bypassmentioning

confidence: 99%

Plasma Kallikrein Inhibitors in Cardiovascular Disease

Kolte

Shariat‐Madar

2016

Cardiology in Review

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“…Intraoperative controlled hypotension was commonly implemented in the past to diminish blood loss; however, this technique has been questioned due to the risk of postoperative visual loss in long and complex spine procedures [128]. Antifibrinolytic therapy including aprotinin, tranexamic acid, and epsilonaminocaproic acid has been shown to decrease blood loss in total knee replacements, scoliosis surgery, and cardiac surgery [129][130][131]. Bednar et al reported their experience using tranexamic acid to minimize operative blood loss during a single-surgeon intralesional tumor excision and instrumentation.…”

Section: Oncological Spine and Sacral Surgerymentioning

confidence: 99%

Blood Loss and Massive Transfusion in Patients Undergoing Major Oncological Surgery: What Do We Know?

Cata

Gottumukkala

2012

ISRN Anesthesiology

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Patients with solid malignancies who were not candidates for tumor resections in the past are now presenting for extensive oncological resections. Cancer patients are at risk for thromboembolic complications due to an underlying hypercoagulable state; however, some patients may have an increased risk for bleeding due to the effects of chemotherapy, the administration of anticoagulant drugs, tumor-related fibrinolysis, tumor location, tumor vascularity, and extent of disease. A common potential complication of all complex oncological surgeries is massive intra-and postoperative hemorrhage and the subsequent risk for massive blood transfusion. This can be anticipated or unexpected. Several surgical and anesthesia interventions including preoperative tumor embolization, major vessel occlusion, hemodynamic manipulation, and perioperative antifibrinolytic therapy have been used to prevent or control blood loss with varying success. The exact incidence of massive blood transfusion in oncological surgery is largely unknown and/or underreported. The current literature mostly consists of purely descriptive observational studies. Thus, recommendation regarding specific perioperative intervention cannot be made at this point, and more research is warranted.

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“…aient démontré qu'une dose plus faible de TXA (45 mg.kg -1 ) est associée à une fréquence moindre de crises convulsives, il est intéressant de noter qu'un essai randomisé récent utilisant deux doses différentes de TXA a décrit une plus grande efficacité, moins de crises convulsives et une mortalité plus basse avec la posologie BART la plus élevée. 10 Ainsi, la dose optimale et le régime posologique doivent être déterminées en trouvant un juste milieu entre le besoin d'une activité fibrinolytique et la nécessité de minimiser les effets indésirables graves postopératoires tels que les crises convulsives.…”

Section: Saisir La Chance De Comprendre Les Antifibrinolytiquesunclassified

“…Though Manji et al demonstrate that a lower TXA dose (45 mgÁkg -1 ) was associated with a lower frequency of seizures, it is noteworthy that a recent randomized trial using two different doses of TXA reported greater efficacy, fewer seizures and lower mortality with the higher BART dosage. 10 Thus, the determination of the optimal dose and dosing regimen must balance the need for antifibrinolytic activity and the necessity of minimizing serious adverse effects, such as postoperative seizures. Seizure following cardiac surgery represents a potentially serious complication that can be associated with prolongation of recovery and increases in morbidity and mortality.…”

mentioning

confidence: 99%