Three-factor prothrombin complex concentrates for refractory bleeding after cardiovascular surgery within an algorithmic approach to haemostasis.

Overview
Dr. Ghadimi is a cardiothoracic anesthesiologist, intensivist (ICU doctor), researcher, educator, and director of the clinical research unit in the Department of Anesthesiology at Duke Health. He has published over 100 peer-reviewed manuscripts, book chapters, online reviews, and editorials. His expertise involves the perioperative and intensive care management of patients undergoing cardiac and noncardiac surgery, with a special focus on the treatment of bleeding and inflammation related to shock and mechanical circulatory support and on the modification of pulmonary circulation to optimize end-organ blood flow.

Clinical Education
Dr. Ghadimi is a medical school graduate of Boston University School of Medicine, completed his internship in general surgery at the University of California Irvine Medical Center and Long Beach Veterans Affairs Medical Center and completed clinical anesthesiology residency at the Allegheny Health Network in Pittsburgh, Pennsylvania. He completed advanced clinical fellowship specialization in adult Critical Care Medicine (surgical focus) and Cardiothoracic Anesthesiology at the University of Pennsylvania Health System in Philadelphia, Pennsylvania. 

Expertise
Dr. Ghadimi's expertise and instruction spans across the cardiothoracic operating rooms and cardiothoracic surgical ICU environments. His expertise includes perioperative hemostasis & thrombosis, critical care of the heart or lung transplant recipient, and critical care for the patient on mechanical circulatory support, which may include extracorporeal life support (ECMO) or ventricular assist devices/systems.

Research Education
Dr. Ghadimi is a clinical and translational researcher and holds a Master in Health Sciences (M.H.Sc.) from the Duke-NIH Clinical Research Training Program. 

My research interest is in statistical genetics, including statistical method development and its application for understanding the genetic predisposition of human complex diseases. Here is the list of research topics:

• Statistical genetics: development of family-based association methods for quantitative traits with or without censoring and for detecting X-linked genes for disease risk.  With the availability of next generation sequencing data, we have ongoing projects to develop the association methods for testing rare variants for different phenotypic measures.  
• Genetics of Alzheimer's disease (AD) and Fuchs endothelial corneal dystrophy (FECD).
• Genetic basis of age-at-onset of Alzheimer disease. 
• Peri-operative genomic studies. Investigate the genetic risk factors for postoperative outcomes of patients underwent non-emergent coronary artery bypass grafting with cardiopulmonary bypass.

My research program investigates the molecular mechanisms whereby various congenital and acquired abnormalities result in ‘dysfunctional’ hemostasis (i.e., hemorrhage or thrombosis) to better understand the molecular mechanisms and interactions that are necessary for normal hemostasis. We are particularly interested in the mechanisms whereby antibodies and other inhibitors can interfere with normal hemostatic mechanisms. Several projects extensively overlap and focus on the assembly and function of procoagulant (e.g., factor X-ase and prothrombinase) and anticoagulant (e.g., activated protein C complex) phospholipid membrane-dependent complexes.

We utilize a variety of approaches in these studies. Monoclonal antibodies, single-chain variable domain fragments, polyclonal antibodies prepared from patients with factor VIII inhibitors, and site-specific mutagenesis have all been used to characterize structure-function relationships in coagulation factor VIII. Our laboratory has also extensively characterized anti-factor V antibodies, investigating autoantibodies as well as xenogenic antibodies developing after exposure to topical bovine thrombin preparations which contain trace amounts of contaminating bovine factor V. We have also characterized how antiphospholipid antibodies interfere with the activated protein C complex, a lipid-dependent natural anticoagulant complex that proteolytically inactivates factor Va and factor VIIIa.

Our current studies are focusing on two antibody-mediated thrombotic syndromes, heparin-induced thrombocytopenia and antiphospholipid antibody syndrome. First, we are initiating a large clinical trial investigating the incidence of clinically-significant heparin-induced thrombocytopenia in patients who develop anti-heparin/platelet factor 4 antibodies following cardiac bypass procedures. While these antibodies are commonly seen following cardiac bypass, the true incidence of thromboembolic complications related to these prothrombotic antibodies remains unknown. We are also collaborating with investigators in the Center for Human Genetics on a large, multi-center study exploring the genetics of familial antiphospholipid antibody syndrome. In addition, we have used a genomic strategy to investigate patients with antiphospholipid antibody syndrome and have identified a gene expression profile that appears to be unique to patients with this syndrome in contrast to patients with venous thromboembolism who do not have these autoantibodies.

We also participate in a variety of collaborative research efforts, both with individual investigators as well as participating in multi-center clinical research studies. For example, we are one of seventeen centers participating in the NIH-supported Transfusion Medicine/Hemostasis Network, and we are currently conducting a trial through this network to define the optimal dose of platelets for patients needing platelet transfusions for hypoproliferative thrombocytopenia. We are also part of a multi-center registry of patients with thrombotic thrombocytopenic purpura, and we are one of eight centers in the Hemostasis and Thrombosis Center pilot program sponsored by the Centers for Disease Control and Prevention. Participation in these registries and networks provides us with access to the patient populations that we study in the research laboratory.

Jerrold Levy is Professor of Anesthesiology, Critical Care, and Surgery (Cardiothoracic) at Duke University Medical Center in Durham, NC. He obtained his medical degree from the University of Miami, where he was an intern in internal medicine, and undertook his residency in the Department of Anesthesiology of the Massachusetts General Hospital and Harvard Medical School in Boston, where he was also Chief Resident, and completed fellowships in both Respiratory ICU and Cardiac Anesthesiology.  He previously was Professor, Deputy Chair for Research, and Chief of Cardiothoracic Anesthesiology at Emory University School of Medicine. His clinical and research interests include anticoagulation and its reversal, therapeutic strategies to prevent and treat coagulopathy and acute inflammatory responses in critically ill patients, clinical applications of recombinant and purified protein concentrates to treat bleeding, and pharmacologic approaches to treat shock.  He is currently Chair of the Subcommittee on Perioperative and Critical Care Thrombosis and Hemostasis for the International Society of Thrombosis and Hemostasis, Executive Editor of Anesthesiology, and consultant to the FDA‘s Biologic Products Advisory Committee.  He is the author of over 450 publications on PubMED, with over 100,000 citations on Google Scholar and a h-index of 95. He is also fluent in French and conversational in Spanish and Japanese.

As a practicing cardiothoracic anesthesiologist, I have contributed to the better understanding of the management and of perioperative thrombosis (particularly HIT). This has been as a Duke site PI for the Rare Thrombotic Diseases Consortium led by Dr T.L Ortel and a clinical collaborator with the basic and translational science approach to HIT led by Dr G Arepally. I have also championed novel approaches to dealing with perioperative HIT such as plasmaperesis.

Similarly, I have been a local leader in establishing management of transfusion approaches to major cardiac surgery including the novel introduction of autologous plateletpheresis to limit exposure to allogeneic platelet transfusions in this highly transfused population, identifying the transfusion requirements during thoracic aortic reconstruction and promoting use of a lower dose of rFVIIa use in this population, changing established clinical practice.

My research interests focus on perioperative transfusion and hematology concerns. Recently, Dr Kor (Mayo Clinic) and I received a multiple PI R-01 award to evaluate point-of-care/bedside washing of packed red blood cells to reduce perioperative lung injury. This novel repurposing of commonly available “cell-saver” technology is, for most surgical cases, the only practical means of delivering a washed product, and promises to be a critical advancement in perioperative transfusion medicine. I also have a longstanding interest in the rejuvenation of RBCs to normalize oxygen delivery capacity of transfused RBCs. Such a development will be of tremendous importance to transfusion practice, particularly for highly transfused populations and with current threats to blood banking inventory. 

In summary, I have dedicated my research career to improving the outcome of patients undergoing cardiothoracic surgery, understanding perioperative coagulopathy, and optimizing transfusion practice.