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1.
Am J Pathol ; 191(1): 90-107, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33157066

RESUMEN

Coronavirus disease 2019 (COVID-19) convalescent plasma has emerged as a promising therapy and has been granted Emergency Use Authorization by the US Food and Drug Administration for hospitalized COVID-19 patients. We recently reported results from interim analysis of a propensity score-matched study suggesting that early treatment of COVID-19 patients with convalescent plasma containing high-titer anti-spike protein receptor binding domain (RBD) IgG significantly decreases mortality. We herein present results from a 60-day follow-up of a cohort of 351 transfused hospitalized patients. Prospective determination of enzyme-linked immunosorbent assay anti-RBD IgG titer facilitated selection and transfusion of the highest titer units available. Retrospective analysis by the Ortho VITROS IgG assay revealed a median signal/cutoff ratio of 24.0 for transfused units, a value far exceeding the recent US Food and Drug Administration-required cutoff of 12.0 for designation of high-titer convalescent plasma. With respect to altering mortality, our analysis identified an optimal window of 44 hours after hospitalization for transfusing COVID-19 patients with high-titer convalescent plasma. In the aggregate, the analysis confirms and extends our previous preliminary finding that transfusion of COVID-19 patients soon after hospitalization with high-titer anti-spike protein RBD IgG present in convalescent plasma significantly reduces mortality.


Asunto(s)
COVID-19/mortalidad , COVID-19/terapia , Inmunoglobulina G/inmunología , Glicoproteína de la Espiga del Coronavirus/inmunología , Adulto , Anciano , Anciano de 80 o más Años , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , Femenino , Estudios de Seguimiento , Hospitalización , Humanos , Inmunización Pasiva , Estimación de Kaplan-Meier , Modelos Lineales , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Modelos de Riesgos Proporcionales , Estudios Retrospectivos , Riesgo , SARS-CoV-2 , Resultado del Tratamiento , Sueroterapia para COVID-19
2.
Am J Pathol ; 190(11): 2290-2303, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32795424

RESUMEN

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has spread globally, and proven treatments are limited. Transfusion of convalescent plasma collected from donors who have recovered from COVID-19 is among many approaches being studied as potentially efficacious therapy. We are conducting a prospective, propensity score-matched study assessing the efficacy of COVID-19 convalescent plasma transfusion versus standard of care as treatment for severe and/or critical COVID-19. We present herein the results of an interim analysis of 316 patients enrolled at Houston Methodist hospitals from March 28 to July 6, 2020. Of the 316 transfused patients, 136 met a 28-day outcome and were matched to 251 non-transfused control COVID-19 patients. Matching criteria included age, sex, body mass index, comorbidities, and baseline ventilation requirement 48 hours from admission, and in a second matching analysis, ventilation status at day 0. Variability in the timing of transfusion relative to admission and titer of antibodies of plasma transfused allowed for analysis in specific matched cohorts. The analysis showed a significant reduction (P = 0.047) in mortality within 28 days, specifically in patients transfused within 72 hours of admission with plasma with an anti-spike protein receptor binding domain titer of ≥1:1350. These data suggest that treatment of COVID-19 with high anti-receptor binding domain IgG titer convalescent plasma is efficacious in early-disease patients.


Asunto(s)
Betacoronavirus/patogenicidad , Infecciones por Coronavirus/mortalidad , Plasma/inmunología , Neumonía Viral/mortalidad , Adulto , Anciano , Anciano de 80 o más Años , Transfusión de Componentes Sanguíneos/métodos , COVID-19 , Infecciones por Coronavirus/diagnóstico , Infecciones por Coronavirus/terapia , Infecciones por Coronavirus/virología , Femenino , Humanos , Inmunización Pasiva/mortalidad , Masculino , Persona de Mediana Edad , Pandemias , Plasma/virología , Neumonía Viral/diagnóstico , Neumonía Viral/virología , Estudios Prospectivos , SARS-CoV-2 , Sueroterapia para COVID-19
3.
Am J Pathol ; 190(8): 1680-1690, 2020 08.
Artículo en Inglés | MEDLINE | ID: mdl-32473109

RESUMEN

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2, has spread globally, and no proven treatments are available. Convalescent plasma therapy has been used with varying degrees of success to treat severe microbial infections for >100 years. Patients (n = 25) with severe and/or life-threatening COVID-19 disease were enrolled at the Houston Methodist hospitals from March 28, 2020, to April 14, 2020. Patients were transfused with convalescent plasma, obtained from donors with confirmed severe acute respiratory syndrome coronavirus 2 infection who had recovered. The primary study outcome was safety, and the secondary outcome was clinical status at day 14 after transfusion. Clinical improvement was assessed on the basis of a modified World Health Organization six-point ordinal scale and laboratory parameters. Viral genome sequencing was performed on donor and recipient strains. At day 7 after transfusion with convalescent plasma, nine patients had at least a one-point improvement in clinical scale, and seven of those were discharged. By day 14 after transfusion, 19 (76%) patients had at least a one-point improvement in clinical status, and 11 were discharged. No adverse events as a result of plasma transfusion were observed. Whole genome sequencing data did not identify a strain genotype-disease severity correlation. The data indicate that administration of convalescent plasma is a safe treatment option for those with severe COVID-19 disease.


Asunto(s)
Infecciones por Coronavirus/terapia , Neumonía Viral/terapia , Adulto , Anciano , Betacoronavirus/genética , COVID-19 , Femenino , Humanos , Inmunización Pasiva , Aplicación de Nuevas Drogas en Investigación , Masculino , Persona de Mediana Edad , Pandemias , SARS-CoV-2 , Texas , Secuenciación Completa del Genoma , Adulto Joven , Sueroterapia para COVID-19
4.
J Clin Apher ; 36(6): 797-801, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34347310

RESUMEN

BACKGROUND: Apheresis procedures require adequate vascular access to achieve adequate inlet flow rates. Central dialysis-type catheters are often used in apheresis, despite their multiple risks. Peripheral venous access is a safe and effective option for many patients. AIM: We previously demonstrated that ultrasound guidance reduces central venous catheter use in apheresis patients; however, no validated criteria for preprocedural evaluation of peripheral veins exist. Here, we hypothesized that ultrasound-based criteria could predict the adequacy of a peripheral vein for apheresis procedures. PATIENTS/METHODS: In this pilot cohort study, we reviewed the procedural outcomes for 50 cases of peripheral venous procedures that used our ultrasound-based criteria. RESULTS: Of the procedures that met our criteria, 96% (46/48) were successfully completed. Overall, our criteria had 100% sensitivity, 50% specificity, 96% positive predictive value, and 100% negative predictive value. CONCLUSION: Our criteria justify an evidence-based ultrasound-guided standard for evaluation of peripheral venous access for apheresis procedures.


Asunto(s)
Eliminación de Componentes Sanguíneos/métodos , Cateterismo Periférico/métodos , Cirugía Asistida por Computador/métodos , Ultrasonografía/métodos , Venas/diagnóstico por imagen , Humanos , Proyectos Piloto , Seguridad
5.
Transfus Apher Sci ; 57(6): 756-758, 2018 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-30274949

RESUMEN

Medication error is a preventable cause of morbidity and death in the inpatient population. We describe a patient with an antifungal overdose treated with therapeutic plasma exchange (TPE). The patient was diagnosed with cryptococcal meningitis and received an acute overdose of amphotericin B deoxycholate instead of the prescribed liposomal amphotericin B. Consequently, the patient developed clinical symptoms including tremors, hypertension, visual hallucinations, vertigo, fever, and acute renal failure. A series of four TPEs was emergently initiated, resulting in complete resolution of most symptoms.


Asunto(s)
Anfotericina B/efectos adversos , Sobredosis de Droga/terapia , Intercambio Plasmático , Utilización de Procedimientos y Técnicas , Anfotericina B/sangre , Humanos , Pruebas de Función Renal , Masculino , Errores de Medicación , Persona de Mediana Edad
6.
Transfusion ; 57(12): 3026-3034, 2017 12.
Artículo en Inglés | MEDLINE | ID: mdl-28960322

RESUMEN

BACKGROUND: Major bleeding in orthotopic liver transplantation is associated with significant morbidity and mortality. Limited literature exists regarding comparative effectiveness of prothrombin complex concentrate and fibrinogen concentrate during orthotopic liver transplantation on blood product utilization. STUDY DESIGN AND METHODS: This retrospective, single-institution study evaluated the impact of prothrombin complex concentrate and fibrinogen concentrate on blood product utilization during orthotopic liver transplantation from December 2013 to April 2016. This study included patients age 18 years or older and excluded patients who received simultaneous heart or lung transplantation or did not meet documentation criteria. A propensity score matching technique was used to match patients who were exposed to prothrombin complex concentrate with unexposed patients, at a 2 to 1 ratio, to control for selection bias. RESULTS: During this study, 212 patients received orthotopic liver transplantation with 39 prothrombin complex concentrate exposures. The matched study population included 39 patients who were exposed to prothrombin complex concentrate and 78 unexposed patients. Overall, 84.6% of patients who were exposed to prothrombin complex concentrate also received concomitant fibrinogen concentrate, whereas only 2% of patients in the control group received fibrinogen concentrate. After propensity score matching, no other factors that were included in the model differed significantly or had a standardized mean difference of 0.11 or greater. There was no statistical difference in the utilization of red blood cells or fresh frozen plasma for the exposed group versus the unexposed group after matching (mean ± standard deviation: red blood cell units, 12.4 ± 8.0 units vs. 9.7 ± 5.6 units [p = 0.058]; fresh-frozen plasma units, 10.0 ± 6.3 vs. 12.7 ± 9.7 units [p = 0.119], respectively). CONCLUSION: The intraoperative use of prothrombin complex concentrate and fibrinogen concentrate during orthotopic liver transplantation did not reduce intraoperative blood product requirements at a single institution.


Asunto(s)
Factores de Coagulación Sanguínea/administración & dosificación , Transfusión Sanguínea/estadística & datos numéricos , Fibrinógeno/administración & dosificación , Cuidados Intraoperatorios/métodos , Trasplante de Hígado/métodos , Adulto , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Puntaje de Propensión , Estudios Retrospectivos
7.
J Clin Apher ; 32(4): 266-269, 2017 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-27509232

RESUMEN

Therapeutic and donor apheresis requires adequate vascular access to achieve inlet flow rates of ∼50-100 mL/min. While central dialysis-type venous catheters can usually provide such access, their use includes several associated risks. Some of these risks can be avoided or diminished if adequate peripheral venous access can be established. Some patients have adequate peripheral veins for apheresis that cannot be readily identified visually or by palpation. We hypothesized that ultrasound-guided peripheral venous access would benefit such patients and would lead to placement of fewer central venous catheters. The technique of ultrasound-guided peripheral access for apheresis has been in use at Houston Methodist Hospital since 2012. We performed a prospective review of patients undergoing inpatient and outpatient apheresis at Houston Methodist Hospital from July 1, 2015 to September 30, 2015, to assess its benefit. During this time, we performed 831 procedures on 186 patients, including 787 therapeutic plasma exchanges, three red blood cell exchanges, 41 peripheral stem cell collections. Ultrasound-guided vascular access was used for 68 procedures (8% of all procedures), including 62 therapeutic plasma exchanges, 4 peripheral stem cell collections, and 2 red blood cell changes. Use of ultrasound-guided peripheral access prevented the placement of central venous catheters in 37 (20%) patients, demonstrating its utility in a busy transfusion service.


Asunto(s)
Eliminación de Componentes Sanguíneos/métodos , Cateterismo Periférico/métodos , Catéteres Venosos Centrales/estadística & datos numéricos , Cateterismo Periférico/estadística & datos numéricos , Endosonografía , Humanos , Centros de Atención Terciaria
8.
J Clin Apher ; 32(6): 584-588, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28455885

RESUMEN

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a rare disease characterized by thrombocytopenia, microangiopathic hemolytic anemia, and acute kidney failure. The disease is difficult to diagnose due to its similarity with other hematologic disorders, such as thrombotic thrombocytopenic purpura (TTP). However, genetic mutations are found in 50-70% of patients with aHUS and can be useful in its diagnosis. STUDY DESIGN AND METHODS: A 40-year-old male presented to our hospital with acute kidney injury, evidenced by high creatinine levels (8.3 mg/dL) and kidney biopsy results. The patient was preliminarily diagnosed with TTP and therapeutic plasma exchange (TPE) was initiated. After four treatments, TPE was discontinued due to lack of ADAMTS13 activity and inhibitor assay results that were not consistent with TTP, improved hematologic laboratory results, and aHUS genetic testing results. RESULTS: Next-generation sequencing showed a rare mutation at a splice site in the gene encoding complement factor I (CFI). Implication of this mutation in aHUS has not been previously described. Treatment with eculizumab reduced creatinine levels below 4.0 mg/dL, and the patient remained on maintenance dosage of eculizumab (1200 mg/14 days) to prevent aHUS recurrence. CONCLUSION: An extremely rare, heterozygous mutation in the gene encoding CFI likely affecting splicing was associated for the first time with aHUS. Sequencing was critical for rapid diagnosis and subsequent timely treatment with eculizumab, which resulted in improved renal function.


Asunto(s)
Síndrome Hemolítico Urémico Atípico/genética , Factor I de Complemento/genética , Sitios de Empalme de ARN/genética , Lesión Renal Aguda/etiología , Adulto , Anticuerpos Monoclonales Humanizados/uso terapéutico , Síndrome Hemolítico Urémico Atípico/complicaciones , Síndrome Hemolítico Urémico Atípico/diagnóstico , Diagnóstico Diferencial , Humanos , Masculino , Mutación , Análisis de Secuencia de ADN
9.
Transfusion ; 54(1): 203-10, 2014 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-23763340

RESUMEN

BACKGROUND: The use of hematopoietic progenitor cell (HPC) transplantation has rapidly expanded in recent years. Currently, several sources of HPCs are available for transplantation including peripheral blood HPCs (PBPCs), cord blood cells, and marrow cells. Of these, PBPC collection has become the major source of HPCs. An important variable in PBPC collection is the response to PBPC mobilization, which varies significantly and sometime causes mobilization failure. STUDY DESIGN AND METHODS: A retrospective study of 69 healthy donors who underwent PBPC donation by leukapheresis was performed. All of these donors received 10 µg/kg/day or more granulocyte-colony-stimulating factor (G-CSF) for 5 days before PBPC harvest. Donor factors were evaluated and correlated with mobilization responses, as indicated by the precollection CD34 count (pre-CD34). RESULTS: Donors with a pre-CD34 of more than 100 × 10(6) /L had higher body mass index (BMI) compared with donors whose pre-CD34 was 38 × 10(6) to 99 × 10(6) /L or less than 38 × 10(6) /L (32.0 ± 1.04 kg/m(2) vs. 28.7 ± 0.93 kg/m(2) vs. 25.9 ± 1.27 kg/m(2) , respectively; p < 0.05). In addition, donors with high BMIs had higher pre-CD34 on a per-kilogram-of-body-weight basis compared with donors with low BMIs. CONCLUSION: BMI is an important factor that affects donor's response to mobilization and consequently the HPC yield. This effect may be due to a relatively high dose of G-CSF administered to donors with higher BMI or due to the presence of unknown intrinsic factors affecting mobilization that correlate with the amount of adipose tissue in each donor.


Asunto(s)
Donantes de Sangre , Índice de Masa Corporal , Movilización de Célula Madre Hematopoyética/métodos , Trasplante de Células Madre Hematopoyéticas , Células Madre Hematopoyéticas/citología , Leucaféresis/métodos , Adulto , Recuento de Células Sanguíneas , Separación Celular , Femenino , Factor Estimulante de Colonias de Granulocitos/administración & dosificación , Células Madre Hematopoyéticas/efectos de los fármacos , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Adulto Joven
10.
Blood Coagul Fibrinolysis ; 35(1): 23-26, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-37994629

RESUMEN

Interpretation of coagulation mixing studies is complicated by interference arising from direct oral anticoagulants (DOACs), which are increasingly prescribed. In this retrospective study, we reviewed 1035 consecutive coagulation mixing studies performed from 2017 to 2021. Three hundred and ninety-nine cases with normal prothrombin time (PT) and activated partial thromboplastin time (aPTT) were excluded. aPTT mixing studies were performed at time 0 and after 60 min of incubation. We confirmed the presence of interfering factors with additional laboratory testing, medication records, and medical history. Mixing corrected most prolonged PT samples (93%), but 32 cases showed incomplete correction. Of these 32 cases, 18 were confounded by DOAC use, and 3 by factor V (FV) inhibitor. We observed an unusual pattern of prolongation of aPTT after incubation, which was previously considered a characteristic of specific factor inhibitors, most commonly FVIII inhibitor. However, we found that lupus anticoagulant (28%) and DOAC (25%) contributed to this pattern similarly as specific factor inhibitors (28%). Coagulation laboratories should be aware of interference arising from DOACs and other factors in PT/aPTT mixing studies, especially in some unusual correction patterns.


Asunto(s)
Anticoagulantes , Coagulación Sanguínea , Humanos , Anticoagulantes/farmacología , Anticoagulantes/uso terapéutico , Pruebas de Coagulación Sanguínea/métodos , Tiempo de Tromboplastina Parcial , Tiempo de Protrombina , Estudios Retrospectivos
12.
Lab Med ; 53(4): e91-e94, 2022 Jul 04.
Artículo en Inglés | MEDLINE | ID: mdl-34940854

RESUMEN

Acquired von Willebrand disease (avWD) arises because of mechanisms that destroy, decrease, absorb, or clear von Willebrand factor (vWF). A 59-year-old man presented with a 3-year history of recurrent gastrointestinal bleeding. Laboratory workup revealed a prolonged platelet function assay-100. The vWF antigen was decreased, and a low vWF immunofunctional activity/antigen ratio, low collagen binding/antigen ratio, and decreased intermediate and high molecular weight multimers were noted. The patient had no high-shear stress conditions, and an antibody-mediated process was suspected. A vWF mixing study showed complete correction of vWF activity, suggesting no direct functional inhibitor. The patient was given a bolus of vWF concentrate with serial measurements of vWF; the vWF half-life was 2.5 hours. The vWF propeptide/antigen ratio was 4:1, supporting a diagnosis of aVWD resulting from increased antibody-mediated vWF clearance. This case study emphasizes the laboratory's role in the diagnosis and treatment of rare, overlooked acquired bleeding disorders.


Asunto(s)
Enfermedades de von Willebrand , Factor de von Willebrand , Pruebas de Coagulación Sanguínea , Hemorragia Gastrointestinal/complicaciones , Hemorragia Gastrointestinal/diagnóstico , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Función Plaquetaria , Enfermedades de von Willebrand/diagnóstico , Enfermedades de von Willebrand/terapia
13.
Commun Biol ; 4(1): 267, 2021 02 24.
Artículo en Inglés | MEDLINE | ID: mdl-33627795

RESUMEN

Millions of individuals who have recovered from SARS-CoV-2 infection may be eligible to participate in convalescent plasma donor programs, yet the optimal window for donating high neutralizing titer convalescent plasma for COVID-19 immunotherapy remains unknown. Here we studied the response trajectories of antibodies directed to the SARS-CoV-2 surface spike glycoprotein and in vitro SARS-CoV-2 live virus neutralizing titers (VN) in 175 convalescent donors longitudinally sampled for up to 142 days post onset of symptoms (DPO). We observed robust IgM, IgG, and viral neutralization responses to SARS-CoV-2 that persist, in the aggregate, for at least 100 DPO. However, there is a notable decline in VN titers ≥160 for convalescent plasma therapy, starting 60 DPO. The results also show that individuals 30 years of age or younger have significantly lower VN, IgG and IgM antibody titers than those in the older age groups; and individuals with greater disease severity also have significantly higher IgM and IgG antibody titers. Taken together, these findings define the optimal window for donating convalescent plasma useful for immunotherapy of COVID-19 patients and reveal important predictors of an ideal plasma donor.


Asunto(s)
Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/sangre , Donantes de Sangre , COVID-19/inmunología , SARS-CoV-2/inmunología , Adulto , Factores de Edad , Anciano , Anticuerpos Neutralizantes/inmunología , Anticuerpos Antivirales/inmunología , COVID-19/sangre , COVID-19/terapia , Femenino , Humanos , Inmunoglobulina G/sangre , Inmunoglobulina G/inmunología , Inmunoglobulina M/sangre , Inmunoglobulina M/inmunología , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Factores de Tiempo , Adulto Joven
14.
J Clin Apher ; 25(6): 323-30, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-20872844

RESUMEN

BACKGROUND: Previous reports had emphasized the importance of humoral immunity in heart failure in humans, primarily determined by the presence of circulating antibodies. However, there is little or no information about the frequency of anticardiac antibodies present in failing human myocardium. METHODS: Clinical data and myocardial tissue samples were analyzed to determine the role of humoral immunity in patients with chronic heart failure (CHF) in different SETTINGS. RESULTS: Anticardiac antibodies were found present in failing hearts but not in normal control hearts. Further, the level of expression of these anticardiac antibodies changed with the severity of the disease state; and in patients with acute heart failure, we found selective activation of B cells. Finally, treatment of CHF patients with therapeutic plasma exchange, a strategy that removes circulating antibodies, resulted in a reduction in anticardiac antibody deposition and improvements in cardiac function. CONCLUSION: These data collectively suggest a role of humoral immunity in the progression of heart failure.


Asunto(s)
Insuficiencia Cardíaca/terapia , Intercambio Plasmático , Adulto , Linfocitos B/inmunología , Enfermedad Crónica , Femenino , Insuficiencia Cardíaca/inmunología , Humanos , Inmunidad Humoral , Inmunoglobulina G/sangre , Activación de Linfocitos , Masculino , Persona de Mediana Edad , Miocardio/inmunología
15.
Lab Med ; 51(3): 310-314, 2020 May 06.
Artículo en Inglés | MEDLINE | ID: mdl-31665395

RESUMEN

A 70-year-old female with a history of hypertension and left A2 segment aneurysm was scheduled for pipeline embolization device (PED) placement. Preinterventional antiplatelet prophylaxis included aspirin and ticagrelor. Unexpectedly, after 13 days of treatment, VerifyNow showed a P2Y12 reaction unit (PRU) value of 216, approximately >5 times the mean PRU of other patients on aspirin and ticagrelor. We confirmed platelet reactivity and ticagrelor resistance with light transmission aggregometry. Antiplatelet therapy was switched to prasugrel, and aspirin was continued. Eight days later, the P2Y12 reaction value (PRU) was 164. PED was placed without complications. Unlike clopidogrel, ticagrelor is a direct P2Y12 inhibitor that does not require metabolism to an active metabolite. Ticagrelor resistance is very rarely reported. To the best of our knowledge, there has been no case of ticagrelor resistance reported in the context of pre-PED placement prophylaxis.


Asunto(s)
Plaquetas/fisiología , Embolización Terapéutica , Pruebas de Función Plaquetaria/métodos , Clorhidrato de Prasugrel/uso terapéutico , Ticagrelor/uso terapéutico , Anciano , Equipos y Suministros , Femenino , Humanos , Agregación Plaquetaria , Ejercicio Preoperatorio , Estudios Prospectivos , Receptores Purinérgicos P2Y12/metabolismo , Resultado del Tratamiento
16.
Acad Pathol ; 7: 2374289520953548, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32995494

RESUMEN

Pathology training programs throughout the United States have endured unprecedented challenges dealing with the ongoing coronavirus disease 2019 pandemic. At Houston Methodist Hospital, the Department of Pathology and Genomic Medicine planned and executed a trainee-oriented, stepwise emergency response. The focus was on optimizing workflows among areas of both clinical and anatomic pathology, maintaining an excellent educational experience, and minimizing trainee exposure to coronavirus disease 2019. During the first phase of the response, trainees were divided into 2 groups: one working on-site and the other working remotely. With the progression of the pandemic, all trainees were called back on-site and further redeployed within our department to meet the significantly increased workload demands of our clinical laboratory services. Adjustments to trainee educational activities included, among others, the organization of a daily coronavirus disease 2019 virtual seminar series. This series served to facilitate communication between faculty, laboratory managers, and trainees. Moreover, it became a forum for trainees to provide updates on individual service workflows and volumes, ongoing projects and research, as well as literature reviews on coronavirus disease 2019-related topics. From our program's experience, redeploying pathology trainees within our department during the coronavirus disease 2019 pandemic resulted in optimization of patient care while ensuring trainee safety, and importantly, helped to maintain continuous high-quality education through active involvement in unique learning opportunities.

17.
J Clin Invest ; 130(12): 6728-6738, 2020 12 01.
Artículo en Inglés | MEDLINE | ID: mdl-32910806

RESUMEN

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) highlights the urgent need for assays that detect protective levels of neutralizing antibodies. We studied the relationship among anti-spike ectodomain (anti-ECD), anti-receptor-binding domain (anti-RBD) IgG titers, and SARS-CoV-2 virus neutralization (VN) titers generated by 2 in vitro assays using convalescent plasma samples from 68 patients with COVID-19. We report a strong positive correlation between both plasma anti-RBD and anti-ECD IgG titers and in vitro VN titers. The probability of a VN titer of ≥160, the FDA-recommended level for convalescent plasma used for COVID-19 treatment, was ≥80% when anti-RBD or anti-ECD titers were ≥1:1350. Of all donors, 37% lacked VN titers of ≥160. Dyspnea, hospitalization, and disease severity were significantly associated with higher VN titer. Frequent donation of convalescent plasma did not significantly decrease VN or IgG titers. Analysis of 2814 asymptomatic adults found 73 individuals with anti-ECD IgG titers of ≥1:50 and strong positive correlation with anti-RBD and VN titers. Fourteen of these individuals had VN titers of ≥1:160, and all of them had anti-RBD titers of ≥1:1350. We conclude that anti-RBD or anti-ECD IgG titers can serve as a surrogate for VN titers to identify suitable plasma donors. Plasma anti-RBD or anti-ECD titers of ≥1:1350 may provide critical information about protection against COVID-19 disease.


Asunto(s)
Anticuerpos Neutralizantes , Anticuerpos Antivirales , COVID-19/terapia , Inmunoglobulina G , SARS-CoV-2 , Adolescente , Adulto , Anciano , Anticuerpos Neutralizantes/administración & dosificación , Anticuerpos Neutralizantes/sangre , Anticuerpos Antivirales/administración & dosificación , Anticuerpos Antivirales/sangre , Femenino , Humanos , Inmunización Pasiva , Inmunoglobulina G/administración & dosificación , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Sueroterapia para COVID-19
18.
bioRxiv ; 2020 Jun 09.
Artículo en Inglés | MEDLINE | ID: mdl-32577662

RESUMEN

Newly emerged pathogens such as SARS-CoV-2 highlight the urgent need for assays that detect levels of neutralizing antibodies that may be protective. We studied the relationship between anti-spike ectodomain (ECD) and anti-receptor binding domain (RBD) IgG titers, and SARS-CoV-2 virus neutralization (VN) titers generated by two different in vitro assays using convalescent plasma samples obtained from 68 COVID-19 patients, including 13 who donated plasma multiple times. Only 23% (16/68) of donors had been hospitalized. We also studied 16 samples from subjects found to have anti-spike protein IgG during surveillance screening of asymptomatic individuals. We report a strong positive correlation between both plasma anti-RBD and anti-ECD IgG titers, and in vitro VN titer. Anti-RBD plasma IgG correlated slightly better than anti-ECD IgG titer with VN titer. The probability of a VN titer ≥160 was 80% or greater with anti-RBD or anti-ECD titers of ≥1:1350. Thirty-seven percent (25/68) of convalescent plasma donors lacked VN titers ≥160, the FDA-recommended level for convalescent plasma used for COVID-19 treatment. Dyspnea, hospitalization, and disease severity were significantly associated with higher VN titer. Frequent donation of convalescent plasma did not significantly decrease either VN or IgG titers. Analysis of 2,814 asymptomatic adults found 27 individuals with anti-RBD or anti-ECD IgG titers of ≥1:1350, and evidence of VN ≥1:160. Taken together, we conclude that anti-RBD or anti-ECD IgG titers can serve as a surrogate for VN titers to identify suitable plasma donors. Plasma anti-RBD or anti-ECD titer of ≥1:1350 may provide critical information about protection against COVID-19 disease.

19.
medRxiv ; 2020 May 13.
Artículo en Inglés | MEDLINE | ID: mdl-32511574

RESUMEN

BACKGROUND: COVID-19 disease, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread globally, and no proven treatments are available. Convalescent plasma therapy has been used with varying degrees of success to treat severe microbial infections for more than 100 years. METHODS: Patients (n=25) with severe and/or life-threatening COVID-19 disease were enrolled at the Houston Methodist hospitals from March 28 to April 14, 2020. Patients were transfused with convalescent plasma obtained from donors with confirmed SARS-CoV-2 infection and had been symptom free for 14 days. The primary study outcome was safety, and the secondary outcome was clinical status at day 14 post-transfusion. Clinical improvement was assessed based on a modified World Health Organization 6-point ordinal scale and laboratory parameters. Viral genome sequencing was performed on donor and recipient strains. RESULTS: At baseline, all patients were receiving supportive care, including anti-inflammatory and anti-viral treatments, and all patients were on oxygen support. At day 7 post-transfusion with convalescent plasma, nine patients had at least a 1-point improvement in clinical scale, and seven of those were discharged. By day 14 post-transfusion, 19 (76%) patients had at least a 1-point improvement in clinical status and 11 were discharged. No adverse events as a result of plasma transfusion were observed. The whole genome sequencing data did not identify a strain genotype-disease severity correlation. CONCLUSIONS: The data indicate that administration of convalescent plasma is a safe treatment option for those with severe COVID-19 disease. Randomized, controlled trials are needed to determine its efficacy.

20.
Leuk Lymphoma ; 58(9): 1-11, 2017 09.
Artículo en Inglés | MEDLINE | ID: mdl-28140714

RESUMEN

Hyperleukocytosis in patients with acute myeloid leukemia (AML) can lead to leukostasis, which if left untreated, has a high mortality. While prompt cytoreductive chemotherapy is essential, treatment with leukapheresis is controversial. This study investigated the outcomes of patients with hyperleukocytosis who received leukapheresis. From 5596 encounters of patients with leukemia seen at Houston Methodist Hospital, we identified 26 patients who had newly diagnosed AML, WBC >50,000/µL, and received leukapheresis. We matched 26 patients who had similar baseline characteristics but did not receive leukapheresis. The primary endpoint was to compare the 28-day mortality rates between the treatment and the control groups. Secondary endpoints were 6-month, 1-year, and 2-year mortality rates. Using multivariate logistic regression analysis, leukapheresis was associated with significantly lower 28-day mortality rate (30.8% vs. 57.7%, p = .022). There was, however, no difference in long-term mortality rate. Our study demonstrates the short-term mortality benefit of using leukapheresis in AML patients presenting with hyperleukocytosis.


Asunto(s)
Leucaféresis , Leucemia Mieloide Aguda/mortalidad , Leucemia Mieloide Aguda/terapia , Adulto , Anciano , Anciano de 80 o más Años , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Médula Ósea/patología , Estudios de Casos y Controles , Femenino , Humanos , Leucaféresis/métodos , Leucemia Mieloide Aguda/patología , Recuento de Leucocitos , Masculino , Persona de Mediana Edad , Sistema de Registros , Estudios Retrospectivos
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