Search Results (25)

Background/Objective: Platelet concentrates (PCs) are used in transfusion medicine to treat bleeding disorders. Staphylococcus aureus, a predominant PC contaminant, has been implicated in several adverse transfusion reactions. The aim of this study was to investigate the impact of PC storage on S. aureus resistance to quinolones, which are commonly used to treat S. aureus infections. Methods/Results: Four transfusion-relevant S. aureus strains (TRSs) were subjected to comparative transcriptome analyses when grown in PCs vs. trypticase soy broth (TSB). Results of these analyses revealed differentially expressed genes involved in antibiotic resistance. Of interest, the norB gene (encodes for the NorB efflux pump, which is implicated in quinolone resistance and is negatively regulated by MgrA) was upregulated (1.2–4.7-fold increase) in all PC-grown TRS compared to TSB cultures. Minimal Bactericidal Concentration (MBC) of ciprofloxacin and norfloxacin in PC-grown TRS compared to TSB showed increased resistance to both quinolones in PC cultures. Complementary studies with non-transfusion-relevant strains S. aureus RN6390 and its norB and mgrA deletion mutants were conducted. MBC of ciprofloxacin and norfloxacin and RT-qPCR assays of these strains showed that not only norB, but also norA and norC may be involved in enhanced quinolone resistance in PC-grown S. aureus. The role of norB in S. aureus virulence was also tested using the silkworm Bombyx mori animal model; lethal dose 50 (LD₅₀) assays revealed slightly higher virulence in larvae infected with the wild-type strain compared to the norB mutant. Conclusions: The PC storage environment enhances quinolone resistance in S. aureus and induces differential expression of efflux pump nor genes. Furthermore, our preliminary data of the involvement of NorB in virulence of S. aureus using a silkworm model merit further investigation with other systems such as a mammal animal model. Our results provide mechanistic insights to aid clinicians in the selection of antimicrobial treatment of patients receiving transfusions of S. aureus-contaminated PCs. Full article

Background: Myelotoxicity, usually manifested by moderate leukopenia (particularly neutropenia), is a well-known adverse drug reaction to azathioprine (AZA) therapy. Thiopurine methyltransferase (TMPT) and nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) genotyping are not routinely performed in patients starting AZA therapy due to their low cost-effectiveness. Additionally, the concomitant use of xanthine oxidase inhibitors and 5-aminosalicylates may slow the metabolism of 6-mercaptopurine. Case Description: We describe a case of a 26-year-old Caucasian man with Crohn’s disease and psoriatic arthritis treated with mesalazine and AZA (100 mg daily) who developed prolonged bone marrow aplasia and neutropenic fever after increasing the daily dose of AZA from 100 to 150 mg (from 44 to 66 mg/m²), without frequent total blood count monitoring. Discontinuation of AZA, multiple transfusions of red blood cells and platelet concentrate, filgrastim, empirical antibiotic therapy, and antiviral and antifungal prophylaxis were obtained after 11 days complete recovery of bone marrow aplasia. Methods: Genomic DNA genotyping of coding regions of TPMT (exons 2–9) and NUDT15 (exons 1–3). Results: Heterozygous alleles in the untranslated region (c.460G>A and c.719A>G) associated with TPMT deficiency and a benign variant (c.*7G>A) in the 3′-UTR of NUDT15 with no effect on enzyme activity were found. Conclusions: This case highlights the importance of monitoring the total blood count frequently during the first weeks of treatment with moderate-to-high doses of AZA. Furthermore, the interaction between AZA and mesalazine may play a significant role in the development of prolonged bone marrow aplasia. Full article

It is important to recognize the significance of acute painful transfusion reactions (APTRs) as a complication of blood transfusions. These adverse reactions are characterized by the onset of acute pain after the administration of blood components. Despite their potential to cause significant discomfort and distress to patients, these reactions are frequently disregarded and under-reported in clinical practice. This review aims to provide a comprehensive analysis of the clinical features, pathophysiology, diagnosis, incidence, and management of APTRs, emphasizing the necessity for heightened awareness and further research in this field. Full article

The use of transfusions, whether involving whole blood or specific blood components, is essential for managing various clinical conditions. Many cases are acute, often requiring post-transfusion imaging evaluation. While there is no absolute contraindication for chest imaging following blood transfusion, it should be approached cautiously. We conducted a comprehensive search across multiple databases and registries. Research studies were limited to full-text original articles, reviews, and case reports published in English, involved human subjects, and focused on the interplay between blood transfusions and contrast-enhanced imaging. Scientific analyses were excluded if they did not focus on transfusion practices in the context of imaging or failed to address issues such as hemoglobin thresholds, transfusion reactions, or the clinical implications of contrast agents. Our research fills this gap by emphasizing the need for a cautious, multidisciplinary approach to post-transfusion computed tomography (CT) scans, especially in the presence of contrast agents. This study calls for increased awareness of the heightened risk of complications, such as autoimmune hemolysis, when both procedures are performed together. New insights from our research recommend individualized assessments and close patient monitoring when combining these interventions. Nevertheless, patients need to be hemodynamically and clinically stable before undergoing CT. Discussions. Symptoms that develop within the first 24 h post-transfusion are classified as secondary post-transfusion reactions unless proven otherwise. The prevalence of side effects from same-day CT scans and blood transfusions is challenging to quantify, as few studies focus on this combination. Transfusions and contrast-enhanced CT scans share overlapping adverse reactions and carry significant risks. Acute hemolytic red blood cell transfusion reactions are among the most frequent side effects, with a prevalence of 1:12,000–38,000. Conclusion. Our study contributes new insights to the literature by filling the gap concerning the interplay between transfusions and contrast media, paving the way for more informed clinical protocols to enhance patient safety. Full article

Blood transfusion is a life-saving procedure widely used in healthcare. However, complications such as transfusion reactions may occur. Knowledge of these reactions is essential for patient safety. Nurses play a crucial role in this process by identifying complications and adverse reactions early on. A lack of professional competence in blood transfusion can lead to errors and serious complications, such as death. The aim of this study was to present evidence of the content validity of a simulated clinical scenario on transfusion reactions for teaching and learning for nursing students. This methodological study was carried out in three phases: (1) development of the simulated scenario of a transfusion reaction; (2) analysis of evidence of content validity by experts (n = 11); and (3) determination of satisfaction and self-confidence in the use of the simulated scenario by the nursing students (n = 45). The Content Validity Index was 94%. After the scenario had been developed, the content was validated and approved by 100% of the experts. All the items in the simulated scenario obtained agreement scores above 0.90. The simulated scenario was validated in terms of content and can be used to teach the management of transfusion reactions. Full article

In recent years, clustered regularly interspaced short palindromic repeats (CRISPRs) and CRISPR-associated (Cas) protein have emerged as a revolutionary gene editing tool to treat inherited disorders affecting different organ systems, such as blood and muscles. Both hematological and neuromuscular genetic disorders benefit from genome editing approaches but face different challenges in their clinical translation. The ability of CRISPR/Cas9 technologies to modify hematopoietic stem cells ex vivo has greatly accelerated the development of genetic therapies for blood disorders. In the last decade, many clinical trials were initiated and are now delivering encouraging results. The recent FDA approval of Casgevy, the first CRISPR/Cas9-based drug for severe sickle cell disease and transfusion-dependent β-thalassemia, represents a significant milestone in the field and highlights the great potential of this technology. Similar preclinical efforts are currently expanding CRISPR therapies to other hematologic disorders such as primary immunodeficiencies. In the neuromuscular field, the versatility of CRISPR/Cas9 has been instrumental for the generation of new cellular and animal models of Duchenne muscular dystrophy (DMD), offering innovative platforms to speed up preclinical development of therapeutic solutions. Several corrective interventions have been proposed to genetically restore dystrophin production using the CRISPR toolbox and have demonstrated promising results in different DMD animal models. Although these advances represent a significant step forward to the clinical translation of CRISPR/Cas9 therapies to DMD, there are still many hurdles to overcome, such as in vivo delivery methods associated with high viral vector doses, together with safety and immunological concerns. Collectively, the results obtained in the hematological and neuromuscular fields emphasize the transformative impact of CRISPR/Cas9 for patients affected by these debilitating conditions. As each field suffers from different and specific challenges, the clinical translation of CRISPR therapies may progress differentially depending on the genetic disorder. Ongoing investigations and clinical trials will address risks and limitations of these therapies, including long-term efficacy, potential genotoxicity, and adverse immune reactions. This review provides insights into the diverse applications of CRISPR-based technologies in both preclinical and clinical settings for monogenic blood disorders and muscular dystrophy and compare advances in both fields while highlighting current trends, difficulties, and challenges to overcome. Full article

Background: Even minor adverse reactions after total hip replacement (THR), including lymphedema, postoperative leg swelling, and blood loss, compromise patient comfort in times of minimally invasive fast-track surgery. Compression dressings are commonly used in surgical practice to reduce swelling or blood loss. However, the use of spica hip compression dressings after primary THR is controversial, and prospective studies are lacking. Methods: We conducted a prospective, single-center, two-arm, randomized controlled trial (RCT) of patients undergoing THR for primary osteoarthritis. A total of 324 patients were enrolled; 18 patients were excluded, and 306 patients were finally analyzed. Leg swelling as primary endpoint was measured pre- and postoperatively with a rotating 3D infrared body scanner. Secondary endpoints were transfusion rate and blood loss, estimated by Nadler and Gross formulas. Results: Postoperative leg swelling was lower in the compression group (241 ± 234 mL vs. 307 ± 287 mL; p = 0.01), even after adjustment for surgery time and Body-Mass-Index (BMI) (p = 0.04). Estimated blood loss was also lower in the compression group on the first (428 ± 188 mL vs. 462 ± 178 mL; p = 0.05) and third (556 ± 247 mL vs. 607 ± 251 mL; p = 0.04) postoperative days and leveled off on the fifth postoperative day, but lost significance after adjustment for BMI and surgery time. Neither group received a transfusion. Conclusions: Compression dressing after THR in the context of minimally invasive surgery slightly reduces leg swelling, but has no effect on blood loss or blood transfusion rate. So, this method could not generally be recommended in primary hip replacement. Full article

Allergic reactions are the most frequent adverse events in blood transfusion, and anaphylactic shock, although less frequent, is systemic and serious. The cause of allergic reactions to blood transfusions are largely unknown, but deficiencies in serum proteins such as haptoglobin (Hp) can lead to anaphylactic shock. A complete deletion of the haptoglobin gene (HP^del) was first identified in families with anomalous inheritance and then verified as a genetic variant that can cause anaphylactic shock because homozygotes for HP^del have complete Hp deficiency. Thereby, they may produce antibodies against Hp from blood transfusions. HP^del is found in East and Southeast Asian populations, with a frequency of approximately 0.9% to 4%, but not in other populations. Diagnosis of Hp deficiency due to HP^del prior to transfusion is advisable because severe adverse reactions can be prevented by washing the red blood cells and/or platelets with saline or by administering plasma products obtained from an Hp-deficient donor pool. This review outlines the background of the identification of HP^del and several genetic and immunological methods developed for diagnosing Hp deficiency caused by HP^del. Full article

Background: Selective IgA deficiency (IgA-D) has been historically considered a high-risk entity for developing allergic/anaphylactic reactions after blood transfusion (AATRs). However, it has been suggested that the IgA-D-related anaphylactic transfusion reaction is not evidence-based. Methods: We conducted three different approaches to collect evidence about epidemiology, AATRs, and transfusion management of patients with IgA-D at La Fe University Hospital. Firstly, we analysed the prevalence of IgA-D in a population of patients diagnosed with acute leukaemia, The second approach consisted of collecting transfusion data from IgA-D patients. Finally, we reviewed the IgA levels of patients recorded in the hemovigilance system suffering an AATR. Results: IgA-D prevalence was 1 in 334 patients. At least one blood component was transfused to 23 patients diagnosed with IgA-D. Plasma was transfused to eight IgA-D patients, while six patients received red blood cells, platelets, and plasma. No adverse reactions were reported in any patient. AATRs occurred in 325 men and 264 women with a median age of 52 years. Severe reactions occurred in 56 patients (1/14,520 components). Mean IgA levels were 215 mg/dL (4–5570) for mild reactions and 214 mg/dL (14–824) for severe reactions (p = ns). Washed platelets were administered to two patients who developed severe and repeated AATRs. Both had normal IgA levels. Conclusions: Since the AATRs related to IgA-D are extremely low, as reported in current hemovigilance systems, IgA-D should not be considered a high-risk entity to develop AATRs. On the contrary, our findings support standard transfusion management of IgA-D patients. Full article

Myelodysplastic syndromes and myeloproliferative neoplasms both represent hematologic diseases associated with bone marrow failure often resulting in anemia. For those patients, transfusion of red blood cell (RBC) units is essential but results in iron overload (IOL) that may affect various organ functions. Therefore, iron chelation therapy plays a major role in anemic patients, not only because it reduces IOL, but also because it may improve hematopoietic function by increasing hemoglobin or diminishing the requirement for RBC transfusions. To assess the utility, efficacy, and safety of the different iron chelation medications approved in Germany, as well as to examine the effect of chelation on hematopoietic insufficiency, a prospective, multicenter, noninterventional study named EXCALIBUR was designed. In total, 502 patients from 106 German hospitals and medical practices were enrolled. A large proportion of patients switched from a deferasirox dispersible tablet to a deferasirox-film-coated tablet, mainly because of more convenient application, which was reflected in the treatment satisfaction questionnaire for medication scores. Iron chelation was effective in lowering serum ferritin levels, with the observed adverse drug reactions being in line with the known safety profile. Hematologic response occurred in a few patients, comparable to other studies that examined hematologic improvement in patients with MDS. Full article

Platelets play a critical role in blood clotting and the development of arterial blockages. Antiplatelet therapy is vital for preventing recurring events in conditions like coronary artery disease and strokes. However, there is a lack of comprehensive guidelines for using antiplatelet agents in elective neurosurgery. Continuing therapy during surgery poses a bleeding risk, while discontinuing it before surgery increases the risk of thrombosis. Discontinuation is recommended in neurosurgical settings but carries an elevated risk of ischemic events. Conversely, maintaining antithrombotic therapy may increase bleeding and the need for transfusions, leading to a poor prognosis. Artificial intelligence (AI) holds promise in making difficult decisions regarding antiplatelet therapy. This paper discusses current clinical guidelines and supported regimens for antiplatelet therapy in neurosurgery. It also explores methodologies like P2Y12 reaction units (PRU) monitoring and thromboelastography (TEG) mapping for monitoring the use of antiplatelet regimens as well as their limitations. The paper explores the potential of AI to overcome such limitations associated with PRU monitoring and TEG mapping. It highlights various studies in the field of cardiovascular and neuroendovascular surgery which use AI prediction models to forecast adverse outcomes such as ischemia and bleeding, offering assistance in decision-making for antiplatelet therapy. In addition, the use of AI to improve patient adherence to antiplatelet regimens is also considered. Overall, this research aims to provide insights into the use of antiplatelet therapy and the role of AI in optimizing treatment plans in neurosurgical settings. Full article

Iron is essential for all organisms and cells. Diseases of iron imbalance affect billions of patients, including those with iron overload and other forms of iron toxicity. Excess iron load is an adverse prognostic factor for all diseases and can cause serious organ damage and fatalities following chronic red blood cell transfusions in patients of many conditions, including hemoglobinopathies, myelodyspasia, and hematopoietic stem cell transplantation. Similar toxicity of excess body iron load but at a slower rate of disease progression is found in idiopathic haemochromatosis patients. Excess iron deposition in different regions of the brain with suspected toxicity has been identified by MRI T2* and similar methods in many neurodegenerative diseases, including Alzheimer’s disease and Parkinson’s disease. Based on its role as the major biological catalyst of free radical reactions and the Fenton reaction, iron has also been implicated in all diseases associated with free radical pathology and tissue damage. Furthermore, the recent discovery of ferroptosis, which is a cell death program based on free radical generation by iron and cell membrane lipid oxidation, sparked thousands of investigations and the association of iron with cardiac, kidney, liver, and many other diseases, including cancer and infections. The toxicity implications of iron in a labile, non-protein bound form and its complexes with dietary molecules such as vitamin C and drugs such as doxorubicin and other xenobiotic molecules in relation to carcinogenesis and other forms of toxicity are also discussed. In each case and form of iron toxicity, the mechanistic insights, diagnostic criteria, and molecular interactions are essential for the design of new and effective therapeutic interventions and of future targeted therapeutic strategies. In particular, this approach has been successful for the treatment of most iron loading conditions and especially for the transition of thalassemia from a fatal to a chronic disease due to new therapeutic protocols resulting in the complete elimination of iron overload and of iron toxicity. Full article

Thawed plasma (TP) refers to defrosted fresh frozen plasma stored refrigerated. TP is used in human medicine for the rapid provision of coagulation factors and resuscitation of haemorrhagic shock, but its use in dogs is poorly described. The objectives of this historical case series were to describe the reasons for TP transfusion, treatment outcomes, and adverse events associated with canine TP transfusions in a veterinary teaching hospital. We hypothesised that TP would be used most commonly for the treatment of haemorrhage secondary to anticoagulant rodenticide intoxication and trauma. Blood bank plasma transfusion logs were searched to identify dogs that received at least one unit of TP between December 2015 and June 2021. Briefly, 166 dogs received a total of 262 units of TP. Anticoagulant rodenticide intoxication (37/166, 22.3%) was the most common reason for transfusion, followed by traumatic haemorrhage (23, 13.9%) and spontaneous haemoperitoneum (22, 13.2%). The majority of dogs received one unit of TP (111/166, 67.1%) and pRBCs were commonly simultaneously transfused with TP (65, 39.2%). Severe prolongations of prothrombin time and activated partial thromboplastin time were reduced following TP transfusions. Allergic reactions were the most common transfusion reaction (19/166, 11.4%). Most dogs survived to discharge (101/166, 60.8%). Full article

Human immunodeficiency virus (HIV) is a lentivirus that is transmissible through blood and other body fluids. During the late 1980s and early 1990s, an estimated 10,000 Romanian children were infected with HIV-1 subtype F nosocomially through contaminated needles and untested blood transfusions. Romania was a special case in the global acquired immunodeficiency syndrome (AIDS) pandemic, displaying the largest population of HIV-infected children by parental transmission between 1987–1990. In total, 205 HIV-infected patients from the western part of Romania were analyzed in this retrospective study. Over 70% of them had experienced horizontal transmission from an unknown source, while vertical transmission was identified in only five cases. Most patients had a moderate to severe clinical manifestation of HIV infection, 77.56% had undergone antiretroviral (ARV) treatment, most of them (71.21%) had experienced no adverse reactions and many of those with HIV (90.73%) had an undetectable viral load. Renal impairment was detected in one third of patients (34.63%). Patients born before 1990, male patients, patients diagnosed with HIV before the age of 10, and those undernourished or with renal impairment had a shorter average survival time than the group born after 1990, female patients, patients receiving ARV treatment, patients with a normal body mass index (BMI) and those without renal impairment. Periodical monitoring of the estimated glomerular filtration rate (eGFR) level, as well as the detection of protein excretion, should be taken into consideration worldwide when monitoring HIV-positive patients; this in order to detect even asymptomatic chronic kidney disease (CKD), and to manage these patients and prolong their lives. Full article

Donor organ-shortage has resulted in the increased use of marginal grafts; however, normothermic machine perfusion (NMP) holds the potential for organ viability assessment and restoration of marginal grafts prior to transplantation. Additionally, cell-, oxygen carrier-free and antioxidants-supplemented solutions could potentially prevent adverse effects (transfusion reactions, inflammation, hemolysis), associated with the use of autologous packed red blood cell (pRBC)-based perfusates. This study compared 6 h NMP of porcine kidneys, using an established pRBC-based perfusate (pRBC, n = 7), with the novel cell- and oxygen carrier-free organ preservation solution Ecosol, containing taurine (Ecosol, n = 7). Despite the enhanced tissue edema and tubular injury in the Ecosol group, related to a suboptimal molecular mass of polyethylene glycol as colloid present in the solution, functional parameters (renal blood flow, intrarenal resistance, urinary flow, pH) and oxygenation (arterial pO₂, absence of hypoxia-inducible factor 1-alpha) were similar to the pRBC group. Furthermore, taurine significantly improved the antioxidant capacity in the Ecosol group, reflected in decreased lactate dehydrogenase, urine protein and tubular vacuolization compared to pRBC. This study demonstrates the feasibility of 6 h NMP using a taurine containing, cell- and oxygen carrier-free perfusate, achieving a comparable organ quality to pRBC perfused porcine kidneys. Full article