The Effects of Chronic Inflammatory Disorders and Storage Lesions on Cytokine Levels in Blood Transfusion Productss

2021 ◽  
Vol 6 (1) ◽  
Author(s):  
Meekers LM ◽  
◽  
Baron B ◽  
Zammit V ◽  
◽  
...  

Whole blood donated for transfusion is processed into four blood products, namely Red Cell Concentrates (RCCs), Fresh Frozen Plasma, Buffy Coats (BCs), and Platelet Concentrates which are obtained by further processing of BCs. These blood products are then given to vulnerable patient cohorts such as anaemic, cancer or post-operative patients requiring RCCs. However, these blood products may contain biomolecules such as inflammatory mediators that may cause adverse yet often overlooked effects in the recipient. Chronic inflammation is characteristic of numerous diseases such as cardiovascular diseases, cancer, type 2 diabetes, rheumatoid arthritis, inflammatory bowel disease, asthma and psoriasis. Such diseases elevate pro-inflammatory cytokines including Interleukin (IL)-1, IL-6 and Tumour Necrosis Factor (TNF)- alpha in the blood. Moreover, pro-inflammatory cytokines also accumulate in blood products during storage, mainly as a result of damaged leucocytes, and may cause Transfusion-Associated Adverse Reactions (TAARs) and transfusion-induced systemic inflammation. Although this is well-known, very little scientific research has investigated the clinical implications and actual adverse effects these abnormal cytokine levels in blood products from donors with underlying chronic inflammatory diseases have on vulnerable recipients, particularly critically-ill patients who are already prone to inflammation.

2021 ◽  
Vol 47 (01) ◽  
pp. 074-083
Author(s):  
Kathryn W. Chang ◽  
Steve Owen ◽  
Michaela Gaspar ◽  
Mike Laffan ◽  
Deepa R. J. Arachchillage

AbstractThis study aimed to determine the impact of major hemorrhage (MH) protocol (MHP) activation on blood administration and patient outcome at a UK major cardiothoracic center. MH was defined in patients (> 16 years) as those who received > 5 units of red blood cells (RBCs) in < 4 hours, or > 10 units in 24 hours. Data were collected retrospectively from patient electronic records and hospital transfusion databases recording issue of blood products from January 2016 to December 2018. Of 134 patients with MH, 24 had activated MHP and 110 did not have activated MHP. Groups were similar for age, sex, baseline hemoglobin, platelet count, coagulation screen, and renal function with no difference in the baseline clinical characteristics. The total number of red cell units (median and [IQR]) transfused was no different in the patients with activated (7.5 [5–11.75]) versus nonactivated (9 [6–12]) MHP (p = 0.35). Patients in the nonactivated MHP group received significantly higher number of platelet units (median: 3 vs. 2, p = 0.014), plasma (median: 4.5 vs. 1.5, p = 0.0007), and cryoprecipitate (median: 2 vs. 1, p = 0.008). However, activation of MHP was associated with higher mortality at 24 hours compared with patients with nonactivation of MHP (33.3 vs. 10.9%, p = 0.005) and 30 days (58.3 vs. 30.9%, p = 0.01). The total RBC and platelet (but not fresh frozen plasma [FFP]) units received were higher in deceased patients than in survivors. Increased mortality was associated with a higher RBC:FFP ratio. Only 26% of patients received tranexamic acid and these patients had higher mortality at 30 days but not at 24 hours. Deceased patients at 30 days had higher levels of fibrinogen than those who survived (median: 2.4 vs. 1.8, p = 0.01). Patients with activated MHP had significantly higher mortality at both 24 hours and 30 days despite lack of difference in the baseline characteristics of the patients with activated MHP versus nonactivated MHP groups. The increased mortality associated with a higher RBC:FFP ratio suggests dilutional coagulopathy may contribute to mortality, but higher fibrinogen at baseline was not protective.


2021 ◽  
pp. 175045892095066
Author(s):  
Minna Kallioinen ◽  
Mika Valtonen ◽  
Marko Peltoniemi ◽  
Ville-Veikko Hynninen ◽  
Tuukka Saarikoski ◽  
...  

Since 2013, rotational thromboelastometry has been available in our hospital to assess coagulopathy. The aim of the study was to retrospectively evaluate the effect of thromboelastometry testing in cardiac surgery patients. Altogether 177 patients from 2012 and 177 patients from 2014 were included. In 2014, the thromboelastometry testing was performed on 56 patients. The mean blood drainage volume decreased and the number of patients receiving platelets decreased between 2012 and 2014. In addition, the use of fresh frozen plasma units decreased, and the use of prothrombin complex concentrate increased in 2014. When studied separately, the patients with a thromboelastometry testing received platelets, fresh frozen plasma, fibrinogen and prothrombin complex concentrate more often, but smaller amounts of red blood cells. In conclusion, after implementing the thromboelastometry testing to the practice, the blood products were given more cautiously overall. The use of thromboelastometry testing was associated with increased possibility to receive coagulation product transfusions. However, it appears that thromboelastometry testing was mostly used to assist in management of major bleeding.


Author(s):  
Rosita Linda ◽  
Devita Ninda

Each year more than 41,000 blood donations are needed every day and 30 million blood components are transfused. Blood products that can be transfused include Packed Red Cells (PRC), Whole Blood (WB), Thrombocyte Concentrate (TC), Fresh Frozen Plasma (FFP). Monitoring Hemoglobin (Hb) after transfusion is essential for assessing the success of a transfusion. The time factor after transfusion for Hemoglobin (Hb) examination needs to be established, analyze to judge the success of a blood transfusion which is performed. The aim of this study was to analyze the differences in changes of hemoglobin between 6-12 hours, and 12-24 hours after-transfusion. This study was retrospective observational using secondary data. The subjects were patients who received PRC, and WBC transfusion. At 6-12, and 12-24 hours after-transfusion, hemoglobin, RBC, and hematocrit were measured. Then the data were analyzed by unpaired t-test. The collected data included the results of the Hb pre-transfusion, 6-12, and 12-24 hours after-transfusion. The subjects of this study were 98 people. The administration of transfusion increased by 10-30% in hemoglobin concentration at 6-12 hours after-transfusion. While at 12-24 hours after-transfusion, hemoglobin after-transfusion increased 15-37% from the baseline. Hemoglobin values were not different at any of the defined after-transfusion times (p = 0.76 (p>0.05)). Hemoglobin values were not different at 6-12 hours, and 12-24 hours after-transfusion.    Keywords: Hemoglobin, measurement, after-transfusion 


2017 ◽  
Vol 7 (2) ◽  
pp. 476-485 ◽  
Author(s):  
Kenny Schlosser ◽  
Mohamad Taha ◽  
Yupu Deng ◽  
Baohua Jiang ◽  
Lauralyn A McIntyre ◽  
...  

Translational research depends on the relevance of animal models and how well they replicate human disease. Here, we investigated plasma levels of three important pro-inflammatory cytokines (TNFα, IL-6, and MCP-1), known to be elevated in human pulmonary arterial hypertension (PAH), and systematically assessed their levels in PAH patients compared to five different rodent models of pulmonary hypertension (PH). A consistent immunoassay platform (Luminex xMAP) and source (Millipore) was used to measure all specimens. PAH patients (n = 29) exhibited significant elevations in all three cytokines (median [IQR] pg/mL; TNFα, 7.0 [4.8–11.7]; IL-6, 9.2 [3.8–17.2]; MCP-1, 109 [65–142]) versus healthy participants (n = 20) (median [IQR] pg/mL; TNFα, 3.0 [2.0–3.6]; IL-6, 1.7 [0.5–7.2]; MCP-1, 79 [49–93]. In contrast, mice with PH established after three weeks of hypoxia (n = 18) or SU5416 plus hypoxia (n = 20) showed no significant change in their plasma cytokine levels versus controls (n = 16), based on three to four independent experiments per group. Similarly, plasma cytokine levels were not elevated in rats with PH established three weeks after monocrotaline (n = 23), eight weeks after SU5416 alone (n = 10) or six to eight weeks after SU5416 plus hypoxia (n = 21) versus controls (n = 36 rats), based on three to eight independent experiments per group. Positive biologic control specimens from sepsis patients (n = 9), cecal-ligation and puncture (CLP)-induced septic mice (n = 6), and lipopolysaccharide-induced septic rats (n = 4) showed robust elevations in all three cytokines. This study suggests that animal models commonly used for the development of novel diagnostic and therapeutic approaches for PAH may have limited construct validity with respect to markers of systemic immune activation seen in human patients.


2021 ◽  
Vol 156 (Supplement_1) ◽  
pp. S156-S157
Author(s):  
M Toprak ◽  
I M Asuzu ◽  
G Morvillo ◽  
F Kiran ◽  
B Chae ◽  
...  

Abstract Introduction/Objective Blood products are precious resources obtained from donors who donate with the intention to help people. These blood products however do not always go to the patients, instead sometimes ending up in the waste. It is inevitable to have some degree of the wastage due to limited blood product shelf life, the inherent need to have stock on hand at all times, and the often unpredictable demand of these products. However, it is possible to minimize the wastage of blood products with careful management of inventories, proper documentation, and education1. In this study, we aim to identify the amount and cost of wasted blood products at Staten Island University Hospital in 2020, the reasons behind the wastage, and solutions to reduce the wastage. Methods/Case Report A retrospective statistical analysis of blood product waste data in 2020 was performed manually with Microsoft Excel. Wastage rate and average cost was calculated, the reasons behind the wastage were identified, and low cost interventions to reduce wastage were planned. Results (if a Case Study enter NA) Total number of the wasted blood product is 425 which represents 3.8% of the total inventory at a total cost of $ 97,309.46 which does not include the hours spend by the lab personnel for the wasted products. The most wasted blood component is fresh frozen plasma (FFP) (Table 1). Thawing the frozen blood products (FFP and cryoprecipitate) significantly shortens the shelf life and triggers a lot of wastage through expiration (Table 2). 32.5 % of the wasted products are wasted due to expiration on the shelf (Diagram 1). Other reasons for the wastage includes patient unreadiness, patient refusal, late return of unused products etc. (Graph 1). Conclusion Educating clinical and laboratory team members about the reasons for wasted blood products and strategies to reduce it might significantly reduce the wastage. Appropriate activation and immediate deactivation of massive transfusion protocol (MTP) would be one of the most important aspect of this education. Expired thawed blood product is the largest contributor to wastage, and MTP is the main reason for thawing. Preventing unnecessary MTP activation minimizes over-thawing and therefore minimizes the expiration and wastage. Documentation of the wasted blood product should be improved to better identify the reasons behind wastage.


Author(s):  
Alison Smith

The transfusion of blood products may be required in the pre- and post-operative periods. However, there are inherent risks associated with blood transfusion, and there is not an unlimited supply of blood donations available. When a patient is anaemic, red blood cells should be transfused to maintain the oxygen-carrying capacity of blood. Blood products, such as platelets and fresh frozen plasma, are transfused to correct a coagulopathy and during major haemorrhage. This chapter reviews the physiology of blood, including ABO compatibility and rhesus status, the main blood products available for transfusion, and transfusion policy, including the treatment of major haemorrhage and the refusal of blood products.


2020 ◽  
pp. 088506662091298
Author(s):  
Suresh Kumar Angurana ◽  
Arun Bansal ◽  
Jayashree Muralidharan ◽  
Ritu Aggarwal ◽  
Sunit Singhi

Objective: To study the baseline cytokine levels and their relation with the severity of illness and mortality in critically ill children with severe sepsis. Design: Subgroup analysis of a randomized, double-blind, placebo-controlled trial. Setting: Pediatric intensive care unit of a tertiary level teaching hospital in India. Patients: Fifty children with severe sepsis aged 3 months to 12 years. Material and Methods: Blood was collected at admission for estimation of pro-inflammatory (interleukin 6 [IL-6], IL-12p70, IL-17, and tumor necrotic factor α [TNF-α]) and anti-inflammatory (IL-10 and transforming growth factor β1 [TGF-β1]) cytokines. Primary Outcome: To find out correlation between cytokine levels and severity of illness scores (Pediatric Risk of Mortality [PRISM] III score, Sequential Organ Failure Assessment [SOFA], and Vasoactive-Inotropic Score [VIS]). Secondary Outcomes: To compare cytokine levels among survivors and nonsurvivors. Results: Baseline pro-inflammatory cytokine levels (median [interquartile range]) were IL-6: 189 (35-285) pg/mL, IL-12p: 48 (28-98) pg/mL, IL-17: 240 (133-345) pg/mL, and TNF-α: 296 (198-430) pg/mL; anti-inflammatory cytokine levels were IL-10: 185 (62-395) pg/mL and TGF-β1: 204 (92-290) ng/mL. Pro-inflammatory cytokines showed positive correlation with PRISM III score: IL-6 (Spearman correlation coefficient, ρ = 0.273, P = .06), IL-12 (ρ = 0.367, P = .01), IL-17 (ρ = 0.197, P = .17), and TNF-α (ρ = 0.284, P = .05), and anti-inflammatory cytokines showed negative correlation: IL-10 (ρ = −0.257, P = .09) and TGF-β (ρ = −0.238, P = .11). Both SOFA and VIS also showed weak positive correlation with IL-12 (ρ = 0.32, P = .03 and ρ = 0.31, P = .03, respectively). Among nonsurvivors (n = 5), the levels of all the measured pro-inflammatory cytokines were significantly higher as compared to survivors, IL-6: 359 (251-499) pg/mL versus 157 (97-223) pg/mL, P < .0001, IL-12p70: 167 (133-196) pg/mL versus 66 (30-100) pg/mL, P < .0001, IL-17: 400 (333-563) pg/mL versus 237 (122-318) pg/mL, P = .009, and TNF-α: 409 (355-503) pg/mL versus 330 (198-415) pg/mL, P = .002, respectively. Conclusion: In critically ill children with severe sepsis, pro-inflammatory cytokines (especially IL-12p70) showed a weak positive correlation with severity of illness and were significantly higher among nonsurvivors.


2020 ◽  
Vol 21 (18) ◽  
pp. 6963
Author(s):  
Jihun Shin ◽  
Hwa Young Song ◽  
Mina Lee

Limonoids, a dominant group of phytochemicals in the Rutaceae family, are known to exhibit several pharmacological activities. To identify natural products having efficacy against inflammatory bowel disease (IBD), we isolated 13 limonoids including a new compound, methyl sudachinoid A, from the seeds of Citrus junos and investigated their anti-inflammatory effects by assessing the expression of pro-inflammatory cytokines in lipopolysaccharide-stimulated RAW 264.7 mouse macrophages and HT-29 human colon epithelial cells. Our findings revealed that limonoids significantly downregulated the pro-inflammatory cytokines, such as interleukin (IL)-1β, IL-6, IL-8, tumor necrosis factor-α, and nuclear transcription factor κB. In particular, sudachinoid-type compounds, methyl sudachinoid A and sudachinoid B, and ichangensin-type compound, 1-O-methyichangensin downregulated the expression of pro-inflammatory cytokines more potently than other limonoids, nomilin and limonin, which have been previously reported to exhibit anti-inflammatory activities in other cells; nomilin and limonin were therefore employed as positive controls in this study. Herein, we reveal that the anti-inflammatory activities of limonoids including a new compound methyl sudachinoid A from C. junos were mediated via the downregulation of pro-inflammatory cytokines and these limonoids can be employed as potential therapeutic phytochemicals for IBD.


1990 ◽  
Vol 63 (01) ◽  
pp. 027-030 ◽  
Author(s):  
Maureen Andrew ◽  
Barbara Schmidt ◽  
Lesley Mitchell ◽  
Bosco Paes ◽  
Frederick Ofosu

SummaryThe ability to generate thrombin is decreased and delayed in plasma from the healthy newborn infant compared to the adult. Only 30 to 50% of peak adult thrombin activity can be produced in neonatal plasma. To test whether this observation can be explained by the low neonatal levels of the contact or vitamin K dependent factors, we measured neonatal thrombin generation after raising the concentration of these factors to adult values. We also determined whether the addition of a variety of blood products to neonatal plasma improved thrombin generation. An amidolytic method was used to quantitate intrinsic (APTT) and extrinsic (PT) pathway thrombin generation in defibrinated pooled cord plasma from healthy term infants. Added individually, factors VII, IX, X or the contact factors (CF) failed to alter the rate or the total amount of thrombin generated in neonatal plasma. In contrast, the addition of prothrombin increased the total amount of thrombin generated to above adult values in both the APTT and the PT systems but did not alter the rate of thrombin generation. The rate of thrombin generation in cord plasma shortened after a combination of II, IX, X and CF was added to the APTT system or II, VII and X to the PT system. In both systems, the total amount of thrombin generated was linearly related to the initial prothrombin concentration. Each of fresh frozen plasma, cryoprecipitate, plasma from platelet concentrates, or factor IX concentrate (in amounts used therapeutically) caused an increase in the total amount of thrombin generated which was related to the increase in prothrombin concentration. Thus, the total amount of thrombin generated in newborn plasma is critically dependent on the prothrombin concentration whereas the rate at which thrombin is generated is dependent on the levels of many other coagulation proteins in combination.


2019 ◽  
Vol 3 (Supplement_1) ◽  
pp. S768-S769
Author(s):  
Bérénice A Benayoun ◽  
Ryan A Lu ◽  
Nirmal K Sampathkumar

Abstract The current cohort of human supercentenarians reveals a surprising predictor for achieving such an exceptional longevity: being female. Indeed, out of 34 living supercentenarians, 33 are women. We obtained samples from 4 and 20 months old female and male mice. Our data indicates that cytokine levels are differentially regulated with age in males vs. females, with pro-inflammatory cytokines specifically upregulated in the serum of old males, but not females. Because of the central role of macrophages in inflammation and their infiltration in tissues with age, we have generated RNA-seq from purified macrophages of aging animals. Female macrophages displayed ~7-20-fold more transcriptional remodeling with aging than males. Pathways specifically downregulated in females with aging included lysosome, inflammation and phagolysosome. Consistently, our data shows that aged female, but not male macrophages, display decreased phagocytic efficiency. Our results support the notion that there are differences in aging trajectories in female vs. male mice.


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