Suchitra Pandey, MD

Abstract

The clinical significance of serologic reactivity of unidentified specificity (SRUS) in pregnancy is not clear based on available literature. The aim of this study is to determine if SRUS is associated with hemolytic disease of the fetus and newborn (HDFN).Retrospective data were collected from eight institutions over an 11-year study period (2010-2020), when available (5/8 sites). The outcome of the pregnancies with SRUS-no, mild, moderate, or severe HDFN-was determined.SRUS was demonstrated in 589 pregnancies. After excluding those with incomplete data, a total of 284 pregnancies were included in the primary HDFN outcome analysis. SRUS was detected in 124 (44%) pregnancies in isolation, and none were affected by HDFN. Of 41 pregnancies with SRUS and ABO incompatibility, 37 (90%) were unaffected, and 4 (10%) were associated with mild HDFN. Of 98 pregnancies with SRUS and concurrent identifiable antibodyreactivity(s), 80 (81%) were unaffected, and 19 (19%) were associated with mild to severe HDFN. There was 1 case of mild HDFN and 1 case of severe HDFN in the 21 pregnancies with SRUS, ABO incompatibility, and concurrent identifiable antibodyreactivity(s), and 19 (90%) were unaffected by HDFN. Among all patients with repeat testing, newly identified alloantibodies or other antibodies were identified in 63 of 212 (30%) patients. Although most were not clinically significant, on occasion SRUS preceded clinically significant antibody(s) associated with HDFN (3%, 5/188).The antenatal serologic finding of SRUS in isolation is not associated with HDFN but may precede clinically significant antibodies.

View details for DOI 10.1111/trf.17276

View details for PubMedID 36815517

Abstract

Bacterial contamination in platelets remain a major public health concern, which prompted the US Food and Drug Administration guidance for bacterial contamination mitigation. Pathogen reduction technology (PRT) is one mitigation strategy that has shown success in Europe over the last decade. Therefore, our center sought to transition from a dual system of bacterial culturing (BacT) and PRT to full PRT.A 1month pilot study was conducted to simulate 100% PRT conditions. Our center also collected baseline data on key platelet production metrics in the 4months prior to 100% PRT and compared it to the 4months post-implementation.The pilot study showed no statistical differences in split rate, proportion of low-yield products, or proportion of single, double, and triple collections. The only observed difference was an 11min increase in the average duration of double collections. Our baseline versus post-implementation monitoring showed no difference in split rate, discard rate, percentage of low-yield units, and average yield of low yield units. Statistical differences were detected in the proportion of single, double, and triple collections, as well as the average yield of full dose products. Roughly 20% of our inventory consisted of low-yield products.With suitable mitigation strategies, transitioning to a full PRT inventory may result in higher net margins while not adversely affecting overall platelet production. A pilot study is a good way to project potential effects of switching from a dual BacT and PRT inventory to full PRT, and can be adopted by other centers aiming to make the transition.

View details for DOI 10.1111/trf.17081

View details for PubMedID 36052676

View details for Web of Science ID 000854334900392

Abstract

Pathogen reduction technology (PRT) effectively mitigates bacterial contamination in platelets but is more likely to produce low yield units. Although low dose transfusion using conventional platelets has not been associated with increased bleeding, these findings have not been reproduced with PRT-treated platelets.Platelet transfusions in a tertiary adult hospital were retrospectively reviewed. Comparisons were made between PRT-treated regular (PRT-PR) and low (PRT-PL) yield platelets. Outcomes examined included the number of platelets and RBCs transfused, transfusion-free interval, and corrected count increment (CCI). Subgroup analyses were also performed on hematology-oncology inpatients and outpatients, as well as non-hematology-oncology patients.Platelet utilization per patient remained mostly unchanged (mean 2.9-4.3units per patient per month) even when the frequency of PRT-PL transfusion increased. Among 1402 patients examined, the number of platelets and RBCs transfused was not significantly different between patients first transfused with PRT-PR versus PRT-PL (mean number of platelet units=2.8 vs. 3.1, p=0.38; mean number of RBC units=4.8 vs. 4.3, p=0.93). Among 10,257 platelet transfusions examined, the transfusion-free interval (hazard ratio=1.05, 95% confidence interval 1.00-1.10) and CCI (10.2 vs. 11.0, p=0.70) were comparable between PRT-PR and PRT-PL units. Similar findings were observed in all subgroups, except for shortened transfusion-free intervals among hematology-oncology inpatients.PRT-PR and PRT-PL units may be used in an equivalent manner to maintain an adequate platelet inventory, since there was only a minor difference in time between transfusions.

View details for DOI 10.1111/trf.17043

View details for PubMedID 35924914

Abstract

BACKGROUND: Blood centers have a dual mission to protect donors and patients; donor safety is paramount to maintaining an adequate blood supply. Elucidating donor factors associated with adverse reactions (AR) is critical to this mission.STUDY DESIGN/METHODS: A retrospective cohort analysis of whole blood donors from 2003 to 2020 was conducted at a single blood center in northern California. Adjusted odds ratios (AORs) with 95% CIs for ARs were estimated via multivariable logistic regression on demographics, donation history, and physical examination data. Where appropriate, Wilcoxon-Rank Sum and chi-squared tests were used to determine significance.RESULTS: First-time blood donors (FTD) exhibited a higher AR rate than repeat donors (4.4% vs. 1.9% p<.0001). When compared with FTDs without AR, FTDs with ARs (FT-AR) were less likely to return (30.0% vs. 47.3%, p<.0001), and, of those who returned, had a higher rate of reaction 20.2% versus 2.8% (p<.001). Factors found to be associated with FT-AR (younger age, increased heart rate, and higher diastolic blood pressure) still correlated positively with AR on return donation, but to a lower degree. FTD who potentially witnessed an AR had a lower return rate (44.6% vs. 47.3%, p=<.001) and donated fewer units (2.38 vs. 3.37, p<.001) when compared to FTD who did not witness an AR.CONCLUSION: The AR on FTD increases the AR likelihood of return donation. Longitudinal analysis shows that a time-based deferral policy targeted at FT-AR young donors can reduce the number of ARs while not dramatically impacting the blood supply.

View details for DOI 10.1111/trf.16893

View details for PubMedID 35510783

Abstract

BACKGROUND: Several risk mitigation steps have improved the safety of platelets in regard to bacterial contamination, but this continues to be a concern today. A Food and Drug Administration (FDA) Guidance issued in December 2018 aims to further limit this risk. The guidance offers multiple pathways for compliance, and hospital blood banks will have to collaborate with blood donor centers to assess various factors before deciding which method is most appropriate for them.METHODS AND MATERIALS: Our institution considered several factors before moving forward with pathogen reduction technology. This included an assessment of platelet shelf-life, bacterial testing requirements, the efficacy of low-yield platelets, and managing a mixed platelet inventory. The decision to transition to pathogen-reduced platelets was associated with complex collection and processing limitations that resulted in either an increase in platelets that were over-concentrated or products with a low platelet yield.RESULTS: Through trials of various collection settings with unique target volumes and target platelet yields, our blood donor center was able to optimize the production. At the hospital end, this transition required a thorough review of low-yield platelet products and their clinical efficacy. Additionally, this implementation necessitated collaboration with clinical colleagues, comprehensive education, and training.CONCLUSIONS: Pathogen-reduced platelets would be the most efficient way for our institution to be compliant. This summary may serve as a roadmap for other institutions that are considering which FDA prescribed method to use and provide support for those that have decided on pathogen reduction technology but need to optimize their collections to best utilize low-yield products.

View details for DOI 10.1111/trf.16744

View details for PubMedID 34796968

View details for Web of Science ID 000697116900078

Abstract

The reported incidence of adverse reactions following Coronavirus disease 2019 (COVID-19) convalescent plasma (CCP) transfusion has generally been lower than expected based on the incidence of transfusion reactions that have been observed in studies of conventional plasma transfusion. This raises the concern for under-reporting of adverse events in studies of CCP that rely on passive surveillance strategies.Our institution implemented a protocol to actively identify possible adverse reactions to CCP transfusion. In addition, we retrospectively reviewed the charts of inpatients who received CCP at Stanford Hospital between May 13, 2020 and January 31, 2021. We determined the incidence of adverse events following CCP transfusion.A total of 49 patients received CCP. Seven patients (14%) had an increased supplemental oxygen requirement within 4h of transfusion completion, including one patient who was intubated during the transfusion. An additional 11 patients (total of 18, 37%) had increased oxygen requirements within 24h of transfusion, including 3 patients who were intubated. Six patients (12%) fulfilled criteria for transfusion-associated circulatory overload (TACO).Using an active surveillance strategy, we commonly observed adverse events following the transfusion of CCP to hospitalized patients. It was not possible to definitively determine whether or not these adverse events are related to CCP transfusion. TACO was likely over-diagnosed given overlap with the manifestations of COVID-19. Nevertheless, these results suggest that the potential adverse effects of CCP transfusion may be underestimated by reports from passive surveillance studies.

View details for DOI 10.1111/trf.16711

View details for PubMedID 34677830

Abstract

Background: Transfusion of COVID-19 convalescent plasma (CCP) containing high titers of anti-SARS-CoV-2 antibodies serves as therapy for COVID-19 patients. Transfusions early during disease course was found to be beneficial. Lessons from the SARS-CoV-2 pandemic could inform early responses to future pandemics and may continue to be relevant in lower resource settings. We sought to identify factors correlating to high antibody titers in convalescent plasma donors and understand the magnitude and pharmacokinetic time course of both transfused antibody titers and the endogenous antibody titers in transfused recipients.Methods: Plasma samples were collected up to 174 days after convalescence from 93 CCP donors with mild disease, and from 16 COVID-19 patients before and after transfusion. Using ELISA, anti-SARS-CoV-2 Spike RBD, S1, and N-protein antibodies, as well as capacity of antibodies to block ACE2 from binding to RBD was measured in an in vitro assay. As an estimate for viral load, viral RNA and N-protein plasma levels were assessed in COVID-19 patients.Results: Anti-SARS-CoV-2 antibody levels and RBD-ACE2 blocking capacity were highest within the first 60 days after symptom resolution and markedly decreased after 120 days. Highest antibody titers were found in CCP donors that experienced fever. Effect of transfused CCP was detectable in COVID-19 patients who received high-titer CCP and had not seroconverted at the time of transfusion. Decrease in viral RNA was seen in two of these patients.Conclusion: Our results suggest that high titer CCP should be collected within 60 days after recovery from donors with past fever. The much lower titers conferred by transfused antibodies compared to endogenous production in the patient underscore the importance of providing CCP prior to endogenous seroconversion.

View details for DOI 10.3389/fimmu.2021.739037

View details for PubMedID 34594341

Abstract

The ongoing coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has elicited a surge in demand for serological testing to identify previously infected individuals. In particular, antibody testing is crucial in identifying COVID-19 convalescent plasma (CCP), which has been approved by the Food and Drug Administration (FDA) under the Emergency Use Authorization (EUA) for use as passive immune therapy for hospitalized patients infected with COVID-19. Currently, high-titer CCP can be qualified by Ortho's Vitros COVID-19 IgG antibody test (VG).To explore the use of an efficient testing method to identify high-titer CCP for use in treating COVID-19 infected patients and track COVID-19 positivity over time.We evaluated an ELISA-based method that detects antibodies specific to the SARSCoV-2 receptor binding domain (RBD) with individual and pooled plasma samples and compared its performance against VG. Using the pooled RBD-ELISA (P-RE) method, we also screened over 10,000 longitudinal healthy blood donor samples to assess seroprevalence.P-RE demonstrates 100% sensitivity in detecting FDA-defined high-titer samples when compared to VG. Overall sensitivity of P-RE when compared to VG and our individual sample RBD-ELISA (I-RE) were 83% and 56%, respectively. When screening 10,218 healthy blood donor samples by P-RE, we found the seroprevalence correlated with the local infection rates with a correlation coefficient of 0.21 (P< .001).Pooling plasma samples can be used to efficiently screen large populations for individuals with high-titer anti-RBD antibodies, important for CCP identification.

View details for DOI 10.5858/arpa.2021-0215-SA

View details for PubMedID 34101801

Abstract

We investigated feasibility and accuracy of an interferon-gamma release assay (IGRA) for detection of T cell responses to SARS-CoV-2. Whole blood IGRA accurately distinguished between convalescents and uninfected healthy blood donors with a predominantly CD4+ T cell response. SARS-CoV-2 IGRA may serve as a useful diagnostic tool in managing the COVID-19 pandemic.

View details for DOI 10.1093/cid/ciaa1537

View details for PubMedID 33035306

View details for Web of Science ID 000502826600211

View details for Web of Science ID 000368020105133