Perioperative risk and antiplatelet management in patients undergoing non-cardiac surgery within 1 year of PCI
Cao, Davide; Levin, Matthew A; Sartori, Samantha; Claessen, Bimmer; Roumeliotis, Anastasios; Zhang, Zhongjie; Nicolas, Johny; Chandiramani, Rishi; Bedekar, Rashi; Waseem, Zaha; Goel, Ridhima; Chiarito, Mauro; Lupo, Bonnie; Jhang, Jeffrey; Dangas, George D; Baber, Usman; Bhatt, Deepak L; Sharma, Samin K; Kini, Annapoorna S; Mehran, Roxana
Perioperative cardiovascular complications are important causes of morbidity and mortality associated with non-cardiac surgery, especially in patients with recent percutaneous coronary intervention (PCI). We aimed to illustrate the types and timing of different surgeries occurring after PCI, and to evaluate the risk of thrombotic and bleeding events according to the perioperative antiplatelet management. Patients undergoing urgent or elective non-cardiac surgery within 1 year of PCI at a tertiary-care center between 2011 and 2018 were included. The primary outcome was major adverse cardiac events (MACE; composite of death, myocardial infarction, or stent thrombosis) at 30 days. Perioperative bleeding was defined as â‰¥â€‰2 units of blood transfusion. A total of 1092 surgeries corresponding to 747 patients were classified by surgical risk (low: 50.9%, intermediate: 38.4%, high: 10.7%) and priority (elective: 88.5%, urgent/emergent: 11.5%). High-risk and urgent/emergent surgeries tended to occur earlier post-PCI compared to low-risk and elective ones, and were associated with an increased risk of both MACE and bleeding. Preoperative interruption of antiplatelet therapy (of any kind) occurred in 44.6% of all NCS and was more likely for procedures occurring later post-PCI and at intermediate risk. There was no significant association between interruption of antiplatelet therapy and adverse cardiac events. Among patients undergoing NCS within 1 year of PCI, perioperative ischemic and bleeding events primarily depend on the estimated surgical risk and urgency of the procedure, which are increased early after PCI. Preoperative antiplatelet interruption was not associated with an increased risk of cardiac events.
The utility and complications of plasma administration in cirrhotic patients undergoing minimally invasive procedures
Diaz, Kelly E; Tremblay, Douglas; Ozturk, Begum; Ezaz, Ghideon; Arinsburg, Suzanne; Jhang, Jeffrey; Schiano, Thomas D
Patients with cirrhosis have coagulopathy often necessitating correction with blood products, such as plasma products (fresh frozen plasma and plasma frozen within 24â€Šh) prior to certain invasive procedures. However, plasma administration has the potential for substantial negative adverse effects such as volume overload, transfusion-related lung injury and allergic/anaphylactic reactions. In addition, its effectiveness in preventing bleeding is similarly unclear. The purpose of this study was to determine the safety and efficacy of plasma administration in cirrhotic patients undergoing minimally invasive procedures, specifically vascular access placement, transjugular liver biopsies, renal biopsies and thoracenteses. In this retrospective cohort study, we identified patients receiving plasma products in preparation for an invasive procedure, with the primary outcomes of volume overload and bleeding. Of the 145 transfusion events that met the criteria from 2015 to 2018, the median INR decreased from 2.7 to 2.2 pre and post plasma administration and 13.8% of recipients had complications of volume overload. The cost of acquisition of plasma administered below clinically impactful doses accumulates to an estimated 19â€Š000 dollars over this time period, not including nursing preparation or production costs. Plasma products minimally, if at all, improved laboratory values of coagulation and in some patients led to adverse effects.
Use of an in-house trypsin-based method to resolve the interference of daratumumab
Ibeh, Nnaemeka; Baine, Ian; Rudon, Louella Fuentes; Lomas-Francis, Christine; Jhang, Jeffrey S; Galdon, Patricia; Westhoff, Connie M; Velliquette, Randall W; Arinsburg, Suzanne A
BACKGROUND:Daratumumab (DARA) is a monoclonal antibody for treatment of plasma cell myeloma targeting CD38, a surface molecule expressed on plasma cells and red blood cells (RBCs). This complicates blood bank testing, requiring dithiothreitol (DTT) to remove DARA interference. A simple in-house method of removing DARA interference without use of DTT, a potentially hazardous chemical, is desirable. We demonstrate a trypsin-based method to remove interference in antibody testing at a medical center (MC), with parallel testing at an immunohematology reference laboratory (IRL). STUDY DESIGN AND METHODS:Pre-DARA type and screen (T&S) samples were obtained from 61 patients for antibody testing and RBC phenotyping using untreated reagent RBCs. Subsequent post-DARA T&S testing was performed with untreated reagent RBCs to demonstrate interference and repeated after trypsin treatment. Positive trypsin-treated antibody screens were reflexed to antibody identification using trypsin-treated panel cells. Parallel testing was performed on the same post-DARA samples at IRL. RESULTS:DARA interference was detected in 61/61 (100%) samples by MC and IRL. After trypsin treatment, DARA interference was eliminated in 60/61 (98.4%) antibody screens by both institutions with an overall percent agreement of 96.7% (95% confidence interval [CI] 88.7%-99.6%). Identification of known alloantibodies was confirmed in 3/3 patients with 100% concordant results between MC and IRL. There were no false-negative results demonstrated by IRL's functionally CD38-negative controls. CONCLUSION:Our in-house trypsin-based method enables pretransfusion testing of patients receiving DARA in an accurate and cost-effective manner without missing clinically significant alloantibodies. This presents an additional testing option where DTT use is undesirable.
Tackling the unknowns in understanding and management of hospital acquired anemia
Bressman, Eric; Jhang, Jeffrey; McClaskey, John; Ginzburg, Yelena Z
Hospital acquired anemia (HAA) has been a recognized entity for nearly 50Â years. Despite multiple hypotheses, a mechanistic understanding is lacking, and targeted interventions have not yet yielded significantly impactful results. Known risk factors include advanced age, multiple co-morbidities, low bone marrow reserve, admission to the intensive care unit, and frequent phlebotomy. However, confounding variables in many studies continues to complicate the identification of additional risk factors. Improved understanding of iron metabolism, erythropoiesis, and the erythroid iron restriction response in the last few decades, as well as the recent demonstration of poor outcomes correlating with increased transfusion have refocused attention on HAA. While retrospective database studies provide ample correlative data between 1) HAA and poor outcomes; 2) reduction of phlebotomy volume and decrease in transfusion requirement; and 3) over-transfusion and increased mortality, no causal link between reduced phlebotomy volume, decreased rates of HAA, and improved mortality or other relevant outcomes have been definitely established. Here, we review the current state of knowledge and provide a summary of potential directions to understand and mitigate HAA. There are at present no clear guidelines on whether and when to evaluate hospitalized patients for underlying causes of anemia. We thus provide a guide for clinicians in general practice toward identifying patients at the highest risk for HAA, decreasing blood loss through phlebotomy to the greatest degree feasible, and evaluating and treating reversible causes of anemia in a targeted population.
RT-PCR/MALDI-TOF mass spectrometry-based detection of SARS-CoV-2 in saliva specimens
Hernandez, Matthew M; Banu, Radhika; Shrestha, Paras; Patel, Armi; Chen, Feng; Cao, Liyong; Fabre, Shelcie; Tan, Jessica; Lopez, Heidi; Chiu, Numthip; Shifrin, Biana; Zapolskaya, Inessa; Flores, Vanessa; Lee, Pui Yiu; Castañeda, Sergio; RamÃrez, Juan David; Jhang, Jeffrey; Osorio, Giuliana; Gitman, Melissa R; Nowak, Michael D; Reich, David L; Cordon-Cardo, Carlos; Sordillo, Emilia Mia; Paniz-Mondolfi, Alberto E
As severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infections continue, there is a substantial need for cost-effective and large-scale testing that utilizes specimens that can be readily collected from both symptomatic and asymptomatic individuals in various community settings. Although multiple diagnostic methods utilize nasopharyngeal specimens, saliva specimens represent an attractive alternative as they can rapidly and safely be collected from different populations. While saliva has been described as an acceptable clinical matrix for the detection of SARS-CoV-2, evaluations of analytic performance across platforms for this specimen type are limited. Here, we used a novel sensitive RT-PCR/MALDI-TOF mass spectrometry-based assay (Agena MassARRAYÂ®) to detect SARS-CoV-2 in saliva specimens. The platform demonstrated high diagnostic sensitivity and specificity when compared to matched patient upper respiratory specimens. We also evaluated the analytical sensitivity of the platform and determined the limit of detection of the assay to be 1562.5 copies/ml. Furthermore, across the five individual target components of this assay, there was a range in analytic sensitivities for each target with the N2 target being the most sensitive. Overall, this system also demonstrated comparable performance when compared to the detection of SARS-CoV-2 RNA in saliva by the cobasÂ® 6800/8800 SARS-CoV-2 real-time RT-PCR Test (Roche). Together, we demonstrate that saliva represents an appropriate matrix for SARS-CoV-2 detection on the novel Agena system as well as on a conventional real-time RT-PCR assay. We conclude that the MassARRAYÂ® system is a sensitive and reliable platform for SARS-CoV-2 detection in saliva, offering scalable throughput in a large variety of clinical laboratory settings.
Pathophysiology of SARS-CoV-2: the Mount Sinai COVID-19 autopsy experience
Bryce, Clare; Grimes, Zachary; Pujadas, Elisabet; Ahuja, Sadhna; Beasley, Mary Beth; Albrecht, Randy; Hernandez, Tahyna; Stock, Aryeh; Zhao, Zhen; AlRasheed, Mohamed Rizwan; Chen, Joyce; Li, Li; Wang, Diane; Corben, Adriana; Haines, G Kenneth; Westra, William H; Umphlett, Melissa; Gordon, Ronald E; Reidy, Jason; Petersen, Bruce; Salem, Fadi; Fiel, Maria Isabel; El Jamal, Siraj M; Tsankova, Nadejda M; Houldsworth, Jane; Mussa, Zarmeen; Veremis, Brandon; Sordillo, Emilia; Gitman, Melissa R; Nowak, Michael; Brody, Rachel; Harpaz, Noam; Merad, Miriam; Gnjatic, Sacha; Liu, Wen-Chun; Schotsaert, Michael; Miorin, Lisa; Aydillo Gomez, Teresa A; Ramos-Lopez, Irene; Garcia-Sastre, Adolfo; Donnelly, Ryan; Seigler, Patricia; Keys, Calvin; Cameron, Jennifer; Moultrie, Isaiah; Washington, Kae-Lynn; Treatman, Jacquelyn; Sebra, Robert; Jhang, Jeffrey; Firpo, Adolfo; Lednicky, John; Paniz-Mondolfi, Alberto; Cordon-Cardo, Carlos; Fowkes, Mary E
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated clinical syndrome COVID-19 are causing overwhelming morbidity and mortality around the globe and disproportionately affected New York City between March and May 2020. Here, we report on the first 100 COVID-19-positive autopsies performed at the Mount Sinai Hospital in New York City. Autopsies revealed large pulmonary emboli in six cases. Diffuse alveolar damage was present in over 90% of cases. We also report microthrombi in multiple organ systems including the brain, as well as hemophagocytosis. We additionally provide electron microscopic evidence of the presence of the virus in our samples. Laboratory results of our COVID-19 cohort disclose elevated inflammatory markers, abnormal coagulation values, and elevated cytokines IL-6, IL-8, and TNFÎ±. Our autopsy series of COVID-19-positive patients reveals that this disease, often conceptualized as a primarily respiratory viral illness, has widespread effects in the body including hypercoagulability, a hyperinflammatory state, and endothelial dysfunction. Targeting of these multisystemic pathways could lead to new treatment avenues as well as combination therapies against SARS-CoV-2 infection.
Repeated cross-sectional sero-monitoring of SARS-CoV-2 in New York City
Stadlbauer, Daniel; Tan, Jessica; Jiang, Kaijun; Hernandez, Matthew M; Fabre, Shelcie; Amanat, Fatima; Teo, Catherine; Arunkumar, Guha Asthagiri; McMahon, Meagan; Capuano, Christina; Twyman, Kathryn; Jhang, Jeffrey; Nowak, Michael D; Simon, Viviana; Sordillo, Emilia Mia; van Bakel, Harm; Krammer, Florian
In late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) was first detected in China and has since caused a pandemic of coronavirus disease 2019 (COVID-19). The first case of COVID-19 in New York City was officially confirmed on 1Â March 2020 followed by a severe local epidemic1. Here, to understand seroprevalence dynamics, we conduct a retrospective, repeated cross-sectional analysis of anti-SARS-CoV-2 spike antibodies in weekly intervals from the beginning of February to July 2020 using more than 10,000 plasma samples from patients at Mount Sinai Hospital in New York City. We describe the dynamics of seroprevalence in an 'urgent care' group, which is enriched in cases of COVID-19 during the epidemic, and a 'routine care' group, which more closely represents the general population. Seroprevalence increased at different rates in both groups; seropositive samples were found as early as mid-February, and levelled out at slightly above 20% in both groups after the epidemic wave subsided by the end of May. From May to July, seroprevalence remained stable, suggesting lasting antibody levels in the population. Our data suggest that SARS-CoV-2 was introduced in New York City earlier than previously documented and describe the dynamics of seroconversion over the full course of the first wave of the pandemic in a major metropolitan area.
Neutralizing Antibody Responses in COVID-19 Convalescent Sera
Lee, William T; Girardin, Roxanne C; Dupuis, Alan P; Kulas, Karen E; Payne, Anne F; Wong, Susan J; Arinsburg, Suzanne; Nguyen, Freddy T; Mendu, Damodara Rao; Firpo-Betancourt, Adolfo; Jhang, Jeffrey; Wajnberg, Ania; Krammer, Florian; Cordon-Cardo, Carlos; Amler, Sherlita; Montecalvo, Marisa; Hutton, Brad; Taylor, Jill; McDonough, Kathleen A
Passive transfer of antibodies from COVID-19 convalescent patients is being used as an experimental treatment for eligible patients with SARS-CoV-2 infections. The United States Food and Drug Administration's (FDA) guidelines for convalescent plasma initially recommended target antibody titers of 160. We evaluated SARS-CoV-2 neutralizing antibodies in sera from recovered COVID-19 patients using plaque reduction neutralization tests (PRNT) at moderate (PRNT50) and high (PRNT90) stringency thresholds. We found that neutralizing activity significantly increased with time post symptom onset (PSO), reaching a peak at 31-35 days PSO. At this point, the number of sera having neutralizing titers of at least 160 was approximately 93% (PRNT50) and approximately 54% (PRNT90). Sera with high SARS-CoV-2 antibody levels (>960 enzyme-linked immunosorbent assay titers) showed maximal activity, but not all high-titer sera contained neutralizing antibody at FDA recommended levels, particularly at high stringency. These results underscore the value of serum characterization for neutralization activity.
The New York State SARS-CoV-2 Testing Consortium: Regional Communication in Response to the COVID-19 Pandemic
Crawford, James M; Aguero-Rosenfeld, Maria E; Aifantis, Ioannis; Cadoff, Evan M; Cangiarella, Joan F; Cordon-Cardo, Carlos; Cushing, Melissa; Firpo-Betancourt, Aldolfo; Fox, Amy S; Furuya, Yoko; Hacking, Sean; Jhang, Jeffrey; Leonard, Debra G B; Libien, Jenny; Loda, Massimo; Mendu, Damadora Rao; Mulligan, Mark J; Nasr, Michel R; Pecora, Nicole D; Pessin, Melissa S; Prystowsky, Michael B; Ramanathan, Lakshmi V; Rauch, Kathleen R; Riddell, Scott; Roach, Karen; Roth, Kevin A; Shroyer, Kenneth R; Smoller, Bruce R; Spitalnik, Steven L; Spitzer, Eric D; Tomaszewski, John E; Waltman, Susan; Willis, Loretta; Sumer-King, Zeynep
The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2, created an unprecedented need for comprehensive laboratory testing of populations, in order to meet the needs of medical practice and to guide the management and functioning of our society. With the greater New York metropolitan area as an epicenter of this pandemic beginning in March 2020, a consortium of laboratory leaders from the assembled New York academic medical institutions was formed to help identify and solve the challenges of deploying testing. This report brings forward the experience of this consortium, based on the real-world challenges which we encountered in testing patients and in supporting the recovery effort to reestablish the health care workplace. In coordination with the Greater New York Hospital Association and with the public health laboratory of New York State, this consortium communicated with state leadership to help inform public decision-making addressing the crisis. Through the length of the pandemic, the consortium has been a critical mechanism for sharing experience and best practices in dealing with issues including the following: instrument platforms, sample sources, test performance, pre- and post-analytical issues, supply chain, institutional testing capacity, pooled testing, biospecimen science, and research. The consortium also has been a mechanism for staying abreast of state and municipal policies and initiatives, and their impact on institutional and laboratory operations. The experience of this consortium may be of value to current and future laboratory professionals and policy-makers alike, in dealing with major events that impact regional laboratory services.
Transfusion reactions associated with COVID-19 convalescent plasma therapy for SARS-CoV-2
Nguyen, Freddy T; van den Akker, Tayler; Lally, Kimberly; Lam, Hansen; Lenskaya, Volha; Liu, Sean T H; Bouvier, Nicole M; Aberg, Judith A; Rodriguez, Denise; Krammer, Florian; Strauss, Donna; Shaz, Beth H; Rudon, Louella; Galdon, Patricia; Jhang, Jeffrey S; Arinsburg, Suzanne A; Baine, Ian
BACKGROUND:Convalescent plasma (CP) for treatment of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has shown preliminary signs of effectiveness in moderate to severely ill patients in reducing mortality. While studies have demonstrated a low risk of serious adverse events, the comprehensive incidence and nature of the spectrum of transfusion reactions to CP is unknown. We retrospectively examined 427 adult inpatient CP transfusions to determine incidence and types of reactions, as well as clinical parameters and risk factors associated with transfusion reactions. STUDY DESIGN AND METHODS:Retrospective analysis was performed for 427 transfusions to 215 adult patients with coronavirus 2019 (COVID-19) within the Mount Sinai Health System, through the US Food and Drug Administration emergency investigational new drug and the Mayo Clinic Expanded Access Protocol to Convalescent Plasma approval pathways. Transfusions were blindly evaluated by two reviewers and adjudicated by a third reviewer in discordant cases. Patient demographics and clinical and laboratory parameters were compared and analyzed. RESULTS:Fifty-five reactions from 427 transfusions were identified (12.9% incidence), and 13 were attributed to transfusion (3.1% incidence). Reactions were classified as underlying COVID-19 (76%), febrile nonhemolytic (10.9%), transfusion-associated circulatory overload (9.1%), and allergic (1.8%) and hypotensive (1.8%) reactions. Statistical analysis identified increased transfusion reaction risk for ABO blood group B or Sequential Organ Failure Assessment scores of 12 to 13, and decreased risk within the age group of 80 to 89â€‰years. CONCLUSION:Our findings support the use of CP as a safe, therapeutic option from a transfusion reaction perspective, in the setting of COVID-19. Further studies are needed to confirm the clinical significance of ABO group B, age, and predisposing disease severity in the incidence of transfusion reaction events.