Roman M. Sniecinski

Activation of the hemostatic system during cardiopulmonary bypass.

Cardiopulmonary bypass (CPB) is a unique clinical scenario that results in widespread activation of the hemostatic system. However, surgery also results in normal increases in coagulation activation, platelet activation, and fibrinolysis that are associated with normal wound hemostasis. Conventional CPB interferes with normal hemostasis by diluting hemostatic cells and proteins, through reinfusion of shed blood, and through activation on the bypass circuit surface of multiple systems including platelets, the kallikrein-kinin system, and fibrinolysis. CPB activation of the kallikrein-kinin system increases activated factor XIIa, kallikrein, bradykinin, and tissue plasminogen activator levels, but has little effect on thrombin generation. Increased tissue plasminogen activator and circulating fibrin result in increased plasmin generation, which removes hemostatic fibrin. The nonendothelial surface of the bypass circuit, along with circulating thrombin and plasmin, lead to platelet activation, platelet receptor loss, and reduced platelet response to wounds. In this review, we highlight the major mechanisms responsible for CPB-induced activation of the hemostatic system and examine some of the markers described in the literature. Additionally, strategies used to reduce this activation are discussed, including limiting cardiotomy suction, increasing circuit biocompatibility, antithrombin supplementation, and antifibrinolytic use. Determining which patients will most benefit from specific therapies will ultimately require investigation into genetic phenotypes of coagulation protein expression. Until that time, however, a combination of approaches to reduce the hemostatic activation from CPB seems warranted.

Reduced Efficacy of Volatile Anesthetic Preconditioning with Advanced Age in Isolated Rat Myocardium

BackgroundIschemic preconditioning and anesthetic preconditioning (APC) are reported to decrease myocardial infarct size during ischemia–reperfusion injury. However, the beneficial effects of ischemic preconditioning have been shown to decrease with advancing age. Although the mechanisms of ischemic preconditioning and APC are thought to be similar, it is not known whether the beneficial effects of APC are also reduced in the aged myocardium. MethodsMale Fischer 344 rats of three age groups (2–4, 10–12, and 20–24 months) were used. Hearts were Langendorff perfused. Six hearts in each age group were pretreated with 10 min of sevoflurane and a 5-min washout before 25 min of ischemia and 60 min of reperfusion. Six control hearts in each age group received no treatment before ischemia. Nuclear magnetic resonance was used to measure intracellular Na, intracellular Ca, and intracellular pH, respectively. Left ventricular developed pressure, creatine kinase, and infarct size were measured. ResultsIschemia decreases intracellular pH and increases intracellular Na and intracellular Ca in all age groups. APC blunts the pH decreases in young adult and middle-aged rats, but not in aged rats. APC decreased intracellular Na and intracellular Ca accumulation during ischemia in young adult and middle-aged hearts. APC improved adenosine triphosphate recovery in young rats but not in aged rats. Creatine kinase and infarct sizes were significantly reduced and left ventricular developed pressure was improved with APC in the young adult and middle-aged groups but not the aged group. ConclusionsThe benefits of APC are significantly reduced with advanced age in an isolated rat heart model.

Bleeding and management of coagulopathy

Bleeding after cardiac surgery remains a significant problem, increasing both length of stay and mortality, and is caused by multiple factors including dilutional changes, ongoing fibrinolysis, and platelet dysfunction. The evaluation of coagulopathy is problematic because of the long turnaround time of standard coagulation tests. Algorithms involving point of care testing, including thromboelastography and thromboelastometry, have been published; all have the potential to reduce transfusion requirements. Massive transfusion coagulopathy that occurs in trauma can also be seen in complex aortic surgery and other massive bleeding patients and should prompt consideration of a transfusion protocol involving fixed ratios of fresh frozen plasma, platelets, and red blood cells. Pharmacologic agents such as antifibrinolytics are commonly administered, but a multimodal approach to management is important. Recombinant and purified coagulation products are being studied and provide clinicians specific agents to treat targeted deficiencies. A general multi-modal approach is required and recommendations are made for the management of bleeding and coagulopathy in cardiac surgical patients.

Perioperative Ultrasound Training in Anesthesiology: A Call to Action.

The purpose of this position paper is to define the scope of perioperative ultrasound (US), review the current status of US training practices during anesthesiology residency, and suggest the recommendations for current and future trainees on how to obtain perioperative US proficiency. We define per

Changing from Aprotinin to Tranexamic Acid Results in Increased Use of Blood Products and Recombinant Factor VIIa for Aortic Surgery Requiring Hypothermic Arrest

OBJECTIVE Aprotinin, once used to reduce allogeneic blood product transfusion during cardiac surgery, was withdrawn from the market in late 2007 over concerns of causing increased mortality. This study was undertaken to determine what, if any, the impact of changing antifibrinolytic agents (from aprotinin to tranexamic acid) for deep hypothermic circulatory arrest cases would have on blood bank resource utilization. DESIGN This a retrospective review. SETTING All cases were performed at a single university hospital. PARTICIPANTS All patients underwent cardiac surgical procedures requiring deep hypothermic circulatory arrest performed by a single cardiac surgeon between January 2006 and November 2008. INTERVENTION All patients prior to November 15, 2007 received aprotinin as antifibrinolytic therapy, while those after that date received tranexamic acid for antifibrinolytic therapy. MEASUREMENTS AND MAIN RESULTS Blood transfusion data and recombinant factor VIIa use during the pre- and immediate postoperative period was collected for all patients during the study time period. There were no significant differences between the aprotinin (n = 82) and tranexamic acid (n = 78) groups with regard to baseline coagulation status or operative characteristics. Patients treated with tranexamic acid required more fresh frozen plasma (2.5 units, p < 0.001), platelets (0.5 units, p < 0.01), and cryoprecipitate (25 units, p < 0.001), and had a higher incidence of recombinant factor VIIa use (34.6% v 12.2%, p < 0.01) compared with patients in the aprotinin group. CONCLUSIONS Patients treated with tranexamic acid required more clotting factors than the control group receiving aprotinin.

Antithrombin: anti-inflammatory properties and clinical applications

Many humoral and cellular components participate in bidirectional communication between the coagulation and inflammation pathways. Natural anticoagulant proteins, including antithrombin (AT), tissue factor pathway inhibitor, and protein C, suppress proinflammatory mediators. Conversely, inflammation blunts anticoagulant activity and, when uncontrolled, promotes systemic inflammation-induced coagulation, such as those that occur in disseminated intravascular coagulation and severe sepsis. This review discusses the mechanisms of action and clinical use of AT concentrate in critically ill patients and in the settings of perioperative anticoagulation management for surgery and obstetrics. AT is a serine protease inhibitor with broad anticoagulant activity and potent anti-inflammatory properties. In clinical conditions associated with hereditary or acquired AT deficiency, administration of AT concentrate has been shown to restore proper haemostasis and attenuate inflammation. Of note, AT modulates inflammatory responses not only by inhibiting thrombin and other clotting factors that induce cytokine activity and leukocyte-endothelial cell interaction, but also by coagulation-independent effects, including direct interaction with cellular mediators of inflammation. An increasing body of evidence suggests that AT concentrate may be a potential therapeutic agent in certain clinical settings associated with inflammation. In addition to the well-known anticoagulation properties of AT for the treatment of hereditary AT deficiency, AT also possesses noteworthy anti-inflammatory properties that could be valuable in treating acquired AT deficiency, which often result in thrombotic states associated with an inflammatory component.

Plasma and cerebral spinal fluid tranexamic acid quantitation in cardiopulmonary bypass patients.

A method for the determination of tranexamic acid (TXA) in human plasma and cerebral spinal fluid (CSF) was developed. Analyses were performed by ultra performance liquid chromatography with tandem mass spectrometry detection (UPLC-MS/MS) using ɛ-aminocaproic acid (ACA) as an internal standard. TXA and ACA were extracted from a 50 μL sample of plasma or CSF using a methanol protein crash protocol, and chromatographic separation was performed on an ACQUITY™ TQD mass spectrometer using a UPLC C18 BEH 1.7 μm column with a water and methanol gradient containing 0.1% formic acid. The detection and quantitation was performed by positive ion electrospray ionization using the multiple reaction monitoring (MRM) mode. The method was linear over the concentration range of 0.1-10.0 μg/mL, with lower limit of quantitation of 0.1 μg/mL for TXA. The intra- and inter-assay precision was less than 12% and 13% respectively at the plasma and CSF TXA concentrations tested. The present method provides a relatively simple and sensitive assay with short turn-around-time. The method has been successfully applied to assess the plasma and CSF concentrations of tranexamic acid achieved with only one dosing regimen of tranexamic acid in patients undergoing cardiopulmonary bypass surgery (CPB).

Reduced levels of fibrin (antithrombin I) and antithrombin III underlie coagulopathy following complex cardiac surgery.

Changes in plasma concentrations of fibrinogen and antithrombin after cardiopulmonary bypass (CPB) and deep hypothermic circulatory arrest (DHCA). Data from 22 patients who underwent ascending aortic and/or arch replacement are shown. The duration of CPB (mean SD) and DHCA were 181 59 min and 25 15 min, respectively. Each bar denotes the molar concentrations as the mean SD ( P<0.001 versus baseline fibrinogen, yP<0.001 versus baseline antithrombin; paired t-test). The median values (first, third quartiles) of fibrinogen and antithrombin III are also shown above the respective bar. Reduced levels of fibrin (antithrombin I) and antithrombin III underlie coagulopathy following complex cardiac surgery Roman M. Sniecinski, Edward P. Chen and Kenichi A. Tanaka

Coagulopathy After Cardiopulmonary Bypass in Jehovah's Witness Patients: Management of Two Cases Using Fractionated Components and Factor VIIa

BACKGROUND:Changes in the Jehovahs Witness (JW) blood refusal policy now give members the personal choice to accept certain processed fractions of blood, such as factor concentrates and cryoprecipitate. METHODS:Two JW patients undergoing complex aortic surgery who developed severe microvascular bleeding after prolonged use of cardiopulmonary bypass were treated with recombinant activated factor VII, cryoprecipitate, and antithrombin concentrate. RESULTS:Cardiopulmonary bypass-induced coagulopathy was successfully treated, allowing chest closure without evidence of thrombotic complications. CONCLUSIONS:Processed blood fractions can be a valuable adjuvant to drugs when treating bleeding in JW patients.

Managing clotting: a North American perspective.

Purpose of review Bleeding in a perioperative setting occurs due to multiple causes, but newer anticoagulant and antiplatelet therapies are increasingly used preoperatively. As a result, patients often can present for surgery with underlying hemostatic disorders due to these acquired disorders or following major surgery or trauma. Because bleeding occurs due to multiple causes, the addition of pharmacologic agents creates an acquired defect that complicates the surgical injury and may result in increased blood loss. An understanding of hemostasis and therapeutic approaches, especially those in our current clinical settings, is crucial in managing these patients. Recent findings Pharmacologic agents including antifibrinolytics and prohemostatic proteins are commonly administered, but a multimodal approach to management is important. Of note is that aprotinin has been reintroduced into the Canadian market in September 2011. Recombinant and purified coagulation therapies are under investigation, and provide clinicians specific agents to treat targeted deficiencies. Summary Nonsurgical bleeding in the operating room is the result of a multitude of factors including preoperative anticoagulants, dilution, fibrinolysis, and factor consumption. Therapeutic prohemostatic pharmacologic approaches, in addition to standard transfusion therapy, need to be considered in the prevention and treatment of coagulopathy in surgical patients.