Thrombin generation and bleeding in cardiac surgery: a clinical narrative review

Fitzgerald, John; McMonnies, Robert; Sharkey, Aidan; Gross, Peter L.; Karkouti, Keyvan

doi:10.1007/s12630-020-01609-4

Cited by 13 publications

(9 citation statements)

References 68 publications

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“…15,18,124 In the presence of normal routine coagulation assays and/or viscoelastic tests and continued bleeding, consideration may be given to empirically targeting impaired thrombin generation via plasma; PCCs; or in select circumstances, recombinant activated factor VII. 125 There is little clinical trial data on how to best manage refractory bleeding, and the risks and benefits of these therapies for this indication are poorly understood. Of note, certain types of cardiac surgical patients are particularly predisposed to a disseminated intravascular coagulopathy (DIC)-like coagulopathy, such as those undergoing repair of acute Stanford Type A dissection, in which profound thrombin generation and coagulation factor consumption may be seen before CPB and even during systemic heparinization.…”

Section: Thrombin Generationmentioning

confidence: 99%

“…There are significant reductions in thrombin generation during CPB that are associated with increased bleeding; however, tests specifically measuring thrombin generation during CPB are still largely restricted to research 15,18,124 . In the presence of normal routine coagulation assays and/or viscoelastic tests and continued bleeding, consideration may be given to empirically targeting impaired thrombin generation via plasma; PCCs; or in select circumstances, recombinant activated factor VII 125 . There is little clinical trial data on how to best manage refractory bleeding, and the risks and benefits of these therapies for this indication are poorly understood.…”

Section: Special Considerations In Refractory Bleedingmentioning

confidence: 99%

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Managing the coagulopathy associated with cardiopulmonary bypass

Bartoszko

Karkouti

2021

Journal of Thrombosis and Haemostasis

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Cardiopulmonary bypass (CPB) has allowed for significant surgical advancements, but accompanying risks can be significant and must be expertly managed. One of the foremost risks is coagulopathic bleeding. Increasing levels of bleeding in cardiac surgical patients at the time of separation from CPB are associated with poor outcomes and mortality. CPB‐associated coagulopathy is typically multifactorial and rarely due to inadequate reversal of systemic heparin alone. The components of the bypass circuit induce systemic inflammation and multiple disturbances of the coagulation and fibrinolytic systems. Anticipating coagulopathy is the first step in managing it, and specific patient and procedural risk factors have been identified as predictors of excessive bleeding. Medication management pre‐procedure is critical, as patients undergoing cardiac surgery are commonly on anticoagulants or antiplatelet agents. Important adjuncts to avoid transfusion include antifibrinolytics, and perfusion practices such as red cell salvage, sequestration, and retrograde autologous priming of the bypass circuit have varying degrees of evidence supporting their use. Understanding the patient's coagulation status helps target product replacement and avoid larger volume transfusion. There is increasing recognition of the role of point‐of‐care viscoelastic and functional platelet testing. Common pitfalls in the management of post‐CPB coagulopathy include overdosing protamine for heparin reversal, imperfect laboratory measures of thrombin generation that result in normal or near‐normal laboratory results in the presence of continued bleeding, and delayed recognition of surgical bleeding. While challenging, the effective management of CPB‐associated coagulopathy can significantly improve patient outcomes.

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Section: Thrombin Generationmentioning

confidence: 99%

Section: Special Considerations In Refractory Bleedingmentioning

confidence: 99%

Managing the coagulopathy associated with cardiopulmonary bypass

Bartoszko

Karkouti

2021

Journal of Thrombosis and Haemostasis

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“…1). 26 Rotational thromboelastometry (ROTEMÒ) and platelet function analysis Rotational thromboelastometry (ROTEMÒ delta; TEM International GmbH, Mississauga, ON, Canada) was used for measurements with 300 lL citrated whole blood. 27 The tests included INTEM (intrinsic coagulation systemcontact phase activation) and EXTEM (extrinsic system -TF activation) performed at the same time points as CAT measurements.…”

Section: Thrombin Generationmentioning

confidence: 99%

The association of thrombin generation with bleeding outcomes in cardiac surgery: a prospective observational study

Bartoszko

Liang

Fitzgerald

et al. 2021

Can J Anesth/J Can Anesth

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Background Cardiac surgery with cardiopulmonary bypass (CPB) is associated with coagulopathic bleeding. Impaired thrombin generation may be an important cause of coagulopathic bleeding but is poorly measured by existing hemostatic assays. We examined thrombin generation during cardiac surgery, using calibrated automated thrombography, and its association with bleeding outcomes. MethodsWe conducted a prospective observational study in 100 patients undergoing cardiac surgery with CPB. Calibrated automated thrombography parameters were expressed as a ratio of post-CPB values divided by pre-CPB values. The association of thrombin generation parameters for bleeding outcomes was compared with conventional tests of hemostasis, and the outcomes of patients with the most severe post-CPB impairment in thrombin generation (C 80% drop from baseline) were compared with the rest of the cohort. Results All 100 patients were included in the final analysis, with a mean age of 63 (12) yr, 31 (31%) female, and 94 (94%) undergoing bypass and/or valve

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“…[ 15 ] Thrombin (Thr) is clinically used to stop bleeding locally during surgery. [ 16 ] It can directly and efficiently activate platelets and convert fibrinogen into fibrin, induce a strong coagulation reaction, thus quickly forming thrombus. [ 17 ] However, owing to the strong coagulation function and no fixed site of action, Thr will directly contact the blood after entering the body and cause non‐specific embolism, resulting in serious toxic side effects.…”

Section: Introductionmentioning

confidence: 99%

Thrombin Based Photothermal‐Responsive Nanoplatform for Tumor‐Specific Embolization Therapy

Yin

Wang

Sun

et al. 2021

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The specific coagulation in the tumor vasculature has the potential for the ablation of solid tumors by cutting off the blood supply. However, the safe delivery of effective vessel occluding agents in the tumor‐specific embolization therapy remains challenging. Herein, it is reported that the photothermal responsive tumor‐specific embolization therapy based on thrombin (Thr) is delivered by intravenous injection via the phase‐change materials (PCM)‐based nanoparticles. The wax sealing profile of PCM enables safe delivery and prevents the preleakage of Thr in the blood circulation. While in the tumor site, the thermal effect induced by IR780 triggers the melting of PCM and rapidly releases Thr to generate coagulation in the tumor blood vessels. Based on the safe delivery and controllable release of Thr, thermal responsive tumor‐specific embolization therapy could be achieved with high efficiency and no significant damage to normal organs and tissues. The safe administration of Thr to induce vascular infarction in tumors based on PCM nanoparticles in this work shows a promising strategy for improving the therapeutic specificity and efficacy of coagulation‐based tumor therapy.

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Thrombin generation and bleeding in cardiac surgery: a clinical narrative review

Cited by 13 publications

References 68 publications

Managing the coagulopathy associated with cardiopulmonary bypass

Managing the coagulopathy associated with cardiopulmonary bypass

The association of thrombin generation with bleeding outcomes in cardiac surgery: a prospective observational study

Thrombin Based Photothermal‐Responsive Nanoplatform for Tumor‐Specific Embolization Therapy

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