Clinical Course and Flow Cytometric Analysis of Paroxysmal Nocturnal Hemoglobinuria in the United States and Japan

Medicine ◽  
2004 ◽  
Vol 83 (3) ◽  
pp. 193-207 ◽  
Author(s):  
Jun-Ichi Nishimura ◽  
Yuzuru Kanakura ◽  
Russell E. Ware ◽  
Tsutomu Shichishima ◽  
Hideki Nakakuma ◽  
...  
Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 34-36
Author(s):  
Anita Mazloom ◽  
Neil Nimkar ◽  
Sonal Paul ◽  
Ayanna Baptiste

Introduction: The outbreak of a novel infection, COVID-19, has greatly impacted the well-being of individuals worldwide. Persons with sickle cell disease (SCD) constitute a vulnerable population, subject to health disparities, who may have worse outcomes from COVID-19. Within the United States, New York has a large population of patients with SCD. Here, we analyze the clinical course and outcomes of SCD patients with COVID-19 who were admitted to a community teaching hospital in Brooklyn, NY. Methods: We conducted a retrospective chart review of adult patients with SCD hospitalized with laboratory- confirmed COVID-19. Electronic health records were reviewed to identify patients and analyze their clinical course. Clinical characteristics, laboratory and radiology data were assessed. Rates of acute chest syndrome (ACS), acute kidney injury (AKI) and venous thromboembolism (VTE) were determined. ACS was defined by the presence of fever and/or respiratory symptoms accompanied by a new pulmonary infiltrate on chest Xray. Data on use of blood transfusion, treatments, length of stay and mortality were collected. Results: Between March 1 to June 30, 2020, 53 adults with SCD were hospitalized at our institution. Of these, 13 patients had COVID-19 infection. The mean (±SD) age of the COVID-19 patients was 34±10 years (range, 22 to 50) with 54% being female. Seven patients (54%) were Hb SS, and 6 patients (46%) were Hb SC. Comorbid conditions included Diabetes Mellitus (1 patient), SLE (1), End-stage renal disease (1), prior VTE (4) and Avascular necrosis of hip (3). Four patients were on hydroxyurea. Clinical, laboratory and radiological findings are summarized in Table 1. While all the Hb SS patients presented with vaso-occlusive crisis, 4 of the 6 patients with Hb SC did not have symptoms of pain crisis. Chest pain and cough were the most common symptoms at presentation. During the hospital stay, 12 patients (92%) had at least one febrile episode >38°C, with 77% having recurrent fevers above 38.5°C. Eleven patients (85%) met criteria for ACS. Seventy-seven percent of all patients required supplemental oxygen. Nine patients (69%) were transfused, with 4 patients undergoing exchange transfusion. Sixty-seven percent of the transfused patients were transfused within 48 hours of admission. No patients required intubation or mechanical ventilation and none were admitted to the intensive care unit (ICU). Five patients (38.5%) received hydroxychloroquine while 84.6% were treated with antibiotics. No patient received remdesivir. Three patients (23%) developed AKI: of these, one patient required acute hemodialysis, the other two cases were mild with peak creatinine less than 2.0 mg/dl. Ninety-two percent of patients received prophylactic anticoagulation with either unfractionated heparin, enoxaparin or fondaparinux. One patient who did not receive an anticoagulant due to thrombocytopenia developed an acute deep vein thrombosis which was also catheter-related. Of note, during the initial phase of the pandemic standard dosing of prophylactic anticoagulants were used but in the later months, some patients received higher prophylactic doses in keeping with hospital protocol. The median length of hospital stay was 9.4 days (interquartile range, 8.1 to 13.3). There were no deaths - all patients were discharged home. Summary: Panepinto et al (Emerg Infect Dis.) reported a mortality of 7% in 178 SCD patients with COVID-19 in the United States. Other published reports have detailed more favorable outcomes (Arlet et al, Lancet and Appiah-Kubi et al, Br J Haematol.). In this small retrospective analysis of hospitalized SCD patients, there was no mortality. Acute chest syndrome was the most common complication observed. VTE and severe AKI were infrequent. Blood transfusion was performed in the majority of patients (69%); two thirds of the patients transfused received blood within 48 hours of hospitalization. There were no ICU admissions and no use of mechanical ventilation indicative perhaps of less severe COVID-19 disease. This may have been due to the young age of the cohort. Early use of blood transfusion may have been a factor in reducing disease severity and improving outcomes. The best approach to managing these patients is unclear. We advocate for the development and dissemination of evidence-based guidelines to manage SCD patients with COVID-19 to reduce morbidity and mortality in this at-risk population. Disclosures No relevant conflicts of interest to declare.


Genome ◽  
2009 ◽  
Vol 52 (2) ◽  
pp. 148-155 ◽  
Author(s):  
Schuyler S. Korban ◽  
Wannasiri Wannarat ◽  
Charlotte M. Rayburn ◽  
Tatiana C. Tatum ◽  
A. Lane Rayburn

The genus Malus has anywhere between 25 and 33 species along with several subspecies. Malus species as well as clones within the same species have varying ploidy levels, as these are more than likely collected from different trees and (or) from different locations. In recent years, large numbers of Malus germplasm accessions have been collected and maintained at the United States National Germplasm Clonal Repository; however, genome sizes of this material have not yet been determined. In this study, leaf tissues from young grafted trees of 100 Malus species and hybrids growing in a nursery at the University of Illinois were collected and immediately used for extracting nuclei. Leaf tissues from apple and maize line W-22, used as an internal standard, were co-chopped and prepared for flow cytometric analysis. Apple nuclei were stained with propidium iodide, an intercalating dye, and a minimum of 8000 nuclei per sample were analyzed. Mean fluorescence of apple nuclei was then determined. A total of four replications per sample was used. Among 100 Malus accessions analyzed, one tetraploid, three triploid, and 96 diploid genotypes were identified. Significant differences in genome size were identified among the three ploidy types observed and also within diploid genotypes. The 2C mean value for tetraploids was 3.13 pg and ranged from 2.27 to 2.41 pg for triploids, whereas 2C values for diploids ranged between 1.44 and 1.72 pg. In addition, leaf impressions of young, fully expanded leaves were collected from young trees of 10 selected genotypes based on their ploidy and flow cytometric analysis and used to measure the nucleotypic parameter stomatal length. Ten stomata were measured per slide, three slides were analyzed per leaf, and three leaves were analyzed per accession. Overall, mean length of stomata ranged between 19.47 μm (diploid) and 27.6 μm (tetraploid), indicating that stomatal length in a tetraploid Malus genotype was 1.4-fold higher than that of a diploid genotype. A positive correlation between genome size and the nucleotypic parameter stomatal length was observed.


Author(s):  
Michael W Fried ◽  
Julie M Crawford ◽  
Andrea R Mospan ◽  
Stephanie E Watkins ◽  
Breda Munoz ◽  
...  

Abstract Background As coronavirus disease 2019 (COVID-19) disseminates throughout the United States, a better understanding of the patient characteristics associated with hospitalization, morbidity, and mortality in diverse geographic regions is essential. Methods Hospital chargemaster data on adult patients with COVID-19 admitted to 245 hospitals across 38 states between 15 February and 20 April 2020 were assessed. The clinical course from admission, through hospitalization, and to discharge or death was analyzed. Results A total of 11 721 patients were included (majority were >60 years of age [59.9%] and male [53.4%]). Comorbidities included hypertension (46.7%), diabetes (27.8%), cardiovascular disease (18.6%), obesity (16.1%), and chronic kidney disease (12.2%). Mechanical ventilation was required by 1967 patients (16.8%). Mortality among hospitalized patients was 21.4% and increased to 70.5% among those on mechanical ventilation. Male sex, older age, obesity, geographic region, and the presence of chronic kidney disease or a preexisting cardiovascular disease were associated with increased odds of mechanical ventilation. All aforementioned risk factors, with the exception of obesity, were associated with increased odds of death (all P values < .001). Many patients received investigational medications for treatment of COVID-19, including 48 patients on remdesivir and 4232 on hydroxychloroquine. Conclusions This large observational cohort describes the clinical course and identifies factors associated with the outcomes of hospitalized patients with COVID-19 across the United States. These data can inform strategies to prioritize prevention and treatment for this disease.


1983 ◽  
Vol 309 (5) ◽  
pp. 257-264 ◽  
Author(s):  
Paul A. Bunn ◽  
Geraldine P. Schechter ◽  
Elaine Jaffe ◽  
Douglas Blayney ◽  
Robert C. Young ◽  
...  

2017 ◽  
Vol 37 (4) ◽  
pp. 855-867 ◽  
Author(s):  
Mike Keeney ◽  
Andrea Illingworth ◽  
D. Robert Sutherland

Blood ◽  
1993 ◽  
Vol 81 (7) ◽  
pp. 1855-1862 ◽  
Author(s):  
T Shichishima ◽  
T Terasawa ◽  
C Hashimoto ◽  
H Ohto ◽  
M Takahashi ◽  
...  

We performed a flow cytometric analysis using monoclonal antibodies to decay accelerating factor (DAF) and CD59/membrane attack complex inhibitory factor (CD59/MACIF) in order to investigate the leukemic cells and erythrocytes from a patient with paroxysmal nocturnal hemoglobinuria (PNH) who developed acute myelocytic leukemia. In May 1990, the leukemic cells comprised 70% of the mononuclear cells in the bone marrow and 76% of those in the peripheral blood. They consisted of a mixture of positive and negative populations, including single DAF- positive cells. In August 1990, almost 100% of the peripheral mononuclear cells were leukemic blasts, and these consisted of a single population with reduced DAF expression. Single-color flow cytometric analysis showed that the leukemic cells lacked CD59/MACIF, while control leukemic cells (n = 3) expressed both DAF and CD59/MACIF. Leukemic blasts from this patient and six control patients expressed lymphocyte function-associated antigen 3 and FcIII receptors (CD 16) both before and after treatment with phosphatidylinositol-specific phospholipase C. The patient's erythrocytes lacking DAF and CD59/MACIF expression corresponded to the proportion of complement-sensitive cells at the onset of acute leukemia. These DAF- and CD59/MACIF-deficient erythrocytes disappeared almost completely with progression of the leukemia. In conclusion, it appears that the expression of glycosylphosphatidylinositol-linked membrane proteins by leukemic cells was heterogeneous and discordant in our patient, and that the leukemic cells were derived from the PNH clone because of their deficiency of CD59/MACIF. It is also suggested that DAF could compete more effectively than CD59/MACIF for a limited number of anchor molecules available on the proliferating leukemic cells.


TH Open ◽  
2020 ◽  
Vol 04 (01) ◽  
pp. e36-e39
Author(s):  
Christina Griesser ◽  
Michael Myskiw ◽  
Werner Streif

AbstractParoxysmal nocturnal hemoglobinuria (PNH) is a chronic disease caused by complement-mediated hemolysis. Clinical symptoms include intravascular hemolysis, nocturnal hemoglobinuria, thromboses, cytopenia, fatigue, abdominal pain, and a strong tendency toward bone marrow failure. It is a rare disease, especially in children, with high mortality rates without appropriate treatment.We here present the case of a 17-year-old girl with unprovoked muscle vein thrombosis. Flow cytometric analysis showed deficiency of glycosyl-phosphatidylinositol-anchored membrane proteins on all three hematopoietic cell lines and confirmed the diagnosis of PNH. Treatment with the monoclonal antibody eculizumab achieved long-term remission.As flow cytometry is normally not part of the routine diagnostics for pediatric thrombosis, awareness is crucial and PNH is important to consider in all children with thrombosis at atypical sites and abnormalities in blood counts with regard to hemolysis and cytopenia.


PEDIATRICS ◽  
1987 ◽  
Vol 79 (4) ◽  
pp. 618-621
Author(s):  
Anthony Alario ◽  
Gary Price ◽  
Richard Stahl ◽  
Peggy Bancroft

Several species of spiders indigenous to the United States can cause a painful and necrotic wound. Recognition of the characteristic clinical course is important to avoid potential complications. A case report and review are presented.


Sign in / Sign up

Export Citation Format

Share Document