RESUMO
PROBLEM: Approximately 100,000 individuals in the United States have sickle cell disease (SCD). These individuals face multiple barriers to equitable care. At Brigham and Women's Hospital, existing health inequities for these patients were compounded by admitting, rounding, and team structures that assigned patients with SCD to multiple medicine teams with a hematologist attending, leading to delays in patient care and gaps in residents' hematology knowledge. APPROACH: A hematology-general medicine hybrid team was created in September 2021 to enhance trainee knowledge, skill, and confidence in managing hematology conditions and improve the quality of care delivered to individuals with SCD. This allowed for regionalization of patients with classical hematology conditions to specific hospital floors under the care of one team with a hematologist as the attending of record. OUTCOMES: From October 1, 2021, to January 11, 2022, the majority (745/824, 90%) of in-hospital days for patients with a primary hematology diagnosis were under the care of the hematology-general medicine hybrid team. Regionalization to the home floor of the hybrid team was achieved on 331 (40%) of these 824 hospital days, consistent with regionalization rates for other teams. From October 1, 2021, to September 30, 2022, there were 128 unique patients with SCD admitted over 511 encounters and cared for by approximately 78 residents and 12 medical students. Feedback from residents reported improved knowledge in the management of hematology conditions, especially SCD. NEXT STEPS: The authors are working on a comprehensive analysis of the hybrid team's impact on trainee skill and confidence in managing SCD. The authors believe that this model can be replicated at other institutions to optimize trainee education, consolidate care, and address implicit bias against patients with SCD, even with the hematology attending as a consultant instead of as the attending of record.
Assuntos
Anemia Falciforme , Hematologia , Equipe de Assistência ao Paciente , Humanos , Anemia Falciforme/terapia , Hematologia/educação , Equipe de Assistência ao Paciente/organização & administração , Medicina Geral/educação , Feminino , Masculino , Competência Clínica , Internato e Residência , Melhoria de Qualidade , AdultoRESUMO
Immune thrombotic thrombocytopenic purpura (iTTP) caused by an autoantibody-mediated deficiency of ADAMTS13 and atypical hemolytic syndrome (aHUS) caused by alternative complement dysregulation are the most common primary thrombotic microangiopathies (TMAs). The evaluation of a patient with TMA is a medical emergency since it is critical to quickly distinguish iTTP and aHUS from other causes of TMA. Untreated iTTP is rapidly fatal, and delays in initiating complement inhibition in aHUS increase the risk of irreversible renal failure. An ADAMTS13 activity level of less than 10% is diagnostic of iTTP in the appropriate clinical setting. In settings where rapid-turnaround ADAMTS13 testing is not available, clinical features and clinical prediction tools are useful to identify patients who should receive emergent plasma exchange. We present an evidence-based approach to the initial (first 24 hours) diagnosis and management of iTTP and review the clinical and laboratory features that can be used to identify patients with aHUS who will benefit from early C5 blockade. We also discuss the potential use of complement blockade to improve outcomes in selected patients with secondary TMA.
Assuntos
Púrpura Trombocitopênica Idiopática , Púrpura Trombocitopênica Trombótica , Microangiopatias Trombóticas , Humanos , Púrpura Trombocitopênica Trombótica/diagnóstico , Púrpura Trombocitopênica Trombótica/terapia , Microangiopatias Trombóticas/diagnóstico , Microangiopatias Trombóticas/terapia , Proteínas do Sistema Complemento , Síndrome , Autoanticorpos , Proteína ADAMTS13RESUMO
This study establishes a Duffy null phenotypespecific absolute neutrophil count reference range to optimize care and improve health equity.
Assuntos
Contagem de Leucócitos , Neutrófilos , Humanos , Valores de Referência , Sistema do Grupo Sanguíneo DuffyRESUMO
Many people of African ancestry have lower absolute neutrophil counts (ANCs) without increased risk for infection. This is associated with the Duffy-null phenotype (nonexpression of the Duffy antigen on red blood cells), which is commonly found in those of African descent. Currently, there are no studies that compare the ANC of individuals with Duffy-null phenotype to those with Duffy non-null phenotypes within a self-identified Black population. The aim of this study was to assess the impact of Duffy status on ANCs based on complete blood counts with differential and Duffy testing in a healthy population of self-identified Black individuals at a single primary care center. This study found that 66.7% (80 of 120) of Black individuals have the Duffy-null phenotype and that there is a significant difference in ANCs between Duffy-null and Duffy non-null individuals (median, 2820 cells per µL vs 5005 cells per µL; P < .001). Additionally, 19 of 80 (23.8%) Duffy-null individuals had an ANC of <2000 cells per µL compared with no (0) Duffy non-null individuals. The Duffy-null phenotype is clinically insignificant; however, inappropriate reference ranges can propagate systemic racism. Therefore, we advocate for the development of Duffy-null-specific ANC reference ranges as well as replacing the term benign ethnic neutropenia with Duffy-nullassociated neutrophil count.
Assuntos
Neutropenia , Neutrófilos , Humanos , Negro ou Afro-Americano/genética , Contagem de Leucócitos , População Negra/genética , Neutropenia/genéticaRESUMO
Myeloproliferative neoplasms (MPNs) are characterized by an increased risk of thrombosis and bleeding. Vitamin K antagonists (VKAs) are the historic anticoagulant recommended for use in MPNs. Direct oral anticoagulants (DOACs) are being increasingly used in general and cancer populations. However, DOAC safety and efficacy in MPN patients remains unclear. We characterized real-world practice patterns of DOAC use in MPN patients and evaluated thrombosis and bleeding risk. We conducted a retrospective cohort study of 133 MPN patients prescribed DOACs for venous thromboembolism (VTE), atrial fibrillation, or arterial thromboembolism (ATE). Practice patterns including duration of anticoagulation, dosing, and concomitant use of antiplatelet/cytoreductive agents, were heterogeneous among MPN patients. The 1-year cumulative incidence of thrombosis and bleeding on DOAC was 5.5% (1.5-9.5%) and 12.3% (6.4-18.2%) respectively. In comparison, reported bleeding rates in MPN patients on DOAC and VKAs are 1-3%. On multivariable analysis, prior history of thrombosis, use of dabigatran or edoxaban, and younger age were significantly associated with a higher risk of recurrent thrombosis, while leukocytosis was associated with a higher risk of bleeding on DOAC. The higher-than-expected bleeding rate found in our study indicates the continued need for rigorous evaluation of DOACs in this population.
Assuntos
Anticoagulantes/administração & dosagem , Neoplasias Hematológicas/tratamento farmacológico , Transtornos Mieloproliferativos/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
Minor histocompatibility antigens (mHAs), recipient-derived peptide epitopes presented on the cell surface, are known to mediate graft-versus-host disease (GVHD); however, there are no current methods to associate mHA features with GVHD risk. This deficiency is due in part to the lack of technological means to accurately predict, let alone confirm, the tremendous number of potential mHAs in each individual transplant. Previous studies have shown that different HLA molecules present varying fractions of candidate peptide epitopes; however, the genetic "distance" between HLA-matched donors and recipients is relatively constrained. From these 2 observations, it is possible that the HLA type for a donor-recipient pair (DRP) would provide a surrogate measurement of the number of predicted mHAs, which could be related to GVHD risk. Because different HLA molecules present variable numbers of peptide antigens, a predicted cumulative peptide-binding efficiency can be calculated for individual DRP based on the pair's HLA type. The purpose of this study was to test whether cumulative peptide-binding efficiency is associated with the risk of acute GVHD (aGVHD) or relapse. In this retrospective Center for International Blood and Marrow Transplant Research study, a total of 3242 HLA-matched DRPs were analyzed for predicted cumulative peptide-binding efficiency using their HLA types and were divided into tertiles based on their scores. Univariable and multivariable analyses was performed to test for associations between cumulative peptide-binding efficiency for DRPs, divided into the HLA-matched related donor (MRD) and HLA-matched unrelated donor (MUD) cohorts, and the primary outcomes of aGVHD and relapse. Secondary outcomes investigated included overall survival, disease-free survival, and transplantation-related mortality. Using a computationally generated peptidome as a test dataset, the tested series of HLA class I displayed peptide-binding frequencies ranging from 0.1% to 3.8% of the full peptidome, and HLA class II molecules had peptide-binding frequencies of 12% to 77% across the HLA-DRB1 allotypes. By increasing binding efficiency tertile, the cumulative incidence of aGVHD at 6 months for MUD patients was 41%, 41%, and 45% for HLA class I (P = .336) and 44%, 41%, and 42% for HLA class II (P = .452). The cumulative incidences of relapse at 3 years for MUD transplant recipients were 36%, 38%, and 38% for HLA class I (P = .533) and 37%, 37%, and 38% for HLA class II (P = .896). The findings were similar for MRD transplant recipients. Multivariable analysis did not identify any impact of peptide-binding efficiency on aGVHD or relapse in MUD or MRD transplant recipients. Whereas GVHD is mediated by minor antigen mismatches in the context of HLA-matched allo-HCT, peptide-binding efficiency, which was used as a surrogate measurement for predicted number of binding antigens, did not provide additional clinical information for GVHD risk assessment. The negative result may be due to the limitations of this surrogate marker, or it is possible that GVHD is driven by a subset of immunogenic mHAs. Further research should be directed at direct mHA epitope and immunogenicity prediction.
Assuntos
Transplante de Células-Tronco Hematopoéticas , Doadores não Relacionados , Humanos , Recidiva Local de Neoplasia , Peptídeos , Estudos RetrospectivosRESUMO
Myeloproliferative neoplasms (MPNs), including polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (MF) are stem cell clonal neoplasms characterized by expansion of late myeloid cells. Thrombosis risk is elevated in MPNs and contributes significantly to morbidity and mortality. Current consensus guidelines make no specific recommendations regarding anticoagulant choice for the treatment of venous thromboembolism (VTE) in MPNs, with most evidence supporting the use of vitamin K antagonists (VKAs) for secondary prophylaxis. However, direct oral anticoagulants (DOACs) are now increasingly being used, although with limited data on safety and efficacy in MPNs specifically. The widespread adoption of DOACs is based on new, high-quality evidence demonstrating safety and efficacy of DOAC treatment for cancer-associated VTE. However, these studies include few if any MPN patients, and MPNs have disease-specific considerations that may elevate thrombosis and bleeding risk. The purpose of this review is to discuss evidence behind current treatment recommendations for thrombosis in MPNs, with special attention to the use of DOACs.
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Janus Quinase 2/metabolismo , Transtornos Mieloproliferativos/tratamento farmacológico , Transtornos Mieloproliferativos/metabolismo , Neoplasias/tratamento farmacológico , Tromboembolia Venosa/prevenção & controle , Humanos , Mutação , Transtornos Mieloproliferativos/complicações , Neoplasias/metabolismo , Prevenção Secundária , Tromboembolia Venosa/metabolismoRESUMO
Tyro3, Axl, Mer (TAM) receptor tyrosine kinases reduce inflammatory, innate immune responses. We demonstrate that tumor-secreted protein S (Pros1), a Mer/Tyro3 ligand, decreased macrophage M1 cytokine expression in vitro and in vivo. In contrast, tumor cells with CRISPR-based deletion of Pros1 failed to inhibit M1 polarization. Tumor cell-associated Pros1 action was abrogated in macrophages from Mer- and Tyro3- but not Axl-KO mice. In addition, several other murine and human tumor cell lines suppressed macrophage M1 cytokine expression induced by IFN-γ and LPS. Investigation of the suppressive pathway demonstrated a role for PTP1b complexing with Mer. Substantiating the role of PTP1b, M1 cytokine suppression was also lost in macrophages from PTP1b-KO mice. Mice bearing Pros1-deficient tumors showed increased innate and adaptive immune infiltration, as well as increased median survival. TAM activation can also inhibit TLR-mediated M1 polarization. Treatment with resiquimod, a TLR7/8 agonist, did not improve survival in mice bearing Pros1-secreting tumors but doubled survival for Pros1-deleted tumors. The tumor-derived Pros1 immune suppressive system, like PD-L1, was cytokine responsive, with IFN-γ inducing Pros1 transcription and secretion. Inhibition of Pros1/TAM interaction represents a potential novel strategy to block tumor-derived immune suppression.