The purpose of this study is to obtain data or information on how blood clotting factors are activated during open heart surgery. In particular, the investigators are interested in how blood clotting factors are activated by the heart-lung bypass machine and by left ventricular assist devices (LVAD). Patients on these two machines have an increased risk of bleeding and blood clot formation. This is because both machines stimulate the intrinsic coagulation pathway, one of the chemical pathways that cause blood to clot. The process of surgery itself also stimulates the "extrinsic coagulation pathway," the other chemical pathway that causes blood to clot. Stimulating these coagulation pathways can use up the body's clotting factors. As a result, patients may be at risk for both bleeding and blood clot formation. The investigators would like to study how the blood factors are activated during and after surgery, to help develop treatments to prevent bleeding and clot formation.
This is a prospective, multi-center, observational study to characterize the epidemiology of bleeding and clotting in patients with underlying systolic ventricular dysfunction undergoing heart transplantation, CABG surgery, or implantation of left ventricular assist devices. Patients will be followed for up to 28 days post-implant, post-CABG, post-heart transplant, or until hospital discharge, whichever comes first. There will be no randomization for this observational study. We will enroll 100 patients (we expect the distribution to be approximately 30 per Groups I - III, but no cap per group, and 10 for Group IV) who have been scheduled to undergo CPB within 24 hours for one of the following: Group I: Cardiopulmonary Bypass + Heart Transplantation CPB for orthotopic heart transplantation (excluding any patients with VADs) Group II: Cardiopulmonary Bypass + Pulsatile LVAD CPB for implantation of a Thoratec HeartMate® I LVAD (for destination therapy or bridge to transplantation) Group III: Cardiopulmonary Bypass + Continuous Flow LVAD CPB for implantation of an axial flow or centrifugal flow LVAD (for destination therapy or bridge to transplantation) (e.g. HeartMate® II, DeBakey VAD® or VentrAssist® LVAS) Group IV: Cardiopulmonary Bypass + CABG/Valve Surgery CPB for CABG or valve surgery Heart transplantation and perioperative care will be performed in accordance with the standard of care at the clinical center. Pulsatile LVAD (e.g. HeartMate® I) implantation and perioperative management will be performed in accordance with the standard of care at the clinical center, and guided by the HeartMate® I Directions for Use. Continuous flow LVAD implantation and perioperative management will be performed in accordance with the standard of care at the clinical center, and guided by the specific VAD manufacturer's Directions for Use. CABG surgery and perioperative care will be performed in accordance with the standard of care at the clinical center. We anticipate that enrollment will be completed over a six-month period. We hypothesize that the initial activation of the intrinsic pathway of coagulation is attenuated for several days in patients undergoing CPB for CABG alone; however, in subjects undergoing CPB with VAD implantation or cardiac transplantation, activation of this pathway is biphasic and sustained.
Study Type
OBSERVATIONAL
Enrollment
94
University of Alabama at Birmingham
Birmingham, Alabama, United States
Sharp Memorial Hospital
San Diego, California, United States
Advocate Christ Medical Center
Oak Lawn, Illinois, United States
Jewish Hospital
Louisville, Kentucky, United States
University of Michigan
Ann Arbor, Michigan, United States
University of Minnesota
Minneapolis, Minnesota, United States
Columbia Presbyterian Medical Center
New York, New York, United States
Montefiore Medical Center
The Bronx, New York, United States
Hospital of the University of Pennsylvania
Philadelphia, Pennsylvania, United States
LDS Hospital
Salt Lake City, Utah, United States
...and 3 more locations
Thrombin Generation Markers
We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.
Time frame: At time of surgery (before initiation of Cardiopulmonary Bypass)
Thrombin Generation Markers
We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.
Time frame: At time of surgery (dismantling the sterile environment)
Thrombin Generation Markers
We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.
Time frame: Post-operative day 1
Thrombin Generation Markers
We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.
Time frame: At time of surgery
Thrombin Generation Markers
We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.
Time frame: Post-operative day12 (while remaining in hosp)
Thrombin Generation Markers
We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.
Time frame: Post-operative day 16 (while remaining in hosp)
Thrombin Generation Markers
We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.
Time frame: Post-operative day 20 (while remaining in hosp)
Thrombin Generation Markers
We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.
Time frame: Post-operative day 24 (while remaining in hosp)
Bleeding
Bleeding will be assessed by measurement of units of packed red blood cells (or whole blood) transfused from initiation of the procedure through the 24 hour post-operative period following LVAD implantation, heart transplantation, or CABG. In addition, we will measure transfusion requirements through the 28 day post-operative period. Units of additional blood products transfused will also be measured, including FFP, cryoprecipitate, and platelets. Hemoglobin, hematocrit and platelet count will be measured as an indirect assessment of blood loss.
Time frame: At time of surgery (dismantling of the sterile environment)
Bleeding
Bleeding will be assessed by measurement of units of packed red blood cells (or whole blood) transfused from initiation of the procedure through the 24 hour post-operative period following LVAD implantation, heart transplantation, or CABG. In addition, we will measure transfusion requirements through the 28 day post-operative period. Units of additional blood products transfused will also be measured, including FFP, cryoprecipitate, and platelets. Hemoglobin, hematocrit and platelet count will be measured as an indirect assessment of blood loss.
Time frame: Post-operative day 1
Bleeding
Bleeding will be assessed by measurement of units of packed red blood cells (or whole blood) transfused from initiation of the procedure through the 24 hour post-operative period following LVAD implantation, heart transplantation, or CABG. In addition, we will measure transfusion requirements through the 28 day post-operative period. Units of additional blood products transfused will also be measured, including FFP, cryoprecipitate, and platelets. Hemoglobin, hematocrit and platelet count will be measured as an indirect assessment of blood loss.
Time frame: Post-operative day 12 (± 3 days) (or at time of discharge, whichever comes first)
Bleeding
Bleeding will be assessed by measurement of units of packed red blood cells (or whole blood) transfused from initiation of the procedure through the 24 hour post-operative period following LVAD implantation, heart transplantation, or CABG. In addition, we will measure transfusion requirements through the 28 day post-operative period. Units of additional blood products transfused will also be measured, including FFP, cryoprecipitate, and platelets. Hemoglobin, hematocrit and platelet count will be measured as an indirect assessment of blood loss.
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Time frame: Post-operative day 20 (± 3 days) (or at time of discharge, whichever comes first)
Bleeding
Bleeding will be assessed by measurement of units of packed red blood cells (or whole blood) transfused from initiation of the procedure through the 24 hour post-operative period following LVAD implantation, heart transplantation, or CABG. In addition, we will measure transfusion requirements through the 28 day post-operative period. Units of additional blood products transfused will also be measured, including FFP, cryoprecipitate, and platelets. Hemoglobin, hematocrit and platelet count will be measured as an indirect assessment of blood loss.
Time frame: Post-operative day 28 (± 3 days) (or at time of discharge, whichever comes first)
Coagulation Markers
Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.
Time frame: At time of surgery ( before initiation of Cardiopulmonary Bypass)
Coagulation Markers
Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.
Time frame: At time of surgery (dismantling the sterile environment)
Coagulation Markers
Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.
Time frame: Post-operative day 1
Coagulation Markers
Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.
Time frame: At time of surgery
Coagulation Markers
Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.
Time frame: Post-operative day 12 (while remaining in hosp)
Coagulation Markers
Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.
Time frame: Post-operative day 16 (while remaining in hosp)
Coagulation Markers
Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.
Time frame: Post-operative day 20 (while remaining in hosp)
Coagulation Markers
Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.
Time frame: Post-operative day 24 (while remaining in hosp)
Coagulation Markers
Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.
Time frame: Post-operative day 28 (± 3 days) (or at time of discharge, whichever comes first)
Serious Adverse Events
The incidence and frequency of all expected and unexpected serious adverse events will be determined. Since this is an observational study, there will be no adverse events directly attributable to a study intervention. However, adverse events that may potentially contribute to the risk or course of bleeding and clotting in patients undergoing heart transplantation, CABG surgery, or implantation of LVADs will be monitored. The adverse events are defined according to the definitions recently finalized by the INTERMACS LVAD registry.
Time frame: Duration of the Study, up to 28 days post-implant, post-CABG, post heart-transplant, or until hospital discharge, whichever comes first.
Thrombin Generation Markers
We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.
Time frame: Post-operative day 2
Thrombin Generation Markers
We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.
Time frame: Post-operative day 3
Thrombin Generation Markers
We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombo Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.
Time frame: Post-operative day 4
Thrombin Generation Markers
We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombo Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.
Time frame: Post-operative day 5
Thrombin Generation Markers
We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.
Time frame: Post-operative day 6
Thrombin Generation Markers
We will compare the following endpoints among the cardiac transplant, CABG, and LVAD recipients: Thrombin Generation Markers: Assays will be performed to quantify the levels of the following markers at the specified time points: Thrombo-antithrombin complex (TAT), Prothrombin Fragment 1 +2 (F1.2), and Thromboelastography (TEG) will be performed when available to assess platelet function.
Time frame: Post-operative day 7
Bleeding
Bleeding will be assessed by measurement of units of packed red blood cells (or whole blood) transfused from initiation of the procedure through the 24 hour post-operative period following LVAD implantation, heart transplantation, or CABG. In addition, we will measure transfusion requirements through the 28 day post-operative period. Units of additional blood products transfused will also be measured, including FFP, cryoprecipitate, and platelets. Hemoglobin, hematocrit and platelet count will be measured as an indirect assessment of blood loss.
Time frame: Post-operative day 2
Bleeding
Bleeding will be assessed by measurement of units of packed red blood cells (or whole blood) transfused from initiation of the procedure through the 24 hour post-operative period following LVAD implantation, heart transplantation, or CABG. In addition, we will measure transfusion requirements through the 28 day post-operative period. Units of additional blood products transfused will also be measured, including FFP, cryoprecipitate, and platelets. Hemoglobin, hematocrit and platelet count will be measured as an indirect assessment of blood loss.
Time frame: Post-operative day 3
Bleeding
Bleeding will be assessed by measurement of units of packed red blood cells (or whole blood) transfused from initiation of the procedure through the 24 hour post-operative period following LVAD implantation, heart transplantation, or CABG. In addition, we will measure transfusion requirements through the 28 day post-operative period. Units of additional blood products transfused will also be measured, including FFP, cryoprecipitate, and platelets. Hemoglobin, hematocrit and platelet count will be measured as an indirect assessment of blood loss.
Time frame: Post-operative day 4
Bleeding
Bleeding will be assessed by measurement of units of packed red blood cells (or whole blood) transfused from initiation of the procedure through the 24 hour post-operative period following LVAD implantation, heart transplantation, or CABG. In addition, we will measure transfusion requirements through the 28 day post-operative period. Units of additional blood products transfused will also be measured, including FFP, cryoprecipitate, and platelets. Hemoglobin, hematocrit and platelet count will be measured as an indirect assessment of blood loss.
Time frame: Post-operative day 5
Bleeding
Bleeding will be assessed by measurement of units of packed red blood cells (or whole blood) transfused from initiation of the procedure through the 24 hour post-operative period following LVAD implantation, heart transplantation, or CABG. In addition, we will measure transfusion requirements through the 28 day post-operative period. Units of additional blood products transfused will also be measured, including FFP, cryoprecipitate, and platelets. Hemoglobin, hematocrit and platelet count will be measured as an indirect assessment of blood loss.
Time frame: Post-operative day 6
Bleeding
Bleeding will be assessed by measurement of units of packed red blood cells (or whole blood) transfused from initiation of the procedure through the 24 hour post-operative period following LVAD implantation, heart transplantation, or CABG. In addition, we will measure transfusion requirements through the 28 day post-operative period. Units of additional blood products transfused will also be measured, including FFP, cryoprecipitate, and platelets. Hemoglobin, hematocrit and platelet count will be measured as an indirect assessment of blood loss.
Time frame: Post-operative day 7
Coagulation Markers
Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.
Time frame: Post-operative day 2
Coagulation Markers
Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.
Time frame: Post-operative day 3
Coagulation Markers
Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.
Time frame: Post-operative day 4
Coagulation Markers
Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.
Time frame: Post-operative day 5
Coagulation Markers
Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.
Time frame: Post-operative day 6
Coagulation Markers
Assays will be performed to assess the levels of following coagulation markers: Prothrombin time (PT) with (INR), Partial thromboplastin time (PTT), Complete Blood Count (CBC) including hemoglobin, hematocrit, and platelets.
Time frame: Post-operative day 7