An Overview of Prion Biology and the Role of Blood Filtration in Reducing the Risk of Transfusion-Transmitted Variant Creutzfeldt-Jakob Disease

Cervia, Joseph S.; Sowemimo-Coker, Samuel; Ortolano, Girolamo A.; Wilkins, Karen; Schaffer, Jeffrey; Wortham, Samuel T.

doi:10.1016/j.tmrv.2006.03.007

Cited by 19 publications

(8 citation statements)

References 107 publications

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“…Leukodepletion significantly reduced the risk of vCJD transmission in human following blood transfusion recipients as well [17,18]. However, a recent study by McCutcheon et al, (2011) revealed that leucoreduction did not prevent the BSE transmission to sheep following a single blood transfusion [11].…”

Section: Discussionmentioning

confidence: 99%

Classical scrapie prions in ovine blood are associated with B lymphocytes and platelet-rich plasma

et al. 2011

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BackgroundClassical scrapie is a naturally occurring transmissible spongiform encephalopathy of sheep and goats characterized by cellular accumulation of abnormal isoforms of prion protein (PrPSc) in the central nervous system and the follicles of peripheral lymphoid tissues. Previous studies have shown that the whole blood and buffy coat blood fraction of scrapie infected sheep harbor prion infectivity. Although PrPSc has been detected in peripheral blood mononuclear cells (PBMCs), plasma, and more recently within a subpopulation of B lymphocytes, the infectivity status of these cells and plasma in sheep remains unknown. Therefore, the objective of this study was to determine whether circulating PBMCs, B lymphocytes and platelets from classical scrapie infected sheep harbor prion infectivity using a sheep bioassay.ResultsSerial rectal mucosal biopsy and immunohistochemistry were used to detect preclinical infection in lambs transfused with whole blood or blood cell fractions from preclinical or clinical scrapie infected sheep. PrPSc immunolabeling was detected in antemortem rectal and postmortem lymphoid tissues from recipient lambs receiving PBMCs (15/15), CD72+ B lymphocytes (3/3), CD21+ B lymphocytes (3/3) or platelet-rich plasma (2/3) fractions. As expected, whole blood (11/13) and buffy coat (5/5) recipients showed positive PrPSc labeling in lymphoid follicles. However, at 549 days post-transfusion, PrPSc was not detected in rectal or other lymphoid tissues in three sheep receiving platelet-poor plasma fraction.ConclusionsPrion infectivity was detected in circulating PBMCs, CD72+ pan B lymphocytes, the CD21+ subpopulation of B lymphocytes and platelet-rich plasma of classical scrapie infected sheep using a sheep bioassay. Combining platelets with B lymphocytes might enhance PrPSc detection levels in blood samples.

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Section: Discussionmentioning

confidence: 99%

Classical scrapie prions in ovine blood are associated with B lymphocytes and platelet-rich plasma

et al. 2011

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“…Therefore, leukoreduction was proposed to reduce the risk of vCJD transmission through blood transfusion in humans. 13,23 However, leukoreduction could not prevent BSE transmission through …”

Section: Discussionmentioning

confidence: 99%

“…10 Due to a limited understanding of the properties of PrP Sc in the blood, several restrictions have been imposed on blood donation and the safety of blood-derived products, 11 which has increased the cost of these products. Reports of the transmission of both scrapie and bovine spongiform encephalopathy (BSE) by blood transfusion into sheep 12 and four cases of transmission of variant CreutzfeldtJakob disease (vCJD) through blood transfusions 13 heightened concerns about the safety of blood and blood products. 12 Another report suggested that the prevalence of subclinical vCJD infections could be as high as one in 4,000 people in certain UK cohorts.…”

Section: Introductionmentioning

confidence: 99%

Magnetic microparticle-based multimer detection system for the detection of prion oligomers in sheep

Lim

Kim²,

Lee

et al. 2015

IJN

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Transmissible spongiform encephalopathies (TSEs) are zoonotic fatal neurodegenerative diseases in animals and humans. TSEs are commonly known as bovine spongiform encephalopathy in cattle, scrapie in sheep and goats, chronic wasting disease in cervids, and Creutzfeldt–Jakob disease in humans. The putative transmissible agents are infectious prion proteins (PrP Sc ), which are formed by the conversion of the normal prion protein on the glycoprotein cell surface in the presence of other PrP Sc . Reports of the transmission of TSEs through blood raised considerable concern about the safety of blood and blood products. To address this issue, many laboratories attempted to develop a sensitive and accurate blood diagnostic test to detect PrP Sc . Previously, we reported that, compared to normal controls, the multimer detection system (MDS) was more efficient in detecting PrP Sc in infected hamster brain homogenate, mouse plasma spiked with purified PrP Sc from scrapie mouse brain, and scrapie-infected hamster plasmas. MDS differentiates prion multimers from the cellular monomer through the multimeric expression of epitopes on prion multimers, in contrast to the monomeric form. In this study, MDS detected PrP Sc in plasma samples from scrapie-infected sheep expressing clinical symptoms, demonstrating 100% sensitivity and specificity in these samples. Plasma samples from asymptomatic lambs at the preclinical stage (8-month-old naturally infected offspring of scrapie-infected parents expressing a highly susceptible genotype) tested positive with 50% sensitivity and 100% specificity. In the first of two coded analyses using clinical scrapie-infected sheep and normal healthy samples, MDS successfully identified all but one of the clinical samples with 92% sensitivity and 100% specificity. Similar results were obtained in the second coded analysis using preclinical samples. MDS again successfully identified all but one of the samples with 87% sensitivity and 100% specificity. The false-negative sample was subjected to a protease pretreatment. In conclusion, MDS could accurately detect scrapie in plasma samples at both preclinical and clinical stages. From these studies, we conclude that MDS could be a promising tool for the early diagnosis of TSEs from blood samples.

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“…Moreover, transfusion-related complications such as transfusion reactions, acute lung injury etc. could further complicate trauma patients receiving blood products (21)(22)(23)(24). Thus, Tranexamic acid would reduce transfusion needs and may decrease morbidity and mortality in traumatic patients in hemorrhagic shock (25)(26)(27).…”

Section: Introductionmentioning

confidence: 99%

Effects of Tranexamic Acid on Mortality and Blood Transfusion in Trauma Patients with Significant Hemorrhage: A Clinical Trial

Kakaei

Virani

Hashemzadeh

et al. 2017

ABCMed

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Extensive hemorrhage is a significant cause of mortality in trauma patients. Tranexamic acid has been used for controlling bleeding in cardiovascular surgeries and dental manipulations in patients with hemophilia. However, in traumatic patients with bleeding, its use dates back to more recent years. This study aims to examine the effects of this drug on reducing mortality and blood transfusion rate in trauma patients with significant hemorrhage. A total of 60 patients with significant trauma-related hemorrhage (systolic blood pressure < 90 mmHg/heart rate > 110/min) from the emergency department of Imam Reza Hospital (Tabriz, Iran), were randomized in two groups. The case group received intravenous Tranexamic acid (1 g in 10 min and then 1 g over 8 h). The control group received placebo. Rate of transfusion and rate of one-month mortality were compared between the study groups. The mean ICU stay and overall hospitalization times did not have significant difference between two groups (p<0.05). Transfusion of packed cells was 6.03±1.50 and 6.03±1.22 units in case and control groups respectively. Transfusion of fresh frozen plasma (FFP) was 2.50±1.36 and 3.03±0.96 units in case and control groups respectively (p=0.09). Transfusion of platelets was 0.40±0.20 1.33±0.31 units in case and control groups respectively (p=0.01). Three patients (10%) in the case group and 4 patients (13.3%) in the control group were expired (p=0.50). Tranexamic acid is safe and effective in reducing platelet transfusion rate in patients with trauma-related significant hemorrhage. However, transfusion need and mortality would not reduce by its use in trauma patients.

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An Overview of Prion Biology and the Role of Blood Filtration in Reducing the Risk of Transfusion-Transmitted Variant Creutzfeldt-Jakob Disease

Cited by 19 publications

References 107 publications

Classical scrapie prions in ovine blood are associated with B lymphocytes and platelet-rich plasma

Classical scrapie prions in ovine blood are associated with B lymphocytes and platelet-rich plasma

Magnetic microparticle-based multimer detection system for the detection of prion oligomers in sheep

Effects of Tranexamic Acid on Mortality and Blood Transfusion in Trauma Patients with Significant Hemorrhage: A Clinical Trial

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