Jay S. Raval

The use of the mechanical fragility test in evaluating sublethal RBC injury during storage

Background  The mechanical fragility index (MFI) is an in vitro measurement of the extent of RBC sublethal injury. Sublethal injury might constitute a component of the RBC storage lesion, thus the MFI was determined serially during routine RBC storage.

Autoantibody-Targeted Treatments for Acute Exacerbations of Idiopathic Pulmonary Fibrosis.

Background Severe acute exacerbations (AE) of idiopathic pulmonary fibrosis (IPF) are medically untreatable and often fatal within days. Recent evidence suggests autoantibodies may be involved in IPF progression. Autoantibody-mediated lung diseases are typically refractory to glucocorticoids and nonspecific medications, but frequently respond to focused autoantibody reduction treatments. We conducted a pilot trial to test the hypothesis that autoantibody-targeted therapies may also benefit AE-IPF patients. Methods Eleven (11) critically-ill AE-IPF patients with no evidence of conventional autoimmune diseases were treated with therapeutic plasma exchanges (TPE) and rituximab, supplemented in later cases with intravenous immunoglobulin (IVIG). Plasma anti-epithelial (HEp-2) autoantibodies and matrix metalloproteinase-7 (MMP7) were evaluated by indirect immunofluorescence and ELISA, respectively. Outcomes among the trial subjects were compared to those of 20 historical control AE-IPF patients treated with conventional glucocorticoid therapy prior to this experimental trial. Results Nine (9) trial subjects (82%) had improvements of pulmonary gas exchange after treatment, compared to one (5%) historical control. Two of the three trial subjects who relapsed after only five TPE responded again with additional TPE. The three latest subjects who responded to an augmented regimen of nine TPE plus rituximab plus IVIG have had sustained responses without relapses after 96-to-237 days. Anti-HEp-2 autoantibodies were present in trial subjects prior to therapy, and were reduced by TPE among those who responded to treatment. Conversely, plasma MMP7 levels were not systematically affected by therapy nor correlated with clinical responses. One-year survival of trial subjects was 46+15% vs. 0% among historical controls. No serious adverse events were attributable to the experimental medications. Conclusion This pilot trial indicates specific treatments that reduce autoantibodies might benefit some severely-ill AE-IPF patients. These findings have potential implications regarding mechanisms of IPF progression, and justify considerations for incremental trials of autoantibody-targeted therapies in AE-IPF patients. Trial Registration ClinicalTrials.gov NCT01266317

Menopausal status affects the susceptibility of stored RBCs to mechanical stress

The mechanical fragility index (MFI) is an in vitro measure of sublethal injury to RBCs. In our previous experiments, we demonstrated that an increase in sublethal injury (increasing MFI) was a component of the RBC storage lesion, and that the MFI was significantly higher amongst the RBC units from male donors compared to pre‐menopausal female donors during storage. It was hypothesized that hormonal or menstrual factors contributed to this difference. In this study, we found that RBC units donated by post‐menopausal women demonstrated an MFI that was significantly higher than those donated by pre‐menopausal women throughout storage.

State of the art: massive transfusion

The aim of this article was to review recent developments in the resuscitation of both trauma and non‐trauma patients in haemorrhagic shock. Strategies for the resuscitation of massively haemorrhaging patients and the use of massive transfusion protocols (MTPs) have been a major focus of the trauma literature over the past several years. The application of haemostatic resuscitation practices and MTPs to non‐trauma populations has long been in practice, but has only recently been the subject of active research. Medline and PubMed were reviewed for ‘massive transfusion’ (MT) from 2012 to present. Non‐English and paediatric articles were excluded. Articles were systematically reviewed for their relevance to MT. There were eight major areas of development identified. In recent MT literature, there was an increased focus on massively haemorrhaging non‐trauma patients, the role of acute traumatic coagulopathy, the use of thromboelastography (TEG), and the impact of MTPs on blood product waste and efficiency of product delivery. Other developments included additional MT prediction tools and The PRospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study. There was also interest in re‐evaluating the clinical relevance of the current MT definition and identifying new foci for MT. These recent developments reflect efforts to better understand and manage non‐traumatic haemorrhage and to address prior limitations in the trauma literature. Inevitably, new questions have been raised, which will likely direct ongoing and future research in MT.

Haemolysis and sublethal injury of RBCs after routine blood bank manipulations.

Objectives: To determine the extent of RBC sublethal injury in male donor units as measured by both the mechanical fragility index (MFI) and percentage haemolysis after RBCs underwent leucoreduction (LR), irradiation (IRRAD), and washing.

Massive Transfusion: An Evidence-Based Review of Recent Developments

The design and implementation of massive transfusion protocols with ratio-based transfusion of blood and blood products are important and active areas of investigation. A significant yet controversial body of literature exists to support the use of hemostatic resuscitation in massive transfusion and new data to support the use of adjuncts, such as recombinant factor VIIa and tranexamic acid. We review the developments in massive transfusion research during the past 5 years, including protocol implementation, hemostatic resuscitation, the use of tranexamic acid, and goal-directed therapy for coagulopathy. Furthermore, we provide a level of evidence analysis of the data surrounding the use of component therapy and recombinant factor VIIa in massive transfusion, summary recommendations for the various agents of resuscitation, and new methods of goal-directed therapy.

Intravascular Talcosis due to Intravenous Drug Use Is an Underrecognized Cause of Pulmonary Hypertension

Intravenous injection of illegal drugs or medications meant for oral administration can cause granulomatous disease of the lung. This intravascular talcosis results in pulmonary fibrosis and pulmonary hypertension. Nine cases of histologically confirmed intravascular talcosis were reviewed with specific attention given to the clinical histories in these patients. Five autopsy cases were included in this series with detailed investigation in the anatomic features associated with intravascular talcosis and pulmonary hypertension. All nine patients showed perivascular and/or intravascular deposition of polarizable foreign material in their lungs. Intravascular talcosis as a result of previous intravenous drug use was not clinically suspected in any patient despite clinically diagnosed pulmonary hypertension in five. All patients showed dilatation of the right and left heart, but none had dilatation of the aortic valve. Congestive heart failure with hepatosplenomegaly was also common. We conclude that intravascular talcosis is an underdiagnosed cause of pulmonary hypertension in patients with known history of intravenous drug use.

Innate Immune Activation After Transfusion of Stored Red Blood Cells

The transfusion of red blood cells (RBCs), although necessary for treatment of anemia and blood loss, has also been linked to increased morbidity and mortality. RBCs stored for longer durations and transfused in larger volumes are often cited as contributory to adverse outcomes. The potential mechanisms underlying deleterious effects of RBC transfusion are just beginning to be elucidated. In this narrative review, we explore the hypothesis that prolonged RBC storage results in elaboration of substances which may function as danger associated molecular pattern molecules that activate the innate immune system with consequences unfavorable to healthy homeostasis. The nature of these chemical mediators and the biological responses to them offers insight into the mechanisms of these pathological responses. Three major areas of activation of the innate immune apparatus by stored RBCs have been tentatively identified: RBC hemolysis, recipient neutrophil priming, and reactive oxygen species production. The possible mechanisms by which each might perturb the innate immune response are reviewed in a search for potential novel pathways through which transfusion can lead to an altered inflammatory response.

Contemporary issues in transfusion medicine informatics

The Transfusion Medicine Service (TMS) covers diverse clinical and laboratory-based services that must be delivered with accuracy, efficiency and reliability. TMS oversight is shared by multiple regulatory agencies that cover product manufacturing and validation standards geared toward patient safety. These demands present significant informatics challenges. Over the past few decades, TMS information systems have improved to better handle blood product manufacturing, inventory, delivery, tracking and documentation. Audit trails and access to electronic databases have greatly facilitated product traceability and biovigilance efforts. Modern blood bank computing has enabled novel applications such as the electronic crossmatch, kiosk-based blood product delivery systems, and self-administered computerized blood donor interview and eligibility determination. With increasing use of barcoding technology, there has been a marked improvement in patient and specimen identification. Moreover, the emergence of national and international labeling standards such as ISBT 128 have facilitated the availability, movement and tracking of blood products across national and international boundaries. TMS has only recently begun to leverage the electronic medical record to address quality issues in transfusion practice and promote standardized documentation within institutions. With improved technology, future growth is expected in blood bank automation and product labeling with applications such as radio frequency identification devices. This article reviews several of these key informatics issues relevant to the contemporary practice of TMS.

Anesthetic management in upper extremity transplantation: the Pittsburgh experience.

BACKGROUND: Hand/forearm/arm transplants are vascularized composite allografts, which, unlike solid organs, are composed of multiple tissues including skin, muscle, tendons, vessels, nerves, lymph nodes, bone, and bone marrow. Over the past decade, 26 upper extremity transplantations were performed in the United States. The University of Pittsburgh Medical Center has the largest single center experience with 8 hand/forearm transplantations performed in 5 recipients between January 2008 and September 2010. Anesthetic management in the emerging field of upper extremity transplants must address protocol and procedure-specific considerations related to the role of regional blocks, effects of immunosuppressive drugs during transplant surgery, fluid and hemodynamic management in the microsurgical setting, and rigorous intraoperative monitoring during these often protracted procedures. METHODS: For the first time, we outline salient aspects of upper extremity transplant anesthesia based on our experience with 5 patients. We highlight the importance of minimizing intraoperative vasopressors and improving fluid management and blood product use. RESULTS: Our approach reduced the incidence of perioperative bleeding requiring re-exploration or hemostasis and shortened in-hospital and intensive care unit stay. Functional, immunologic and graft survival outcomes have been highly encouraging in all patients. CONCLUSIONS: Further experience is required for validation or standardization of specific anesthetic protocols. Meanwhile, our recommendations are intended as pertinent guidelines for centers performing these novel procedures.