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Abstract Introduction This study investigates the effects of fucoidan extracted from Sargassum angustifolium on coagulation factors and biochemical parameters in male Wistar rats. Fucoidan, a sulfated polysaccharide from brown algae, is known for its anticoagulant, anti-cancer, and antioxidant properties Methods The study involved 25 rats, divided into control, sham, and three experimental groups, receiving varying doses of fucoidan (100, 150, and 200 mg/kg body weight) over 28 days. The research focused on Prothrombin Time, Thrombin Time, and Partial Thromboplastin Time, along with biochemical markers like glucose, total protein, iron-related parameters, and albumin Results This study found that fucoidan administration did not significantly affect the hemostasis tests, suggesting minimal impact on coagulation pathways in vivo. However, a dose-dependent reduction in glucose levels was observed, highlighting the potential of fucoidan as a hypoglycemic agent. Additionally, significant increases in transferrin, iron, and ferritin levels were noted, implying enhanced iron absorption and storage Conclusion The findings underscore the therapeutic potential of fucoidan, particularly in managing glucose metabolism and iron homeostasis, while its minimal anticoagulant effect suggests safe usage in clinical settings where anticoagulation is undesirable. Further research is recommended to explore the full clinical benefits of fucoidan.

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Abstract Introduction This study aims to support our hypothesis regarding compositional changes in the intestinal microbiota by characterizing these changes through pre- and post-transplantation analyses. Additionally, it seeks to determine whether monitoring the intestinal flora could provide predictive or therapeutic insights into graft versus host disease. Methods This study included adult patients who underwent allogeneic hematopoietic stem cell transplantation. Microbiota assessments were performed through stool analyses. Stool samples were collected twice: once before transplantation and once after engraftment. Following nucleic acid isolation, the samples were processed using New Generation Sequencing. Microbiota-associated pathways were examined using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database. Statistical analyses were performed using R statistical software. In addition to microbiota analysis, resistance genes common in Gram-negative bacteria in the region (such as OXA-48-like, KPC-like, NDM-like, and CTX-M-like) were identified via classical polymerase chain reaction in stool samples collected after transplantation. The pathways were analyzed using the KEGG database. Results Fifteen transplant recipients participated in the study. The Proteobacteria phylum increased in patients who tested positive for the CTXM-1 group and OXA-48-like resistance genes. Blautia caecimuris and Enterococcus exhibited significant changes following transplantation, while Tyzzerella spp. and Dialister spp. showed significant alterations after the onset of graft-versus-host disease. A marked change in Eubacterium spp. was also noted in patients with disease relapse. Two key metabolic pathways—acridone alkaloid biosynthesis and the D-arginine and D-ornithine metabolism—were associated with clinical outcomes. Conclusions This study demonstrates that allogeneic hematopoietic stem cell transplants lead to significant alterations in intestinal microbiota composition, including increased pathogenic bacteria associated with graft-versus-host disease exacerbation. These findings suggest that microbiota monitoring may be a promising strategy for the prevention and treatment of graft-versus-host disease. Moreover, modulation of specific microbial metabolic pathways may influence disease clinical outcomes. As the first study of its kind conducted within the Turkish population, this research contributes novel insights to the existing literature and highlights the potential of microbiota-based approaches in post-transplant patient management.

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Abstract Introduction Atypical chemokine receptor 1 (ACKR1) which carries the Duffy antigens, is not just a blood group antigen but serves many more functions. It is a receptor for various pro-inflammatory and inflammatory chemokines and for Plasmodium vivax. Genetic variations in ACKR1 are the basis for Duffy blood group antigens. Methods Routine serological Fya/Fyb typing and ACKR1 genotyping by Polymerase Chain Reaction-Restriction Fragment Length Polymorphism was employed in a population study that included 331 samples from the Agri community. Results Weak Fyb expression was detected by serological findings in five unrelated samples, which prompted further investigation by molecular means. By Polymerase Chain Reaction an aberrant pattern was demonstrated on polyacrylamide gel electrophoresis, which led to the identification of an alteration by sequence analysis. This study describes a 3-bp insertion, present in the FY*B allele (c.144_146dupTGC), resulting in the insertion of the amino acid alanine (p.A49dup) within the full-length protein. Conclusion The 3-bp in-frame insertion (c.144_146dupTGC, p.A49dup) (rs765671589) in the ACKR1 gene was identified in five individuals from the Agri community. Despite apparently carrying an FY*B allele, a very weak Fyb antigen expression was found in association with this genotype. This insertion may also have implications for some physiological roles of ACKR1 and be of interest in malaria research and population genetics.

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Abstract Introduction Comprehensive sickle cell care is a holistic, multidisciplinary approach spanning from birth to adulthood. It includes newborn screening, routine investigations, medications, specific therapies and structured referrals. It is recognised since the 1972 US Sickle Cell Control Act and reinforced by the American Society of Haematology initiatives. This study evaluates the adoption of these strategies by physicians in Nigeria. Aim To examine the extent to which comprehensive care strategies are implemented in the management of sickle cell disease by adult and paediatric haematologists in Nigeria. Methodology This cross-sectional study was conducted from September to November 2022 across six tertiary hospitals. An adapted and pretested primary care assessment tool was used to collect data on physician demographics and strategic components of comprehensive care. Descriptive statistics and chi-square tests were used to analyse the data. Results A total of 157 doctors participated with most working in tertiary hospitals. Folic acid and proguanil hydrochloride were the most prescribed drugs; fewer than 50% used hydroxyurea. A complete blood count was the most requested investigation with 58% routinely scheduling investigations. Adult haematologists ordered more echocardiograms and paediatric haematologists requested more transcranial Dopplers. Adult haematologists referred more across specialities (p-value = 0.0001). All participants routinely counselled patients on clinic attendance, medication adherence and healthy lifestyle practices. Conclusion Key components of comprehensive care are practised at varying levels by health professionals in Nigeria, mainly in urban/tertiary hospitals. To strengthen nationwide delivery of care, health policies should prioritise equitable workforce distribution and integration of additional services, like neonatal screening and emerging therapies.

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Abstract Background This study aims to compare the outcomes of bone marrow (BM) to peripheral blood stem cells (PBSC) grafts in haploidentical hematopoietic cell transplantation using post-transplant cyclophosphamide-based graft-versus-host disease (GvHD) prophylaxis. Methods A single-center retrospective analysis of all adult patients who underwent haploidentical transplants with at least one year of follow-up was conducted. Bivariate analyses were performed using chi-square tests and t-tests. Data were analyzed using SPSS with statistical significance being defined at p-value <0.05. Results The study included 176 transplant recipients: 65 % received PBSC and 35 % received BM grafts. After a median follow-up of 21 months (range: 0-73 months), neither median overall survival nor disease-free survival had been reached. One-year overall survival (BM 75 % versus PBSC 74 %; p-value = 0.898) and one-year disease-free survival (63 % both groups; p-value = 0.994) were similar between groups. PBSC recipients exhibited earlier neutrophil engraftment (17 days versus 18 days; p-value = 0.022). The incidence of cytokine release syndrome was higher in PBSC (90 % versus 37 %) grafts (p-value <0.001). The incidences of Grade II-IV acute GvHD, relapse, non-relapse mortality, platelet engraftment, one-year chronic GvHD, and GvHD-free relapse-free survival were similar across both groups. Conclusions Haploidentical HSCT recipients observed similar outcomes regardless of graft source. Marginally faster neutrophil engraftment was observed in PBSC recipients. These findings suggest flexibility in using graft source for haploidentical transplants, though prospective studies are needed to confirm these results.

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Abstract Background In patients with suspected immune thrombotic thrombocytopenic purpura, guidelines suggest that therapeutic plasma exchange should be initiated within eight hours. However, this time threshold may be difficult to attain. This study sought to identify the optimal time to plasma exchange to maximize outcomes. Study Design and Methods Patients with international classification of disease codes for thrombotic microangiopathy were identified in a retrospective cross-sectional analysis of public use data files from the Recipient Epidemiology and Donor Evaluation Study-III (REDS-III). The assumption of linearity between time to therapeutic plasma exchange and the composite outcome of bleeding, thrombosis, and mortality were evaluated. Subsequently, the optimal time for plasma exchange was identified using a nonparametric approach with bootstrapping. Results For 149 patients with a suspected diagnosis of thrombotic thrombocytopenic purpura, the association between time to plasma exchange and the primary outcome was non-linear. With regard to the primary composite outcome, this time had a low predictive capacity (area under the curve: 0.62). The optimal time that maximized outcomes was 13.5 h. Conclusion Although this study found that time to therapeutic plasma exchange did not independently predict outcome, future studies might evaluate how this time interacts with other variables to predict clinical outcomes.

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Abstract Introduction Polycythemia vera is a myeloproliferative neoplasm marked by an increased proliferation of erythroid mature and precursors cells in bone marrow and peripheral blood. The pathophysiology is linked to the presence of the JAK2 driver mutation, epigenetic deregulation, and alterations in the bone marrow hematopoietic niche. Multipotent mesenchymal stromal cells (MSC) in the bone marrow, which are crucial for maintenance and development of hematopoietic stem cells, play a role in the communication between neoplastic cells and resident bone marrow cells by releasing various mediators that either suppress or promote tumor progression. These mediators include several essential immunomodulatory molecules, pro-angiogenic and growth factors. We hypothesized that MSC from polycythemia vera patients (Patient Group) would exhibit distinct properties compared to those from healthy donors (Control Group), thereby influencing the hematopoietic niche and contributing to disease pathogenesis. Methods This study characterized MSC from patients, focusing on their secretory, proteomic, and phenotypic properties. Results MSC from the Patient and Control Groups had similar immunophenotypes and multipotentiality. However, MSC from the Patient Group exhibited reduced immunomodulatory properties, and released distinct soluble immune and angiogenic mediators when compared with the Control Group. Global proteomic analysis revealed that MSC from patients presented upregulated expressions of FAM175B, VP526A, CTTN, MAP4, BAX, and TPD52L2 but a downregulated TNC expression. These results indicate that MSC contribute to the inflammation pattern in the hematopoietic niche. The secretory and proteomic profile of MSC from patients, indicate that these cells may influence immune cell function, induce neoangiogenesis, and alter cell-to-cell interactions within the bone marrow, thereby fostering a pro-tumor microenvironment and favoring disease pathogenesis. Conclusion These findings highlight the potential of targeting MSC-mediated pathways as a therapeutic strategy in polycythemia vera.

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Abstract Introduction Intravenous immunoglobulin is widely used for various conditions but faces challenges such as limited supply, high cost, and substantial off-label use. Obstetrical intravenous immunoglobulin use remains underexplored, despite its relevance to maternal and neonatal care and resource management. Methods This single-center retrospective cohort study examined intravenous immunoglobulin administration in 136 pregnancies (122 patients) from 2007-2020, focusing on adherence to Health Canada licensed indications and Ontario Immunoglobulin Utilization Management Guidelines. Results Maternal thrombocytopenia (56.6 %) and treatment for fetal/neonatal alloimmune thrombocytopenia (16.2 %) were the most common indications, accounting for 16.9 % and 64.3 % of total intravenous immunoglobulin volume, respectively. Intravenous immunoglobulin use represented 1.6 % of the center's total consumption during the study period, with notable non-adherence to guidelines in 38.2 % (Health Canada) and 17.6 % (provincial guidelines) of pregnancies. Conclusion Findings highlight the need for optimized intravenous immunoglobulin use in obstetrics and future research to ensure safety, efficacy, and evidence-based guidance in clinical practice and policy.

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Abstract Background Acute promyelocytic leukemia (APL) is a subtype of acute myeloid leukemia (AML) marked by a high incidence of coagulopathy. Podoplanin, a glycoprotein involved in platelet activation through interaction with CLEC-2, has recently been identified on leukemic promyelocytes and suggested as a potential contributor to APL coagulopathy. Identification of novel biomarkers and therapeutic targets for APL coagulopathy can potentially improve the outcomes of this condition Aim To explore whether levels of soluble podoplanin in plasma are different in APL, and to evaluate its association with laboratory and clinical outcomes in these patients Methods Samples were obtained from consecutive patients with APL at the time of diagnosis in an academic hospital. Biobank samples from 35 patients with non-APL AML matched for age and sex were used as comparators. Circulating podoplanin levels were measured in plasma using a commercial ELISA kit. The study was approved by the institutional ethics committee and all participants provided written informed consent Results APL patients showed significantly higher plasma soluble podoplanin concentrations compared to non-APL AML. Using the median soluble podoplanin value as a cutoff, a higher proportion of APL patients presented elevated levels. Soluble podoplanin levels correlated with CD40L in APL cases, but not in non-APL AML patients, suggesting a possible interaction with thrombo-inflammatory activation pathways Conclusion These findings represent a proof-of-concept that measuring soluble podoplanin in plasma samples can contribute to the diagnosis of APL, while also providing novel data on the association of podoplanin with the pathogenesis of APL coagulopathy.

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Abstract Background Neuropathic pain represents a complex and often underdetected component of the pain spectrum in Sickle Cell Disease, particularly among individuals with chronic or treatment-resistant symptoms. Despite its clinical relevance, neuropathic pain is not routinely screened for in hematology practice, where pain is frequently attributed solely to vaso-occlusive mechanisms. Method A cross-sectional study was conducted with 214 individuals diagnosed with Sickle Cell Disease at a hematology referral center in northeastern Brazil. Two validated instruments, Douleur Neuropathique 4 and PainDETECT were utilized to screen for neuropathic pain. Clinical and demographic data were collected, and the correlation between the instruments was assessed using Pearson’s coefficient. Results The Douleur Neuropathique 4 tool identified neuropathic pain in 29 % of participants. PainDETECT indicated 8.4 %, which increased to 22 % when including uncertain-range scores. The correlation between the two tools was strong (r = 0.87). Neuropathic pain was more prevalent among older individuals, those who reported recurrent painful episodes in the past year (p-value <0.001), and those with recent opioid use (p-value = 0.042). Sensory descriptors such as tingling, numbness, and electric shock sensations were commonly reported. Conclusion The combined use of Douleur Neuropathique 4 and PainDETECT, both of which are quick and simple to administer, proved to be a complementary strategy for identifying neuropathic pain, with each instrument capturing distinct features. Incorporating this approach into hematology care may facilitate the detection of pain profiles beyond vaso-occlusion and support more individualized treatment decisions.

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Abstract Background Impaired iron metabolism has been linked to the pathogenesis of multiple myeloma. Redox active iron chelators have gained attention as potential anti-cancer agents as they target the high iron dependency of cancer cells. This study explored the potential mechanisms underlying the anti-multiple myeloma effect of the redox active iron chelator Dp44mT (Di-2-pyridylketone 4,4-dimethyl-3-thiosemicarbazone). Methods The effect of Dp44mT was tested on both immunomodulatory drug-sensitive and drug-resistant multiple myeloma cell lines using the MTT assay. Proteomic and phosphoproteomics characterization were utilized to explore the mechanisms of Dp44mT action on multiple myeloma cells. In addition, a real-time polymerase chain reaction assay was performed to examine the expressions of major iron metabolism genes. Reactive oxygen species, lipid peroxidation, mitochondrial membrane potential, and intracellular iron compartmentalization were measured using flow-cytometry. Results The high potency of Dp44mT in killing multiple myeloma cell lines was confirmed. Treatment with Dp44mT showed evidence of deregulated cellular iron metabolism, reactive oxygen species homeostasis, and mitochondrial membrane potential in multiple myeloma cell lines. As possible mechanistic pathways of Dp44mT, there was overrepresentation of the AMPK pathway, cell cycle, endoplasmic stress, and down regulation of ACSL4 (acyl-CoA synthetase long chain family member 4). Conclusion This study suggests an in vitro, anti-multiple myeloma effect of Dp44mT that appears to be mediated by dysregulated iron metabolism, reactive oxygen species, and other biological pathways.

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Abstract Introduction Diffuse large B-cell lymphoma is a complex disease, and prognostic scores are inadequate for identifying high-risk patients. Recently, leukocyte indices, like the neutrophil-to-lymphocyte ratio, have become a marker of prognosis. The purpose of this study is to evaluate the performance of this marker as a risk predictor in adult patients with newly diagnosed diffuse large B-cell lymphoma in Colombia. Materials and methods A retrospective cohort study, calculated the neutrophil-to-lymphocyte ratio and its performance as a predictor for 2-year progression-free survival. Patients were divided into two groups; patients with high ratios in Group One and patients with low ratios in Group Two. Both groups were followed for at least 24 months from diagnosis. Results The cohort comprised 198 patients with a median age at diagnosis of 61 years. A neutrophil-to-lymphocyte ratio cutoff point of 6.2 was calculated. Patients with ratios higher than 6.2 (n = 45) were placed in Group One, and the patients with ratios below 6.2 (n = 153) in Group Two. The median follow-up time was 45 months. The 24-month progression-free survivals were 55.2 % (95 % confidence interval: 42.3-71.9 %) and 73.2 % (95 % confidence interval: 66.2-81.0 %) for high and low ratios, respectively (Hazard ratio 0.62; 95 % confidence interval: 0.44-0.89; p-value = 0.009). The 24-month overall survivals were 70.7 %; (95 % confidence interval: 58.5 - 85.5 %) and 80.4 %; (95 % confidence interval: 66.2-87.3 %), respectively. Conclusion A neutrophil-to-lymphocyte ratio with a cutoff point at ≥6.2 could differentiate a diffuse large B-cell lymphoma population with an unfavorable prognosis for progression-free survival.

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Abstract Hereditary thrombocytopenias are often difficult to diagnose. Since most of them are rare diseases, their characteristics are less known by physicians who deal with adults. While pediatricians are accustomed to considering genetic diseases in the differential diagnosis of diseases affecting their young patients, clinicians who treat adults often overlook this possibility. Making a definitive diagnosis usually requires complex laboratory techniques. In addition, because this is a very dynamic field half of the patients have forms that have not yet been identified with new disease definitions being made every month with next-generation sequencing (NGS). These patients are often mistakenly diagnosed with immune thrombocytopenia, and, accordingly, they are at risk of receiving unnecessary immunosuppressive therapy. Misdiagnosis is widespread in patients whose low platelet count is discovered in adulthood because, in these cases, the hereditary origin of thrombocytopenia can be overlooked. The age of manifestation and the duration/chronicity of symptoms are crucial clinical features for identifying hereditary thrombocytopenia disorders. It is important to establish the correct diagnosis because it has recently been shown that some hereditary forms of thrombocytopenia predispose to other diseases such as leukemia, renal failure, and bone marrow failure; therefore, affected individuals should be kept under close surveillance and, when necessary, treated for concomitant diseases. This review aims to determine when to suspect and how to diagnose and manage inherited thrombocytopenias. It also intends to detail the less common kinds of isolated thrombocytopenias highlighting that not all isolated thrombocytopenias that emerge in adults are immune thrombocytopenia.

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Abstract Hemophagocytic lymphohistiocytosis is a severe, rare condition characterized by excessive immune activation, leading to significant morbidity and mortality. Lymphoma is the most common trigger for malignancy-related hemophagocytic lymphohistiocytosis in adults, with large B-cell non-Hodgkin, T- and NK-cell lymphomas being the most diagnosed. Hodgkin lymphoma is less frequently observed. Lymphoma-associated hemophagocytic lymphohistiocytosis poses diagnostic and therapeutic challenges due to its complex pathogenesis and heterogeneous presentation. Treatment aims to control the overactive immune system, identify and treat modifying factors, optimize clinical support, and treat the underlying lymphoma. Early etoposide (Etoposide) combined with dexamethasone for immunomodulation results in rapid control of hyperinflammation and clinical improvement. It has increasingly been adopted as a standard initial approach followed by lymphoma-specific treatment. However, the outcomes for patients with lymphoma-associated hemophagocytic lymphohistiocytosis remain poor, especially for patients with T- and NK-cell lymphomas. In relapsed or refractory cases, emerging therapies have been explored, with ruxolitinib showing the most promising results. This paper reviews current understanding of the epidemiology, pathogenesis, clinical features, diagnosis, and treatment of lymphoma-associated hemophagocytic lymphohistiocytosis in adults and proposes an appropriate treatment protocol based on the most recent data from the literature.

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ABSTRACT Cold-stored platelets were abandoned in the 1960s after demonstration of an increased clearance in vivo due to an irreversible activated phenotype. Difficulties in storage, logis-tics, and the increased requirement of therapeutic platelet transfusions for haemostasis have sparked renewed interest in cold-stored platelets. This systematic review compared two primary outcomes: in vivo recovery for autologous cold-stored platelets versus room-temperature platelets in healthy volunteers, and chest drain output at 24 h for allogeneic cold-stored platelets versus room-temperature platelets after complex cardiothoracic sur-gery. A total of 4215 articles were found in the ProQuest, PubMed, Scopus, Embase, and Cochrane electronic databases. Seven eligible papers were included in this meta-analysis. Cold-stored platelets showed a decreased in vivo recovery two hours after retransfusion following storage for two to seven days compared to a room-temperature platelet control group (mean difference: -25.85 %; 95 % confidence interval: -41.98 to -9.71 %; p-value = 0.002). Further, cold-stored platelets showed a decreased chest cavity output when transfused within 24 h after complex cardiothoracic surgery (mean difference: 249.68 mL; 95 % confidence interval: 85.68 to 413.67 mL; p-value = 0.003). While cold-stored platelets are not a substitute for room-temperature platelets in a prophylactic scenario, their ability to significantly reduce chest cavity output suggests they may be optimal for the manage-ment of bleeding in surgical patients, especially in the context of logistical difficulties.