Mechanisms and attenuation of hemostatic activation during extracorporeal circulation

doi:10.1016/S0003-4975(01)03211-8

The Annals of Thoracic Surgery

Volume 72, Issue 5, November 2001, Pages S1821-S1831

Presented at Mechanisms and Attenuation of Abnormalities in Hemostasis/Inflammation and Neurologic Injury: Implications for Patient Outcomes, Vancouver, BC, Canada, May 6, 2001.

https://doi.org/10.1016/S0003-4975(01)03211-8 Get rights and content

Abstract

Patients undergoing cardiac surgery with cardiopulmonary bypass are at risk for excessive microvascular bleeding, which often leads to transfusion of allogeneic blood and blood components as well as reexploration in a smaller subset of patients. Excessive bleeding after cardiac surgery is generally related to a combination of several alterations in the hemostatic system pertaining to hemodilution, excessive activation of the hemostatic system, and potentially the use of newer, longer-acting antiplatelet or antithrombotic agents.

Although several nonpharmacologic strategies have been proposed, this review summarizes the role of pharmacologic interventions as means to attenuate the alterations in the hemostatic system during CPB in an attempt to reduce excessive bleeding, transfusion, and reexploration. Specifically, agents that inhibit platelets, fibrinolysis, factor Xa and thrombin, as well as broad-spectrum agents, have been investigated with respect to their role in reducing consumption of clotting factors and better preservation of platelet function.

Prophylactic administration of agents with antifibrinolytic, anticoagulant, and possibly antiinflammatory properties can decrease blood loss and transfusion. Although aprotinin seems to be the most effective blood conservation agent (which is most likely related to its broad-spectrum nature), agents with isolated antifibrinolytic properties may be as effective in low-risk patients. The ability to reduce blood product transfusions and to decrease operative times and reexploration rates favorably affects patient outcomes, availability of blood products, and overall health care costs.

Section snippets

Pathophysiology of excessive bleeding

Excessive bleeding after cardiac surgery is generally related to a combination of several cardiopulmonary bypass (CBP) –related alterations in the hemostatic system (Fig 1). In addition to hemodilution [8], there is excessive activation of the hemostatic system, which is related to interaction of blood with the extensive, nonendothelial CPB surfaces [9], activation of the extrinsic clotting pathway [10] secondary to surgical trauma and retransfusion of pericardial blood [11]. The contact

Attenuation of hemostatic system activation

Numerous pharmacologic and nonpharmacologic strategies have been proposed as means to attenuate the alterations in the hemostatic system during CPB. This review focuses on pharmacologic interventions including agents that inhibit platelets, fibrinolysis, factor Xa and thrombin.

Conclusion

Numerous strategies and interventions can reduce hemostatic activation during cardiac surgical procedures using CPB. This results in less consumption of clotting factors and better preservation of platelet function. Prophylactic administration of agents with antifibrinolytic, anticoagulant, and possibly antiinflammatory properties can decrease blood loss and the need for transfusion. The ability to reduce blood product transfusions and to decrease both operative times and reexploration rates

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Multiple Electrode Aggregometry After Cardiopulmonary Bypass to Assess Platelet (Dys)-Function and Transfusion Threshold: A Concordance Study
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Cardiac surgery patients have a high risk of postoperative bleeding. Historically, the platelet count has been one of the main parameters used to establish the need for platelet transfusions, and the recent introduction of point-of-care tests for platelet function has allowed clinicians to rationalize platelet transfusion needs by assessing the platelet (dys-)function of the patient. For the present study, the authors evaluated how the introduction of one of these systems—the adenosine diphosphate (ADP) test, performed using a Multiplate electrode analyzer (Roche Diagnostics, Basel, Switzerland)—into their clinical practice had modified their platelet transfusion practice. The relationship between the platelet count and the functional evaluation of platelet aggregation (via the ADP test) also was examined.
This was a retrospective, single-center, observational study.
Cardiac surgery department of a tertiary care center in North-east Italy.
Cardiac surgery patients requiring cardiac bypass in 2017 and 2019.
The primary outcome was to compare platelet transfusion practice before and after the implementation of a platelet function test (the ADP test) into the institution's transfusion algorithm, which replaced the platelet count as the trigger. Secondary outcomes were assessing whether the incorporation of the ADP test into their transfusion algorithm brought about a reduction in the frequency of platelet transfusions compared with previous rates (when only platelets counts were used); assessing patient blood loss in the first 12 postoperative hours; and ascertaining the percentage of patients requiring surgical reexplorations.
The study comprised 110 patients undergoing cardiac surgery from the platelet count period (2017) and 110 patients from the ADP test period (2019). Agreement between platelet counts versus ADP tests in determining the need for platelet transfusion was moderate (κ = 0.483; 95% confidence interval [CI] 0.239-0.728), and the general linear regression relationship between platelet counts and the ADP test (Akaike information criterion = 2536; p < 0.001) was determined. Since the introduction of ADP testing, a highly significant reduction in platelet transfusions has occurred: 41.82% (platelet count period) versus 13.64% (ADP test period) (p < 0.001); average blood loss in the 12 hours postsurgery also was less in the ADP test period (p < 0.001) at 300 mL (95% CI 150-730) compared with 440 mL in the platelet count period (95% CI 135-900). Furthermore, a decreasing trend was observed in the number of patients requiring reexploration to optimize hemostasis in the first 12 hours postsurgery (6.36% v 2.73%); however, this trend did not achieve statistical significance (p = 0.195).
The application of new Multiplate analyzer technologies, like the ADP test, have the potential to reduce platelet transfusion rates in cardiac surgery patients compared with the use of platelet counts alone; this point-of-care test may constitute an important strategy to help spare the use of allogeneic blood products. Additional studies are needed to confirm this trend and establish the best cutoff values to apply.
Microvascular Alterations During Cardiac Surgery Using a Heparin or Phosphorylcholine-Coated Circuit
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Heparin biocompatible coating frequently is used to reduce inflammation and blood coagulation during cardiopulmonary bypass (CPB) in cardiac surgery. Whether heparin coating is protective or damaging to the vascular endothelium is unclear. The authors investigated whether heparin-coated (HC) circuits are associated with better preservation of microcirculatory perfusion and glycocalyx dimensions compared with nonheparin phosphorylcholine-coated (PC) circuits.
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The study included 64 patients, out of a cohort of 678 patients, of whom 32 required surgical re-exploration due to bleeding within the first 24 h. Between patients of the RE and non-RE group, a significantly reduced FXIII activity was observed postoperatively (59.0 vs 71.1; p = .014). Multivariable analysis revealed reduced FXIII activity (p = .048) as a parameter independently associated with surgical re-exploration. Further, reduced FXIII activity (p = .037) and surgical re-exploration (p = .01) were significantly associated with increased 30 day mortality. In multivariable analysis re-exploration was independently associated with increased risk of 30 day mortality (p = .004, HR 9.68).
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^☆: Dr Despotis discloses that he has a financial relationship with Medtronic Blood Management, Genzyme Transgenics, and Bayer Corporation; Dr. Hogue with Bayer Corporation; and Dr Avidan with Medtronic Blood Management.

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Mechanisms and attenuation of hemostatic activation during extracorporeal circulation☆

Abstract

Section snippets

Pathophysiology of excessive bleeding

Attenuation of hemostatic system activation

Conclusion

J Thorac Cardiovasc Surg

Blood

J Thorac Cardiovasc Surg

Blood

Ann Thorac Surg

J Thorac Cardiovasc Surg

Chest

Blood

Blood

J Thorac Cardiovasc Surg

Ann Thorac Surg

J Thorac Cardiovasc Surg

Ann Thorac Surg

J Cardiothorac Vasc Anesth

J Thorac Cardiovasc Surg

Ann Thorac Surg

Ann Thorac Surg

J Thorac Cardiovasc Surg

J Cardiothorac Vasc Anesth

Chest

Ann Thorac Surg

N Engl J Med

Ann Thorac Surg

J Thorac Cardiovasc Surg

Thromb Res

J Cardiothorac Vasc Anesth

Br J Anaesth

Ann Thorac Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Ann Thorac Surg

J Thorac Cardiovasc Surg

J Cardiothorac Vasc Anesth

J Thorac Cardiovasc Surg

Ann Thorac Surg

J Cardiothorac Anesth

Ann Thorac Surg

Ann Thorac Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

J Thorac Cardiovasc Surg

Thromb Res

Ann Thorac Surg

J Thorac Cardiovasc Surg