Ignite Creation Date:
2024-05-06 @ 12:10 AM
Last Modification Date:
2024-10-26 @ 10:45 AM
Study NCT ID:
NCT01504945
Status:
TERMINATED
Last Update Posted:
2018-02-23
First Post:
2011-04-25
Brief Title:
Red Blood Cell Transfusion in Patients With Coronary Artery Disease CAD
Sponsor:
Beth Israel Deaconess Medical Center
Organization:
Beth Israel Deaconess Medical Center
Study Overview
Official Title:
Red Blood Cell Transfusion in Patients With Acute and Chronic Coronary Syndrome
Status:
TERMINATED
Status Verified Date:
2018-02
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Recruitment difficulty
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
Patients with a low blood count anemia with stable or unstable coronary artery disease consistently show worse clinical outcomes It is unclear whether this association is confounded since anemic patients tend to be also sicker ie have lower ejection fractions or more comorbidities and this would be the reason for the worse outcomes rather than anemia The coronary arteries are a unique vascular bed insofar that across the cardiac circulation oxygen extraction is close to maximal at rest Thus increases in demand can only be met by increases in blood flow and hemoglobin concentration since oxygen extraction is maximal at rest It is natural to assume that maximization of oxygen delivery in the setting of active coronary syndrome ACS is beneficial to the patient since oxygen extraction and coronary blood flow is fixed In fact in most intensive care units patients with ACS are transfused to a HCT of 30 However retrospective analysis of trial data showed at best mixed results in clinical outcome when patients with ACS were transfused and in fact in some studies showed consistently worse outcomes than non-transfused patients Similar disappointing results have recently published in patient who underwent coronary artery bypass grafting CABG
This study is designed to determine the effect of red blood cell RBC transfusion on oxygen consumption cardiac microcirculatory and endothelial function in patients with active coronary artery disease For this study active coronary artery disease will be defined as the patient having undergone within the past 4 days of recruitment either a myocardial infarction due to atherothrombosis AHA type I myocardial infarction or surgery for coronary artery bypass grafting
In specific this study will test the hypothesis whether RBC transfusions improves cardiac and vascular function in patients with a hematocrit of less than 30 with active coronary artery disease
Aims of this study are to determine whether RBC transfusion in patients with active coronary artery disease and anemia
increases oxygen delivery to the peripheral tissues
increases whole-body oxygen consumption
decreases nitric oxide bioavailability endothelial microcirculatory and myocardial function andor increases platelet aggregation
This study is designed to determine the effect of red blood cell RBC transfusion on oxygen consumption cardiac microcirculatory and endothelial function in patients with active coronary artery disease For this study active coronary artery disease will be defined as the patient having undergone within the past 4 days of recruitment either a myocardial infarction due to atherothrombosis AHA type I myocardial infarction or surgery for coronary artery bypass grafting
In specific this study will test the hypothesis whether RBC transfusions improves cardiac and vascular function in patients with a hematocrit of less than 30 with active coronary artery disease
Aims of this study are to determine whether RBC transfusion in patients with active coronary artery disease and anemia
increases oxygen delivery to the peripheral tissues
increases whole-body oxygen consumption
decreases nitric oxide bioavailability endothelial microcirculatory and myocardial function andor increases platelet aggregation
Detailed Description:
Adverse clinical outcomes are reduced when critically ill patients are only transfused if their hematocrit drops below 21 Hematocrit HCT is a measure of the severity of anemia A HCT is considered normal if it ranges between 38 and 48 of total blood volume In critically ill patients anemia is very common about 95 of patients admitted to the intensive care unit have hemoglobin levels below normal by intensive care unit ICU day 3Corwin 1995 8809Rodriguez 2001 8810 The transfusion trigger of 3010 HCT 30 hemoglobin 10 gdl has been suggested in a case series of trauma patients as early as 1942Adam 1942 8811 Since then these triggers have largely been a matter of faith without prospective data supporting an improvement in clinical outcome Several clinical trials conducted in the past two decades have shown at least equivalence in clinical outcomes when a more conservative transfusion trigger of hemoglobin 7-9 gdL is applied to a critically-ill patient populationHebert 1999 8812Vincent 2002 8814Corwin 2004 8813 The transfusion trigger in patients with acute coronary syndrome ACS or recent coronary artery bypass grafting as a subset of critically ill patients is more controversial and in most intensive care units a more liberal approach to transfusions for these patients is typically chosenGerber 2008 8815 However the efficacy of RBC transfusion appears to be significantly more limited than empirically assumed in patients with active coronary artery disease The TRICC investigators performed a subset analysis and independent study of their patient cohort of critically-ill patients with cardiovascular diseaseHebert 1997 8835 They found that a transfusion hemoglobin trigger of 7 gdL is safe Furthermore greater end-organ dysfunction was recorded in patients with a liberal transfusion trigger and the overall mortality was similar between the study cohorts for any time interval intensive care unit over the course of hospital stay at 30-d and 60-d follow-upHebert 1999 8812
ACS patients should receive a transfusion if their HCT is less than 24 Several retrospective studies have shown that in general transfusion of RBC in patients with ACS and a hematocrit 24 is neutral or very slightly beneficial and causes harm if HCT 30 Rao 2004 8836Yang 2005 8837Sabatine 2005 8827Singla 2007 8838Singla 2007 8838 Such small if any benefit is not intuitive in light of an increase in arterial oxygen content by a PRBC transfusion and therefore decrease in cardiac output and oxygen consumption Two very beneficial effects in patients with active coronary artery disease Indeed increasing arterial oxygen content by transfusion may either 1 not increase oxygen delivery to the myocardium distal to an anatomic coronary stenosis or 2 have other deleterious biological effects on the cardiovascular system Despite the results that RBC transfusion in unstable coronary artery disease has very little beneficial effects most clinicians standard of care transfuse patients with ACS to a HCT of 30 regardless of potential adverse side effects of RBC transfusions The guidelines for transfusion practice at the BIDMC for instance differentiate between hemodynamically stable and bleeding patients The HCT of bleeding patients should be greater then 30 In hemodynamically stable patient they further differentiate between patients with and without signs of end-organ ischemia In patients without end-organ ischemia a HCT of 21 is tolerated and in patients with end-organ ischemia such as active coronary artery disease the HCT should be 30
Storage of RBC before transfusion lowers the function of the RBCs In a retrospective study in patients undergoing coronary artery bypass grafting CABG a recent study found that RBC transfusions were associated with an increased risk of mortality and short term and long term postoperative complications when patients were transfused with stored RBCs older than 14 days This association remained significant even after controlling for the assumption that patients receiving blood transfusions are in general sicker and therefore more prone to complicationsKoch 2008 8847 Since the introduction of acid-citrate-dextrose as a preservative it was possible to store blood for several weeks currently up to 42 days The criteria for the decision when is blood storage too long is based arbitrarily on red blood cell survival in the recipient after 24 hours and should be greater than 70Mollison 1942 8848 In the past decades however it has been established that transfused and surviving red blood cells exhibit quite different physiologic properties when compared to native RBCs This phenomenon is called the storage lesion There is a rapid depletion of 23 diglycerophosphate 23-DPG with storageBunn 1968 8849 This has a profound impact on hemoglobin affinity reducing oxygen release from hemoglobin by as much as 25 at similar change in oxygen saturation Of note within 72h about 50 of the 23-DPG is restored in the transfused RBCs Moreover there is a marked decrease of adenosine triphosphate ATP which reduces deformability of transfused RBCs and the ability of the RBCs to navigate the microcirculationDern 1967 8850
Infusion of stored RBCs causes hemolysis which in turn reduces nitric oxide bioavailability Significant hemolysis a condition in which RBC burst and the contents of RBC leak outside in particular free hemoglobin occurs both during storage and in particular during transfusionSowemimo-Coker 2002 8851 Free hemoglobin outside of RBCs scavenges nitric oxide Nitric oxide NO is a colorless gas which is produced by the inner lining of the vessels endothelium It acts as D5W lubricant for vessels It keeps blood vessels open and lubricates them so blood cell can flow through these blood vessels more easily A decrease in nitric oxide bioavailability causes vasoconstriction and increased RBC adhesion to endothelium which in turn decreases microcirculatory flowReiter 2002 6096 RBCs also contain arginase which released into the circulation will further enhance nitric oxide depletion by reducing its precursor arginineKato 2005 7955
The investigators will systematically examine the effects of RBC transfusion on systemic oxygen delivery whole body oxygen consumption nitric oxide bioavailability endothelial function cardiac performance microcirculatory function and platelet aggregation in patients with active coronary artery disease presenting to the BIDMC with anemia defined as hematocrit of 30 This is to test our hypothesis that depletion of the nitric oxide pool by transfusion-associated hemolysis causes a decrease in microcirculation endothelial and platelet function To the best of our knowledge there is no study to date that explores the physiologic effects of RBC transfusion in patients with active coronary artery disease
ACS patients should receive a transfusion if their HCT is less than 24 Several retrospective studies have shown that in general transfusion of RBC in patients with ACS and a hematocrit 24 is neutral or very slightly beneficial and causes harm if HCT 30 Rao 2004 8836Yang 2005 8837Sabatine 2005 8827Singla 2007 8838Singla 2007 8838 Such small if any benefit is not intuitive in light of an increase in arterial oxygen content by a PRBC transfusion and therefore decrease in cardiac output and oxygen consumption Two very beneficial effects in patients with active coronary artery disease Indeed increasing arterial oxygen content by transfusion may either 1 not increase oxygen delivery to the myocardium distal to an anatomic coronary stenosis or 2 have other deleterious biological effects on the cardiovascular system Despite the results that RBC transfusion in unstable coronary artery disease has very little beneficial effects most clinicians standard of care transfuse patients with ACS to a HCT of 30 regardless of potential adverse side effects of RBC transfusions The guidelines for transfusion practice at the BIDMC for instance differentiate between hemodynamically stable and bleeding patients The HCT of bleeding patients should be greater then 30 In hemodynamically stable patient they further differentiate between patients with and without signs of end-organ ischemia In patients without end-organ ischemia a HCT of 21 is tolerated and in patients with end-organ ischemia such as active coronary artery disease the HCT should be 30
Storage of RBC before transfusion lowers the function of the RBCs In a retrospective study in patients undergoing coronary artery bypass grafting CABG a recent study found that RBC transfusions were associated with an increased risk of mortality and short term and long term postoperative complications when patients were transfused with stored RBCs older than 14 days This association remained significant even after controlling for the assumption that patients receiving blood transfusions are in general sicker and therefore more prone to complicationsKoch 2008 8847 Since the introduction of acid-citrate-dextrose as a preservative it was possible to store blood for several weeks currently up to 42 days The criteria for the decision when is blood storage too long is based arbitrarily on red blood cell survival in the recipient after 24 hours and should be greater than 70Mollison 1942 8848 In the past decades however it has been established that transfused and surviving red blood cells exhibit quite different physiologic properties when compared to native RBCs This phenomenon is called the storage lesion There is a rapid depletion of 23 diglycerophosphate 23-DPG with storageBunn 1968 8849 This has a profound impact on hemoglobin affinity reducing oxygen release from hemoglobin by as much as 25 at similar change in oxygen saturation Of note within 72h about 50 of the 23-DPG is restored in the transfused RBCs Moreover there is a marked decrease of adenosine triphosphate ATP which reduces deformability of transfused RBCs and the ability of the RBCs to navigate the microcirculationDern 1967 8850
Infusion of stored RBCs causes hemolysis which in turn reduces nitric oxide bioavailability Significant hemolysis a condition in which RBC burst and the contents of RBC leak outside in particular free hemoglobin occurs both during storage and in particular during transfusionSowemimo-Coker 2002 8851 Free hemoglobin outside of RBCs scavenges nitric oxide Nitric oxide NO is a colorless gas which is produced by the inner lining of the vessels endothelium It acts as D5W lubricant for vessels It keeps blood vessels open and lubricates them so blood cell can flow through these blood vessels more easily A decrease in nitric oxide bioavailability causes vasoconstriction and increased RBC adhesion to endothelium which in turn decreases microcirculatory flowReiter 2002 6096 RBCs also contain arginase which released into the circulation will further enhance nitric oxide depletion by reducing its precursor arginineKato 2005 7955
The investigators will systematically examine the effects of RBC transfusion on systemic oxygen delivery whole body oxygen consumption nitric oxide bioavailability endothelial function cardiac performance microcirculatory function and platelet aggregation in patients with active coronary artery disease presenting to the BIDMC with anemia defined as hematocrit of 30 This is to test our hypothesis that depletion of the nitric oxide pool by transfusion-associated hemolysis causes a decrease in microcirculation endothelial and platelet function To the best of our knowledge there is no study to date that explores the physiologic effects of RBC transfusion in patients with active coronary artery disease
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None