In the mid-20th century, Hemolytic Disease of the Fetus and Newborn, caused by maternal alloimmunization to the Rh(D) blood group antigen expressed by fetal red blood cells (i.e., "Rh disease"), was ...a major cause of fetal and neonatal morbidity and mortality. However, with the regulatory approval, in 1968, of IgG anti-Rh(D) immunoprophylaxis to prevent maternal sensitization, the prospect of eradicating Rh disease was at hand. Indeed, the combination of antenatal and post-partum immunoprophylaxis is ~99% effective at preventing maternal sensitization to Rh(D). To investigate global compliance with this therapeutic intervention, we used an epidemiological approach to estimate the current annual number of pregnancies worldwide involving an Rh(D)-negative mother and an Rh(D)-positive fetus. The annual number of doses of anti-Rh(D) IgG required for successful immunoprophylaxis for these cases was then calculated and compared with an estimate of the annual number of doses of anti-Rh(D) produced and provided worldwide. Our results suggest that ~50% of the women around the world who require this type of immunoprophylaxis do not receive it, presumably due to a lack of awareness, availability, and/or affordability, thereby putting hundreds of thousands of fetuses and neonates at risk for Rh disease each year. The global failure to provide this generally acknowledged standard-of-care to prevent Rh disease, even 50 years after its availability, contributes to an enormous, continuing burden of fetal and neonatal disease and provides a critically important challenge to the international health care system.
Although convalescent plasma has been widely used to treat severe coronavirus disease 2019 (COVID-19), data from randomized controlled trials that support its efficacy are limited.
We conducted a ...randomized, double-blind, placebo-controlled trial among adults hospitalized with severe and critical COVID-19 at five sites in New York City (USA) and Rio de Janeiro (Brazil). Patients were randomized in a 2:1 ratio to receive a single transfusion of either convalescent plasma or placebo (normal control plasma). The primary outcome was clinical status at 28 days following randomization, measured using an ordinal scale and analyzed using a proportional odds model in the intention-to-treat population.
Of 223 participants enrolled, 150 were randomized to receive convalescent plasma and 73 to normal control plasma. At 28 days, no significant improvement in clinical status was observed in participants randomized to convalescent plasma (OR 1.50, 95% confidence interval (CI) 0.83-2.68, p=0.180). However, 28-day mortality was significantly lower in participants randomized to convalescent plasma versus control plasma (19/150 12.6% versus 18/73 24.6%, OR 0.44, 95% CI 0.22-0.91, p=0.034). The median titer of anti-SARS-CoV-2 neutralizing antibody in infused convalescent plasma units was 1:160 (IQR 1:80-1:320). In a subset of nasopharyngeal swab samples from Brazil that underwent genomic sequencing, no evidence of neutralization-escape mutants was detected.
In adults hospitalized with severe COVID-19, use of convalescent plasma was not associated with significant improvement in clinical status at day 28. However, a significant improvement in mortality was observed, which warrants further evaluation.
ClinicalTrials.gov, NCT04359810FUNDING. Amazon Foundation. Skoll Foundation.
Transfusions of RBCs stored for longer durations are associated with adverse effects in hospitalized patients. We prospectively studied 14 healthy human volunteers who donated standard leuko-reduced, ...double RBC units. One unit was autologously transfused “fresh” (3-7 days of storage), and the other “older” unit was transfused after 40 to 42 days of storage. Of the routine laboratory parameters measured at defined times surrounding transfusion, significant differences between fresh and older transfusions were only observed in iron parameters and markers of extravascular hemolysis. Compared with fresh RBCs, mean serum total bilirubin increased by 0.55 mg/dL at 4 hours after transfusion of older RBCs (P = .0003), without significant changes in haptoglobin or lactate dehydrogenase. In addition, only after the older transfusion, transferrin saturation increased progressively over 4 hours to a mean of 64%, and non–transferrin-bound iron appeared, reaching a mean of 3.2μM. The increased concentrations of non–transferrin-bound iron correlated with enhanced proliferation in vitro of a pathogenic strain of Escherichia coli (r = 0.94, P = .002). Therefore, circulating non–transferrin-bound iron derived from rapid clearance of transfused, older stored RBCs may enhance transfusion-related complications, such as infection. The trial was registered with www.clinicaltrials.gov as #NCT01319552.
To describe validation and performance of epoc, a blood gas analysis point-of-care system, in a live clinical setting.
Data were collected for 156 epoc systems over 12 months. Preimplementation ...precision and correlation studies and postimplementation quality assurance data were collected, including test card, reader, and personal data assistant (PDA) failure rates.
The coefficient of variation was clinically acceptable for all analytes. Correlation studies yielded an R(2) from 0.901 (for sodium) to 0.994 (for potassium) with the Nova analyzer and from 0.961 (sodium) to 0.991 (glucose) with the i-STAT. Average test card failure rate was 13%. Of the PDA/reader units, 55% needed repair within 1 year.
The analytical performance showed high precision and good correlation with the Nova and i-STAT platforms. Test card and instrument failure rates were higher than that of the i-STAT system.
Abstract
Objectives
The aim of this study is to evaluate the efficacy and safety of human anti-SARS-CoV-2 convalescent plasma in hospitalized adults with severe SARS-CoV-2 infection.
Trial Design
...This is a prospective, single-center, phase 2, randomized, controlled trial that is blinded to participants and clinical outcome assessor.
Participants
Eligible participants include adults (≥ 18 years) with evidence of SARS-CoV-2 infection by PCR test of nasopharyngeal or oropharyngeal swab within 14 days of randomization, evidence of infiltrates on chest radiography, peripheral capillary oxygen saturation (SpO2) ≤ 94% on room air, and/or need for supplemental oxygen, non-invasive mechanical ventilation, or invasive mechanical ventilation, who are willing and able to provide written informed consent prior to performing study procedures or who have a legally authorized representative available to do so. Exclusion criteria include participation in another clinical trial of anti-viral agent(s)* for coronavirus disease-2019 (COVID-19), receipt of any anti-viral agent(s)* with possible activity against SARS-CoV-2 <24 hours prior to plasma infusion, mechanical ventilation (including extracorporeal membrane oxygenation ECMO) for ≥ 5 days, severe multi-organ failure, history of allergic reactions to transfused blood products per NHSN/CDC criteria, known IgA deficiency, and pregnancy. Included participants will be hospitalized at the time of randomization and plasma infusion.
*Use of remdesivir as treatment for COVID-19 is permitted.
The study will be undertaken at Columbia University Irving Medical Center in New York, USA.
Intervention and comparator
The investigational treatment is anti-SARS-CoV-2 human convalescent plasma. To procure the investigational treatment, volunteers who recovered from COVID-19 will undergo testing to confirm the presence of anti-SARS-CoV-2 antibody to the spike trimer at a 1:400 dilution. Donors will also be screened for transfusion-transmitted infections (e.g. HIV, HBV, HCV, WNV, HTLV-I/II, T.
cruzi,
ZIKV). If donors have experienced COVID-19 symptoms within 28 days, they will be screened with a nasopharyngeal swab to confirm they are SARS-CoV-2 PCR-negative. Plasma will be collected using standard apheresis technology by the New York Blood Center. Study participants will be randomized in a 2:1 ratio to receive one unit (200 – 250 mL) of anti-SARS-CoV-2 plasma versus one unit (200 – 250 mL) of the earliest available control plasma. The control plasma cannot be tested for presence of anti-SARS-CoV-2 antibody prior to the transfusion, but will be tested for anti- SARS-CoV-2 antibody after the transfusion to allow for a retrospective per-protocol analysis.
Main outcomes
The primary endpoint is time to clinical improvement. This is defined as time from randomization to either discharge from the hospital or improvement by one point on the following seven-point ordinal scale, whichever occurs first.
1. Not hospitalized with resumption of normal activities
2. Not hospitalized, but unable to resume normal activities
3. Hospitalized, not requiring supplemental oxygen
4. Hospitalized, requiring supplemental oxygen
5. Hospitalized, requiring high-flow oxygen therapy or non-invasive mechanical ventilation
6. Hospitalized, requiring ECMO, invasive mechanical ventilation, or both
7. Death
This scale, designed to assess clinical status over time, was based on that recommended by the World Health Organization for use in determining efficacy end-points in clinical trials in hospitalized patients with COVID-19. A recent clinical trial evaluating the efficacy and safety of lopinavir- ritonavir for patients hospitalized with severe COVID-19 used a similar ordinal scale, as have recent clinical trials of novel therapeutics for severe influenza, including a post-hoc analysis of a trial evaluating immune plasma.
The primary safety endpoints are cumulative incidence of grade 3 and 4 adverse events and cumulative incidence of serious adverse events during the study period.
Randomization
Study participants will be randomized in a 2:1 ratio to receive anti-SARS-CoV-2 plasma versus control plasma using a web-based randomization platform. Treatment assignments will be generated using randomly permuted blocks of different sizes to minimize imbalance while also minimizing predictability.
Blinding (masking)
The study participants and the clinicians who will evaluate post-treatment outcomes will be blinded to group assignment. The blood bank and the clinical research team will not be blinded to group assignment.
Numbers to be randomized (sample size)
We plan to enroll 129 participants, with 86 in the anti-SARS-CoV-2 arm, and 43 in the control arm. Among the participants, we expect ~70% or n = 72 will achieve clinical improvement. This will yield an 80% power for a one-sided Wald test at 0.15 level of significance under the proportional hazards model with a hazard ratio of 1.5.
Trial Status
Protocol AAAS9924, Version 17APR2020, 4/17/2020
Start of recruitment: April 20, 2020
Recruitment is ongoing.
Trial registration
ClinicalTrials.gov: NCT04359810
Date of trial registration: April 24, 2020
Retrospectively registered
Full protocol
The full protocol is attached as an additional file, accessible from the Trials website (Additional file 1). In the interest of expediting dissemination of this material, the familiar formatting has been eliminated; this Letter serves as a summary of the key elements of the full protocol.
Primary immune thrombocytopenia (ITP) is an autoimmune disease that affects children and adults. WinRho SDF is a D immune globulin product that is Food and Drug Administration approved for the ...treatment of ITP in D+ pediatric and adult patients. WinRho is a plasma‐derived biologic product dispensed from blood banks. Transfusion medicine physicians serve as a resource to health care providers regarding blood component and derivative usage and, as such, should be familiar with the use of WinRho for ITP, including the dosage, administration, and contraindications. This report details the transfusion medicine consultation practice and guidelines at a tertiary care academic medical center for the usage of WinRho SDF in patients with ITP.
Objectives: To evaluate the impact that an electronic ordering system has on the rate of rejection of blood type and screen testing samples and the impact on the number of ABO blood-type ...discrepancies over a 4-year period.
Methods: An electronic ordering system was implemented in May 2011. Rejection rates along with reasons for rejection were tracked between January 2010 and December 2013.
Results: A total of 40,104 blood samples were received during this period, of which 706 (1.8%) were rejected for the following reasons: 382 (54.0%) unsigned samples, 235 (33.0%) mislabeled samples, 57 (8.0%) unsigned requisitions, 18 (2.5%) incorrect tubes, and 14 (1.9%) ABO discrepancies. Of the samples, 2.5% were rejected in the year prior to implementing the electronic ordering system compared with 1.2% in the year following implementation (P < .0001).
Conclusions: Our data demonstrate that implementation of an electronic ordering system significantly decreased the rate of blood sample rejection.
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