Publications by authors named "Cheryl L Maier"

36 Publications

Anticoagulation Monitoring for Perioperative Physicians.

Anesthesiology 2021 10;135(4):738-748

Anesthesiology, Emory University School of Medicine, Atlanta, Georgia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/ALN.0000000000003903DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8440469PMC
October 2021

Retinopathy and Systemic Disease Morbidity in Severe COVID-19.

Ocul Immunol Inflamm 2021 Aug 31:1-8. Epub 2021 Aug 31.

Emory Eye Center, Emory University School of Medicine, Atlanta, GA, USA.

Purpose: To assess the prevalence of retinopathy and its association with systemic morbidity and laboratory indices of coagulation and inflammatory dysfunction in severe COVID-19.

Design: Retrospective, observational cohort study.

Methods: Adult patients hospitalized with severe COVID-19 who underwent ophthalmic examination from April to July 2020 were reviewed. Retinopathy was defined as one of the following: 1) Retinal hemorrhage; 2) Cotton wool spots; 3) Retinal vascular occlusion. We analyzed medical comorbidities, sequential organ failure assessment (SOFA) scores, clinical outcomes, and laboratory values for their association with retinopathy.

Results: Thirty-seven patients with severe COVID-19 were reviewed, the majority of whom were female (n = 23, 62%), Black (n = 26, 69%), and admitted to the intensive care unit (n = 35, 95%). Fourteen patients had retinopathy (38%) with retinal hemorrhage in 7 (19%), cotton wool spots in 8 (22%), and a branch retinal artery occlusion in 1 (3%) patient. Patients with retinopathy had higher SOFA scores than those without retinopathy (8.0 vs. 5.3, = .03), higher rates of respiratory failure requiring invasive mechanical ventilation and shock requiring vasopressors ( < .01). Peak D-dimer levels were 28,971 ng/mL in patients with retinopathy compared to 12,575 ng/mL in those without retinopathy ( = .03). Peak CRP was higher in patients with cotton wool spots versus those without cotton wool spots (354 mg/dL vs. 268 mg/dL, = .03). Multivariate logistic regression modeling showed an increased risk of retinopathy with higher peak D-dimers (aOR 1.32, 95% CI 1.01-1.73, = .04) and male sex (aOR 9.6, 95% CI 1.2-75.5, = .04).

Conclusion: Retinopathy in severe COVID-19 was associated with greater systemic disease morbidity involving multiple organs. Given its association with coagulopathy and inflammation, retinopathy may offer insight into disease pathogenesis in patients with severe COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/09273948.2021.1952278DOI Listing
August 2021

Assessment of Coagulation and Hemostasis Biomarkers in a Subset of Patients With Chronic Cardiovascular Disease.

Clin Appl Thromb Hemost 2021 Jan-Dec;27:10760296211032292

Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.

Measurement of a single marker of coagulation may not provide a complete picture of hemostasis activation and fibrinolysis in patients with chronic cardiovascular diseases. We assessed retrospective orders of a panel which included prothrombin fragment 1.2 (PF1.2), thrombin: antithrombin complexes, fibrin monomers, and D-dimers in patients with heart assist devices, cardiomyopathies, atrial fibrillation and intracardiac thrombosis (based on ordering ICD-10 codes). During 1 year there were 117 panels from 81 patients. Fifty-six (69%) patients had heart assist devices, cardiomyopathy was present in 17 patients (21%) and 29 patients (36%) had more than 1 condition. PF1.2 was most frequently elevated in patients with cardiomyopathy (61.1%) compared to those with cardiac assist devices (15.7%; = 0.0002). D-dimer elevation was more frequent in patients with cardiac assist devices (98.8%) compared to those patients with cardiomyopathy (83.3%; = 0.014). Patients with cardiomyopathy show increases of PF1.2 suggesting thrombin generation. In contrast, elevations of D-dimers without increase in other coagulation markers in patients with cardiac assist devices likely reflect the presence of the intravascular device and not necessarily evidence of hemostatic activation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/10760296211032292DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8274080PMC
July 2021

Broad auto-reactive IgM responses are common in critically ill patients, including those with COVID-19.

Cell Rep Med 2021 Jun 28;2(6):100321. Epub 2021 May 28.

Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA, USA.

The pathogenesis of severe coronavirus disease 2019 (COVID-19) remains poorly understood. While several studies suggest that immune dysregulation plays a central role, the key mediators of this process are yet to be defined. Here, we demonstrate that plasma from a high proportion (93%) of critically ill COVID-19 patients, but not healthy controls, contains broadly auto-reactive immunoglobulin M (IgM) and less frequently auto-reactive IgG or IgA. Importantly, these auto-IgMs preferentially recognize primary human lung cells , including pulmonary endothelial and epithelial cells. By using a combination of flow cytometry, analytical proteome microarray technology, and lactose dehydrogenase (LDH)-release cytotoxicity assays, we identify high-affinity, complement-fixing, auto-reactive IgM directed against 260 candidate autoantigens, including numerous molecules preferentially expressed on the cellular membranes of pulmonary, vascular, gastrointestinal, and renal tissues. These findings suggest that broad IgM-mediated autoimmune reactivity may be involved in the pathogenesis of severe COVID-19, thereby identifying a potential target for therapeutic interventions.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.xcrm.2021.100321DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8160082PMC
June 2021

Are We Forgetting About IgA? A Re-examination of Coronavirus Disease 2019 Convalescent Plasma.

Transfusion 2021 06 26;61(6):1740-1748. Epub 2021 May 26.

Center for Transfusion Medicine and Cellular Therapies, Emory University, Atlanta, Georgia, USA.

Background: While convalescent plasma (CP) may benefit patients with COVID-19, fundamental questions remain regarding its efficacy, including the components of CP that may contribute to its therapeutic effect. Most current serological evaluation of CP relies on examination of total immunoglobulin or IgG-specific anti-SARS-CoV-2 antibody levels. However, IgA antibodies, which also circulate and are secreted along the respiratory mucosa, represent a relatively uncharacterized component of CP.

Study Design And Methods: Residual samples from patients and CP donors were assessed for IgM, IgG, and IgA anti-SARS-CoV-2 antibody titers against the receptor-binding domain responsible for viral entry. Symptom onset was obtained by chart review.

Results: Increased IgA anti-SARS-CoV-2 antibody levels correlated with clinical improvement and viral clearance in an infant with COVID-19, prompting a broader examination of IgA levels among CP donors and hospitalized patients. Significant heterogeneity in IgA levels was observed among CP donors, which correlated weakly with IgG levels or the results of a commonly employed serological test. Unlike IgG and IgM, IgA levels were also more likely to be variable in hospitalized patients and this variability persisted in some patients >14 days following symptom onset. IgA levels were also less likely to be sustained than IgG levels following subsequent CP donation.

Conclusions: IgA levels can be very heterogenous among CP donors and hospitalized patients and do not necessarily correlate with commonly employed testing platforms. Examining isotype levels in CP and COVID-19 patients may allow for a tailored approach when seeking to fill specific gaps in humoral immunity.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/trf.16435DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8242454PMC
June 2021

Interdisciplinary Approach to Thrombosis Management in COVID-19 at a Large Academic Center.

JCO Oncol Pract 2021 09 21;17(9):517-521. Epub 2021 May 21.

Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA.

There is an increasing recognition of association of COVID-19 with a distinct coagulopathy and increased risk of thrombosis. Unfortunately, effective strategies to prevent and treat thrombosis in this patient population remain uncertain. In the setting of a worsening pandemic, there is an urgent need to provide practical guidance to the clinicians on management of the coagulopathy, while waiting for the results from large systematic trials to establish best practices. At our institution, we convened an interdisciplinary group of 25 experts in the field of thrombosis from different medical specialties to review available literature and brainstorm management strategies. The group provided a 3-tiered anticoagulation algorithm for patients with COVID-19 along with a pathway for multidisciplinary review of difficult or refractory cases, which are described in this manuscript. In these unprecedented times where medical decision making is made difficult by both the novelty of the disease and paucity of robust data, clinical algorithms such as the one presented here may prove to be helpful for frontline providers caring for individual patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1200/OP.20.01056DOI Listing
September 2021

COVID-19 patient plasma demonstrates resistance to tPA-induced fibrinolysis as measured by thromboelastography.

J Thromb Thrombolysis 2021 Apr 7. Epub 2021 Apr 7.

Department of Anesthesiology, Emory University Hospital, Emory University School of Medicine, 3rd Floor, 1364 Clifton Rd, NE, Atlanta, GA, 30322, USA.

Patients critically ill with COVID-19 are at risk for thrombotic events despite prophylactic anticoagulation. Impaired fibrinolysis has been proposed as an underlying mechanism. Our objective was to determine if fibrinolysis stimulated by tissue plasminogen activator (tPA) differed between COVID patients and controls. Plasma from 14 COVID patients on prophylactic heparin therapy was obtained and compared with heparinized plasma from 14 different healthy donors to act as controls. Kaolin activated thromboelastography with heparinase was utilized to obtain baseline measurements and then repeated with the addition of 4 nM tPA. Baseline fibrinogen levels were higher in COVID plasma as measured by maximum clot amplitude (43.6 ± 6.9 mm vs. 23.2 ± 5.5 mm, p < 0.0001) and Clauss assay (595 ± 135 mg/dL vs. 278 ± 44 mg/dL, p < 0.0001). With the addition of tPA, fibrinolysis at 30 min after MA (LY30%) was lower (37.9 ± 16.5% vs. 58.9 ± 18.3%, p = 0.0035) and time to 50% lysis was longer (48.8 ± 16.3 vs. 30.5 ± 15.4 min, p = 0.0053) in the COVID-19 samples. Clotting times and rate of fibrin polymerization ('R' or 'α' parameters) were largely the same in both groups. Clot from COVID patients contains a higher fibrin content compared to standard controls and shows resistance to fibrinolysis induced by tPA. These findings suggest the clinical efficacy of thrombolytics may be reduced in COVID-19 patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s11239-021-02438-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8026096PMC
April 2021

Validation of an admission coagulation panel for risk stratification of COVID-19 patients.

PLoS One 2021 19;16(3):e0248230. Epub 2021 Mar 19.

Department of Neurology & Pediatrics, Emory University, Atlanta, Georgia, United States of America.

Background: There is limited data on the markers of coagulation and hemostatic activation (MOCHA) profile in Coronavirus disease 2019 (COVID-19) and its ability to identify COVID-19 patients at risk for thrombotic events and other complications.

Methods: Hospitalized patients with confirmed SARS-COV-2 from four Atlanta hospitals were included in this observational cohort study and underwent admission testing of MOCHA parameters (plasma d-dimer, prothrombin fragment 1.2, thrombin-antithrombin complex, fibrin monomer). Clinical outcomes included deep vein thrombosis, pulmonary embolism, myocardial infarction, ischemic stroke, access line thrombosis, ICU admission, intubation and mortality.

Main Results: Of 276 patients (mean age 59 ± 6.4 years, 47% female, 62% African American), 45 (16%) had a thrombotic endpoint. Each MOCHA parameter was independently associated with a thrombotic event (p<0.05) and ≥ 2 abnormalities was associated with thrombotic endpoints (OR 3.3, 95% CI 1.2-8.8) as were admission D-dimer ≥ 2000 ng/mL (OR 3.1, 95% CI 1.5-6.6) and ≥ 3000 ng/mL (OR 3.6, 95% CI 1.6-7.9). However, only ≥ 2 MOCHA abnormalities were associated with ICU admission (OR 3.0, 95% CI 1.7-5.2) and intubation (OR 3.2, 95% CI 1.6-6.4). MOCHA and D-dimer cutoffs were not associated with mortality. MOCHA with <2 abnormalities (26% of the cohort) had 89% sensitivity and 93% negative predictive value for a thrombotic endpoint.

Conclusions: An admission MOCHA profile is useful to risk-stratify COVID-19 patients for thrombotic complications and more effective than isolated d-dimer for predicting risk of ICU admission and intubation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0248230PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7979266PMC
April 2021

Clinical Outcomes of Critically III Patients with COVID-19 by Race.

J Racial Ethn Health Disparities 2021 Jan 19. Epub 2021 Jan 19.

Department of Neurology & Pediatrics, Emory University, 1365 Clifton Road, Clinic B, Suite 2200, Atlanta, GA, 30322, USA.

Background: Studies of COVID-19 have shown that African Americans have been affected by the virus at a higher rate compared to other races. This cohort study investigated comorbidities and clinical outcomes by race among COVID-19 patients admitted to the intensive care unit.

Methods: This is a case series of critically ill patients admitted with COVID-19 to an academic healthcare system in Atlanta, Georgia. The study included all critically ill hospitalized patients between March 6, 2020, and May 5, 2020. Clinical outcomes during hospitalization included mechanical ventilation, renal replacement therapy, and mortality stratified by race.

Results: Of 288 patients included (mean age, 63 ± 16 years; 45% female), 210 (73%) were African American. African Americans had significantly higher rates of comorbidities compared to other races, including hypertension (80% vs 59%, P = 0.001), diabetes (49% vs 34%, P = 0.026), and mean BMI (33 kg/m vs 28 kg/m, P < 0.001). Despite African Americans requiring continuous renal replacement therapy during hospitalization at higher rates than other races (27% vs 13%, P = 0.011), rates of intubation, intensive care unit length of stay, and overall mortality (30% vs 24%, P = 0.307) were similar.

Conclusion: This racially diverse series of critically ill COVID-19 patients shows that despite higher rates of comorbidities at hospital admission in African Americans compared with other races, there was no significant difference in mortality.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1007/s40615-021-00966-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815200PMC
January 2021

Therapeutic plasma exchange for COVID-19-associated hyperviscosity.

Transfusion 2021 04 9;61(4):1029-1034. Epub 2020 Dec 9.

Department of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Emory University School of Medicine, Atlanta, Georgia, USA.

Background: Recent data suggests an association between blood hyperviscosity and both propensity for thrombosis and disease severity in patients with COVID-19. This raises the possibility that increased viscosity may contribute to endothelial damage and multiorgan failure in COVID-19, and that therapeutic plasma exchange (TPE) to decrease viscosity may improve patient outcomes. Here we sought to share our experience using TPE in the first 6 patients treated for COVID-19-associated hyperviscosity.

Study Design And Methods: Six critically ill COVID-19 patients with plasma viscosity levels ranging from 2.6 to 4.2 centipoise (cP; normal range, 1.4-1.8 cP) underwent daily TPE for 2-3 treatments.

Results: TPE decreased plasma viscosity in all six patients (Pre-TPE median 3.75 cP, range 2.6-4.2 cP; Post-TPE median 1.6 cP, range 1.5-1.9 cP). TPE also decreased fibrinogen levels in all five patients for whom results were available (Pre-TPE median 739 mg/dL, range 601-1188 mg/dL; Post-TPE median 359 mg/dL, range 235-461 mg/dL); D-dimer levels in all six patients (Pre-TPE median 5921 ng/mL, range 1134-60 000 ng/mL; Post-TPE median 4893 ng/mL, range 620-7518 ng/mL); and CRP levels in five of six patients (Pre-TPE median 292 mg/L, range 136-329 mg/L; Post-TPE median 84 mg/L, range 31-211 mg/L). While the two sickest patients died, significant improvement in clinical status was observed in four of six patients shortly after TPE.

Conclusions: This series demonstrates the utility of TPE to rapidly correct increased blood viscosity in patients with COVID-19-associated hyperviscosity. Large randomized trials are needed to determine whether TPE may improve clinical outcomes for patients with COVID-19.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/trf.16218DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7753437PMC
April 2021

Trends and diagnostic value of D-dimer levels in patients hospitalized with coronavirus disease 2019.

Medicine (Baltimore) 2020 Nov;99(46):e23186

Department of Neurology, Emory University School of Medicine, Atlanta, GA.

Coronavirus disease 2019 (COVID-19) has been associated with increased incidence of venous thromboembolic events (VTE) as well as mortality. D-dimer is a marker of fibrinolysis and has been used as a diagnostic and prognostic marker in VTE among other diseases. The purpose of our study is to describe outcomes from out center and to examine trends in D-dimer levels as it relates to VTE and mortality.Patients admitted with confirmed COVID-19 cases to Emory Healthcare from March 12, 2020 through April 6, 2020 with measured plasma D-dimer levels were included in our retrospective analysis. Relevant data about comorbidities, hospitalization course, laboratory results, and outcomes were analyzed.One hundred fifteen patients were included in our study. Mean age was 64 ± 15 years, 47 (41%) females and 84 (73%) African-American. Hypertension was present in 83 (72%) and diabetes in 60 (52%). Mean duration of hospitalization was 19 ± 11 days with 62 (54%) patients intubated (mean duration of 13 ± 8 days). VTE was diagnosed in 27 (23%) patients (mean time to diagnosis 14 ± 9 days). Median D-dimer within the first 7 days of hospitalization was higher (6450 vs. 1596 ng/mL, p < 0.001) in VTE cases compared to non-VTE cases, and was predictive of VTE (area under the curve [AUC] = 0.72, optimal threshold 2500 ng/mL) although not of mortality (AUC 0.55, P = .34). Change in D-dimer level (AUC = 0.72 P = .004) and rate of D-dimer rise (AUC = 0.75 P = .001) were also predictive of VTE, though neither predicted death (P > .05 for all). Within the first 7 days of hospitalization, peak D-dimer level of >2500 ng/mL and a rate of change exceeding 150 ng/mL/d were predictive of future diagnosis of VTE. Rise in D-dimer >2000 ng/mL within any 24 hour period through hospital day 10 had 75% sensitivity and 74% specificity for diagnosis of VTE.We found that both magnitude and rate of rise in d-dimer within the first 10 days of hospitalization are predictive of diagnosis of VTE but not mortality. These parameters may aid in identifying individuals with possible underlying VTE or at high risk for VTE, thereby guiding risk stratification and anticoagulation policies in COVID-19 patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/MD.0000000000023186DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7668476PMC
November 2020

Towards characterized convalescent plasma for COVID-19: The dose matters.

EClinicalMedicine 2020 Sep 19;26:100545. Epub 2020 Sep 19.

Department of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Emory University School of Medicine, 1364 Clifton Road NE, Atlanta, GA 30322, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.eclinm.2020.100545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7501526PMC
September 2020

Fibrinolysis Shutdown and Thrombosis in a COVID-19 ICU.

Shock 2021 03;55(3):316-320

Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia.

Abstract: The coronavirus disease (COVID-19) pandemic has threatened millions of lives worldwide with severe systemic inflammation, organ dysfunction, and thromboembolic disease. Within our institution, many critically ill COVID-19-positive patients suffered major thrombotic events, prompting our clinicians to evaluate hypercoagulability outside of traditional coagulation testing.We determined the prevalence of fibrinolysis shutdown via rotational thromboelastometry (ROTEM, Instrumentation Laboratories, Bedford, Mass) in patients admitted to the intensive care unit over a period of 3 weeks. In 25 patients who had a ROTEM test, we found that 11 (44%) met criteria for fibrinolysis shutdown. Eight of 9 (73%) of the VTE patients met criteria for fibrinolysis shutdown.Given the high rate of fibrinolysis shutdown in these patients, our data support using viscoelastic testing to evaluate for the presence of impaired fibrinolysis. This may help identify patient subsets who might benefit from the administration of fibrinolytics.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SHK.0000000000001635DOI Listing
March 2021

Fc Gamma Receptors and Complement Component 3 Facilitate Anti-fVIII Antibody Formation.

Front Immunol 2020 9;11:905. Epub 2020 Jun 9.

Department of Pathology and Laboratory Medicine, Center for Transfusion Medicine and Cellular Therapies, Emory University School of Medicine, Atlanta, GA, United States.

Anti-factor VIII (fVIII) alloantibodies, which can develop in patients with hemophilia A, limit the therapeutic options and increase morbidity and mortality of these patients. However, the factors that influence anti-fVIII antibody development remain incompletely understood. Recent studies suggest that Fc gamma receptors (FcγRs) may facilitate recognition and uptake of fVIII by recently developed or pre-existing naturally occurring anti-fVIII antibodies, providing a mechanism whereby the immune system may recognize fVIII following infusion. However, the role of FcγRs in anti-fVIII antibody formation remains unknown. In order to define the influence of FcγRs on the development of anti-fVIII antibodies, fVIII was injected into WT or FcγR knockout recipients, followed by evaluation of anti-fVIII antibodies. Anti-fVIII antibodies were readily observed following fVIII injection into FcγR knockouts, with similar anti-fVIII antibody levels occurring in FcγR knockouts as detected in WT mice injected in parallel. As antibodies can also fix complement, providing a potential mechanism whereby anti-fVIII antibodies may influence anti-fVIII antibody formation independent of FcγRs, fVIII was also injected into complement component 3 (C3) knockout recipients in parallel. Similar to FcγR knockouts, C3 knockout recipients developed a robust response to fVIII, which was likewise similar to that observed in WT recipients. As FcγRs or C3 may compensate for each other in recipients only deficient in FcγRs or C3 alone, we generated mice deficient in both FcγRs and C3 to test for potential antibody effector redundancy in anti-fVIII antibody formation. Infusion of fVIII into FcγRs and C3 (FcγR × C3) double knockouts likewise induced anti-fVIII antibodies. However, unlike individual knockouts, anti-fVIII antibodies in FcγRs × C3 knockouts were initially lower than WT recipients, although anti-fVIII antibodies increased to WT levels following additional fVIII exposure. In contrast, infusion of RBCs expressing distinct alloantigens into FcγRs, C3 or FcγR × C3 knockout recipients either failed to change anti-RBC levels when compared to WT recipients or actually increased antibody responses, depending on the target antigen. Taken together, these results suggest FcγRs and C3 can differentially impact antibody formation following exposure to distinct alloantigens and that FcγRs and C3 work in concert to facilitate early anti-fVIII antibody formation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2020.00905DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295897PMC
April 2021

COVID-19-associated hyperviscosity: a link between inflammation and thrombophilia?

Lancet 2020 06 25;395(10239):1758-1759. Epub 2020 May 25.

Department of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Emory University School of Medicine, Atlanta, GA30322, USA.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/S0140-6736(20)31209-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247793PMC
June 2020

Falsely Low Fibrinogen Levels in COVID-19 Patients on Direct Thrombin Inhibitors.

Anesth Analg 2020 08;131(2):e117-e119

Department of Anesthesiology, Emory University School of Medicine, Atlanta, Georgia,

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1213/ANE.0000000000004949DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7219828PMC
August 2020

Electronic charting of transfusion medicine consults: implementation, challenges and opportunities.

Vox Sang 2020 Jul 20;115(5):443-450. Epub 2020 Mar 20.

Department of Pathology & Laboratory Medicine, Emory University Hospital, Emory University School of Medicine, Atlanta, GA, USA.

Background: The Joint Commission lists improving staff communication (handoffs) as part of several National Safety Goals. In this study, we developed an electronic web-based charting system for clinical pathology handoffs, which primarily consist of transfusion medicine calls, and evaluated the advantages over a paper-based handwritten call log.

Materials And Methods: A secure online web browser application using Research Electronic Data Capture (REDCap) was designed to document on-call pathology resident consults. A year after implementation, an online survey was administered to our pathology residents in order to evaluate and compare the usability of the electronic application (e-consults) to the previous handwritten call log, which was a notebook where trainees hand wrote different components of the consult.

Results: The REDCap web-based application includes discrete fields for patients' information, requesting physician contact, type of consult, action items for follow-up and faculty responses, as well as other information. These components have eventually progressed to be an online consult call catalog. With approximately 1079 consults per year, transfusion medicine-related calls account for ~90% of the encounters, while clinical chemistry, microbiology and immunology calls constitute the remainder. The overall response rate of the survey was 96% (29 of 30 participants). Of the 16 respondents who experienced both call log systems, 100% responded that REDCap was an improvement over the handwritten call log (P < 0·0001).

Conclusion: E-consult documentation entered into a web-based application was a user-friendly, secure clinical information access and effective handoff system as compared to a paper-based handwritten call log.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/vox.12913DOI Listing
July 2020

Challenges in preventing and treating hemolytic complications associated with red blood cell transfusion.

Transfus Clin Biol 2019 May 25;26(2):130-134. Epub 2019 Mar 25.

Center for Transfusion Medicine and Cellular Therapies, Department of Laboratory Medicine and Pathology, Emory University School of Medicine, 101, Woodruff Circle, 30322 Atlanta, GA, USA. Electronic address:

Red blood cell (RBC) transfusion support represents a critical component of sickle cell disease (SCD) management. However, as with any therapeutic intervention, RBC transfusion is not without risk. Repeat exposure to allogeneic RBCs can result in the development of RBC alloantibodies that can make it difficult to find compatible RBCs for future transfusions and can directly increase the risk of developing acute or delayed hemolytic transfusion reactions, which can be further complicated by hyperhemolysis. Several prophylactic and treatment strategies have been employed in an effort to reduce or prevent hemolytic transfusion reactions. However, conflicting data exist regarding the efficacy of many of these approaches. We will explore the challenges associated with predicting, preventing and treating different types of hemolytic transfusion reactions in patients with SCD in addition to describing future strategies that may aid in the management of the complex transfusion requirements of SCD patients.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.tracli.2019.03.002DOI Listing
May 2019

Challenges in the treatment and prevention of delayed hemolytic transfusion reactions with hyperhemolysis in sickle cell disease patients.

Transfusion 2019 05 8;59(5):1698-1705. Epub 2019 Mar 8.

Center for Transfusion and Cellular Therapy, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia.

Background: Delayed hemolytic transfusion reactions (DHTRs) are serious complications of RBC transfusion that can occur in previously alloimmunized patients. Patients who require episodic transfusions during heightened inflammatory states, such as patients with sickle cell disease (SCD), are particularly prone to alloimmunization and developing DHTRs with hyperhemolysis. While efforts to mitigate these hemolytic episodes via immunosuppressive drugs can be employed, the relative efficacy of various treatment options remains incompletely understood.

Case Reports: In this study, we explored five patients with SCD and multiple RBC alloantibodies who received various forms of immunosuppressive therapy in an attempt to prevent or treat severe DHTRs.

Results: The clinical course for these five patients provides insight into the difficulty of effectively treating and preventing DHTRs in patients with SCD with currently available immunosuppressive therapies.

Conclusion: Based on our experience, and the current literature, it is difficult to predict the potential impact of various immunosuppressive therapies when seeking to prevent or treat DHTRs. Future mechanistic studies are needed to identify the optimal treatment options for DHTRs in the presence or absence of distinct alloantibodies in patients with SCD.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/trf.15227DOI Listing
May 2019

Using an old test for new tricks: Measuring direct oral anti-Xa drug levels by conventional heparin-calibrated anti-Xa assay.

Am J Hematol 2019 05 21;94(5):E132-E134. Epub 2019 Feb 21.

Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia.

View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1002/ajh.25434DOI Listing
May 2019

Marginal Zone B Cells Induce Alloantibody Formation Following RBC Transfusion.

Front Immunol 2018 16;9:2516. Epub 2018 Nov 16.

Department of Laboratory Medicine and Pathology, Center for Transfusion Medicine and Cellular Therapies, Emory University School of Medicine, Atlanta, GA, United States.

Red blood cell (RBC) alloimmunization represents a significant immunological challenge for some patients. While a variety of immune constituents likely contribute to the initiation and orchestration of alloantibodies to RBC antigens, identification of key immune factors that initiate alloantibody formation may aid in the development of a therapeutic modality to minimize or prevent this process. To define the immune factors that may be important in driving alloimmunization to an RBC antigen, we determined the specific immune compartment and distinct cells that may initially engage transfused RBCs and facilitate subsequent alloimmunization. Our findings demonstrate that the splenic compartment is essential for formation of anti-KEL antibodies following KEL RBC transfusion. Within the spleen, transfused KEL RBCs are found within the marginal sinus, where they appear to specifically co-localize with marginal zone (MZ) B cells. Consistent with this, removal of MZ B cells completely prevented alloantibody formation following KEL RBC transfusion. While MZ B cells can mediate a variety of key downstream immune pathways, depletion of follicular B cells or CD4 T cells failed to similarly impact the anti-KEL antibody response, suggesting that MZ B cells may play a key role in the development of anti-KEL IgM and IgG following KEL RBC transfusion. These findings highlight a key contributor to KEL RBC-induced antibody formation, wherein MZ B cells facilitate antibody formation following RBC transfusion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.3389/fimmu.2018.02516DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6250814PMC
October 2019

Complement serves as a switch between CD4+ T cell-independent and -dependent RBC antibody responses.

JCI Insight 2018 11 15;3(22). Epub 2018 Nov 15.

Center for Transfusion Medicine and Cellular Therapies, Department of Laboratory Medicine and Pathology.

RBC alloimmunization represents a significant immunological challenge for patients requiring lifelong transfusion support. The majority of clinically relevant non-ABO(H) blood group antigens have been thought to drive antibody formation through T cell-dependent immune pathways. Thus, we initially sought to define the role of CD4+ T cells in formation of alloantibodies to KEL, one of the leading causes of hemolytic transfusion reactions. Unexpectedly, our findings demonstrated that KEL RBCs actually possess the ability to induce antibody formation independent of CD4+ T cells or complement component 3 (C3), two common regulators of antibody formation. However, despite the ability of KEL RBCs to induce anti-KEL antibodies in the absence of complement, removal of C3 or complement receptors 1 and 2 (CR1/2) rendered recipients completely reliant on CD4+ T cells for IgG anti-KEL antibody formation. Together, these findings suggest that C3 may serve as a novel molecular switch that regulates the type of immunological pathway engaged following RBC transfusion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/jci.insight.121631DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6302935PMC
November 2018

Antibody-mediated immune suppression by antigen modulation is antigen-specific.

Blood Adv 2018 11;2(21):2986-3000

Center for Transfusion and Cellular Therapies, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA; and.

Alloantibodies developing after exposure to red blood cell (RBC) alloantigens can complicate pregnancy and transfusion therapy. The only method currently available to actively inhibit RBC alloantibody formation is administration of antigen-specific antibodies, a phenomenon termed antibody-mediated immune suppression (AMIS). A well-known example of AMIS is RhD immune globulin prophylaxis to prevent anti-D formation in RhD individuals. However, whether AMIS is specific or impacts alloimmunization to other antigens on the same RBC remains unclear. To evaluate the specificity of AMIS, we passively immunized antigen-negative recipients with anti-KEL or anti-hen egg lysozyme (HEL) antibodies, followed by transfusion of murine RBC expressing both the HEL-ovalbumin-Duffy (HOD) and human KEL antigens (HOD × KEL RBC). Significant immunoglobulin G deposition on transfused HOD × KEL RBC occurred in all passively immunized recipients. Complement deposition and antigen modulation of the KEL antigen occurred on transfused RBC only in anti-KEL-treated recipients, whereas HEL antigen levels decreased only in the presence of anti-HEL antibodies. Western blot analysis confirmed the specificity of antigen loss, which was not attributable to RBC endocytosis and appears distinct for the 2 antigens. Specifically, removal of KEL was attenuated by clodronate treatment, whereas loss of HEL was unaffected by clodronate in vivo but sensitive to protease treatment in vitro. Antigen-specific modulation correlated with antigen-specific AMIS, with anti-KEL treated recipients forming antibodies to the HOD antigen and anti-HEL-treated recipients developing antibodies to the KEL antigen. Together, these results demonstrate that passively administered antibodies can selectively inhibit the immune response to a specific antigen.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2018018408DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6234375PMC
November 2018

Multiple hemolytic transfusion reactions misinterpreted as severe vaso-occlusive crisis in a patient with sickle cell disease.

Transfusion 2019 02 9;59(2):448-453. Epub 2018 Nov 9.

Center for Transfusion and Cellular Therapy, Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, Georgia.

Background: Hemolytic transfusion reactions are a rare, yet serious complication of red blood cell (RBC) transfusion. Patients with sickle cell disease (SCD) are at an increased risk for such reactions, because they are prone to make alloantibodies against transfused RBCs, complicating this integral part of their disease management. These reactions may be missed, and the patient's state may be attributed to vaso-occlusive crisis (VOC), with misguided therapy ensuing.

Case Report: Herein, we report the clinical course of a patient with complex SCD with a delayed hemolytic transfusion reaction, followed by multiple acute hemolytic transfusion reactions mistaken for severe VOC. These reactions were diagnosed on retrospective review of the patient's clinical course in consult with the transfusion medicine service. Optimal immunosuppressive therapy ensued and resulted in the stabilization of the anemia and hemolysis laboratory values. Despite these efforts, the patient died 2 months after admission.

Conclusion: This case provides insight into some of the challenges of managing patients with SCD with multiple comorbidities. Hemolytic transfusion reactions can be difficult to diagnose and may be overlooked in patients with SCD with severe VOC.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/trf.15010DOI Listing
February 2019

Transfusion-transmitted malaria masquerading as sickle cell crisis with multisystem organ failure.

Transfusion 2018 06 9;58(6):1550-1554. Epub 2018 Mar 9.

Department of Pathology and Laboratory Medicine, Center for Transfusion and Cellular Therapies, Emory University School of Medicine, Atlanta, Georgia.

Background: Fever accompanying vaso-occlusive crisis is a common presentation in patients with sickle cell disease (SCD) and carries a broad differential diagnosis. Here, we report a case of transfusion-transmitted malaria in a patient with SCD presenting with acute vaso-occlusive crisis and rapidly decompensating to multisystem organ failure (MSOF).

Case Report: An 18-year-old African American male with SCD was admitted after multiple days of fever and severe generalized body pain. He received monthly blood transfusions as stroke prophylaxis. A source of infection was not readily identified, but treatment was initiated with continuous intravenous fluids and empiric antibiotics. The patient developed acute renal failure, acute hypoxic respiratory failure, and shock. He underwent red blood cell (RBC) exchange transfusion followed by therapeutic plasma exchange and continuous veno-venous hemodialysis. A manual peripheral blood smear revealed intraerythrocytic inclusions suggestive of Plasmodium, and molecular studies confirmed Plasmodium falciparum infection. Intravenous artesunate was given daily for 1 week. A look-back investigation involving two hospitals, multiple blood suppliers, and state and federal public health departments identified the source of malaria as a unit of RBCs transfused 2 weeks prior to admission.

Conclusions: Clinical suspicion for transfusion-related adverse events, including hemolytic transfusion reactions and transfusion-transmitted infections, should be high in typically and atypically immunocompromised patient populations (like SCD), especially those on chronic transfusion protocols. Manual blood smear review aids in the evaluation of patients with SCD presenting with severe vaso-occlusive crisis and MSOF and can alert clinicians to the need for initiating aggressive therapy like RBC exchange and artesunate therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/trf.14566DOI Listing
June 2018

Recipient priming to one RBC alloantigen directly enhances subsequent alloimmunization in mice.

Blood Adv 2018 01;2(2):105-115

Center for Transfusion Medicine and Cellular Therapies, Department of Laboratory Medicine and Pathology, Emory University School of Medicine, Atlanta, GA; and.

Individuals that become immunized to red blood cell (RBC) alloantigens can experience an increased rate of antibody formation to additional RBC alloantigens following subsequent transfusion. Despite this, how an immune response to one RBC immunogen may impact subsequent alloimmunization to a completely different RBC alloantigen remains unknown. Our studies demonstrate that Kell blood group antigen (KEL) RBC transfusion in the presence of inflammation induced by poly (I:C) (PIC) not only enhances anti-KEL antibody production through a CD4 T-cell-dependent process but also directly facilitates anti-HOD antibody formation following subsequent exposure to the disparate HOD (hen egg lysozyme, ovalbumin, fused to human blood group antigen Duffy b) antigen. PIC/KEL priming of the anti-HOD antibody response required that RBCs express both the KEL and HOD antigens (HOD × KEL RBCs), as transfusion of HOD RBCs plus KEL RBCs or HOD RBCs alone failed to impact anti-HOD antibody formation in recipients previously primed with PIC/KEL. Transfer of CD4 T cells from PIC/KEL-primed recipients directly facilitated anti-HOD antibody formation following (HOD × KEL) RBC transfusion. RBC alloantigen priming was not limited to PIC/KEL enhancement of anti-HOD alloantibody formation, as HOD-reactive CD4 T cells enhanced anti-glycophorin A (anti-GPA) antibody formation in the absence of inflammation following transfusion of RBCs coexpressing GPA and HOD. These results demonstrate that immune priming to one RBC alloantigen can directly enhance a humoral response to a completely different RBC alloantigen, providing a potential explanation for why alloantibody responders may exhibit increased immune responsiveness to additional RBC alloantigens following subsequent transfusion.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/bloodadvances.2017010124DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5787868PMC
January 2018

Pharmacogenetics in Oral Antithrombotic Therapy.

Clin Lab Med 2016 Sep 15;36(3):461-72. Epub 2016 Jun 15.

Department of Pathology and Laboratory Medicine, Emory University Hospital, Emory University School of Medicine, 1364 Clifton Road Northeast, Atlanta, GA 30322, USA.

Certain antithrombotic drugs exhibit high patient-to-patient variability that significantly impacts the safety and efficacy of therapy. Pharmacogenetics offers the possibility of tailoring drug treatment to patients based on individual genotypes, and this type of testing has been recommended for 2 oral antithrombotic agents, warfarin and clopidogrel, to influence use and guide dosing. Limited studies have identified polymorphisms that affect the metabolism and activity of newer oral antithrombotic drugs, without clear evidence of the clinical relevance of such polymorphisms. This article provides an overview of the current status of pharmacogenetics in oral antithrombotic therapy.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.cll.2016.05.002DOI Listing
September 2016

Development and validation of CALR mutation testing for clinical diagnosis.

Am J Clin Pathol 2015 Nov;144(5):738-45

From the Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, GA.

Objectives: To validate a diagnostic assay for detecting CALR mutations in the clinical setting.

Methods: Traditional polymerase chain reaction (PCR) was performed on DNA previously extracted from 60 specimens (30 bone marrow aspirates [BMAs] and 30 peripheral blood [PB] samples) from 55 patients. Nearly all reported CALR mutations are insertions or deletions in exon 9. Therefore, we performed amplicon sizing by capillary electrophoresis and fragment length analysis (FLA) to determine mutation status. Mutations were confirmed by Sanger sequencing.

Results: Fourteen samples from 10 patients with JAK2 and MPL wild-type myeloproliferative neoplasms were positive for CALR mutation. Detected mutations included a 52-base pair (bp) deletion (n = 6), a 5-bp insertion (n = 2), a 31-bp deletion (n = 1), and a 61-bp deletion (n = 1). Sanger sequencing of 15 samples showed 100% concordance. Matched patient PB and BMA samples (n = 5) harbored identical mutations, and samples run multiple times (n = 8) showed 100% reproducibility.

Conclusions: We conclude that CALR mutations may be quickly and accurately detected by FLA of PCR amplicons by capillary electrophoresis. These methods are routine procedures for most molecular laboratories and should allow for straightforward incorporation of the CALR assay into the clinical diagnostic testing menu.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1309/AJCPXPA83MVCTSOQDOI Listing
November 2015

Infantile hemangiomas exhibit neural crest and pericyte markers.

Ann Plast Surg 2015 Feb;74(2):230-6

From the Departments of *Surgery, †Immunobiology, and ‡Dermatology, Yale University School of Medicine, New Haven, CT; and §Vascular Birthmarks Institute of New York, New York, NY.

Infantile hemangiomas (IHs) are the most common benign tumors of infancy and occur with greater than 60% prevalence on the head and neck. Despite their prevalence, little is known about the pathogenesis of this disease. Given the predilection of hemangioma incidence on the face and its nonrandom distribution on embryological fusion plates, we postulated that IHs are derived from pericytes of the neural crest. We performed an analysis on 15 specimens at various stages of the IH progression. Experiments performed included immunohistochemical staining, immunofluorescent staining, quantitative real-time polymerase chain reaction, and flow cytometry. We analyzed a number of cell markers using these methods, including cell markers for the neural crest, pericytes, endothelial cells, stem cells, and the placenta. We observed that neural crest markers such as NG2 and nestin were expressed in the hemangioma samples, in addition tomultiple pericytes markers including δ-like kinase, smooth muscle actin, calponin, and CD90. Stem cell markers such as c-myc, oct4, nanog, and sox2 were also more highly expressed in hemangioma samples compared to controls. Our work demonstrates that hemangiomas express pericyte, neural crest, and stem cell markers suggesting a possible pathogenetic mechanism.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1097/SAP.0000000000000080DOI Listing
February 2015
-->