Faculty Bibliography

BACKGROUND:New York City (NYC) bore the greatest burden of COVID-19 in the United States early in the pandemic. In this case series, we describe characteristics and outcomes of racially and ethnically diverse patients tested for and hospitalized with COVID-19 in New York City's public hospital system. METHODS:We reviewed the electronic health records of all patients who received a SARS-CoV-2 test between March 5 and April 9, 2020, with follow up through April 16, 2020. The primary outcomes were a positive test, hospitalization, and death. Demographics and comorbidities were also assessed. RESULTS:22254 patients were tested for SARS-CoV-2. 13442 (61%) were positive; among those, the median age was 52.7 years (interquartile range [IQR] 39.5-64.5), 7481 (56%) were male, 3518 (26%) were Black, and 4593 (34%) were Hispanic. Nearly half (4669, 46%) had at least one chronic disease (27% diabetes, 30% hypertension, and 21% cardiovascular disease). Of those testing positive, 6248 (46%) were hospitalized. The median age was 61.6 years (IQR 49.7-72.9); 3851 (62%) were male, 1950 (31%) were Black, and 2102 (34%) were Hispanic. More than half (3269, 53%) had at least one chronic disease (33% diabetes, 37% hypertension, 24% cardiovascular disease, 11% chronic kidney disease). 1724 (28%) hospitalized patients died. The median age was 71.0 years (IQR 60.0, 80.9); 1087 (63%) were male, 506 (29%) were Black, and 528 (31%) were Hispanic. Chronic diseases were common (35% diabetes, 37% hypertension, 28% cardiovascular disease, 15% chronic kidney disease). Male sex, older age, diabetes, cardiac history, and chronic kidney disease were significantly associated with testing positive, hospitalization, and death. Racial/ethnic disparities were observed across all outcomes. CONCLUSIONS AND RELEVANCE/CONCLUSIONS:This is the largest and most racially/ethnically diverse case series of patients tested and hospitalized for COVID-19 in New York City to date. Our findings highlight disparities in outcomes that can inform prevention and testing recommendations.

Background/Case Studies: The COVID-19 pandemic has altered almost everything. The first case of COVID-19 was confirmed in New York (NY) on 3/1/20. As of 6/30, there were >212,000 confirmed cases, >50,000 patients hospitalized, and >18000 confirmed and >4600 probable deaths in NYC. The governor declared a state of emergency on 3/7. Social distancing and mandatory quarantines implemented on 3/12 have resulted in dramatic reductions in the blood supply. To preserve the blood supply and available hospital beds, all elective surgery was canceled effective 3/16. I sought to assess the usage of blood products in our hospitalized confirmed and suspected COVID-19 patients. Study Design/Methods: After obtaining IRB approval, an Epic report to identify all patients, who had a positive SARS-CoV-2 PCR test result and were transfused from 3/1/20 to 6/30/20, was created to identify how many COVID-19 patients had been transfused and the number and type of blood products they received. Results/Findings: From 3/1-6/30, 993 patients tested positively for COVID-19. 1669 confirmed and suspected patients had been admitted to the hospital, 1361 had been discharged (excluding deaths), and 253 had died. Of the admitted confirmed COVID-19 patients, 121 patients were transfused at least one blood product. A massive transfusion protocol was activated on 3 patients. A total of 519 RBCs, 78 SDPs, 40 plasmas, and 15 pooled cryoprecipitate (CRYO) units were transfused to COVID-19 patients. Table 1 depicts the mean number, range, and percent of transfusions by product type administered to COVID-19 patients.
Conclusion(s): 121 COVID-19 patients were transfused a total of 652 blood products. 21.8% of all blood products during the period were transfused to COVID-19 patients. COVID-19 patients received 23.6% of RBCs, 16.8% of plasmas, 24.2% of SDPs, and 21.4% of pooled CRYO transfused in the hospital. Although their needs were only a portion of the hospital's overall blood usage, maintaining an ample blood inventory is required to support the care of COVID-19 patients especially those requiring ECMO and long-term mechanical ventilation

BACKGROUND:A small body of literature assessing the efficacy and safety of pathogen reduced (PR) plasma has been published. STUDY DESIGN AND METHODS/METHODS:An AABB committee systematically reviewed the literature and graded the clinical trial evidence with the assistance of a GRADE expert. RESULTS:Most studies identified were low quality and had a small sample size; in addition, efficacy and safety were monitored in many different ways making it difficult to quantify therapeutic benefit and risk. The data analyzed in this systematic review showed that pathogen inactivation did not adversely affect the efficacy of S/D or amotosalen plasma transfusions in any patient population studied. In addition, there were no significant safety issues for these patient populations, other than the specific contraindications noted in their respective package inserts. CONCLUSION/CONCLUSIONS:Larger, well-designed trials are needed to further evaluate the efficacy and safety of all of the PR plasma products.

Background/Case Studies: Many in our public health system have long believed that the racially and ethnically diverse patient population we serve had a higher proportion of both O-positive and O-negative patients than was characteristic of the general US population. Although our blood supplier routinely reported that we purchased a higher percentage of O-positive and O-negative RBCs than their other customers, we did not know the ABO/Rh percentages of our patients. Poor reporting tools limited our ability to extract this type of data from our blood bank computer system. Our system recognized the need to develop better reporting tools.We sought to determine if the long held belief was correct and justified our higher percentage of O-positive and O-negative RBCs. Study Design/Methods: Reports were created to extract ABO/Rh typing results performed on type and screen (T&S) samples performed from January 1, 2017 to December 31, 2018 from our system's blood bank computer system by individual hospital and aggregated system data. The data were analyzed to evaluate our patient ABO/Rh mix to determine if the long held belief was true or false. O-positive and O-negative percentages were also compared between facilities. The percentages of O-positive and Onegative RBC purchases were assessed with regard to the patient ABO/Rh percentages. P values were calculated and evaluated using Student's t test. Results/Findings: From January 1, 2017 to December 31, 2018, 466,444 T&Ss were resulted system-wide, and we purchased 68,853 RBC units. A total of 3.3% of patients were O-negative (facility range, 2.8%-4.8%), and 49.2% were O-positive (facility range, 40.4%-58.3%). Of the RBC units, 15.4% were O-negative and 71.2% were O-positive (overall 86.9% type O). The percentage of type O RBCs purchased far exceeded the percentage of type O patients. The percentage of type O RBC purchases surpassed the percentage of type O patients (p < 0.0007 for 2017 purchases and p < 0.00008 for 2018). The percentage of type O-negative RBC purchases surpassed the percentage of type O-negative patients (p < 0.0039 for 2017 purchases and p < 0.00002 for 2018). A total of 6.9% of patients were Rhnegative. Despite communication to better monitor inventory ordering practices, there was no statistical difference between the percentage of Opositive or O-negative RBC purchases between 2017 and 2018.
Conclusion(s): Contrary to our perception, our patient population has a lower percentage of type O-negative patients (3.3%) than the general US population (6.6%). Our patients are also less likely to be Rh-negative (6.9%; range, 5.3%-13.4%) than the US population (15.0%). Our percentage of type O-positive patients (49.2%) is higher than that of the general US population (37.4%) and more closely resembles the type O-positive rates reported in many African, Central American, and Asian countries from which many of our patients come. Antigen-negative RBCs were only 5.0% of all RBCs purchased and thus cannot alone explain the high type O RBC rate. Our system, including five Level 1 trauma centers, should be able to safely reduce our ordering of O-negative RBCs without negatively impacting patient safety. Access to timely reporting tools should help us drive change

Background: An ABO blood group subtype is called a subgroup and/or variant. Subgroups of ABO are often distinguished by decreased amounts of A, B or O (H) antigens on red blood cells. Blood type A appears to have the most variation in subgroups. In general, serologic distinction between A1 and other subgroups of A is based on the ability of anti- A1 lectin (an extract of Dolichos biflorus seeds) to agglutinate A1 red blood cells (RBC) but not cells of other A subgroups. As A2 is most common A subtype and is frequently detected at regular hospital transfusion services. Definitive identification of ABO subgroups is usually performed at a reference laboratory using molecular techniques and special immunohematology methods. Here we report an interesting case where a subgroup B was detected by an astute technologist using manual immunohematology tests and conventional reagents at our hospital transfusion service. Our hospital transfusion service received a blood specimen requesting a type and screen from a pregnant woman with no known medical problems. Testing the specimen showed a front type of O and a back type of B, with a negative antibody screening.
Aim(s): To resolve the typing discrepancy and to correctly Identify the ABO blood type of the pregnant patient.
Method(s): In an attempt to enhance the typing reactions with the patient's RBCs and plasma, mixtures of the front typing and back typing were incubated separately for 15 minutes at room temperature. This however did not result in any change in reactivity. The technologist became suspicious of a possible B subgroup as this was a healthy young woman and it would be rare for such a young patient to exhibit missing antibodies in the reverse type. He then performed a DAT on the specimen to assure that nothing was coating the patient's RBCs which might interfere with further testing. The DAT was negative for IgG and C3d. He subsequently performed an absorption on vigorously washed patient RBC) with anti-B reagent from Ortho. The reaction mixture was incubated at room temperature (RT) for 15 minutes, followed by an elution. The eluate was added to washed A cells, B cells, and screening cells (Ortho), and then incubated at room temperature for 15 minutes. The mixtures were washed with eluate washing solution. Anti-IgG Coombs reagent was added, the tubes were centrifuged, and results were recorded.
Result(s): A cells: Negative B cells: 2 + Screen cell #1: negative Screen cell #2: negative Screen cell #3: negative Summary/Conclusions: Based on the manual tests the technologist designed and performed, he was able to demonstrate the 2 + reactivity with type B reagent RBCs and concluded that the patient's blood type is a B subgroup. The patient's specimen was then sent to New York Blood Center Immunohematology Reference Laboratory for further confirmation and identification. The B group of the patient's RBCs was not detectable again by the conventional immunohematology tests. Molecular tests (PCR-RFLP) and full gene sequencing were performed. A B allele (*B1.01) and an O1 allele (*O1.09) were identified, which predicts a B weak subtype. The molecular testing confirms the conclusion made by our technologist using conventional manual immunohematology tests

BACKGROUND: PCC (Kcentra(R)) is an Food and Drug Administration (FDA)-approved 4-factor PCC used for the treatment of warfarin-related coagulopathy (WRC), but it has also been used off-label to treat non-WRC. Three-factor PCC in the form of coagulation factor IX human (Bebulin(R)) has also been used for WRC and off-label to treat non-WRC. It is unclear whether the use of 3- or 4-factor PCCs is effective for the treatment of non-WRC,. OBJECTIVE: Our aim is to characterize the use of 3- and 4-factor PCCs for patients identified with a non-WRC. METHODS: A retrospective analysis of patients who received PCCs for both WRC and non-WRC between January 2012 and July 2015 was conducted. RESULTS: A total of 187 patients with elevated international normalized ratio (INR) who received PCCs were analyzed; 53.9% of patients in the WRC group and 27.7% in the non-WRC group corrected to an INR of 1.3 or less after 3- or 4-factor PCC administration. In those patients with non-WRC and who had underlying liver disease, 3- and 4-factor PCCs reduced mean INR by 0.98 and 1.43, respectively. CONCLUSION: Three and 4-factor PCCs can reduce INR in patients with WRC and in those with non-WRC secondary to liver disease.

BACKGROUND: Bacterially contaminated platelets (PLTs) remain a serious risk. The Food and Drug Administration has issued draft guidance recommending hospitals implement secondary testing or transfuse PLTs that have been treated with pathogen reduction technology (PRT). The cost implications of these approaches are not well understood. STUDY DESIGN AND METHODS: We modeled incurred costs when hospitals acquire, process, and transfuse PLTs that are PRT treated with INTERCEPT (Cerus Corp.) or secondary tested with the PLT PGD Test (Verax Biomedical). RESULTS: Hospitals will spend $221.27 (30.0%) more per PRT-treated apheresis PLT unit administered compared to a Zika-tested apheresis PLT unit that is irradiated and PGD tested in hospital. This difference is reflected in PRT PLT units having: 1) a higher hospital purchase price ($100.00 additional charge compared to an untreated PLT); 2) lower therapeutic effectiveness than untreated PLTs among hematologic-oncologic patients, which contributes to additional transfusions ($96.05); or 3) fewer PLT storage days, which contributes to higher outdating cost from expired PLTs ($67.87). Only a small portion of the incremental costs for PRT-treated PLTs are offset by costs that may be avoided, including primary bacterial culture, secondary bacterial testing ($26.65), hospital irradiation ($8.50), Zika testing ($4.47), and other costs ($3.03). CONCLUSION: The significantly higher cost of PRT-treated PLTs over PGD-tested PLTs should interest stakeholders. For hospitals that outdate PLTs, savings associated with expiration extension to 7 days by adding PGD testing will likely be substantially greater than the cost of implementing PGD-testing. Our findings might usefully inform a hospital's decision to select a particular blood safety approach.

Transfusion-transmitted cytomegalovirus (TT-CMV) is often asymptomatic, but certain patient populations, such as very low birth weight neonates, fetuses requiring intrauterine transfusion, pregnant women, patients with primary immunodeficiencies, transplant recipients, and patients receiving chemotherapy or transplantation for malignant disease, may be at risk of life-threatening CMV infection. It is unclear whether leukoreduction of cellular blood components is sufficient to reduce TT-CMV or whether CMV serological testing adds additional benefit to leukoreduction. The AABB CMV Prevention Work Group commissioned a systematic review to address these issues and subsequently develop clinical practice guidelines. However, the data were of poor quality, and no studies of significant size have been performed for over a decade. Rather than creating guidelines of questionable utility, the Work Group (with approval of the AABB Board of Directors) voted to prepare this Committee Report. There is wide variation in practices of using leukoreduced components alone or combining CMV-serology and leukoreduction to prevent TT-CMV for at-risk patients. Other approaches may also be feasible to prevent TT-CMV, including plasma nucleic acid testing, pathogen inactivation, and patient blood management programs to reduce the frequency of inappropriate transfusions. It is unlikely that future large-scale clinical trials will be performed to determine whether leukoreduction, CMV-serology, or a combination of both is superior. Consequently, alternative strategies including pragmatic randomized controlled trials, registries, and collaborations for electronic data merging, nontraditional approaches to inform evidence, or development of a systematic approach to inform expert opinion may help to address the issue of CMV-safe blood components.