Hematology. American Society of Hematology. Education Program最新文献

Catastrophic antiphospholipid syndrome (CAPS) is a rare but life-threatening form of antiphospholipid syndrome (APS) defined by the rapid onset of large and small vessel thrombosis occurring simultaneously across multiple sites, resulting in multiorgan dysfunction. The presence of underlying immune dysfunction causing activation of coagulation and, in many cases, abnormal complement regulation predisposes these patients to thrombotic events. CAPS is often preceded by triggering factors such as infection, surgery, trauma, anticoagulation discontinuation, and malignancy. Given the high mortality rate, which may exceed 50%, prompt recognition and initiation of management is required. The detection of antiphospholipid antibodies and the histopathologic identification of microvascular ischemia via tissue biopsy are required to diagnose CAPS. However, these patients are often too unwell to obtain results and wait for them. As such, investigations should not delay CAPS therapy, especially if there is strong clinical suspicion. Management of CAPS requires "triple therapy" with glucocorticoids, intravenous heparin, therapeutic plasma exchange, and/or intravenous immunoglobulin. Treatment for refractory disease is based on poor-quality evidence but includes anti-CD20 (rituximab) or anticomplement (eculizumab) monoclonal antibodies and other immunosuppressant agents, either alone or in combination. The rarity of this syndrome and the subsequent lack of randomized clinical trials have led to a paucity of high-quality evidence to guide management. Continued international collaboration to expand ongoing CAPS registries will allow a better understanding of the response to newer targeted therapy.

Chronic lymphocytic leukemia (CLL) patients who are refractory to both Bruton's tyrosine kinase and B-cell/CLL lymphoma 2 (BCL2) inhibitors face a significant treatment challenge, with limited and short-lasting disease control options. This underscores the urgent need for novel therapeutic strategies. Immunotherapy has emerged as a promising approach to address this unmet need, offering the potential for durable remissions and improved patient outcomes. Historically, allogeneic stem cell transplantation has been used for high-risk CLL patients, demonstrating promising survival rates. However, its applicability is limited by high treatment-related mortality and chronic graft-versus-host disease, especially in older and frail patients. Chimeric antigen receptor (CAR) T-cell therapy is gaining attention for its potential in relapsed/refractory CLL. Early clinical trials have shown that CAR T cells can induce durable remissions, with encouraging overall response rates in heavily pretreated patients. Additionally, bispecific antibodies are being explored as immunotherapeutic strategies, showing promising preclinical and early clinical results in targeting CLL cells effectively. One of the major challenges in CLL treatment with T-cell-based therapies is the acquired T-cell dysfunction observed in patients. To overcome these limitations, strategies such as combining targeted agents with cellular immunotherapies, modifying CAR designs, and incorporating immunomodulatory compounds into the manufacturing process are being investigated. These innovative approaches aim to enhance T-cell engagement and improve outcomes for CLL patients, offering hope for more effective and sustainable treatments in the future.

von Willebrand disease (VWD) is a common inherited bleeding disorder caused by von Willebrand factor (VWF) deficiency and is an important cause of heavy menstrual bleeding in young patients. A clinical evaluation using standardized bleeding scores helps determine when screening hemostatic testing is indicated by identifying patients with a moderate or high probability of an inherited bleeding disorder. The diagnosis of VWD is made when VWF levels are under 30 IU/dL or between 30 and 50 IU/dL when there is a positive bleeding history. Activity levels above 100 IU/dL have a high negative predictive value. Multiple factors, including stress from acute bleeding and anemia, pregnancy, and medications, can affect VWF levels, hence testing for VWD is best performed when a person's health is at its baseline level, although this is not always possible in clinical practice. Variation in assay methodologies measuring VWF activity can have a significant impact on the diagnostic evaluation, and it is important for clinicians to be familiar with the limitations of the assay used by their local or reference laboratory. Genetic testing can be useful in establishing the VWD subtype and providing accurate reproductive counseling but is not required to make a diagnosis.

Sickle cell disease (SCD) is a genetic blood disorder in high prevalence in sub-Saharan Africa (SSA) that leads to high morbidity and early mortality. Newborn screening (NBS) with evidence-based interventions saves lives of individuals with SCD. SSA accounts for 75% of the global prevalence of SCD, but it has not been able to implement universal NBS for SCD. This article examines policy framework for NBS in SSA; the methods, processes, barriers, and enablers of NBS; and enrollment in comprehensive care to make available the evidence-based interventions that caregivers need to access in order to save the lives of babies with SCD.

This educational program outlines the importance of evolving clinical care models in response to increased life expectancy and variability in individual patient experiences, particularly in the context of sickle cell disease (SCD). It emphasizes the need for personalized and adaptive care models, in which the patient should play a central role, and the need for collaborative networks of physicians and caregivers, taking into account the multisystemic nature of the disease. The proposal also discusses the role of personalized medicine and technological advances, highlighting the need for a shared medical record; the balance between rare center expertise and widespread dissemination of knowledge; and the challenges in high- and low-income countries. It emphasizes the need to move toward personalized medicine, given the significant interindividual variability in both follow-up and treatment, and the introduction of more appropriate biomarkers and predictive algorithms to aid decision-making. The proposal includes real-world examples of successful adaptation in clinical care models. It concludes with a summary of the importance and benefits of evolving clinical care models and a future outlook on the evolution of clinical care in response to demographic changes. These proposals are intended to provide a comprehensive overview of the current state and future directions of clinical care models for SCD.

Anticoagulation is central to the management of antiphospholipid syndrome (APS), an acquired thrombo-inflammatory disorder characterized by thrombosis (venous, arterial, or microvascular) or pregnancy morbidity, in association with persistent antiphospholipid antibodies (aPL; ie, 1 or more of lupus anticoagulant [LA], anticardiolipin, anti-beta-2- glycoprotein I, IgG, or IgM antibodies). The mainstay of anticoagulation in patients with thrombotic APS is warfarin or an alternative vitamin K antagonist (VKA) and, in certain situations, low-molecular-weight heparin (LMWH) or unfractionated heparin (UFH). Accurate assessment of anticoagulation intensity underpins optimal anticoagulant dosing for thrombus treatment or primary/secondary prevention. In patients with APS on warfarin, the international normalized ratio (INR) may not be representative of anticoagulation intensity due to an interaction between LA and the thromboplastin reagent used in the INR determination. In this review, we summarize the use of warfarin/VKA in patients with APS, along with venous and point-of-care INR monitoring. We also discuss the role and monitoring of LMWH/UFH, including in the anticoagulant refractory setting and during pregnancy.

Common variable immunodeficiency (CVID) is one of the most common groups of human inborn errors of immunity. In addition to infections resulting from insufficient levels of immunoglobulins and antibodies, a significant proportion of patients develop autoimmune cytopenias, especially immune thrombocytopenia, hemolytic anemia, or neutropenia. They may be the initial manifestation of CVID in a patient who has not had significant infections, and similar episodes may recur at intervals over time. Treatment of these hematologic complications includes the use of corticosteroids or other medications, often including rituximab; splenectomy is discouraged. Here we outline the overall occurrence of these blood cytopenias in a cohort of 408 patients, as well as the clinical and genetic associations noted in these individuals.

The overall survival in patients with multiple myeloma has increased over recent decades. This trend is anticipated to further advance with the emergence of T-cell-redirecting therapies, including chimeric antigen receptor T-cell (CAR T) therapy and T-cell-engaging bispecific antibodies. Despite these therapeutic improvements, treatment-related adverse events impede quality of life. This underscores the imperative of optimizing supportive care strategies to maximize treatment outcomes. Such optimization is crucial not only for patient well-being but also for treatment adherence, which may translate into long-term disease control. We here describe a) how to prevent bone disease, b) a risk-adapted thrombosis prophylaxis approach, c) the management of on-target, off-tumor toxicity of G-protein-coupled receptor class C group 5 member D-targeting T-cell-redirecting therapies, and d) infectious prophylaxis, with a focus on infections during T-cell-redirecting therapies.

Antibodies to platelet factor 4 (PF4) have been primarily linked to classical heparin-induced thrombocytopenia (cHIT). However, during the rollout of the COVID-19 vaccine program a new condition, vaccine-induced thrombocytopenia and thrombosis (VITT), was identified, related to adenoviral-based COVID-19 vaccines. The differences between these 2 conditions, both clinically and in laboratory testing, set the scene for the development of a new rapid anti-PF4 assay that is not linked with heparin (as relevant for cHIT). Concurrently, there has been a reassessment of those cases described as autoimmune HIT. Such scenarios do not follow cHIT, but there is now a clearer differentiation of heparin-dependent and heparin-independent anti-PF4 conditions. The importance of this distinction is the identification of heparin-independent anti-PF4 antibodies in a new subgroup termed VITT-like disorder. Cases appear to be rare, precipitated by infection and in a proportion of cases, orthopaedic surgery, but are associated with high mortality and the need for a different treatment pathway, which includes immunomodulation therapy.

End-of-life (EOL) care is a critical part of sickle cell disease (SCD) management. However, barriers to high-quality EOL care remain, including (1) disease-related barriers (prior opioid exposure, risk of vaso-occlusive crises, chronic conditions with conflicting needs, and limitations of receiving disease-directed therapy on hospice); (2) communication-related barriers (challenges of identifying and responding to religious and spiritual concerns, limited health literacy, and previous health care system experience); (3) systemic issues (social determinants of health, structural racism, and mistrust of the medical system). However, palliative care and interdisciplinary collaboration can overcome many of these barriers. In addition, we can improve EOL care by accounting for opioid exposures, multimodal symptom management, and exploring (1) who people want involved in decision-making, (2) the role of religion and spirituality in decision-making, and (3) previous experiences with EOL. Systemic barriers can be addressed through the social determinants of health screening, minimizing financial burdens of care, and building longitudinal relationships with people with SCD. This requires the continued education of SCD providers about primary palliative care and palliative care providers about SCD. With such strategies, high-quality EOL care is possible for this vulnerable population.