Investigators in this section are involved in many aspects of hematology research, including optimization of the treatment of patients with clotting disorders, developing new therapies for sickle cell disease, and improving our understanding of immune perturbations associated with blood transfusions.
Naomi Luban, MD, leads a team whose overall goals are to investigate the adverse consequences of transfusion through epidemiological, clinical, and device/ laboratory methods development and evaluation. Our multidisciplinary team works in concert with colleagues in the divisions of Hematology, Blood and Marrow Transplantation, Critical Care Medicine, Center for Genetic Medicine Research, and the Sheikh Zayed Institute for Pediatric Surgical Innovation and colleagues at NHLBI, NIDDK and the Division of Transfusion Medicine, National Institutes of Health Clinical Center, the American Red Cross, and the Food and Drug Administration.
Sickle cell disease immunopathology
We continue our studies on the immunologic basis of red blood cell (RBC) alloimmunization in sickle cell disease (SCD). Zoreh Tatari-Calderone, PhD, Ross Fasano, MD, and Edward Wong, MD, have expanded patient enrollment, evaluated serial cytokine profiles, and abstracted patient-specific data on more than 300 SCD patients to correlate the development of RBC allo antibodies with B cell activation due to RBC antigen exposure during the inflammatory response associated with vaso-occlusive crises. An abstract of this study received the most valuable abstract award at the 2012 American Association of Blood Banks annual meeting. Dr. Fasano continues his studies on molecular RBC antigen genotyping and has developed a computer algorithm for donor/ recipient RBC matching which will be matched for more than 30 RBC antigens. Dr. Fasano, in collaboration with Drs. Wong and Jacobsohn, has developed a study which will utilize Luminex methodology to quantify and categorize pro- and anti-inflammatory and pro-coagulant profiles of children undergoing extracorporeal photopheresis (ECP), a procedure used to treat graft-vs-host disease (GVHD) following hematopoietic stem cell transplantation; the study will focus on children with SCD undergoing transplant who have a chronic, heightened inflammatory state.
Coagulopathy and necrotising enterocolitis diagnosis and treatment
Collaborative investigations with our colleagues in the Division of Neonatology were expanded this past year beyond transfusion. The effect of core body temperature and specimen handling on thromboelastogram (TEG) values in neonates requiring both ECMO and hypothermia for encephalopathy were completed. From these studies we developed the first neonatal reference ranges for TEGs; these results were presented at several meetings and are in the process of publication. TEG provides analysis of complex fibrinolytic, antifibrinolytic pathways and platelet function in a point of care device; TEG’s usefulness in neonates with critical bleeding was limited by an absence of reference ranges. With Yaser Diab, MD, Richard Levy, MD, and American Red Cross colleagues, we completed studies to improve methods for aliquoting platelets for neonatal transfusion and established that depletion of ADP in platelet concentrates occurs due to acquired depletion of cytochrome C oxidase.
We created a multidisciplinary Special Interest Group (SIG) on Necrotizing Enterocolitis, a particularly devastating disorder of the newborn. Utilizing whole exome sequencing, members of the SIG hope to dissect the immunologic, molecular, and metabolic causes of this disorder, which has pathophysiologic similarities to RBC alloimmunization and posttransfusion microchimerism seen after massive transfusion.
Our studies with the FDA on the plasticizers BPA and DEHP and metabolites continue and to date, we are the only group to generate PK data on BPA in a transfused pediatric population as compared to children exposed to plasticizers within the setting of the PICU. Our focus is on children undergoing cardiopulmonary bypass and catheterization. Ongoing public health concerns over the estrogenic/antiandrogenic effects of BPA leaching from medical devices make this work highly relevant.
Faculty with interests in hematology and transfusion medicine include: