Drs. Edward Snyder, Mark Shlomchik, Gary Stack, Diane Krause, Chris Tormey, and Yan Wu
Transfusion Medicine is comprised of the Blood and Tissue Bank, the Apheresis and Transfusion Service, and the Cellular Processing Laboratory. A full range of routine and special transfusion medicine services are provided. There are especially close interactions with the hematology/oncology program, the bone marrow and solid organ transplantation programs, the trauma and cardiac surgery service. An approved Transfusion Medicine Fellowship is funded for those wishing to pursue Transfusion Medicine as a career.
During the rotation the resident will learn the principles and skills involved in the workup of transfusion reactions, interpreting of antibody panel workup, the indications for and the performance of apheresis procedures, the indications for use of various blood products, and the interpretation of tests for transfusion transmitted diseases. The fundamentals of blood typing and screening, antibody identification, cross matching, etc., are learned through a comprehensive series of laboratory exercises designed to introduce the trainee to safe transfusion practice. Clinical rounds are held daily in the Blood Bank with the discussion of the use of uncrossmatched blood, massive transfusions, serology problems, transfusion reactions, special blood product management, positive transfusion transmitted disease testing, stem cell processing and infusion, and other relevant issues. Patient rounds are held daily in the Apheresis and Transfusion Service to discus all patients who receive apheresis treatments including peripheral blood stem cell collection and therapeutic apheresis, and patients who receive transfusion, phlebotomy, or medication infusion and have adverse reactions, deferral, and other issues.
Attending on-call coverage is available at all times; please refer to the on-call schedule. The Medical Director MUST be called when any of the following conditions are suspected or proven: acute intravascular hemolytic transfusion reaction, septic transfusion reaction, TRALI, new apheresis patient referral, incompatible blood is given to any patient, death as a result of transfusion, anaphylactic reaction to blood, seizures in a blood donor, inadequate blood inventory or Red Cross supply available as back-up, disagreement with members of the medical staff regarding blood ordering or transfusion reaction work-up, cardiac arrest in an apheresis patient, need to switch component blood type for a patient, patient has multiple antibodies and a limited number of RBCs are available, or simply if you think maybe you should.
Drs. John McClaskey, Michael Hodsdon, Herbert Malkus, and Tore Eid
The Clinical Chemistry Laboratory performs over 150 different tests and provides a window on all aspects of clinical medicine. Rapid progress in areas such as automation, toxicology, endocrinology, therapeutic drug monitoring and "wellness testing" keeps the lab in a state of constant evolution with new or improved methods being introduced at a rate of one or more per month. Clinical Chemistry also provides oversight for all point-of-care testing in the hospital. The rotation is a busy one in which the resident takes first call for all consultations on the selection and interpretation of tests and for clinical problems arising in the laboratory. Daily rounds are held in which current cases presented by the resident form the basis for discussions of all aspects of Clinical Chemistry. These rounds are supplemented by frequent informal discussions with the Chemistry faculty as needed. Monthly Toxicology Rounds are conducted by Dr. Hodsdon. The Clinical Chemistry section also participates in the weekly endocrine rounds of the Department of Internal Medicine. During this rotation the resident will learn the basic principles of laboratory management, laboratory automation, quality control, serum protein and isoenzyme electrophoresis, clinical enzymology, laboratory endocrinology, pharmacokinetics and the clinical interpretation of therapeutic and toxic drug levels, and the clinical interpretation of markers of cardiac injury, as well as personnel and data management in a large laboratory. Research opportunities include assay development and pharmacokinetic studies of the latest drugs for HIV infection, the neurobiology of cocaine use, and clinical outcome studies of testing algorithms, including point-of-care testing and strategies for cardiac risk assessment.
Drs. Brian Smith, Henry Rinder, Greg Howe, Chris Tormey, Tore Eid, Michael Hodsdon, Stephanie Eisenbarth, David Hudnall, and Richard Torres
The CP-1 and CP-2 resident rotations in Flow Cytometry are separate rotations, each combined with the Hematology and Immunology rotations, respectively. This provides an integrated case-oriented approach to education. For example, flow cytometry studies are examined in the context of hematopathology morphology and cytogenetic and molecular diagnostic assessment and rheumatologic work-ups are interpreted with knowledge of immunologic and complementary chemical analysis results. The focus is derived from the typical patterns of association between disease driven patient testing and helps maintain improved continuity of care when interacting with clinical teams, particularly hematologists, clinical immunologists, and other specialties.
For similar reasons, virology serologic assays are carried out in the virology laboratory and these and bacterial serologic assays are mainly the purview of the Microbiology/Virology resident for use in consultative evaluation of patients performed in conjunction with the microbiology fellow and infectious disease clinical team. Some immunology rotation interpretative work (such as IFEs) is more associated with hematologic workups, but it reduces the hematology/flow cytometry resident workload and fits better with other associated rotation duties (such as SPEP). In each of the sections, emphasis is placed on the acquisition of integrated consultative skills related to the specific discipline.
All rotations are characterized by close interaction with other hospital clinical teams and participation of the resident in joint Pathology-Medicine-Pediatric-Surgery conferences and rounds. Specifically, in Flow Cytometry/Hematology, the resident works with the resident rotating on surgical hematopathology and with the Hematopathology fellow, preparing cases for weekly joint Hematopathology Conference with Medicine and Pediatric attendings and housestaff, and at weekly joint Lymphoma/Stem Cell Transplant Conference. The more senior residents on Flow Cytometry or Immunology may also participate in monthly Hematopathology/Molecular administrative rounds for a managerial perspective on the planning of development work. In Immunology, the resident is responsible for collecting data and preparing interpretive assessments together with the immunology attending for the monthly Laboratory-Clinical Immunology Conference at which lab medicine presents together with adult and pediatric Immunology/Allergy and Rheumatology attendings and house staff, providing an excellent forum both for ongoing clinical diagnostic/therapeutic care and for education. These joint conferences also provide quality assurance functions for all clinical services involved.
Responsibilities are graded, increasing as the resident acquires experience. In Flow Cytometry, residents are responsible for initial formal interpretation of all immunophenotyping and DNA ploidy reports, including collecting clinical history data from online chart notes and evaluating cytometry data in the context of all other relevant morphologic and molecular studies. Learning to appropriately apply ICD-9 coding is also a resident responsibility as it is within the scope of pathologist responsibilities. All immunophenotyping (blood, marrow, lymph node, fluids) is handled in the same laboratory. The total number of flow cytometry studies is more than 7500 per year and growing, including leukemia/lymphoma evaluations, studies for myelodysplasia, transplant/stem cell assessments, and immunodeficiency (including both HIV and congenital immunodeficiencies) evaluations. At the start of the day, the resident, attending or fellow, and technologists review the day's upcoming work by looking over the morphology and clinical data for each case and jointly choosing an appropriate 'panel' of tests. Residents later review each flow result independently and record their preliminary interpretation; at afternoon signout rounds, this is then reviewed with the attending and a final interpretive report generated. The result is frequently called to the ordering clinician by the resident, under supervision of the attending. Communication skills are regarded as one of the core components of clinical pathology training and such interactions are taught, monitored, and formally evaluated.
Graduated responsibility occurs both throughout the rotation and between the CP-1 and CP-2 rotations. First year residents initially may handle only a subset of the total daily workload in terms of detailed evaluation and gradually move to handling the entire repertoire; consultation with Medicine/Pediatric/Surgical attendings (by phone or in person) is initially carried out in the presence of the pathology attending, but over time, residents take sole responsibility for this. While the goal is for residents to enter their own preliminary flow interpretations into the computerized system, part of the process of acquiring experience with this involves transcribing attending written flow diagnoses into the computerized report. Residents attend joint conferences initially and gradually take responsibility for presentation at those conferences. CP-1 residents learn technical aspects of flow cytometry and gradually acquire skills to manage gating adjustments on the flow cytometry raw data files during evaluation for which a specific computer has been designated. The Hematopathology fellow, when on a Flow rotation, takes a senior educational role, substituting for the attending in the education of the resident as appropriate and responsible for education of medicine and pediatric housestaff rotating through the service. He/she assumes managerial responsibility, generally not assumed by CP-1 residents.
Consultative interpretive studies in Immunology include: immunofixation electrophoresis, CSF oligoclonal banding, and interpretive analysis for all molecular studies. The latter include many different types of assays for among others: diagnosis of inherited hypercoagulability, gene rearrangements for NHL, diagnosis and treatment of myeloproliferative disorders, quantitative transcript assays (e.g. EBV, BCR-ABL1) for therapeutic response, UGT polymorphisms for predicting complications, and screening for cystic fibrosis risk. Some of these studies are done in support of the approximately 350 stem cell transplants and >500 solid organ transplants performed at YNHH per year. There are also >2,000 ANA, >2,600 quantitative Ig, >10,000 syphilis serologies, and >1,000 mycoplasma/toxoplasma serologies per annum. Graduated responsibility is similar to that outlined above: CP-1 residents take all initial consultative calls to the laboratory but do not carry out managerial responsibility; CP-2 residents assume a junior managerial role, consult and approve serologic studies, and take primary responsibility for education of allergy/immunology housestaff rotating through as well as serving as primary liaison for guiding and interpreting immune deficiency patient workups with allergy/immunologists, immunology lab attendings, and the resident on flow cytometry. Such cases serve as basis for the monthly combined rheumatology/immunology/lab medicine conferences which residents help prepare. CAP challenges that require pathologist interpretation are also reviewed initially by residents in the respective rotation and then reviewed with the corresponding attending prior to submission. In addition, QC/QI duties (as an elective) are gradually assumed based on what other rotations the resident may have had previously.
Drs. Henry Rinder, Brian Smith, Chris Tormey, David Hudnall, and Richard Torres
The complexities of identifying blood-borne parasitic infections, deciphering abnormal hemostasis, diagnosing a hematologic malignancy or identifying hemoglobinopathies demand a particularly close collaboration between the laboratory medicine and the clinical care physicians. Our goal is to bring the latest developments in cellular, protein, and molecular biotechnology directly from the research bench to the clinical hematology laboratory for patient care.
During the rotation in hematology, the resident has the opportunity to learn general hematology as well as various specialty areas including coagulation, urinalysis, bone marrow interpretation, and flow cytometry. The resident is responsible for the daily review of abnormal differential counts, blood or body fluid smears containing atypical cells, platelet function testing, hemoglobin electrophoreses, and special hematology cytochemistries. The resident also reviews flow cytometry and special coagulation studies and prepares all reports on these studies in consultation with the attending staff. Drs. Smith and Rinder have joint appointments in Internal Medicine (and, in the case of Dr. Smith, Pediatrics) and rounding with the clinical hematology team is available to interested residents.
As noted in the section on Flow cytometry and Immunology resident responsibilities, residents in Hematology enjoy graduated duties as they progress in their training. For example, CP-1 residents focus on learning diagnostic criteria, honing their skills in microscopy, and becoming familiar in general with the technical aspects of the hematology laboratory. Over time, residents begin to field questions independently and direct the activities of the technical staff. Finally, CP-2 residents take on the role of an assistant director of the laboratory, handling complex technical and clinical issues, overseeing QC/QA and regulatory components, and handling all clinical interpretive work. Upon completion of the hematology laboratory rotations, the senior resident will be competent to independently interpret hematology assays and supervise a professional staff.
Drs. David Peaper, Sheldon Campbell, and Thomas Murray
During the rotation, the resident will learn general microbiology techniques as well as the interpretation of cultures from blood, CSF, the respiratory tract, genital areas, wounds and stools. Skill will also be obtained in mycobacteriology, mycology, parasitology, molecular diagnostic methods, and the interpretation of antibiotic sensitivity profiles. These skills are learned by rotations through the various stations of the laboratory as well as daily rounds in which instructive cases are discussed from both the microbiological and clinical points of view.
Cancer chemotherapy, organ transplantation, and HIV infections have let to an increasing number of patients with immunodeficiency who in turn are susceptible to a large number of opportunistic pathogens causing disease. The development of sensitive and specific diagnostic procedures for these opportunistic pathogens presents an ongoing challenge. Novel, emerging infections and changes in the pathogenic mechanisms and antimicrobial resistance of familiar pathogens also provide new problems. In addition, the application of monoclonal antibodies and molecular techniques is revolutionizing all of microbiology.
In order to provide clinical correlation, Infectious Disease teams from adult and pediatric services round in the laboratory daily and review laboratory tests relevant to their patients. Residents help to collect, demonstrate and explain the laboratory tests to the I.D. team, as requested on specific patients. The resident also attends the weekly clinical conference of the Infectious Disease Service. An approved Clinical Microbiology Fellowship is funded for those wishing to pursue Microbiology as a career.
Patient Care:
Dr. Marie Landry and David Peaper
The Clinical Virology Laboratory is a full-service virology laboratory operating 7 days a week that performs rapid detection of viral antigens in clinical samples, a large and ever increasing menu of molecular tests, conventional and rapid virus isolation techniques, and determination of viral antibody response.
Direct detection of viral antigens by cytospin-enhanced direct immunofluorescence (DFA) is employed for VZV and HSV in skin lesions; HSV, VZV and adenovirus in eye swabs; and RSV, influenza A and B, parainfluenza types 1-3, adenovirus and HMPV in respiratory samples. Hepatitis B surface antigen is detected in serum and rotavirus in stool by ELISA. Molecular methods include commercial Roche assays to detect and quantify HIV-1 RNA, HCV RNA and HBV DNA in plasma or serum, and to detect HIV-1 provirus in peripheral blood mononuclear cells. Real-time TaqMan PCR assays, developed in-house, are used to detect DNA viruses (HSV, VZV, CMV, EBV, HHV-6, JC virus, BK virus, adenovirus, parvovirus B19) and RNA viruses (enteroviruses, human metapneumovirus, RSV, influenza A and B, influenza A subtypes, parainfluenza types 1-3, rhinovirus and norovirus. HCV genotyping (Line prove assay)and HIV-1 drug resistance genotyping (sequencing) are also available. A variety of cell cultures are maintained for isolation of common viruses. Rapid shell vial centrifugation cultures are routinely performed for CMV. Antibody tests are available for hepatitis A, B, C, HIV, HSV 1 and 2, CMV, VZV, EBV, rubella, measles, and mumps by random access chemiluminescence; and for parvovirus B19 and West Nile virus by ELISA; and for EBV by IF. Immunoblots are performed for HIV-1 and HCV. The detection of Clostridium difficile by GDH bacterial antigen followed by cytotoxin neutralization in cell culture is performed in the Virology Laboratory.
A teaching schedule has been organized so that residents will become familiar with all testing done within Virology. The resident is expected to investigate problems, determine clinical correlations when needed, consult with physicians, interpret HIV western blots, and correlate virology results with pathologic findings. A close working relationship between the virology laboratory and the transplant and AIDS care programs is essential and the resident helps to communicate and maintain this relationship.
Patient Care:
Drs. Gary Stack, Sheldon Campbell, Nelofar Shafi, Chris Tormey, Donald Mayo, Rick Torres, David Peaper, and Brigitte Griffith
The VA-1 rotation provides the resident with the opportunity to practice Clinical Pathology in the setting of an integrated Pathology and Laboratory Medicine Service. Residents cover all sections of the clinical laboratories and have the option to interact more closely with the Anatomic Pathology laboratories. This allows the resident to gain a broader view of patient diagnostic services than is possible in the more specialized rotations.
Of particular interest are two national reference laboratories for virology and mycobacteriology. These laboratories serve the entire Veterans Administration health care system, as well as many non-government medical facilities. The VA has a recently established molecular diagnostics laboratory with state-of-the-art equipment, which provides opportunities for residents to participate in new test development.
During this rotation, the resident also has the opportunity to observe and perform bone marrow aspirations and biopsies, and to interpret those tissues for final diagnosis, providing a 360-degree experience in aspirate procedures.
The VA-2 rotation provides residents with a formal graduated responsibility with senior level duties. The resident may elect to act as the assistant director of a subspecialty laboratory, handling all procedural and personnel issues, CAP surveys, budget and capital issues, and of course, all interpretative aspects of that laboratory. In addition, the VA-2 rotation offers specialized experience at the central virology laboratory, the state epidemiologic center, and other VA sites of excellence.
Dr. Henry Rinder
Senior (CP-2) residents have a mandatory 4 week rotation during their YNHH clinical pathology time in Laboratory Management. Residents may choose several options for accomplishing the goals of this rotation that are namely: to experience and participate in the daily management of a clinical laboratory. Residents may rotate among different labs or elect to work within a single laboratory for the entire rotation block. Residents work directly with a medical director to gain experience in the following areas of lab management:
Residents are asked to initially shadow a director to observe management issues and the style of the director in handling problems. Residents are then encouraged to directly undertake solving management problems and work on some of the above issues, with immediate attending supervision available. This enables residents to develop their own personal way of addressing management problems and gain skills at management while having attending support for any and all management issues. Residents who elect to work within a single lab for the rotation are asked to also select a limited scope single management project for that period.
Examples of prior lab management projects:
Dr. Peining Li, Director
Cytogenetics is now an integral diagnostic and prognostic tool in various branches of medicine (e.g. oncology, pediatrics, cardiology, neurology, and internal medicine). The number of syndromes identified as associated with chromosome abnormalities has increased from less than a dozen in the 1960s to over 400 today. More recently, cancer cytogenetics has provided valuable diagnostic and prognostic information for hematopoietic tumors and tumors of solid tissues. The cytogenetics laboratory at the Yale University School of Medicine has been updated and staffed and now offers a full range of services for clinicians and researchers from Yale and beyond.
The cytogenetics laboratory services include routine and specialized chromosome karyotype analysis, fluorescence in situ hybridization (FISH) and genome-wide array comparative genomic hybridization (aCGH), and collaborative research services. Types of specimens processed include blood, amniotic fluids, chorionic villus, products of conception, bone marrow, skin, solid tumors, and many others.
Dr. Greg Howe
Molecular techniques are changing the face of medicine. Few areas are being more intensely affected than Laboratory Medicine, which has the duty of translating assays developed in the research laboratory into routine, rapid and cost-efficient clinical laboratory assays. Believing that techniques based on recognition of nucleic acid sequences will become widely applicable, we have established a Molecular Diagnostics Laboratory that has the job of developing molecular assays, transferring them to routine clinical use and overseeing their continued use. We are currently developing a wide range of molecular diagnostic assays that will affect all aspects of Laboratory Medicine and are at the forefront of the molecular diagnostics field. A large number of tests, including those for genetic disorders such as hemochromatosis, prothrombin G20210A mutation, Factor V Leiden, and cystic fibrosis screening, as well as those for tumor diagnosis and minimal residual disease detection, are carried out. Techniques include several amplification strategies, sequencing, quantitative PCR and RFLP analysis. Bacterial and mycobacterial identification by 16S ribosomal amplification and sequencing are also performed. Residents are regularly exposed to molecular techniques in the majority of their rotations. For example, the Virology and Microbiology laboratories test for a number of organisms by molecular diagnostics methods, such as HIV, HSV, enterovirus, chlamydia, and mycobacterium. In addition, the pathology department at the affiliated VA performs molecular diagnostics testing for HCV and Factor V Leiden. Residents also have the opportunity to work on new assays in the Molecular Diagnostics Laboratory, either as a rotation project or as a development project in their rotation. Finally, a lecture series in molecular diagnostics is taught jointly by Anatomic and Clinical Pathology.