The Mortality of Adults With Sickle Cell Disease at a Comprehensive Sickle Cell Center.

Introduction: Sickle cell disease (SCD) is the most common hemoglobinopathy in North America. The life expectancy of SCD has extended into adulthood with screenings, preventative care, and hydroxyurea. However, comorbidities arise as adults with SCD age, leading to early mortality.

The impact of sickle cell disease and its treatment on ovarian reserve in reproductive-aged Black women.

We compared serum anti-Mullerian hormone (AMH) levels in women with sickle cell disease (SCD) (n = 152) to those of Black comparison women (n = 128) between the ages of 20 and 45 years and evaluated the impact of hydroxyurea (HU) and iron overload on ovarian reserve in those with SCD. SCD treatment was abstracted from medical records. Linear regression models were fit to examine the relationship between log(AMH) and SCD, adjusting for age.

Post-transfusion biotin-labeled red blood cell survival studies in pediatric sickle cell disease with antibodies of uncertain significance.

Background: Red blood cell (RBC) antibodies are common in multiply transfused patients with sickle cell disease (SCD). Unlike RBC alloantibodies, the potential of autoantibodies to cause post-transfusion hemolysis may be uncertain. Biotin-labeling provides a direct measurement of red cell survival (RCS) over time, thus can be used to assess the clinical significance of RBC antibodies.

Results of clinical effectiveness of conventional versus Mirasol-treated Apheresis Platelets in Patients with Hypoproliferative Thrombocytopenia (MiPLATE) trial.

Background: The Mirasol® Pathogen Reduction Technology System was developed to reduce transfusion-transmitted diseases in platelet (PLT) products.

Study Design And Methods: MiPLATE trial was a prospective, multicenter, controlled, randomized, non-inferiority (NI) study of the clinical effectiveness of conventional versus Mirasol-treated Apheresis PLTs in participants with hypoproliferative thrombocytopenia. The novel primary endpoint was days of ≥Grade 2 bleeding with an NI margin of 1.

RH genotypes and red cell alloimmunization rates in chronically transfused patients with sickle cell disease: A multisite study in the USA.

Background: Red cell alloimmunization remains a challenge for individuals with sickle cell disease (SCD) and contributes to increased risk of hemolytic transfusion reactions and associated comorbidities. Despite prophylactic serological matching for ABO, Rh, and K, red cell alloimmunization persists, in part, due to a high frequency of variant RH alleles in patients with SCD and Black blood donors.

Study Design And Methods: We compared RH genotypes and rates of alloimmunization in 342 pediatric and young adult patients with SCD on chronic transfusion therapy exposed to >90,000 red cell units at five sites across the USA.

Optimizing RBC Transfusion Outcomes in Patients with Acute Illness and in the Chronic Transfusion Setting.

Red blood cell (RBC) transfusion is a common clinical intervention used to treat patients with acute and chronic anemia. The decision to transfuse RBCs in the acute setting is based on several factors but current clinical studies informing optimal RBC transfusion decision making (TDM) are largely based upon hemoglobin (Hb) level. In contrast to transfusion in acute settings, chronic RBC transfusion therapy has several different purposes and is associated with distinct transfusion risks such as iron overload and RBC alloimmunization.

Prophylactic Platelet Transfusion: Is There Evidence of Benefit, Harm, or No Effect?

The optimal use of prophylactic platelet transfusion remains uncertain in a number of clinical scenarios. Platelet count thresholds have been established in patients with hematologic malignancies, yet thresholds backed by scientific data are limited or do not exist for many patient populations. Clinical scenarios involving transfusion thresholds for thrombocytopenic patients with critical illness, need for surgery or invasive procedures, or those involving specials populations like children and neonates, lack clear evidence for discerning favorable outcomes without undue risk related to platelet transfusion.

Novel approaches to measure transfusion effectiveness.

Purpose Of Review: This review encompasses different considerations of transfusion effectiveness based upon clinical scenario and transfusion indication. Tissue oxygenation, cerebral metabolic oxygen use, and red blood cell (RBC) survival are important elements of transfusion effectiveness in individuals with acute and chronic transfusion requirements.

Recent Findings: Noninvasive measures of tissue and cerebral oxygen extraction include near-infrared spectroscopy (NIRS) and specialized MRI sequences.

Antibody-mediated antigen loss switches augmented immunity to antibody-mediated immunosuppression.

Antibodies against fetal red blood cell (RBC) antigens can cause hemolytic disease of the fetus and newborn (HDFN). Reductions in HDFN due to anti-RhD antibodies have been achieved through use of Rh immune globulin (RhIg), a polyclonal antibody preparation that causes antibody-mediated immunosuppression (AMIS), thereby preventing maternal immune responses against fetal RBCs. Despite the success of RhIg, it is only effective against 1 alloantigen.

Enhanced IgG immune response to COVID-19 vaccination in patients with sickle cell disease.

Patients with sickle cell disease (SCD) are considered to be immunocompromised, yet data on the antibody response to SARS-CoV-2 vaccination in SCD is limited. We investigated anti-SARS-CoV-2 IgG titres and overall neutralizing activity in 201 adults with SCD and demographically matched non-SCD controls. Unexpectedly, patients with SCD generate a more robust and durable COVID-19 vaccine IgG response compared to matched controls, though the neutralizing activity remained similar across both cohorts.

Massively parallel base editing to map variant effects in human hematopoiesis.

Systematic evaluation of the impact of genetic variants is critical for the study and treatment of human physiology and disease. While specific mutations can be introduced by genome engineering, we still lack scalable approaches that are applicable to the important setting of primary cells, such as blood and immune cells. Here, we describe the development of massively parallel base-editing screens in human hematopoietic stem and progenitor cells.

Requests for Directed Blood Donations.

This Ethics Rounds presents a request for directed blood donation. Two parents feel helpless in the setting of their daughter's new leukemia diagnosis and want to directly help their child by providing their own blood for a transfusion. They express hesitancy about trusting the safety of a stranger's blood.

Storage differentially impacts alloimmunization to distinct red cell antigens following transfusion in mice.

Introduction: The impact of blood storage on red blood cell (RBC) alloimmunization remains controversial, with some studies suggesting enhancement of RBC-induced alloantibody production and others failing to observe any impact of storage on alloantibody formation. Since evaluation of storage on RBC alloimmunization in patients has examined antibody formation against a broad range of alloantigens, it remains possible that different clinical outcomes reflect a variable impact of storage on alloimmunization to specific antigens.

Methods: RBCs expressing two distinct model antigens, HEL-OVA-Duffy (HOD) and KEL, separately or together (HOD × KEL), were stored for 0, 8, or 14 days, followed by detection of antigen levels prior to transfusion.

Characteristics and outcomes of pediatric oncology patients at risk for guardians declining transfusion of blood components.

Background: Transfusion of blood products is a necessary part of successful delivery of myelosuppressive regimens in pediatric cancer. There is a paucity of literature characterizing outcomes or management of pediatric patients with cancer when transfusion is declined.

Aims: The objective of this paper is to describe the clinical characteristics, care, and outcomes of patients with cancer at risk for declining transfusion.

Clodronate inhibits alloimmunization against distinct red blood cell alloantigens in mice.

Background: Alloimmunization can be a significant barrier to red blood cell (RBC) transfusion. While alloantigen matching protocols hold promise in reducing alloantibody formation, transfusion-dependent patients can still experience RBC alloimmunization and associated complications even when matching protocols are employed. As a result, complementary strategies capable of actively preventing alloantibody formation following alloantigen exposure are warranted.

Procedural adverse events in pediatric patients with sickle cell disease undergoing chronic automated red cell exchange.

Background: Chronic automated red cell exchange (RCE) is increasingly employed for sickle cell disease (SCD). There is a paucity of data on the incidence of RCE adverse events (AEs) and potential patient and procedural risk factors for AEs.

Methods: A retrospective review of pediatric SCD patients receiving chronic RCE over 3 years was performed to determine the frequency of AEs and identify procedural and patient AE risk factors.

Glucose-6-phosphate dehydrogenase deficiency is more prevalent in Duffy-null red blood cell transfusion in sickle cell disease.

Background: Resistance to malaria infection may be conferred by erythrocyte genetic variations including glucose-6-phosphate dehydrogenase (G6PD) deficiency and lack of Duffy antigens. In red blood cell (RBC) transfusion, G6PD deficiency may shorten transfusion survival. Because Duffy-null units are commonly transfused in sickle cell disease (SCD) due to antigen matching protocols, we examined whether Duffy-null donor RBC units have a higher prevalence of G6PD deficiency.