A Case Report of Rotational Thromboelastometry-Assisted Decision Analysis for Two Pregnant Patients With Platelet Storage Pool Disorder.

Platelet storage pool disorders (PSPDs) constitute a diverse group of hematologic abnormalities, which share the common feature of a deficiency in the ability of platelets to aggregate. Parturients with PSPD can present management challenges to their care team when they present for childbirth, especially with regard to neuraxial anesthesia. We report a series of 2 deliveries from unrelated patients affected by PSPD. In particular, we highlight the utility of rotational thromboelastometry (ROTEM) and the need for a multidisciplinary approach to the care of patients with this hematologic abnormality.

Persistence of Unequal Access to Classical Hematology Telemedicine Visits by Race and Other Demographics During the COVID-19 Pandemic.

Background: Unequal access to telemedicine services exacerbates health inequities and was evident at the start of the COVID-19 pandemic. We sought to explore whether unequal access persisted within a classical hematology division beyond the peak of COVID-19. Methods: Patient demographics by virtual visit type (telephone only [TO] or video only [VO]) between March 2020 and December 2021 were analyzed using adjusted odds ratio (aOR). Results: Of 8,207 patients, 18.4% had TO and 28.4% had VO visits. Fewer Black (21.8%; aOR 0.5 [0.4-0.62]), Hispanic or Latino (18.8%; 0.45 [0.34-0.59]), Spanish-speaking (7.6%; 0.32 [0.19-0.54]), high school (21.2%; 0.64 [0.52-0.78]), and older (24.2%) patients used VO compared with White (30.6%), English-speaking (29.5%), college (31%), postgraduate (34.9%), and younger (35.4%) patients. Conclusions: Groups that historically experience health inequities had fewer VO visits during and beyond the pandemic peak. Thus, there is a need to continue digital inclusion efforts to promote video access equity.

ß-Thalassemia: evolving treatment options beyond transfusion and iron chelation.

After years of reliance on transfusion alone to address anemia and suppress ineffective erythropoiesis in ß-thalassemia, many new therapies are now in development. Luspatercept, a transforming growth factor-ß inhibitor, has demonstrated efficacy in reducing ineffective erythropoiesis, improving anemia, and possibly reducing iron loading. However, many patients do not respond to luspatercept, so additional therapeutics are needed. Several medications in development aim to induce hemoglobin F (HbF): sirolimus, benserazide, and IMR-687 (a phosphodiesterase 9 inhibitor). Another group of agents seeks to ameliorate ineffective erythropoiesis and improve anemia by targeting abnormal iron metabolism in thalassemia: apotransferrin, VIT-2763 (a ferroportin inhibitor), PTG-300 (a hepcidin mimetic), and an erythroferrone antibody in early development. Mitapivat, a pyruvate kinase activator, represents a unique mechanism to mitigate ineffective erythropoiesis. Genetically modified autologous hematopoietic stem cell transplantation offers the potential for lifelong transfusion independence. Through a gene addition approach, lentiviral vectors have been used to introduce a ß-globin gene into autologous hematopoietic stem cells. One such product, betibeglogene autotemcel (beti-cel), has reached phase 3 trials with promising results. In addition, 2 gene editing techniques (CRISPR-Cas9 and zinc-finger nucleases) are under investigation as a means to silence BCL11A to induce HbF with agents designated CTX001 and ST-400, respectively. Results from the many clinical trials for these agents will yield results in the next few years, which may end the era of relying on transfusion alone as the mainstay of thalassemia therapy.

Acquired von Willebrand Syndrome.

Acquired von Willebrand syndrome can occur in the setting of myeloproliferative neoplasms; plasma cell dyscrasias and other lymphoproliferative disorders; autoimmune conditions; and causes of increased shear forces, such as aortic stenosis or other structural heart disease and mechanical circulatory support. The depletion of von Willebrand factor, especially high-molecular-weight multimers, can lead to mucocutaneous bleeding and the formation of arteriovenous malformations, particularly in the gastrointestinal tract. Management focuses on correction of the underlying cause when possible, but may include intravenous immunoglobulins, von Willebrand factor concentrate, rituximab, or antiangiogenic therapy depending on the clinical context.

Building upon the foundational science curriculum with physiology-based grand rounds: a multi-institutional program evaluation.

Introduction: Vertically integrating physiology into patient care has the potential to improve clinical reasoning. Clinical Physiology Grand Rounds (CPGR) is a case-based teaching method that brings together students from all years of medical school to focus on linking clinical presentations to core basic science concepts including anatomy, physiology, and pathophysiology. In this study, we describe the implementation of CPGR at two different institutions in the United States and assess student-reported outcomes.Methods: We survey students who participated in CPGR at Columbia University College of Physicians & Surgeons (P&S) and Medical University of South Carolina (MUSC). Subjects were queried across three domains: the benefits of attending, the impact of concept maps, and the impact of the mixed-learner environment.Results: Despite differences in session leadership and the underlying medical school curricula, conference attendees reported similar benefits at the two schools included in this study. Students overwhelmingly (92.9%) reported that remembering clinical presentations was easier when they understood the underlying physiology. They also reported gaining a true understanding of concepts that were previously memorized (87.5%). Both clinical (92.5%) and preclinical students (93.1%) valued the mixed-learner environment as a component of the conference.Discussion: By assuring a mixed-learner environment with near-peer interactions, using concept maps as a teaching tool, and rigorously linking clinical presentation and management to physiological concepts, we found that the key benefits of CPGR were replicable across different institutions, despite several local differences in how CPGR was implemented, led, and conducted.

Long-term Outcomes of team-based learning.

BACKGROUND: Team-based learning (TBL) is associated with improved end-of-course exam performance, but the impact on long-term retention is unknown. We compared the impact of three teaching methods: traditional case-based small group discussion (TSG), TBL or no small group reinforcement on short-term understanding and long-term retention after a haematology course. METHODS: Knowledge assessments were conducted prior to, immediately after and 14 months after course completion. Several topics covered by TSG were switched to TBL and could be directly compared. RESULTS: We recruited 24% of eligible students (n = 70). Of these, 48 completed the final assessment (69% retention). Pre-course, participants scored 31% correctly, which increased to 78% post-course with significant differences: TBL 87%; TSG 78%; no small group 76% (p < 0.01 for both comparisons). At long-term follow-up, the effect of the teaching method was no longer significant: TBL 75%; TSG 67% (p = 0.14); no small group 70% (p = 0.36). When restricted to topics converted from TSG to TBL, the long-term benefit was not shown: TSG 59%; TBL 54% (p = 0.47). FINDINGS AND DISCUSSION: We confirm increased understanding gained by using TBL, but this did not lead to better long-term retention. Improved scores on short-term testing has value for student well-being and competitiveness for residency application. TBL may still be of long-term benefit through modelling team decision making and self-directed learning that are core features of how clinical medicine is practiced. However, our findings argue against justifying the adoption of TBL on the basis of superior long-term retention.

Hemolysis and Hemoglobin Structure and Function: A Team-Based Learning Exercise for a Medical School Hematology Course.

Introduction: This team-based learning (TBL) exercise focused on hemolysis and hemoglobin structure and function. The goal was to emphasize content that directly impacts clinical practice, but obliges students to understand underlying pathophysiology. The readiness assurance test (RAT) covers oxygen affinity, diagnosing hemolysis, inherited causes of hemolysis (G6PD deficiency, hereditary spherocytosis, sickle cell disease, thalassemia) and acquired causes of hemolysis (thrombotic microangiopathies, autoimmune hemolytic anemia). The application activity focused on thalassemia, sickle cell disease, and autoimmune hemolytic anemia. Methods: Second-year students were divided into teams of five to six students each with one facilitator for each classroom. Students completed an individual RAT (iRAT) followed by a group RAT (gRAT). The facilitator reviewed answers of the RATs emphasizing questions where there was a lack of clarity about the correct answer. Students completed the application activity within their teams followed by a discussion guided by the facilitator. Results: On average, students answered 63% of answers correctly on the iRAT. The average team score on the gRAT was 26.7 out of 30 points. The session was well reviewed by both students and facilitators. Students ranked the quality of all facilitators as excellent with an average rating of 4.4 of 5. Exam scores improved compared to prior to the introduction of TBL, but this was also found for material not covered. Discussion: The use of TBL to emphasize the relationship between pathophysiology and the diagnosis and management of patients was both an effective teaching method and a successful way to engage medical students.

Billing Codes Determine Lower Physician Income for Primary Care and Non-Procedural Specialties.

The income gap between specialists and primary care physicians and among specialists is well established, but the drivers of this difference are not well delineated. Using the Community Tracking Study (CTS) Physician Survey, we sought to isolate and compare premiums paid to physicians for specialization and the proportion of time spent on offices visit rather than procedures. We divided medical subspecialties according the proportion of Medicare billing for Evaluation and Management (E&M) codes for the specialty as a whole. We report substantial differences in income across physician specialty, and over 70 percent of the difference in income remained controlling for factors that may confound the relationship between income and specialty including gender, location and type of practice, and hours. We note a large variation in premiums for specialization: 11.3-46.8 percent above family medicine after controlling for confounders. Classifying medical subspecialties by E&M billing as procedural versus non-procedural specialties revealed clear income differences. Controlling for confounders, procedural medical specialties earned 37.5 percent more than family medicine, as compared with 15.3 percent for non-procedural medical specialties. This analysis suggests that differences in physician income and resulting incentives are a direct consequence of the payment structure itself, rather than compensation for additional years of training or a reflection of different underlying demographics.

Inhaled steroids associated with decreased macrophage markers in nonasthmatic individuals with sickle cell disease in a randomized trial.

Inhaled mometasone was shown to improve pain scores and decrease soluble vascular cell adhesion molecule (sVCAM) concentration in a randomized controlled trial of nonasthmatic patients with sickle cell disease. We sought to explore potential changes in systemic inflammation as a mechanism underlying this effect. Serum samples from 41 trial participants (15 placebo- and 26 mometasone-treated) were analyzed using a 92 inflammatory marker panel at baseline and after 8 weeks of mometasone therapy. Individual marker analysis and correlation analysis were conducted. Adjusted for age, the mometasone-treated group decreased the concentration of CXCL9, CXCL11, CD40, IL-10, and IL-18 relative to placebo-treated participants. Hierarchical clustering and correlation analysis identified additional evidence for a decrease in cytokines linking to macrophage signaling and migration. There was no statistically significant change in markers of asthma and allergy, indicating that the improvement was unlikely mediated by modulation of occult reactive airway disease. This analysis of inflammatory markers suggests that decrease in macrophage activity may be involved in the mediation of the clinical benefit seen with use of inhaled mometasone in nonasthmatic patients with sickle cell disease.Trial registration: clinicaltrials.gov identifier: NCT02061202.

Hemophagocytic Lymphohistiocytosis Due to Primary HHV-8 Infection in a Liver Transplant Recipient.

Human herpesvirus-8 (HHV-8) remains best known as an oncogenic virus, but nonneoplastic disease manifestations, such as bone marrow failure or hemophagocytic lymphohistiocytosis (HLH) have gained greater recognition in recent years. In organ transplantation, HHV-8 infection commonly occurs with reactivation of latent virus among recipients from endemic regions of the world or due to transmission from the organ donor. We describe a case of HHV-8-associated HLH in a liver transplant recipient at increased risk for primary infection. Our case highlights the risk of non-donor-derived, posttransplant primary HHV-8 infection, and demonstrates that HLH can be a life-threatening complication of this infection.

Evaluating the safety of emicizumab in patients with hemophilia A.

INTRODUCTION: Patients affected by hemophilia A often require frequent prophylactic and therapeutic self-infusion. For those who develop inhibitors, treatment options are limited and mortality is increased. Emicizumab, a bispecific antibody to Factors IXa and X that carries out the function of Factor VIII (FVIII), represents a novel therapeutic approach. Areas covered: We review the clinical trials and key laboratory assay research for emicizumab. Emicizumab reduced the annualized bleeding rate by 87% compared to placebo in patients with inhibitors. For patients without inhibitors, emicizumab reduced the annualized bleeding rate 96-97% compared to no prophylaxis and 68% compared to prior FVIII prophylaxis. Three patients developed a thrombotic microangiopathy (TMA) and two patients had thrombotic events while on emicizumab in combination with activated prothrombin complex concentration (aPCC) alone or concurrent with activated recombinant factor FVII (rFVIIa). Expert opinion: Emicizumab represents a much-needed alternative approach to managing Factor VIII deficiency, especially for those with inhibitors or limited ability to self-infuse. For patients with inhibitors, thrombotic complications including TMA, not seen with other bypassing agents, raises concern about the use of emicizumab in combination with aPCC and how patients who have breakthrough bleeding can be safely managed.

Hospital Admissions, Mortality and Comorbidities Among New York State Sickle Cell Patients, 2005-2013.

Analyses of administrative and large data sources in Sickle Cell Disease (SCD) can answer questions not suitable for prospective study but have been hampered by lack of validated methods to adjust for individual comorbidities and lack of baseline utilization data over time. We sought to develop a database to characterize inpatient SCD care across New York State and generate a re-weighted sickle-cell specific Charlson Comorbidity index (S-CCI) for use in future large data SCD research. We identified 18,541 individual SCD patients admitted to New York State hospitals between 2005 and 2013 from the SPARCS database. We present data from both a randomly selected derivation cohort, used to develop the S-CCI and a validation cohort, The S-CCI resulted in small improvements in model fit and discrimination while using fewer covariates, allowing a more parsimonious model. Despite being the most common comorbidity, chronic pulmonary disease was not predictive of mortality. Mortality per hospitalization was 0.61%. Many patients (32%) were admitted only once during the nine year period. However, the majority was admitted more frequently with over 15% of patients being admitted more than once per year.

Role of hepcidin-ferroportin axis in the pathophysiology, diagnosis, and treatment of anemia of chronic inflammation.

Anemia of chronic inflammation (ACI) is a frequently diagnosed anemia and portends an independently increased morbidity and poor outcome associated with multiple underlying diseases. The pathophysiology of ACI is multifactorial, resulting from the effects of inflammatory cytokines which both directly and indirectly suppress erythropoiesis. Recent advances in molecular understanding of iron metabolism provide strong evidence that immune mediators, such as IL-6, lead to hepcidin-induced hypoferremia, iron sequestration, and decreased iron availability for erythropoiesis. The role of hepcidin-ferroportin axis in the pathophysiology of ACI is stimulating the development of new diagnostics and targeted therapies. In this review, we present an overview of and rationale for inflammation-, iron-, and erythropoiesis-related strategies currently in development.