Advances in paediatric haematopoietic cell transplantation strategies using immune-effector cells (HCT-IEC) and in intensive care management have improved survival expectations for patients with malignant and non-malignant diseases. However, critical illness still complicates the clinical course for 10-35% of patients undergoing HCT-IEC because of disease-related complications or treatment-related toxicities. Given the improvement in survival for these patients in paediatric intensive care units (PICU), the European Society of Paediatric and Neonatal Intensive Care (ESPNIC), the HCT-Cancer Immunotherapy Subgroup of the Paediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network, and the Paediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation (EBMT) derived expert consensus statements to guide PICU admission and early critical care management of patients following HCT-IEC. 27 statements were drafted by the steering committee and subsequently voted on by 20 expert panel members with expertise in HCT and IEC. 20 statements received strong agreement and seven received weak agreement. This consensus statement serves as a guide for intensivists, haematologists, and oncologists during the challenging process of PICU admission and critical care management of patients who have undergone HCT-IEC and can serve as a basis for prioritising future research in the field.

Platelet transfusions are frequently used in the Intensive Care Unit (ICU) as prophylaxis against bleeding complications. Several guidelines exist on when to administer platelet transfusions in the ICU, but studies indicate that these guidelines are not necessarily followed. The aim of this qualitative study was to understand how experienced ICU physicians make decisions on prescribing prophylactic platelet transfusions and to gain insight into their general concerns and views on blood product transfusions.

Descriptive qualitative study using semi-structured, in-depth interviews with clinicians working in ICUs in Austria, Denmark, France, Germany, Spain, and the United Kingdom. The interviews were recorded, transcribed verbatim, and analyzed using thematic analysis.

We identified four main themes influencing the decision to prescribe prophylactic platelet transfusions: Guidelines, social and cultural aspects (including religion), previous personal experiences, and fear of consequences.

Most doctors expressed uncertainty about balancing benefits and harm. Platelet transfusions were often used to prevent bleeding despite uncertainty on the effect and were typically triggered by fear of consequences when performing a procedure, which was an important driver. The departmental culture and colleagues' attitudes were far more important influencers on decision-making than guideline recommendations. Most doctors thought it was possible for blood products to transfer unknown and potentially harmful substances to patients, although this did not appear to influence their daily practice.

Hematopoietic stem cell transplantation (HSCT) is an essential and increasing therapeutic approach for treating conditions such as leukemia, lymphoma, and other blood cancers. However, its widespread use faces significant challenges, including limited donor availability, pathogens, and the risk of immune rejection. The emergence of pluripotent stem cells (PSCs) offers a potential solution to these challenges. By enabling the generation of hematopoietic stem cells (HSCs) and blood cells in vitro, PSCs open pathways to address the limitations of traditional HSC sources. Self-induced or gene-edited PSCs from patients may provide an accessible and personalized option for clinical applications. In this review, we examine the current protocols for differentiating PSCs into HSCs and blood cells, highlighting their benefits and shortcomings. Despite advancements in this field, two primary challenges persist: low differentiation efficiency and difficulties in isolating and enriching functional HSCs. These problems make it difficult to obtain HSCs for long-term survival. Thus, we propose innovative strategies and potential improvements including induction scheme optimization, reprogramming, and cell fate tracking. Future research should prioritize the development of efficient and reliable differentiation protocols for PSCs to obtain more functional HSCs. Additionally, establishing effective methods for enriching functional HSCs and blood cells will be critical for optimizing their use in clinical applications. These efforts hold the promise of overcoming current limitations and advancing the therapeutic potential of PSC-derived blood cells.

Although blood transfusion is a life-saving procedure, it is associated with a number of preventable and unpreventable transfusion reactions. Transfusion errors account for the majority of preventable causes. The aim of our study was to determine the frequency and characteristics of acute transfusion reactions (ATR) and preventable transfusion errors in our center.

Data on transfusion reactions and transfusions administered between January 2019 and December 2023 were collected retrospectively from reported transfusion reaction forms and transfusion center records.

Among 163.114 transfusion administered, 116 (0.071%) acute transfusion reactions were reported (71.1 reaction per 100.000 transfusion). The most common type of ATR was allergic reactions and the most common blood product associated with reaction was red blood cell (RBC). The ABO incompatible RBC transfusion due to human error rate is 1.22/100.000 per transfusion. None of the reactions resulted in death.

In our study, the incidence and type of transfusion reactions are similar to the literature. However, the incidence of transfusion of ABO incompatible RBC due to human error is slightly higher than the reported rates. In addition to raising awareness about reporting, immediate action should be taken by closely monitoring transfusion errors especially during pre-transfusion safety.

Patients with acute-on-chronic liver failure (ACLF) have a high mortality rate, poor prognosis, and often experience concurrent thrombocytopenia and bleeding events.

To evaluate the efficacy and safety of recombinant human thrombopoietin (rhTPO) in patients with ACLF with concomitant severe thrombocytopenia.

This was a prospective, open-label study. We assigned 70 ACLF patients with severe thrombocytopenia into the rhTPO group and control group, with 35 patients in each group. Patients in the rhTPO group received subcutaneous injections of rhTPO at a dose of 15000 IU/day for 7 consecutive days, while patients in the control group did not receive rhTPO treatment. The primary endpoint was the proportion of patients with platelet count > 50 × 109/L on day 14.

The proportion of patients with platelet count > 50 × 109/L on day 14 was 60.7% in the rhTPO group, which was significantly higher than that (12.0%) in the control group (P < 0.001). The platelet count in the rhTPO group on day 14 was 64 × 109/L, exceeding the baseline of 28 × 109/L. Compared to the control group, the rhTPO group exhibited a significant increase in platelet count from baseline (P < 0.05). Model for end-stage liver disease score, albumin level and international normalized ratio improved significantly from baseline on day 14 after rhTPO injection. The concentrations of serum thrombopoietin and hepatocyte growth factor in the rhTPO group after 7 days were 143.7 and 195.4 pg/mL, respectively, showing a significant increase from baseline (P < 0.05). Eight (22.9%) patients had bleeding events in the control group compared with four (11.4%) in the rhTPO group. The incidence of 90-day mortality was also higher in the control group (6, 17.1%) than that in the rhTPO group (3, 8.6%).

rhTPO significantly increased the platelet count in ACLF patients with thrombocytopenia and reduce the occurrence of bleeding events, with a good safety profile.

Central venous access through tunneled central venous catheters (CVCs) are one of the cornerstones of modern oncologic practice in pediatric patients since CVCs provide a reliable access route for the administration of chemotherapy. Establishing best practices for CVC management in children with cancer is essential to optimize care. This article reviews current best practices, including types of devices, their placement, complications, and long-term outcomes. Additionally, nutrition status and nutritional support are also very important determinants of outcomes and care in pediatric surgical oncology patients. We review current nutritional assessment, support, access for enteral and parenteral nutrition delivery, and their complications, mainly from a surgical perspective. Overall, access surgery, whether for CVCs, or for enteral access can be challenging, and best practice guidelines supported by current though limited evidence are necessary to minimize complications and optimize outcomes.

Platelet (PLT) transfusion is an essential strategy to prevent bleeding in children with thrombocytopenia associated to cancer treatment. However, data on optimal pediatric dosing and transfusion thresholds are limited.

This retrospective study analyzed data from 607 pediatric patients with hematologic malignancies, nonmalignant disorders, and solid tumors who developed hypoproliferative thrombocytopenia during therapy. In the first phase (Objective 1), the effective response to transfusion (ERTR) was assessed following International Collaboration for Transfusion Medicine guidelines (ICTMG), comparing low-dose (1.1 × 1011 PLT/m2 body surface area) transfusions for inpatients and medium dose (2.2 × 1011) for outpatients. Transfusion thresholds were set at less than 10,000/µL versus 10,000-20,000/µL, and overall PLT concentrate consumption was analyzed. The second phase (Objective 2) examined the total number of transfusions per patient, incidence of major bleeding events, and bleeding-related mortality rates across dosing groups.

ERTR ranged from 65% to 82%, with significantly higher rates in outpatients compared to inpatients. In outpatients with PLT less than 10,000/µL, the medium dose showed no significant advantage over the lower inpatient dose. Similar efficacy was observed between low (<10,000/µL) and high (10,000-20,000/µL) transfusion triggers, with no statistically significant difference in the incidence of major bleeding events across groups. The low-dose strategy was significantly associated with a reduction in PLT volume transfused compared to the standard expected dose.

These findings support the application of ICTMG in pediatric settings. The lower PLT dose for inpatients is safe and effective, providing benefits in resource utilization, while a higher transfusion trigger (20,000/µL) does not improve outcomes.

The administration of blood components and their alternatives can be lifesaving. Anaemia, bleeding and transfusion are all associated with poor peri-operative outcomes. Considerable changes in the approaches to optimal use of blood components and their alternatives, driven by the findings of large randomised controlled trials and improved haemovigilance, have become apparent over the past decade. The aim of these updated guidelines is to provide an evidence-based set of recommendations so that anaesthetists and peri-operative physicians might provide high-quality care.

An expert multidisciplinary, multi-society working party conducted targeted literature reviews, followed by a three-round Delphi process to produce these guidelines.

We agreed on 12 key recommendations. Overall, these highlight the importance of organisational factors for safe transfusion and timely provision of blood components; the need for protocols that are targeted to different clinical contexts of major bleeding; and strategies to avoid the need for transfusion, minimise bleeding and manage anticoagulant therapy.

All anaesthetists involved in the care of patients at risk of major bleeding and peri-operative transfusion should be aware of the treatment options and approaches that are available to them. These contemporary guidelines aim to provide recommendations across a range of clinical situations.

This narrative review aims to describe the epidemiology and aetiologies of thrombocytopenia in critically ill patients, the bleeding risk assessment in thrombocytopenic patients, and provide an update on platelet transfusion indications.

Thrombocytopenia is a common disorder in critically ill patients. The classic definition relies on an absolute platelet count below 150 × 109/L. Alternatively, the definition has extended to a relative decrease in platelet count (typically within a range of >30->50% decrease) from baseline, yet remaining above 150 × 109/L. Thrombocytopenia may result from multiple mechanisms depending upon the underlying conditions and the current clinical setting. Regardless of the causes, thrombocytopenia accounts as an independent determinant of poor outcomes in critically ill patients, albeit often of unclear interpretation. Nevertheless, it is well established that thrombocytopenia is associated with an increased incidence of bleeding complications. However, alternative factors also contribute to the risk of bleeding, making it difficult to establish definite links between nadir platelet counts at the expense of potential adverse events. Platelet transfusion represents the primary supportive treatment of thrombocytopenia to prevent or treat bleeding. As randomised controlled trials comparing different platelet count thresholds for prophylactic platelet transfusion in the ICU are lacking, the prophylactic transfusion strategy is largely derived from studies performed in stable haematology patients. Similarly, the platelet count transfusion threshold to secure invasive procedures remains based on a low level of evidence. Indications of platelet transfusions for the treatment of severe bleeding in thrombocytopenic patients remain largely empirical, with platelet count thresholds ranging from 50 to 100 × 109/L. In addition, early and aggressive platelet transfusion is part of massive transfusion protocols in the setting of severe trauma-related haemorrhage.

Thrombocytopenia in critically ill patients is very frequent with various etiologies, and is associated with worsened prognosis, with or without bleeding complications. Interventional trials focused on critically ill patients are eagerly needed to better delineate the benefits and harms of platelet transfusions.

Major bleeding is a life-threatening condition with high morbidity and mortality. Trauma, gastrointestinal bleeding, haemoptysis, intracranial haemorrhage or other causes of bleeding represent major concerns in the Emergency Department (ED), especially when complicated by haemodynamic instability. Severity and source of bleeding, comorbidities, and prior use of anticoagulants are pivotal factors affecting both the clinical status and the patients' differential response to haemorrhage. Thus, risk stratification is fundamental in the initial assessment of patients with bleeding. Aggressive resuscitation is the principal step for achieving haemodynamic stabilization of the patient, which will further allow appropriate interventions to be made for the definite control of bleeding. Overall management of major bleeding in the ED should follow a holistic individualized approach which includes haemodynamic stabilization, repletion of volume and blood loss, and reversal of coagulopathy and identification of the source of bleeding. The aim of the present practical guide is to provide an update on recent epidemiological data about the most common etiologies of bleeding and summarize the latest evidence regarding the bundles of care for the management of patients with major bleeding of traumatic or non-traumatic etiology in the ED.

A large, retrospective study was designed to interrogate current NHS Blood and Transplant (NHSBT) HLA matching strategies for the provision of HLA selected platelets (HLA SP) and to determine whether additional factors such as ABO blood group matching, patient diagnosis, patient and/or donor age, sex, ethnicity, age of platelet unit at transfusion and possibly seasonal variation also play a role in transfusion efficacy.

Data for 56 640 HLA SP transfusions over a 3-year period were collected. Transfusions with missing data for any factor under consideration were excluded, resulting in a cohort of 13 044 transfusions for analysis. Univariable and multivariable regression models were used to determine if any factors influenced an increase in platelet count of ≥10 × 109/L. A stepwise logistic regression was applied, such that each influential factor was adjusted for effects on other factors included in the study.

HLA match grade was confirmed as a significant factor in transfusion efficacy, with ABO mismatched units 20% less likely to give an adequate platelet increment (≥10 × 109/L). Platelet donor age, gender and ethnicity were not significant. Conversely, patient diagnosis, ethnicity, gender and age showed significant associations with platelet increments. Some seasonal variation in efficacy of platelet transfusion was also demonstrated.

This study has demonstrated the efficacy of HLA SP transfusions in refractory patients with a wide range of diagnoses, the importance of HLA match grade, plus the marginal effect of ABO matching. A wide range of donor-related factors was excluded, while a number of patient-related factors were identified, requiring more extensive investigation in ongoing and independent studies, with implications for donor registry, clinical and laboratory practices.

To guide clinical blood transfusion practices for pediatric patients, the National Health Commission has issued the health standard "Guideline for pediatric transfusion" (WS/T 795-2022). Blood transfusion is one of the most commonly used supportive treatments for children with hematological diseases. This guideline provides guidance and recommendations for blood transfusions in children with aplastic anemia, thalassemia, autoimmune hemolytic anemia, glucose-6-phosphate dehydrogenase deficiency, acute leukemia, myelodysplastic syndromes, immune thrombocytopenic purpura, and thrombotic thrombocytopenic purpura. This article presents the evidence and interpretation of the blood transfusion provisions for children with hematological diseases in the "Guideline for pediatric transfusion", aiming to assist in the understanding and implementing the blood transfusion section of this guideline.

Von Willebrand's disease (vWD) is an inherited coagulopathy. In women, this condition can present as periovulatory intra-abdominal bleeding or bleeding from the corpus luteum. A diagnosed case of vWD presented as an emergency with nausea, acute abdominal pain and dizziness. There was no history of amenorrhoea, abdominal trauma or bleeding from any other site. Urine pregnancy test was negative. Intra-abdominal bleeding was suspected as her repeat blood counts showed progressive fall in haemoglobin. Emergency laparoscopy was performed with provisional diagnosis of a ruptured ovarian cyst, which confirmed haemoperitoneum. However, both ovaries were normal and no bleeder was identified despite thorough intraoperative exploration. This case highlights that Von Willebrand factor replacement may suffice as the treatment even if the cause of haemorrhage remains unidentified in vWD. The challenges of undertaking surgery in patients with coagulopathy and perioperative management are discussed.

Platelet transfusions, used as prophylaxis or treatment for bleeding, are potentially life-saving. In many countries, demand for platelet transfusion is rising. Platelets are a limited and costly resource, and it is vital that they are used appropriately. This study will explore the evidence behind platelet transfusions in different contexts, in particular recent and important research in this area.

Recent randomized clinical trials demonstrate the efficacy of platelet transfusions in some contexts but potential detrimental effects in others. Platelet transfusions also carry risk of transfusion reactions, bacterial contamination and platelet transfusion refractoriness. Observational and clinical studies, which highlight approaches to mitigate these risks, will be discussed. There is growing interest in cold-stored or cryopreserved platelet units, which may improve platelet function and availability. Clinical trials also highlight the efficacy of other supportive measures such as tranexamic acid or thrombopoietin receptor agonists in patients with bleeding.

Although platelet transfusions are beneficial in many patients, there remain many settings in which the optimal use of platelet transfusions is unclear, and some situations in which they may have detrimental effects. Future clinical trials are needed to determine optimal use of platelet transfusions in different patient populations.

Bleeding is common in patients with haematological malignancies undergoing intensive therapy. We aimed to assess the effect of tranexamic acid on preventing bleeding and the need for platelet transfusions.

TREATT was an international, randomised, double-blind, parallel, phase 3 superiority trial conducted at 27 haematology centres in Australia and the UK. We enrolled adults (aged ≥18 years) receiving intensive chemotherapy or haematopoietic stem-cell transplantation for a haematological malignancy, with a platelet count of 10 × 109 platelets per L or less for 5 days or longer. Patients were randomly assigned (1:1) using block randomisation, stratified by site, to tranexamic acid (1 g every 8 h intravenously or 1·5g every 8 h orally) or placebo when their platelet count was less than 30 × 109 platelets per L. Treatment was continued until platelet recovery or day 30. Prophylactic platelet transfusions were maintained as standard of care. The primary endpoint was the proportion of patients who died or had WHO grade 2 or higher bleeding up to day 30. A modified intention-to-treat population including randomly assigned patients whose platelet count decreased to 30 × 109 platelets per L or less was used for analysis. This trial is registered with ClinicalTrials.gov (NCT03136445), ISRCTN (ISRCTN73545489), and the European Clinical Trials Register (EudraCT 2014-001513-35).

Between June 23, 2015, and Feb 17, 2022, 1736 patients were screened for eligibility, 616 of whom were enrolled and randomly assigned (310 to tranexamic acid and 306 to placebo). 19 participants were excluded from the modified intention-to-treat analysis, leaving 300 participants in the tranexamic acid group and 297 in the placebo group. Participant median age was 58 years (IQR 49-65), 380 (62%) of 616 participants were male, and 235 (38%) were female. The proportion of participants who died or had WHO grade 2 or higher bleeding was 31·7% (90/298 [95% CI 26·6-37·4]) in the tranexamic acid group and 34·2% (98/295 [29·0-40·0]) in the placebo group (hazard ratio 0·92 [95% CI 0·67-1·27]; p=0·62). There were no differences in thrombotic events or veno-occlusive disease. 94 serious adverse events in 77 participants were reported up to day 60 in the tranexamic acid group and 103 events in 82 participants in the placebo group.

There is insufficient evidence to support routine use of tranexamic acid to reduce bleeding in patients with haematological malignancies undergoing intensive chemotherapy.

UK National Health Service Blood and Transplant and Australian National Health and Medical Research Council.

It is known that the rapid clearance of cold-stored platelets is attributed to various storage lesions, including an abnormal increase in reactive oxygen species when platelets are exposed to cold temperatures. As an antioxidant, N-acetylcysteine exhibits some significant effects on scavenging various reactive oxygen species and inhibiting cell damage and apoptosis.

This study aimed to investigate the effects of N-acetylcysteine on reducing reactive oxygen species production and protecting cold-stored platelets from phagocytosis and clearance, and to determine the optimal concentration of N-acetylcysteine.

Platelet concentrates were divided into three groups: room-temperature-stored platelets, cold-stored platelets, and cold-stored platelets with the addition of different concentrations of N-acetylcysteine. After five days of storage, reactive oxygen species production, lipid peroxidation levels, activation marker expressions, GPIb/ɑ desialylation with exposure of glycan residues and other quality parameters of platelets were measured and compared between the groups. Phagocytosis of platelets was detected by phorbol 12-myristate 13-acetate-activated THP-1 or Hep G2 cells. Moreover, the recovery of infused platelets was measured in severe combined immunodeficient mice at different timepoints.

After 5 days of storage, cytoplasmic reactive oxygen species significantly increased in chilled compared to non-chilled platelets; they were notably reduced with the addition of N-acetylcysteine, particularly at a concentration of 5 mM. Compared with chilled platelets, the P-selectin and phosphatidylserine expressions, as well as exposure of GPIb/ɑ glycan residues, were significantly reduced with 5 mM of N-acetylcysteine. Phagocytosis of platelets by THP-1 or Hep G2 cells was significantly lower in 5 mM of N-acetylcysteine compared to cold-stored platelets without N-acetylcysteine.

This study demonstrated correlations between reactive oxygen species production and their pro-oxidant effects on platelet clearance after cold storage. The addition of N-acetylcysteine at an appropriate concentration do not only protects chilled platelets from storage lesions caused by reactive oxygen species overproduction but also prevents platelet phagocytosis in vitro and clearance in vivo, thereby extending circulating time.

Myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML) are severe myeloid disorders associated with significant morbidity and mortality. Because of patient and disease factors, many older adults are treated as outpatients with less-intensive therapy. Optimal supportive care strategies to minimize bleeding and infectious complications in this patient population have not been systematically evaluated. We conducted a survey of Canadian hematologists to explore current practice in the use of tranexamic acid (TXA) and prophylactic antimicrobials in patients with MDS/AML treated with less-intensive therapy, and to evaluate equipoise for future trials. Survey items were generated through a combination of literature review and discussion with content experts. The survey was disseminated to 304 potential respondents with a response rate of 52%. Prophylactic platelet transfusions were used by 95%, while prophylactic TXA was used by 57%; the most frequent reason for not using TXA was uncertainty about benefit or harm. Use of prophylactic antimicrobials varied by chemotherapy regimen. If antimicrobial prophylaxis was used, the most frequently prescribed antibacterials were fluroquinolones (90%) and trimethoprim/sulfamethoxazole (21%); the most commonly used antifungals were fluconazole (66%) and voriconazole (36%). The most common reason for not using prophylactic antimicrobials was insufficient evidence of benefit. Most respondents agreed that clinical trials are needed to define the use of TXA and prophylactic antimicrobials in this patient population. Among survey respondents, there was variation in the use of supportive care strategies to address bleeding and infection risk in older adults with MDS/AML. The results of this survey will help to inform clinical trials to assess the benefits and risks of these prophylactic strategies.

Avatrombopag is a next-generation thrombopoietin receptor agonist approved for the treatment of thrombocytopenia in patients with chronic liver disease scheduled to undergo surgery and thrombocytopenia in patients with chronic immune thrombocytopenia. However, realistic data on its post-marketing long-term safety and tolerability in large sample populations are incomplete. The adverse event (AE) reports of avatrombopag were analyzed based on the FAERS database. By extracting large-scale data from the FAERS database, this study used various signal quantification techniques such as reporting odds ratios, proportional reporting ratios, Bayesian confidence propagation neural network, and multi-item gamma Poisson shrinker to calculate and evaluate the ratio and association between avatrombopag and specific AEs. In the FAERS database, data from the second quarter of 2018 to the fourth quarter of 2023 were extracted for this study, a total of 1217 avatrombopag-related AEs reports were included for analysis. Based on four calculation methods, this study identified and 32 preferred terms associated with avatrombopag. Common AEs in the product label such as thrombosis, headache, contusion, petechiae, and gingival bleeding were detected. AEs not mentioned in the product label, such as photopsia and ear discomfort were also detected. The first 30 days after initiation of medication were the most common period for both serious and non-serious AEs. This study demonstrates the common AEs and the potential AEs associated with avatrombopag in real-world practice, which could provide valuable cautionary evidence for clinicians and pharmacists to manage safety issues with avatrombopag.

X-irradiation of blood products is an alternative for gamma-ray to prevent post-transfusion GvHD. However, commercial X-irradiators are not widely available while little is known about their safety and efficacy for platelet products. This study introduces an efficient, accessible and cost-effective "X irradiation system" for platelet concentrates (PCs). By constructing a suitable radiation box (phantom) for a clinically available linear accelerator, an "X irradiation system" was designed specifically for PCs. PCs were divided into three equal bags either exposed to X- and gamma-irradiation or kept unirradiated (control). Irradiation-induced inhibition of T cells proliferation was examined by MTT and cell cycle assays on mononuclear cells (MNCs) obtained from PCs. The inhibitory effect of irradiation on allorecognition ability of MNCs was assessed by mixed lymphocyte reaction where MTT evaluated lymphocyte proliferation responses and flowcytometry examined CD8+T lymphocytes activity. Platelet activation was also examined with P-selectin expression and PAC-1 binding by flowcytometry. X- and gamma-irradiation reduced T cell proliferation while disturbing the cell-cycle with reduced entry of T-cells into the S phase and their G2 arrest. Both types of irradiations also effectively reduced "lymphocyte allorecognition responses" while inactivating CD8+T lymphocytes in platelet products but with no significant effect on platelet activity. This is the first study that showed "X irradiation system" effectively suppresses T cell proliferation and CD8+T lymphocyte activity in platelet products, with no effect to platelet quality and activation markers. This may suggest the LINAC-based "X irradiation system" with a dose of 30Gy as efficient and safe as gamma-irradiation for platelet products.

Generally, invasive treatment is contraindication for patients with severe thrombocytopenia, because it may increase risk of bleeding. However, many early hepatocellular carcinoma (HCC) patients with cirrhosis have platelet counts (PC) less than 50 × 109/L due to hypersplenism. These patients are often accompanied by hepatic insufficiency, which makes hepatectomy impossible, and local thermal ablation (LTA) has become a major treatment. The aim of our study is to investigate the correlation between severe thrombocytopenia and bleeding after LTA in HCC patients with cirrhosis, and evaluate risk factors of bleeding. 473 patients with cirrhosis who underwent LTA for HCC from 2016 to 2020 were enrolled, and 709 ablations were performed in total. Based on preoperative PC, cases were divided into three groups, namely, group A (PC > 50 × 109/L), group B (30 × 109/L < PC ≤ 50 × 109/L) and group C (PC ≤ 30 × 109/L). The incidence of bleeding after LTA was compared among the three groups. Logistic regression was used to explore the risk factors for bleeding after ablation. The overall incidence of bleeding complications was 4.4%, and no significant difference was observed between group A, B, and C (3.9% vs. 6.4% vs. 3.3%, P = 0.410). In multivariate analysis, tumor diameter (OR = 2.657 per 1 cm, P < 0.001), and multiple lesions (≥ 3) (OR = 3.723, P = 0.006) were found to be independent predictors of bleeding after LTA. In small HCC patients with cirrhosis and hypersplenism, the PC range 30-50 × 109/L will not increase the risk of bleeding after LTA. Tumor diameter and number of lesions are independent predictors for bleeding after LTA in HCC patients.

Hemorrhage is a significant medical problem that has been an active area of research over the past few decades. The human body has a complex response to bleeding that leads to blood clot formation and hemostasis. Many biomaterials based on various biomacromolecules have been developed to either accelerate or improve the body's natural response to bleeding. This review examines the mechanisms of hemostasis, types of bleeding, and the in vitro or in vivo models and techniques used to study bleeding and hemostatic materials. It provides a detailed overview of the diverse hemostatic materials, including those that are highly absorbent, wet adhesives, and those that accelerate the biochemical cascade of blood clotting. These materials are currently marketed, under preclinical testing, or being researched. In exploring the latest advancements in hemostatic technologies, this paper highlights the potential of these materials to significantly improve bleeding control in clinical and emergency situations.

Peri-operative anemia is a common condition encountered in adult surgical patients. It is increasingly recognized as a predictor of post-operative morbidity and mortality. Evaluation and treatment of anemia pre-operatively can reduce transfusion needs and potentially improve outcomes in surgical patients. This article discusses anemia optimization strategies in peri-operative setting with special focus on use of intravenous iron therapy. Additionally, the authors describe the role of transfusion medicine and best practices around red blood cell, platelet, and plasma transfusions.

Herein we present the update for the Mexican Guidelines for the Treatment of Systemic Lupus Erythematosus. It involves the participation of several experts along the country, following the GRADE system. We included aspects regarding vaccines, pregnancy and cardiovascular risk which were not presented in the previous guidelines in 2017.

Glanzmann thrombasthenia (GT) is a very rare autosomal inherited bleeding disease affecting megakaryocyte lineage with impacts on oral health such as gingival bleeding, which requires specific management protocols. Very few clinical cases have been published in the dental and hematologic literature.

This study focuses on a series of 21 patients affected specifically by GT and their hemorrhagic prophylaxis management with the use of recombinant activated factor VII (rFVIIa) for dental extractions and full-mouth debridement.

Data were collected from medical and dental records. rFVIIa was administered prophylactically for oral procedures, following a standardized protocol. Each sessions were performed by experienced oral surgeons, and outcomes were analyzed with a focus on bleeding complications and adverse events.

Forty-one full-mouth debridements and 176 dental extractions were performed during 102 sessions of dental care in an outpatient setting. A total of 226 injections of rFVIIa was delivered. The mean number of injections was 2.2 (range, 1-4) per dental procedure. The overall rate of bleeding complications was 5.9% (n = 6). All 6 hemorrhagic complications were classified as minor bleeding. No thromboembolic event or allergic reaction was observed.

The data presented in this retrospective observational study support the efficacy and safety of rFVIIa for the prevention of bleeding during invasive dental procedures in patients affected by GT. The rFVIIa protocol presented here seems to be a safe and efficient protocol for the prevention of bleeding during invasive oral procedures.

Hematopoietic stem cell transplantation (HSCT) is pivotal in treating hematologic disorders, yet it poses the risk of post-transplantation pancytopenia. Prophylactic platelet transfusions are often administered to mitigate this risk. Utilizing practical markers, such as immature platelet fraction (IPF), to predict hematopoietic recovery in advance could reduce unnecessary prophylactic transfusions. Our prospective study, involving 53 HSCT patients at Taipei Veterans General Hospital between September 2022 and May 2023, utilized the Sysmex XN analyzer to assess peripheral blood cell parameters. We investigated whether IPF could predict platelet recovery early, determined the optimal cut-off value, and compared platelet usage. Neutrophil and platelet engraftment occurred 10 (median; range: 10-12) and 15 (median; range: 15-18) days post-HSCT. Notably, 71.7% of patients exhibited an IPF increase exceeding 2% before platelet recovery. The optimal cut-off IPF on day 10 for predicting platelet recovery within five days was 2.15% (specificity 0.89, sensitivity 0.65). On average, patients received 3.89 units of post-transplantation platelet transfusion. Our results indicate that IPF serves as a predictive marker for platelet engraftment, peaking before the increase in platelet count. This insight aids clinicians in assessing the need for prophylactic platelet transfusions. Integrating reference IPF values alongside platelet counts enhances the accuracy of evaluating a patient's hematopoietic recovery status. Anticipating the timing of platelet recovery optimizes blood product usage and mitigates transfusion reaction risks.

Bleeding events are common complications in critically ill patients with haematological malignancies. The objective of this study was to assess the incidence and identify determinants of ICU-acquired severe bleeding events in critically ill patients with haematological malignancies. We conducted a single-center retrospective study including all adult patients with a history of haematological malignancy requiring unplanned ICU admission over a 12-year period (2007-2018). The primary endpoint was the occurrence of ICU-acquired (i.e. after the first 24 h in the ICU) severe bleeding events, as defined as grades 3 or 4 of the World Health Organization classification.

A total of 1012 patients were analysed, mainly with a diagnosis of lymphoma (n = 434, 42.9%) and leukaemia or myelodysplastic syndrome (n = 266, 26.3%). Most patients were recently diagnosed (n = 340, 33.6%) and under active cancer treatment within the last 3 months (n = 604, 59.7%). The main cause for admission was infection (n = 479, 47.3%), but a significant proportion of patients were admitted for a primary haemorrhage (n = 99, 10%). ICU-acquired severe bleeding events occurred in 109 (10.8%) patients after 3.0 days [1.0-7.0] in the ICU. The main source of bleeding was the gastrointestinal tract (n = 44, 40.3%). Patients experiencing an ICU-acquired severe bleeding event displayed prolonged in-ICU length of stay (9.0 days [1.0-6.0] vs. 3.0 [3.5-15.0] in non-bleeding patients, p < 0.001) and worsened outcomes with increased in-ICU and in-hospital mortality rates (55% vs. 18.3% and 65.7% vs. 33.1%, respectively, p < 0.001). In multivariate analysis, independent predictors of ICU-acquired severe bleeding events were chronic kidney disease (cause-specific hazard 2.00 [1.19-3.31], p = 0.008), a primary bleeding event present at the time of ICU admission (CSH 4.17 [2.71-6.43], p < 0.001), non-platelet SOFA score (CSH per point increase 1.06 [1.01-1.11], p = 0.02) and prolonged prothrombin time (CSH per 5-percent increase 0.90 [0.85-0.96], p = 0.001) on the day prior to the event of interest.

Major bleeding events are common complications in critically ill patients with haematological malignancies and are associated with a worsened prognosis. We identified relevant risk factors of bleeding which may prompt closer monitoring or preventive measures.

Prophylactic platelet transfusions (PT) aim to reduce bleeding. We assessed whether restrictive PT compared to prophylactic strategy could apply in ICU.

We conducted a retrospective monocentric study including patients >18 yo with haematological malignancy admitted to the ICU with thrombocytopenia <20 G/L between 2018 and 2021. Patients were classified in 2 groups according transfusion strategy applied during the first 3 days: prophylactic or restrictive transfusion.

180 patients were included, 87 and 93 in the restrictive and prophylactic groups respectively. After propensity-score analysis, 2 groups of 54 matched patients were analyzed. Restrictive strategy led to a significant reduction in PT with incidence rate for 100-ICU-patients-days of 34.9 and 49.9, incidence rate ratio = 0.699 [0.5-0.9], p = 0.006, representing a 31% decrease. Decreased PT persisted until day 28 with platelet concentrates transfusions-free days at day 28 of 21 [13-25] and 16.5 [10.2-21] in the 2 groups (p = 0.04). Restrictive strategy did not result in higher grade ≥ 2 bleeding. Transfusion efficiency was low with similar number of days with platelet <10 or < 20 G/L regardless of strategy. Platelet transfusion strategy was not associated with 28-day mortality. Platelet nadir <5G/L was associated with day-28 mortality with HR = 1.882 [1.011-3.055], p = 0.046.

A restrictive PT strategy appears feasible in the ICU.

The International Neuromodulation Society convened a multispecialty group of physicians based on expertise with international representation to establish evidence-based guidance on using intrathecal drug delivery in chronic pain treatment. This Polyanalgesic Consensus Conference (PACC)® project's scope is to provide evidence-based guidance for clinical pharmacology and best practices for intrathecal drug delivery for cancer pain.

Authors were chosen on the basis of their clinical expertise, familiarity with the peer-reviewed literature, research productivity, and contributions to the neuromodulation literature. Section leaders supervised literature searches using Medline, EMBASE, Cochrane CENTRAL, BioMed Central, Web of Science, Google Scholar, PubMed, Current Contents Connect, Meeting Abstracts, and Scopus from 2017 (when the PACC last published guidelines) to the present. Identified studies were graded using the United States Preventive Services Task Force criteria for evidence and certainty of net benefit. Recommendations were based on the strength of evidence, and when evidence was scant, recommendations were based on expert consensus.

The PACC evaluated the published literature and established evidence- and consensus-based expert opinion recommendations to guide best practices in treating cancer pain. Additional guidance will occur as new evidence is developed in future iterations of this process.

The PACC recommends best practices regarding the use of intrathecal drug delivery in cancer pain, with an emphasis on managing the unique disease and patient characteristics encountered in oncology. These evidence- and consensus-based expert opinion recommendations should be used as a guide to assist decision-making when clinically appropriate.

Bone marrow aplasia is a common feature in acute myeloid leukemia (AML) patients during their remission induction treatment, and is associated with potential complications such as bleeding, infection and anemia. Frequent platelet and red cell transfusions are administered to prevent and treat these complications. However, platelet counts are poorly associated with bleeding events in this population. Therefore, plasma protein levels could add valuable insights to improve our understanding of the patient's health state. In this study, we aimed to delineate the plasma proteome, including inflammatory pathways, hemostatic and immune components, of AML patients during treatment with intensive transfusion support.

We employed unbiased mass spectrometry (MS)-based proteomics on longitudinal plasma samples from 10 AML patients during intensive-transfusion treatment phase with healthy individuals as baseline control.

A total of 450 proteins were quantified in plasma samples from AML patients and healthy controls. Alteration in proteins levels were mainly observed for proteins involved in inflammation (e.g. SAA1 and CRP), and complement (e.g. C9 and MASP2) when comparing AML versus healthy individuals. Correlation analysis revealed additional affected protein dynamics, including proteins associated with coagulation cascade, endopeptidase inhibitors activity and lipoprotein remodeling.

The plasma proteome from AML patients during intensive treatment shows a disbalance in inflammation, endopeptidase inhibitors activity, lipoprotein remodeling, coagulation and complement. These effects and potential associations with bleeding risk will be further studied in a bigger cohort.

The online version contains supplementary material available at 10.1186/s41231-024-00189-5.

Peripherally inserted central catheters (PICCs) are successfully increasingly used in children in onco-hematologic setting. PICC insertion, especially in oncologic patients, can be associated with adverse events (thrombosis, mechanical complications, and infections). Data regarding the use of PICC, as long-term access in pediatric patients with severe hematologic diseases, are still limited.

We retrospectively evaluated the safety and efficacy of 196 PICC, inserted in 129 pediatric patients with acute leukemia diagnosed and treated at Pediatric Hematology Unit, Sapienza University of Rome.

The 196 PICC analyzed were in situ for a median dwell time of 190 days (range 12-898). In 42 children, PICC was inserted twice and in 10, three times or more due to hematopoietic stem cell transplant, disease recurrence, or PICC-related complications. The overall complication rate was 34%: catheter-related bloodstream infections (CRBSI) occurred in 22% of cases after a median time of 97 days; a catheter-related thrombosis (CRT) in 3.5% and mechanical complications in 9% of cases. Premature removal for complications occurred in 30% of PICC. One death from CRBSI was observed.

To our knowledge, this study represents the largest cohort of pediatric patients who have inserted the PICC for acute leukemia. In our experience, PICC was a cheap, safe, and reliable device for long-term intravenous access in children with acute leukemia. This has been possible with the help of dedicated PICC team.

Some blood operators routinely screen blood donations for high-titre (HT) anti-A/B to reduce the risk of a haemolytic transfusion reaction due to out-of-group plasma-rich components. We assessed donor factors associated with an increased likelihood of screening positive and compared routine data between England and Australia.

Data were assessed from HT screening during 2018-2020 in Australia and 2018-2021 in England, totalling nearly 6 million blood donations. Screening was performed using a Beckman Coulter PK7300 analyser with a micro-titre plate saline direct agglutination test in both countries, although different reagent red cells were chosen. HT-positive was defined as testing positive at a titre of 128 or above.

The likelihood of a donor testing HT-positive was greater for females than males, declined with age and was dependent on the ABO group. However, the proportion of donors testing HT-positive was consistently higher in Australia than in England: overall, 14% of group O donations and 5% of group A donations in England tested HT-positive, compared with 51% and 22%, respectively in Australia. English data also showed that donors from Black, Asian or mixed ethnic backgrounds were more likely to test HT-positive than White donors.

These data demonstrate that donor sex, age, ABO group and ethnicity affect the likelihood of testing HT-positive. Differences in testing methods likely had a significant impact on the proportion of donors testing as HT-positive or -negative rather than any differences in donor populations.

Recently, the rising incidence of trauma, cancer, and critical illnesses has led to a growing necessity for Central Venous Access Devices (CVADs). Inserting CVADs in thrombocytopenic patients is still challenging. This study tries to shed light on the safety and associated risks of CVADs insertion in this high-risk group, with the ultimate goal of informing clinical practice and aiding in decision-making processes.

This study was conducted as prospective cohort study from September 2020 to September 2023 in Mazandaran University of Medical Sciences, Iran. Individuals aged 18-80 years with a platelet count of less than 50,000/dL included and those designated for subcutaneous port procedures or on anticoagulant and antiplatelet therapy, excluded. Ultrasound-guided CVAD insertion using the Seldinger technique and SIC/FIC strategies performed for participants. Incidence of hemorrhagic complications post-CVAD insertion, requirement for blood product transfusions to amend platelet counts, frequency of non-bleeding complications, and complications related to blood product transfusions monitored.

The study comprised 137 participants, 54% of whom were men, with an average age of 46.90 ± 15.70 years. No significant correlation was found between the site of CVAD placement (jugular vs femoral) and the incidence of major or minor bleeding. Femoral catheters were associated with a higher rate of infection. No complications related to transfusion of blood products or mortality seen, indicating that CVAD implantation can be safely performed in patients with thrombocytopenia or coagulation disorders.

CVAD insertion in thrombocytopenic patients, even with platelet counts below 10 × 109/L, is safe and associated with minimal complications when performed under ultrasound guidance by experienced surgeons. This finding supports the use of a lower platelet count threshold for CVAD insertion than currently recommended in guidelines, potentially reducing the need for platelet transfusions prior to CVAD placement.

Thrombocytopenic patients have an increased risk of bleeding when undergoing invasive procedures. In a multicentre, phase II, blinded, randomised, controlled feasibility trial, critically ill patients with platelet count 100 × 109/L or less were randomised 1:1 to intravenous desmopressin (0.3 µg/kg) or placebo before an invasive procedure. Forty-three participants (18.8% of those eligible) were recruited, with 41 eligible for analysis. Post-procedure bleeding occurred in one of 22 (4.5%) in the placebo arm and zero of 19 in the desmopressin arm. Despite liberal inclusion criteria, there were significant feasibility challenges recruiting patients in the critical care setting prior to invasive procedures.

Inherited thrombocytopenias have been considered exceedingly rare for a long time, but recent advances have facilitated diagnosis and greatly enabled the discovery of new causative genes. MYH9-related disease (MYH9-RD) represents one of the most frequent forms of inherited thrombocytopenia, usually presenting with nonspecific clinical manifestations, which renders it difficult to establish an accurate diagnosis. MYH9-RD is an autosomal dominant-inherited thrombocytopenia caused by deleterious variants in the MYH9 gene encoding the heavy chain of nonmuscle myosin IIA. Patients with MYH9-RD usually present with thrombocytopenia and platelet macrocytosis at birth or in infancy, and most of them may develop one or more extrahematologic manifestations of progressive nephritis, sensorial hearing loss, presenile cataracts, and elevated liver enzymatic levels during childhood and adult life. Here, we have reviewed recent advances in the study of MYH9-RD, which aims to provide an updated and comprehensive summary of the current knowledge and improve our understanding of the genetic spectrum, underlying mechanisms, clinical phenotypes, diagnosis, and management approaches of this rare disease. Importantly, our goal is to enable physicians to better understand this rare disease and highlight the critical role of genetic etiologic analysis in ensuring accurate diagnosis, clinical management, and genetic counseling while avoiding ineffective and potentially harmful therapies for MYH9-RD patients.

Tunneled central venous catheters (CVCs) are the cornerstone of modern oncologic practice. Establishing best practices for catheter management in children with cancer is essential to optimize care, but few guidelines exist to guide placement and management.

To address four questions: 1) Does catheter composition influence the incidence of complications; 2) Is there a platelet count below which catheter placement poses an increased risk of complications; 3) Is there an absolute neutrophil count (ANC) below which catheter placement poses an increased risk of complications; and 4) Are there best practices for the management of a central line associated bloodstream infection (CLABSI)?

Data Sources: English language articles in Ovid Medline, PubMed, Embase, Web of Science, and Cochrane Databases.

Independently performed by 2 reviewers, disagreements resolved by a third reviewer.

Performed by 4 reviewers on forms designed by consensus, quality assessed by GRADE methodology.

Data were extracted from 110 manuscripts. There was no significant difference in fracture rate, venous thrombosis, catheter occlusion or infection by catheter composition. Thrombocytopenia with minimum thresholds of 30,000-50,000 platelets/mcl was not associated with major hematoma. Limited evidence suggests a platelet count <30,000/mcL was associated with small increased risk of hematoma. While few studies found a significant increase in CLABSI in CVCs placed in neutropenic patients with ANC<500Kcells/dl, meta-analysis suggests a small increase in this population. Catheter removal remains recommended in complicated or persistent infections. Limited evidence supports antibiotic, ethanol, or hydrochloric lock therapy in definitive catheter salvage. No high-quality data were available to answer any of the proposed questions.

Although over 15,000 tunneled catheters are placed annually in North America into children with cancer, there is a paucity of evidence to guide practice, suggesting multiple opportunities to improve care.

III. This study was registered as PROSPERO 2019 CRD42019124077.