Excessive Postoperative Bleeding and Outcomes in Neonates Undergoing Cardiopulmonary Bypass

Guzzetta, Nina A.; Allen, Nadine N.; Wilson, Elizabeth; Foster, Gregory S.; Ehrlich, Alexandra; Miller, Bruce E.

doi:10.1213/ane.0000000000000531

Cited by 91 publications

(85 citation statements)

References 16 publications

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“…Bleeding after cardiopulmonary bypass (CPB) is a serious complication of cardiac surgery and often requires significant transfusion of adult blood products to achieve hemostasis 1–4 . Neonates are particularly susceptible to the coagulopathic effects of CPB.…”

Section: Introductionmentioning

confidence: 99%

Fibrin Network Changes in Neonates after Cardiopulmonary Bypass

et al. 2016

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Background Quantitative and qualitative differences in the hemostatic systems exist between neonates and adults, including the presence of “fetal” fibrinogen, a qualitatively dysfunctional form of fibrinogen that exists until 1 yr of age. The consequences of “fetal” fibrinogen on clot structure in neonates, particularly in the context of surgery-associated bleeding, have not been well characterized. Here, the authors examine the sequential changes in clotting components and resultant clot structure in a small sample of neonates undergoing cardiac surgery and cardiopulmonary bypass (CPB). Methods Blood samples were collected from neonates (n = 10) before surgery, immediately after CPB, and after the transfusion of cryoprecipitate (i.e., adult fibrinogen component). Clots were formed from patient samples or purified neonatal and adult fibrinogen. Clot structure was analyzed using confocal microscopy. Results Clots formed from plasma obtained after CPB and after transfusion were more porous than baseline clots. Analysis of clots formed from purified neonatal and adult fibrinogen demonstrated that at equivalent fibrinogen concentrations, neonatal clots lack three-dimensional structure, whereas adult clots were denser with significant three-dimensional structure. Clots formed from a combination of purified neonatal and adult fibrinogen were less homogenous than those formed from either purified adult or neonatal fibrinogen. Conclusions The results of this study confirm that significant differences exist in clot structure between neonates and adults and that neonatal and adult fibrinogen may not integrate well. These findings suggest that differential treatment strategies for neonates should be pursued to reduce the demonstrated morbidity of blood product transfusion.

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Section: Introductionmentioning

confidence: 99%

Fibrin Network Changes in Neonates after Cardiopulmonary Bypass

et al. 2016

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“…Thrombin also activates platelets, FXIII and thrombin‐activated fibrinolysis inhibitor to further contribute to the stabilization of the fibrin clot. In addition, tissue factor‐dependent and independent mechanisms of thrombin generation as a result of the presence of FVIIa within FEIBA may also be at play . In contrast, the introduction of rFVIIa to post‐CPB neonatal plasma resulted in clots with intensified but similar alignment to baseline clots.…”

Section: Discussionmentioning

confidence: 99%

“…In these patients, bleeding is currently addressed through the transfusion of adult blood products, including platelets and cryoprecipitate (fibrinogen component), and multiple transfusions are often required to restore hemostasis. However, transfusion of allogeneic blood products is associated with substantial morbidity and mortality . Moreover, our recent studies show that neonatal and adult fibrin networks are structurally distinct and do not fully integrate with each other, resulting in an incomplete fibrin matrix structure .…”

Section: Introductionmentioning

confidence: 99%

Analysis of the structural and mechanical effects of procoagulant agents on neonatal fibrin networks following cardiopulmonary bypass

Nellenbach

Guzzetta

Brown

2018

Journal of Thrombosis and Haemostasis

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To cite this article: Nellenbach K, Guzzetta NA, Brown AC. Analysis of the structural and mechanical effects of procoagulant agents on neonatal fibrin networks following cardiopulmonary bypass. J Thromb Haemost 2018; 16: 2159-67. Essentials• The standard of care (SOC) for treating neonatal bleeding is transfusion of adult blood products. • We compared neonatal clots formed with cryoprecipitate (SOC) to two procoagulant therapies. • The current SOC resulted in clots with increased stiffness and decreased fibrinolytic properties. • Procoagulant therapies may be a viable alternative to SOC treatment for neonatal bleeding.Summary. Background: Bleeding is a serious complication of neonates undergoing cardiopulmonary bypass (CPB) and associated with substantial morbidity and mortality. Bleeding is addressed through the transfusion of adult blood products, including platelets and cryoprecipitate. However, significant differences exist between neonatal and adult clotting components, specifically fibrinogen. Our recent ex vivo studies have shown that neonatal fibrinogen does not fully integrate with adult fibrinogen, leading to decreased susceptibility to fibrinolysis. These differences may contribute to ineffective clot formation and/or an increased risk of thrombosis. A need exists to identify more effective and safer methods to promote clotting in neonates. Objectives: Procoagulant agents, such as prothrombin complex concentrates (PCCs) and recombinant activated factor VII (rFVIIa), are being used off-label to treat excessive bleeding in neonates after CPB. Because these agents stimulate endogenous fibrin formation, we hypothesize that their addition to post-CPB neonatal plasma will better recapitulate native clot properties than cryoprecipitate. Methods: We analyze the structural, mechanical and degradation properties of fibrin matrices formed by neonatal plasma collected after CPB in the presence of an activated four-factor (F) PCC (FEIBA), rFVIIa, or cryoprecipitate using confocal microscopy, atomic force microscopy and a fluidics-based degradation assay. Results: The ex vivo addition of FEIBA and rFVIIa to post-CPB neonatal plasma resulted in enhanced clot networks with differences in fibrin alignment, mechanics and degradation properties. Conclusions: Our results suggest that these procoagulant agents could be used as an alternative to the transfusion of adult fibrinogen for the treatment of bleeding after CPB in neonates.

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“…The majority of hybrid strategies involving bPAB with or without PDA stenting is described in the setting of HLHS. An advantage of the hybrid palliative surgery as stage I is the mitigation of risk associated with very complex procedures in low‐birth‐weight neonates in the presence of severe comorbidities or poor metabolic status . This strategy can result in better survival and neurological development and enhanced cardiac function.…”

Section: Discussionmentioning

confidence: 99%

Hybrid strategies for high-risk non-hypoplastic left heart syndrome patients

et al. 2018

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Single-stage repair of complex cardiac abnormalities in high-risk neonates presents formidable challenges. The majority of hybrid strategies involving bilateral pulmonary artery banding (bPAB) with or without patent ductus arteriosus (PDA) stenting is described in the setting of hypoplastic left heart syndrome. We present a series of cases describing two-stage repair with initial palliative hybrid procedures involving bPAB with or without PDA stenting. This allows weight gain and stabilization of circulation before complete repair, provides good results, and may overcome risk factors associated with single-stage repair in neonates.

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Excessive Postoperative Bleeding and Outcomes in Neonates Undergoing Cardiopulmonary Bypass

Cited by 91 publications

References 16 publications

Fibrin Network Changes in Neonates after Cardiopulmonary Bypass

Fibrin Network Changes in Neonates after Cardiopulmonary Bypass

Analysis of the structural and mechanical effects of procoagulant agents on neonatal fibrin networks following cardiopulmonary bypass

Hybrid strategies for high-risk non-hypoplastic left heart syndrome patients

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