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Journal of Thrombosis and Haemostasis :... Jul 2020Glycosylation is highly prevalent, and also one of the most complex and varied posttranslational modifications. This large glycan diversity results in a wide range of... (Review)
Review
Glycosylation is highly prevalent, and also one of the most complex and varied posttranslational modifications. This large glycan diversity results in a wide range of biological functions. Functional diversity includes protein degradation, protein clearance, cell trafficking, cell signaling, host-pathogen interactions, and immune defense, including both innate and acquired immunity. Glycan-based ABO(H) antigens are critical in providing compatible products in the setting of transfusion and organ transplantation. However, evidence also suggests that ABO expression may influence cardiovascular disease, thrombosis, and hemostasis disorders, including alterations in platelet function and von Willebrand factor blood levels. Glycans also regulate immune and hemostasis function beyond ABO(H) antigens. Mutations in glycogenes (PIGA, COSMC) lead to serious blood disorders, including Tn syndrome associated with hyperagglutination, hemolysis, and thrombocytopenia. Alterations in genes responsible for sialic acids (Sia) synthesis (GNE) and UDP-galactose (GALE) and lactosamine (LacNAc) (B4GALT1) profoundly affect circulating platelet counts. Desialylation (removal of Sia) is affected by human and pathogenic neuraminidases. This review addresses the role of glycans in transfusion medicine, hemostasis and thrombosis, and red blood cell and platelet survival.
Topics: Blood Platelets; Erythrocytes; Glycosylation; Humans; Transfusion Medicine; von Willebrand Factor
PubMed: 32350996
DOI: 10.1111/jth.14874 -
BMJ Open May 2022Globally, haemorrhage is the leading cause of both maternal mortality and preventable trauma death. For patients suffering from haemorrhage, prompt blood transfusion can...
INTRODUCTION
Globally, haemorrhage is the leading cause of both maternal mortality and preventable trauma death. For patients suffering from haemorrhage, prompt blood transfusion can be life-saving; however, safe and sufficient blood is often lacking in low-resource settings (LRS). Autotransfusion (AT), in which the patient's own blood is collected and transfused back, is an established alternative to donor blood transfusions, although one that is primarily performed with advanced AT systems. Research on basic AT in LRS is scarce. Therefore, we aimed to consolidate all available information on the current use of basic AT in LRS and to identify AT techniques and devices described for use in such settings.
DESIGN
Scoping review.
METHODS
We systematically searched four key databases: PubMed, Web of Science, Global Health and Cochrane Library as well as several grey literature databases and databases of relevant organisations. The final search was conducted on 22 April 2019. We included all types of studies referring to any information on basic AT used or sought to be used in LRS, published in English and dated after 31 December 2008. We synthesised the data from the included studies, results were charted or summarised narratively.
RESULTS
Some 370 records were reviewed, yielding 38 included documents. We found a paucity of scientific evidence as well as contradictory information on the extent of AT use and that AT use is largely undocumented. The most commonly described indications were haemoperitoneum (primarily among obstetric patients) and haemothorax. We identified three AT techniques used in LRS. Additionally, two new devices and one filter are described for potential use in LRS.
CONCLUSIONS
Basic AT is practiced for certain obstetric and trauma indications. However, context-specific studies are needed to determine the technique's safety and effectiveness. Extent of use is difficult to assess, but our results indicate that basic AT is not a widely established practice in LRS. Future research should address the bottlenecks hampering basic AT availability. New AT devices for use in LRS are described, but their utility and cost-effectiveness remain to be assessed.
Topics: Blood Transfusion, Autologous; Cost-Benefit Analysis; Female; Hemorrhage; Humans; Pregnancy
PubMed: 35577473
DOI: 10.1136/bmjopen-2021-056018 -
Cancer Control : Journal of the Moffitt... Jan 2015Platelet transfusion is a critical and often necessary aspect of managing cancer. Low platelet counts frequently lead to bleeding complications; however, the drugs used... (Review)
Review
BACKGROUND
Platelet transfusion is a critical and often necessary aspect of managing cancer. Low platelet counts frequently lead to bleeding complications; however, the drugs used to combat malignancy commonly lead to decreased production and destruction of the very cell whose function is essential to stop bleeding. The transfusion of allogeneic platelet products helps to promote hemostasis, but alloimmunization may make it difficult to manage other complications associated with cancer.
METHODS
The literature relating to platelet transfusion in patients with cancer was reviewed.
RESULTS
Platelet storage, dosing, transfusion indications, and transfusion response are essential topics for health care professionals to understand because many patients with cancer will require platelet transfusions during the course of treatment. The workup and differentiation of non-immune-mediated compared with immune-mediated platelet refractoriness are vital because platelet management is different between types of refractoriness.
CONCLUSIONS
A combination of appropriate utilization of platelet inventory and laboratory testing coupled with communication between those caring for patients with cancer and those providing blood products is essential for effective patient care.
Topics: Blood Platelets; Hemorrhage; Humans; Neoplasms; Platelet Count; Platelet Transfusion; Thrombocytopenia
PubMed: 25504278
DOI: 10.1177/107327481502200107 -
Biomolecules Oct 2022Haemorrhage into the brain parenchyma can be devastating. This manifests as spontaneous intracerebral haemorrhage (ICH) after head trauma, and in the context of vascular... (Review)
Review
Haemorrhage into the brain parenchyma can be devastating. This manifests as spontaneous intracerebral haemorrhage (ICH) after head trauma, and in the context of vascular dementia. Randomised controlled trials have not reliably shown that haemostatic treatments aimed at limiting ICH haematoma expansion and surgical approaches to reducing haematoma volume are effective. Consequently, treatments to modulate the pathophysiological responses to ICH, which may cause secondary brain injury, are appealing. Following ICH, microglia and monocyte derived cells are recruited to the peri-haematomal environment where they phagocytose haematoma breakdown products and secrete inflammatory cytokines, which may trigger both protective and harmful responses. The transcription factor Nrf2, is activated by oxidative stress, is highly expressed by central nervous system microglia and macroglia. When active, Nrf2 induces a transcriptional programme characterised by increased expression of antioxidant, haem and heavy metal detoxification and proteostasis genes, as well as suppression of proinflammatory factors. Therefore, Nrf2 activation may facilitate adaptive-protective immune cell responses to ICH by boosting resistance to oxidative stress and heavy metal toxicity, whilst limiting harmful inflammatory signalling, which can contribute to further blood brain barrier dysfunction and cerebral oedema. In this review, we consider the responses of immune cells to ICH and how these might be modulated by Nrf2 activation. Finally, we propose potential therapeutic strategies to harness Nrf2 to improve the outcomes of patients with ICH.
Topics: Humans; NF-E2-Related Factor 2; Antioxidants; Cerebral Hemorrhage; Hematoma; Phagocytosis; Hemostatics; Cytokines; Heme
PubMed: 36291647
DOI: 10.3390/biom12101438 -
Platelets Dec 2023When platelet concentrates (PCs) were first introduced in the 1960s as a blood component therapy, they were stored in the cold. As platelet transfusion became more... (Review)
Review
When platelet concentrates (PCs) were first introduced in the 1960s as a blood component therapy, they were stored in the cold. As platelet transfusion became more important for the treatment of chemotherapy-induced thrombocytopenia, research into ways to increase supply intensified. During the late 1960s/early 1970s, it was demonstrated through radioactive labeling of platelets that room temperature platelets (RTP) had superior post-transfusion recovery and survival compared with cold-stored platelets (CSP). This led to a universal switch to room temperature storage, despite CSP demonstrating superior hemostatic effectiveness upon being transfused. There has been a global resurgence in studies into CSP over the last two decades, with an increase in the use of PC to treat acute bleeding within hospital and pre-hospital care. CSP demonstrate many benefits over RTP, including longer shelf life, decreased bacterial risk and easier logistics for transport, making PC accessible in areas where they have not previously been, such as the battlefield. In addition, CSP are reported to have greater hemostatic function than RTP and are thus potentially better for the treatment of bleeding. This review describes the history of CSP, the functional and metabolic assays used to assess the platelet storage lesion in PC and the current research, benefits and limitations of CSP. We also discuss whether the application of new technology for studying mitochondrial and glycolytic function in PC could provide enhanced understanding of platelet metabolism during storage and thus contribute to the continued improvements in the manufacturing and storage of PC.
Topics: Humans; Blood Preservation; Blood Platelets; Cold Temperature; Platelet Transfusion; Hemorrhage; Energy Metabolism
PubMed: 36922733
DOI: 10.1080/09537104.2023.2188969 -
Journal of Cellular and Molecular... Feb 2018The products of erythrocyte lyses, haemoglobin (Hb) and haem, are recognized as neurotoxins and the main contributors to delayed cerebral oedema and tissue damage after... (Review)
Review
The products of erythrocyte lyses, haemoglobin (Hb) and haem, are recognized as neurotoxins and the main contributors to delayed cerebral oedema and tissue damage after intracerebral haemorrhage (ICH). Finding a means to efficiently promote absorption of the haemolytic products (Hb and haem) around the bleeding area in the brain through stimulating the function of the body's own garbage cleaning system is a novel clinical challenge and critical for functional recovery after ICH. In this review, available information of the brain injury mechanisms underlying ICH and endogenous haematoma scavenging system is provided. Meanwhile, potential intervention strategies are discussed. Intracerebral blood itself has 'toxic' effects beyond its volume effect after ICH. Haptoglobin-Hb-CD163 as well as haemopexin-haem-LRP1 is believed to be the most important endogenous scavenging pathway which participates in blood components resolution following ICH. PPARγ-Nrf2 activates the aforementioned clearance pathway and then accelerates haematoma clearance. Meanwhile, the scavenger receptors as novel targets for therapeutic interventions to treat ICH are also highlighted.
Topics: Animals; Brain Injuries; Cerebral Hemorrhage; Hematoma; Humans; Models, Biological; Phagocytosis; Receptors, Scavenger
PubMed: 29278306
DOI: 10.1111/jcmm.13441 -
Transfusion and Apheresis Science :... Aug 2021Blood transfusions come with risks and high costs, and should be utilized only when clinically indicated. Decisions to transfuse are however not always well informed,...
Blood transfusions come with risks and high costs, and should be utilized only when clinically indicated. Decisions to transfuse are however not always well informed, and lack of clinician knowledge and education on good clinical transfusion practices contribute to the inappropriate use of blood. Low and middle-income countries in particular take much strain in their efforts to address blood safety challenges, demand-supply imbalances, high blood costs as well as high disease burdens, all of which impact blood usage and blood collections. Patient blood management (PBM), which is a patient-focused approach aimed at improving patient outcomes by preemptively diagnosing and correcting anaemia and limiting blood loss by cell salvage, coagulation optimization and other measures, has become a major approach to addressing many of the challenges mentioned. The associated decrease in the use of blood and blood products may be perceived as being in competition with blood conservation measures, which is the more traditional, but primarily product-focused approach. In this article, we hope to convey the message that PBM and blood conservation should not be seen as competing concepts, but rather complimentary strategies with the common goal of improving patient care. This offers opportunity to improve the culture of transfusion practices with relief to blood establishments and clinical services, not only in South Africa and LMICs, but everywhere. With the COVID-19 pandemic impacting blood supplies worldwide, this is an ideal time to call for educational interventions and awareness as an active strategy to improve transfusion practices, immediately and beyond.
Topics: Anemia; Blood Banks; Blood Loss, Surgical; Blood Safety; Blood Transfusion; Blood-Borne Infections; Bloodless Medical and Surgical Procedures; COVID-19; Clinical Decision-Making; Developing Countries; Donor Selection; Evidence-Based Medicine; Female; HIV Infections; Health Services Needs and Demand; Humans; Male; Pandemics; Postpartum Hemorrhage; Practice Guidelines as Topic; Pregnancy; Prevalence; Procedures and Techniques Utilization; SARS-CoV-2; South Africa; Transfusion Medicine
PubMed: 34353706
DOI: 10.1016/j.transci.2021.103207 -
Pediatric Critical Care Medicine : a... Jan 2022To present consensus statements and supporting literature for plasma and platelet product variables and related laboratory testing for transfusions in general critically...
What Laboratory Tests and Physiologic Triggers Should Guide the Decision to Administer a Platelet or Plasma Transfusion in Critically Ill Children and What Product Attributes Are Optimal to Guide Specific Product Selection? From the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of...
OBJECTIVES
To present consensus statements and supporting literature for plasma and platelet product variables and related laboratory testing for transfusions in general critically ill children from the Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding.
DESIGN
Systematic review and consensus conference of international, multidisciplinary experts in platelet and plasma transfusion management of critically ill children.
SETTING
Not applicable.
PATIENTS
Critically ill pediatric patients at risk of bleeding and receiving plasma and/or platelet transfusions.
INTERVENTIONS
None.
MEASUREMENTS AND MAIN RESULTS
A panel of 10 experts developed evidence-based and, when evidence was insufficient, expert-based statements for laboratory testing and blood product attributes for platelet and plasma transfusions. These statements were reviewed and ratified by the 29 Transfusion and Anemia EXpertise Initiative - Control/Avoidance of Bleeding experts. A systematic review was conducted using MEDLINE, EMBASE, and Cochrane Library databases, from inception to December 2020. Consensus was obtained using the Research and Development/University of California, Los Angeles Appropriateness Method. Results were summarized using the Grading of Recommendations Assessment, Development, and Evaluation method. We developed five expert consensus statements and two recommendations in answer to two questions: what laboratory tests and physiologic triggers should guide the decision to administer a platelet or plasma transfusion in critically ill children; and what product attributes are optimal to guide specific product selection?
CONCLUSIONS
The Transfusion and Anemia EXpertise Initiative-Control/Avoidance of Bleeding program provides some guidance and expert consensus for the laboratory and blood product attributes used for decision-making for plasma and platelet transfusions in critically ill pediatric patients.
Topics: Anemia; Blood Component Transfusion; Child; Critical Care; Critical Illness; Erythrocyte Transfusion; Evidence-Based Medicine; Hemorrhage; Humans; Plasma; Platelet Transfusion
PubMed: 34989701
DOI: 10.1097/PCC.0000000000002854 -
Health Technology Assessment... Oct 2021Tranexamic acid reduces blood loss in surgery and the risk of death in trauma patients. Meta-analyses of small trials suggest that tranexamic acid decreases the number... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Tranexamic acid reduces blood loss in surgery and the risk of death in trauma patients. Meta-analyses of small trials suggest that tranexamic acid decreases the number of deaths from gastrointestinal bleeding, but these meta-analyses are prone to selection bias.
OBJECTIVE
The trial provides reliable evidence of the effect of tranexamic acid on mortality, rebleeding and complications in significant acute gastrointestinal bleeding.
DESIGN
A multicentre, randomised, placebo-controlled trial and economic analysis. Patients were assigned by selecting one treatment pack from a box of eight, which were identical apart from the pack number. Patients, caregivers and outcome assessors were masked to allocation. The main analyses were by intention to treat.
SETTING
The setting was 164 hospitals in 15 countries, co-ordinated from the London School of Hygiene & Tropical Medicine.
PARTICIPANTS
Adults with significant upper or lower gastrointestinal bleeding ( = 12,009) were eligible if the responsible clinician was substantially uncertain about whether or not to use tranexamic acid. The clinical diagnosis of significant bleeding implied a risk of bleeding to death, including hypotension, tachycardia or signs of shock, or urgent transfusion, endoscopy or surgery.
INTERVENTION
Tranexamic acid (a 1-g loading dose over 10 minutes, then a 3-g maintenance dose over 24 hours) or matching placebo.
MAIN OUTCOME MEASURES
The primary outcome was death due to bleeding within 5 days of randomisation. Secondary outcomes were all-cause and cause-specific mortality; rebleeding; need for endoscopy, surgery or radiological intervention; blood product transfusion; complications; disability; and days spent in intensive care or a high-dependency unit.
RESULTS
A total of 12,009 patients were allocated to receive tranexamic acid ( = 5994, 49.9%) or the matching placebo ( = 6015, 50.1%), of whom 11,952 (99.5%) received the first dose. Death due to bleeding within 5 days of randomisation occurred in 222 (3.7%) patients in the tranexamic acid group and in 226 (3.8%) patients in the placebo group (risk ratio 0.99, 95% confidence interval 0.82 to 1.18). Thromboembolic events occurred in 86 (1.4%) patients in the tranexamic acid group and 72 (1.2%) patients in the placebo group (risk ratio 1.20, 95% confidence interval 0.88 to 1.64). The risk of arterial thromboembolic events (myocardial infarction or stroke) was similar in both groups (0.7% in the tranexamic acid group vs. 0.8% in the placebo group; risk ratio 0.92, 95% confidence interval 0.60 to 1.39), but the risk of venous thromboembolic events (deep-vein thrombosis or pulmonary embolism) was higher in tranexamic acid-treated patients than in placebo-treated patients (0.8% vs. 0.4%; risk ratio 1.85, 95% confidence interval 1.15 to 2.98). Seizures occurred in 38 patients who received tranexamic acid and in 22 patients who received placebo (0.6% vs. 0.4%, respectively; risk ratio 1.73, 95% confidence interval 1.03 to 2.93). In the base-case economic analysis, tranexamic acid was not cost-effective and resulted in slightly poorer health outcomes than no tranexamic acid.
CONCLUSIONS
Tranexamic acid did not reduce death from gastrointestinal bleeding and, although inexpensive, it is not cost-effective in adults with acute gastrointestinal bleeding.
FUTURE WORK
These results caution against a uniform approach to the management of patients with major haemorrhage and highlight the need for randomised trials targeted at specific pathophysiological processes.
LIMITATIONS
Although this is one of the largest randomised trials in gastrointestinal bleeding, we cannot rule out a modest increase or decrease in death due to bleeding with tranexamic acid.
TRIAL REGISTRATION
Current Controlled Trials ISRCTN11225767, ClinicalTrials.gov NCT01658124 and EudraCT 2012-003192-19.
FUNDING
This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in ; Vol. 25, No. 58. See the NIHR Journals Library website for further project information.
Topics: Adult; Antifibrinolytic Agents; Blood Transfusion; Cost-Benefit Analysis; Gastrointestinal Hemorrhage; Humans; Stroke; Tranexamic Acid
PubMed: 34663491
DOI: 10.3310/hta25580 -
GeroScience Jun 2022Chronic subdural hematoma (CSH) affects mostly elderly subjects. Previously, pathophysiological concepts suggested that CSH is secondary to degradation of subdural... (Review)
Review
Chronic subdural hematoma (CSH) affects mostly elderly subjects. Previously, pathophysiological concepts suggested that CSH is secondary to degradation of subdural collections of blood and its products exerting merely a mass effect on the underlying brain. During the last decades, however, new insights into the pathogenetic mechanisms urge us to reconsider such a simplistic view. Here, we critically review novel pathophysiological, imaging, interventional, and medical treatment aspects and establish an integrative concept of the pathogenesis of CSH stressing the role of age as key factor. Trauma is considered a trigger event that unleashes a cascade of immunological and angiogenic age-dependent responses. These are associated with hypervascularization of the outer hematoma membrane, rebleeding, and exsudation which are crucial determinants for further development and propagation of CSH. Neurosurgical evacuation of the hematoma has long been thought the only viable treatment option, and it is still the method of choice in the majority of cases. Only more recently, embolization of the middle meningeal artery has been introduced as an alternative to surgery, and pharmacological treatment options are being investigated. Persons with advanced age trauma and other trigger events encounter a repair system with characteristics of senescence. This repair system implies a dysfunctional secretory phenotype of senescent cells and results in an insufficient repair process including chronic inflammation and fibrosis. Increased knowledge about the pathomechanisms of CSH will inform future studies and open new perspectives for its treatment and possibly also for its prevention.
Topics: Aged; Hematoma, Subdural, Chronic; Humans
PubMed: 35461468
DOI: 10.1007/s11357-022-00570-y