Asciminib represents a significant advancement in the treatment of chronic myeloid leukemia, establishing a novel therapeutic paradigm by specifically targeting the ABL1 myristoyl pocket, a mechanism distinct from that of conventional adenosine triphosphate-competitive inhibitors. Such a selective inhibitor offers an alternative treatment strategy for patients with chronic myeloid leukemia who have developed resistance to previous tyrosine kinase inhibitor therapies. Although asciminib demonstrates a superior safety profile, primarily characterized by a reduction in cardiovascular adverse events associated with prior tyrosine kinase inhibitors, its clinical significance extends further. The effectiveness of asciminib, combined with its capacity to overcome resistance through combination strategies with adenosine triphosphate-binding site tyrosine kinase inhibitors, establishes it as a focal point in emerging chronic myeloid leukemia treatment approaches. It remains essential to continue research and clinical trials to enhance the therapeutic efficacy of asciminib and manage its associated side effects.

Chronic myeloid leukaemia (CML) is driven by the t(9;22) forming the BCR::ABL1 fusion gene, leading to the development of hyper-myeloid proliferation. This led to development of tyrosine kinase inhibitors (TKIs) such as Imatinib, Nilotinib, and Ponatinib. However, resistance or intolerance to ATP-competitive TKIs remains a challenge for some patients. asciminib (ABL001), a novel TKI, targets the myristoyl pocket of ABL1 instead of the ATP-binding site, reducing resistance to mutations. As asciminib is linked to thrombocytopenia, its effects on platelet activation, endothelial function, and inflammation must be studied to assess its potential to promote thrombosis. The main objective of this study is to determine the potential of asciminib as a monotherapy in inducing pathological responses to platelets and endothelium over time within the vasculature. This study assessed the effects of TKIs including asciminib on platelets and thrombotic biomarkers. Washed platelets were used to measure granule secretion, thrombus formation, surface expression of glycoproteins, apoptosis, and viability. Plasma from chronically Asciminib-treated CML patients was analysed using sandwich ELISA for inflammatory and platelet-endothelial biomarkers, and thrombin generation assays were performed to study coagulation. This approach combined in vitro and ex vivo methods to explore the impact of asciminib on platelet function and thrombotic potential. The study shows that acute treatment with asciminib does not promote platelet activation or thrombus formation. Instead, it exhibits an inhibitory effect on thrombus formation in vitro and is associated with reduced thrombo-inflammatory biomarkers ex vivo in chronically treated CML patients. Asciminib was associated with increased thrombin generation over time, suggesting an effect on secondary haemostasis. Asciminib does not appear to induce a prothrombotic or proinflammatory state under the conditions studied, which may be advantageous for CML patients. However, the observed increase in thrombin generation over time suggests a potential effect on secondary haemostasis that warrants further investigation in controlled studies.

Introduction: Determining foetal RhD status guides the targeted use of RhIg prophylaxis to prevent sensitisation. While Non-Invasive Prenatal Testing (NIPT) enables this targeted approach in RhD-negative pregnant women, concerns remain about the risk of alloimmunisation and the cost-effectiveness of NIPT. Despite these uncertainties, screening programs are being adopted worldwide. Objectives: To evaluate the effectiveness of NIPT-guided RhIg prophylaxis in reducing maternal sensitisation and to assess its cost-effectiveness compared with universal RhIg prophylaxis. Methods: In compliance with PRISMA guidelines, a systematic review was conducted using Google Scholar, PubMed, Scopus, and Embase. Eligible studies included the incidence of RhD alloimmunisation and healthcare costs associated with RhIg prophylaxis. Data were statistically analysed using RevMan (Review Manager) software. Results and discussion: From 2,856 records, six studies met the inclusion criteria. RhD alloimmunisation was significantly less frequent in the targeted group (0.2%) compared to the routine group (0.4%) (p<0.001; 95% CI: 0.39-0.68). However, targeted prophylaxis showed higher mean costs (p=0.01; 95% CI: 0.11-0.80), mainly due to genotyping expenses. Despite increased costs, NIPT demonstrated clinical, ethical, and sustainability benefits, including reduced incidence of RhD alloimmunisation, RhIg wastage, lower disease transmission risk, and improved patient compliance through personalised care. Conclusion: NIPT offers a safe and effective approach for targeted RhIg prophylaxis. Although it is expensive at present, long-term clinical and economic advantages are encouraging. Further studies are required to verify these results and support broader use in routine antenatal care. Keywords: NIPT; Alloimmunisation; RhIg prophylaxis; Cost; RhD-negative pregnant women.

Haemostasis in Chronic Kidney Disease (CKD) is complex, with patients experiencing both thrombotic and haemorrhagic risks. Current therapies, such as dialysis and blood transfusions, often rely on clinical judgment, which may not fully address these haemostatic abnormalities. This systematic review and meta-analysis aimed to determine whether Thromboelastography (TEG) offers a better ability to assess coagulation abnormalities in CKD compared to standard coagulation tests like activated partial thromboplastin time (aPTT), and prothrombin time (PT). A search across five databases identified 10 studies comparing TEG parameters in CKD patients versus healthy controls. TEG detected hypercoagulability in CKD, with significant reductions in Kinetics Time (P = 0.04), increases in Alpha angles (P = 0.02), and elevated Maximum Amplitude values (P = 0.0006). However, Reaction Time (P = 0.43) and Lysis 30 (P = 0.28) showed no significant differences. Standard coagulation tests, including aPTT and PT, also showed no significant differences between groups (P = 0.30 and P = 1.00), suggesting their limitations in detecting the complex haemostatic changes in CKD. Platelet counts were lower in CKD patients (P = 0.0009) but remained within normal ranges. Elevated fibrinogen levels (P = 0.003), linked to chronic inflammation, indicated a prothrombotic profile. Despite high heterogeneity in some parameters due to variability in CKD stages and treatment types, TEG demonstrates a more detailed assessment of haemostatic changes in CKD, suggesting its potential as a predictive tool for managing coagulation abnormalities.

Background: The reversal of warfarin in emergency haemorrhage situations is critical for maintaining patient survival. This review evaluates whether four-factor PCC is superior in INR correction and safety when compared with three-factor PCC. Given inconsistent evidence and limited direct comparisons, a meta-analysis was conducted to assess INR reversal, thromboembolic outcomes, and mortality. Study design and method: This systematic review follows PRISMA guidelines to compare three-factor and fourfactor PCC for warfarin reversal in emergency haemorrhagic situations. Literature was gathered from PubMed, Scopus, Google Scholar and Embase, then screened using pre-defined eligibility criteria. Analyses were conducted in Review Manager using mean INR change and risk ratios for thromboembolic and mortality outcomes. Results: From 3,536 literature articles identified from the aforementioned databases, seven retrospective US-based studies met eligibility criteria. The study periods ranged from 2007 to 2015 and primarily assessed INR reversal and thromboembolic outcomes. Study quality was evaluated using the STROBE checklist. The data was analysed and forest plots for mean INR change, thromboembolic outcomes and mortality were generated. Conclusion: The use of four-factor PCC was statistically significant in reducing the INR in warfarin-treated patients experiencing haemorrhage when compared to the use of three-factor PCC. Four-factor PCC showed a greater INR reduction. There was no significant difference observed in both thromboembolic or mortality outcomes between the two groups. However, given the smaller patient populations in the included studies, further research with larger cohorts is warranted to confirm these findings. Keywords: Blood; Haemorrhage; Deep vein thrombosis; Direct oral anticoagulants

OBJECTIVE:Antibody screening and identification facilitates the issue of antigen-negative blood for patients with alloantibodies to red blood cell (RBC) antigens, thereby maximizing blood safety and the survival of transfused donor cells. The sensitivity and specificity of reagent red blood cells (RRBCs) used in pre-transfusion testing varies between manufacturers. This Phase II study aimed to build on a previously published Phase I study comparing the analytical performance of four manufacturers' RRBCs in column agglutination technology (CAT). A total of 231 patient samples with a negative indirect antiglobulin test (IAT) results were tested using Immulab, Bio-Rad, Grifols, and QuidelOrtho RRBCs. Phase II results were pooled with Phase I results to provide more accurate calculations of the RRBC analytical performance. RESULTS:The sensitivity of the RRBCs used in the combined studies was 94.52% (95%CI 86.56-98.49%) for Bio-Rad, 81.48% (95%CI 71.30-89.25%) for Grifols, and 95.71% (95%CI 87.98-99.11%) for QuidelOrtho RRBCs. The sensitivity of Immulab RRBCs were stratified based on performance in the three CAT platforms: 100%, 95%CI 95.07-100.00% in Bio-Rad CAT, 100%, 95%CI 95.55-100.00% in Grifols CAT and 100%, 95%CI 94.87-100.00% in QuidelOrtho CAT. CONCLUSIONS:Immulab 0.8% RRBCs showed greater sensitivities and NPVs than the equivalent Bio-Rad, Grifols, and QuidelOrtho RRBCs in Bio-Rad, Grifols, and QuidelOrtho CAT, respectively. These differences may have implications in clinical pre-transfusion settings.

Background: Red Blood Cell (RBC) alloimmunisation represents a major complication in transfused Myelodysplastic Syndrome (MDS) patients. Frequent transfusion dependency increases the risk of alloantibody formation, while Hypomethylating Agent (HMA) therapy may have immunomodulatory effects that influence this outcome. This meta-analysis aimed to evaluate the incidence of RBC alloimmunisation in transfused MDS patients and assess the impact of HMA therapy. Methods: A systematic review and meta-analysis was conducted according to PRISMA guidelines. Relevant studies were identified through PubMed, Scopus, Embase, and Google Scholar databases. Study quality was assessed using the STROBE checklist. Pooled Odds Ratios (ORs) with 95% Confidence Intervals (CIs) were calculated for alloimmunisation outcomes using a random-effects model in RevMan 5.4.1. Results: Seven studies published between 2001 and 2024 met the inclusion criteria. The pooled analysis demonstrated a significantly higher risk of RBC alloimmunisation in transfused MDS patients compared with non-MDS controls (OR=1.68; 95% CI 1.13-2.51; P=0.01). A higher transfusion burden was associated with an even greater risk (OR=3.43; 95% CI 1.83-6.43; P=0.0001). HMA-treated MDS patients showed a lower risk compared with untreated controls, though this trend did not reach statistical significance (OR=0.42; 95% CI 0.17-1.03; P=0.06). Conclusion: Transfused MDS patients are at increased risk of RBC alloimmunisation, particularly with higher transfusion exposure. Although not statistically significant, HMA therapy showed a trend toward reducing alloimmunisation, suggesting a potential immunomodulatory effect that requires further investigation. These findings may inform transfusion strategies and guide future research. Keywords Myelodysplastic syndrome; RBC alloimmunisation; Hypomethylating agents; Transfusion; Meta-analysis.

Background The aim of this study was to evaluate the blood film assessment of CellaVision DC-1 compared to conventional microscopy in stained peripheral blood (PB) films from paediatric samples. Methods Blood films (n = 50) including clinically normal samples as well as common pathological conditions, were collected and examined by conventional microscopy and CellaVision DC-1. Manual microscopy counts vs. automated WBC differentiation and RBC grading via Cellavision, including manual re-classification, were compared to expert morphologist reporting. Using statistical analysis, the following metrics were measured including sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). Results The reliability of RBC grading ranged between 60 and 100 % sensitivity and 55–74 % specificity for CellaVision method compared to 78–93 % sensitivity with manual microscopy, demonstrating the latter as the superior method. Additionally, DC-1 misclassified the presence of blasts for lymphocytes, with 67 % compared to 100 % specificity with the gold standard microscopy. Both pre- and post-classification, re-classifications, and manual microscopy showed strong correlations of WBC differential counts with expert/known readings, mainly for neutrophils and lymphocytes (R2: 0.60–0.85). In terms of time, CellaVision took 1 min longer to scan and assess each slide than did light microscopy, which could affect timely diagnosis and treatment decisions. Conclusion The use of CellaVision DC-1 may be beneficial to diagnostic laboratories in the adult setting; however, further research should focus on enhancing automated analysis when assessing paediatric samples that demand human intellect and critical thinking. Medical Scientist training and software development are recommended. Manual microscopy is faster and more accurate. Slide signing and DC-1 classifications of unclassified WBCs need scientist intervention.

Chronic lymphocytic leukemia (CLL), a malignant tumour, is characterized by expansion of mature monoclonal B lymphocytes expressing CD23 and CD5 in secondary lymphocytic organs, blood, and bone marrow. Here, we provide an in-depth review of CLL, emphasizing its pathophysiology, cytogenic changes, and treatment strategies, particularly the efficacy and challenges of treatments, such as Bruton tyrosine kinase (BTK) inhibitors, B cell lymphoma 2 (BCL2) inhibitors, and phosphatidylinositol 3-kinase (PI3K) inhibitors, as well as the need to understand their role in managing disease progression, chemoresistance, and intolerance. In addition, we explore efficacy based on patient response and comparison between monotherapy and combination therapy. We also highlight the need for innovative strategies to overcome treatment resistance and enhance patient outcomes.

Introduction: The detection and identification of clinically significant antibodies to red cell antigens form the foundation for safe transfusion practices. The reagent red blood cells (RRBCs) used in antibody detection and identification vary in sensitivity and specificity and should therefore be carefully considered before being implemented in routine patient testing. This study aimed to evaluate the diagnostic performance of RRBCs in Australia.Methods: 166 patient-derived plasma samples containing clinically significant alloantibodies were tested using column agglutination technology (CAT) with Immulab, Bio-Rad, Grifols and QuidelOrtho screening and identification RRBCs. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy were calculated for Immulab RRBCs on each platform with direct comparisons to equivalent Bio-Rad, Grifols, and Ortho RRBC performance measures. Differences in reaction strength were scrutinized, and the additional effort required to resolve different antibody specificities was investigated.Results: Immulab 0.8% RRBCs demonstrated superior sensitivities, NPVs, and accuracies compared to the equivalent Bio-Rad, Grifols and QuidelOrtho RRBCs in the detection of clinically significant antibodies when tested using Bio-Rad, Grifols and Ortho CAT respectively. Factoring in the occurrence of false-negative results, differences in reaction strength and antibody resolution efficiency; the 0.8% RRBCs with the overall greatest diagnostic accuracy were found to be manufactured by Immulab > QuidelOrtho > Bio-Rad > Grifols.Conclusion: Failure to detect weak clinically significant alloantibodies during pre-transfusion testing may increase the risk of hemolytic transfusion reactions in patients requiring treatment. The selection of RRBCs should be carefully scrutinized by any laboratory that performs transfusion testing.

OBJECTIVE:The detection/identification of clinically significant antibodies to red cell antigens form the foundation for safe transfusion practices. This study aimed to evaluate the diagnostic performance of commercially available 0.8% reagent red blood cells (RRBCs) in Australia. 166 patient-derived plasma samples with a positive indirect antiglobulin test (IAT) were tested using column agglutination technology (CAT) with Immulab, Bio-Rad, Grifols and QuidelOrtho screening and identification RRBCs with the respective manufacturer's proprietary CAT system. RESULTS:False-negative antibody screening and identification results were obtained with Bio-Rad (3/61), Grifols (14/68) and Quidel-Ortho (3/59) RRBCs when tested with the respective manufacturer's proprietary CAT system. Zero false-negative results were observed with Immulab RRBCs when tested with samples across all platforms. The sensitivity of the RRBCs used in this study were calculated to be 95.83% (95%CI 88.30-99.13%) for Bio-Rad RRBCs, 82.50% (95%CI 72.38-90.09%) for Grifols RRBCs and 95.65% (95%CI 87.82-99.09%) for QuidelOrtho RRBCs. The sensitivity of Immulab RRBCs were stratified based on performance in the 3 CAT platforms: Bio-Rad CAT (100%, 95%CI 95.01-100%), Grifols CAT (100%, 95%CI 95.49-100%) and QuidelOrtho CAT (100%, 95%CI 94.79-100%). CONCLUSIONS:RRBCs used in antibody detection and identification vary in diagnostic performance and should therefore be carefully considered before being implemented in routine patient testing.

The clinical manifestation of foetal anaemia caused by maternal Kell alloantibodies differs from that caused by non-Kell alloantibodies. Severe anaemia develops in the foetus in the early weeks of gestation; therefore, proper management and early intervention are important. A systematic review and meta-analysis was performed to determine whether the anti-K1 titre can determine the sequelae of Kell alloimmunised pregnancies. Prospective and retrospective cohort studies were used to conduct a systematic review following a comprehensive literature search, in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) guidelines. Studies were screened based on a defined set of inclusion and exclusion criteria. A total of 5143 potential articles were identified. Ten studies were used in the meta-analysis of pregnancy outcomes for a specific anti-K1 titre cut-off. The meta-analysis identified statistical significance for intrauterine transfusion (ARD: 0.351; 95 % CI: 0.593–0.109; p-value = 0.004), hydrops (ARD: 0.808; 95 % CI: 1.145–0.472; p-value <0.001), intrauterine foetal death (ARD: 0.938; 95 % CI:1.344 to -0.533; p-value <0.001) and intrauterine transfusion for Doppler middle cerebral artery >1.5 MoM (ARD: 0.381; 95 % CI:1.079 to -0.317; p-value = 0.285). It was concluded that there is no correlation between anti-K1 titre and Kell sensitised pregnancy outcomes, but monitoring the anti-K1 titre is important to manage the pregnancy and it helps clinicians determine the need for intrauterine transfusions. Doppler middle cerebral artery peak systolic velocity is strongly correlated with foetal anaemia and is an efficient routine method for determining the need for intrauterine transfusions in pregnancies affected by anti-K1.

Background and Objectives: Haemolytic disease of the foetus and newborn (HDFN) occurs when maternal antibodies, often triggered by foetal antigens, destroy foetal and neonatal red blood cells. Factors like antibody strength, quantity and gestational age influence HDFN severity. Routine antenatal anti-D prophylaxis (RAADP) has significantly reduced HDFN cases. However, the effect of overweight/obesity (body mass index [BMI] > 25/30 kg/m(2)) on anti-D prophylaxis efficacy remains unclear. This systematic review will examine the impact of BMI on anti D prophylaxis effectiveness in Rh(D) negative pregnant women. Materials and Methods: We conducted a systematic review and meta-analysis following Preferred Reporting Items for Systematic Review and Meta-Analysis (PRISMA) protocols. We searched databases from 1996 to 2023, focusing on studies exploring the link between high BMI/weight and anti-D serum levels in Rh(D)-negative pregnant women with Rh(D)-positive foetuses. Ten eligible studies were included, three suitable for meta-analysis. Study quality was assessed using the Strengthening the Reporting Observation Studies in Epidemiology (STROBE) checklist. Statistical analyses included Pearson correlation coefficients and risk differences. Results: Our meta-analysis revealed a significant negative correlation (r = -0.59, 95% confidence interval [CI]: -0.83 to -0.35, p = 0.007) between high BMI/weight and serial anti-D levels in in Rh(D)-negative pregnant women with Rh(D)-positive foetuses. High BMI/weight had lower odds of serial anti-D level exceeding 30 ng/mL (arcsine risk difference [ARD] = 0.376, 95% CI: 0.143-0.610, p = 0.002). Heterogeneity among studies was low (I-2 = 0). Conclusion: While our analysis suggests a potential linkage between high BMI/weight and reduced efficacy of anti-D prophylaxis, caution is warranted due to study limitations. Variability in study design and confounding factors necessitate careful interpretation. Further research is needed to confirm these findings and refine clinical recommendations.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is still a global concern with high morbidity and mortality rates. The role of endothelial cells in the progress of COVID-19 is well established. Therefore, the current study aimed to measure the endothelial markers and their correlation with the hematological parameters in intensive care unit-admitted COVID-19 patients. This study involved 111 adult participants, including 55 ICU-admitted patients with COVID-19 and 56 healthy controls. Levels of E-selectin, ICAM-1, and VCAM-1 in the plasma of the study participants were measured and correlated with hematological parameters. The study demonstrates that COVID-19 patients admitted to the ICU have higher levels of E-selectin, ICAM-1, and VCAM-1 compared to healthy controls (p < .05). These elevated levels can serve as reliable indicators of endothelial dysfunction and early markers for the detection and prediction of endothelial cell involvement in COVID-19 complications. The findings of this study suggest that increased levels of E-selectin, VCAM-1, and ICAM-1 in patients with COVID-19 are indicative of the participation of endothelial cells in the pathogenesis of COVID-19 complications. Consequently, these endothelial markers are proposed as potential early indicators for predicting the severity of COVID-19.

Introduction: Coronavirus disease-19 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is still posing detrimental effects on people. An association between contracting COVID-19 and the ABO blood group type has been determined. However, factors that determine the severity of COVID-19 are not yet fully understood. Thus, the current study aimed to investigate whether the ABO blood group type has a role in the severity of complications due to COVID-19. Materials and methods: Eighty-Six ICU-admitted COVID-19 patients and 80 matched -healthy controls were recruited in the study from Baish general hospital, Saudi Arabia. ABO blood grouping, complete blood count (CBC), CBC-derived inflammatory markers, coagulation profile, D-Dimer and anti-T antigen were reported. Results: Our data showed that patients with blood groups O and B are more protective against severe complications from COVID-19, as compared to patients with blood groups A and AB. This could be partially attributed to the presence of anti-T in blood group A individuals, compared to non-blood group A. Conclusion: The current study reports an association between the ABO blood group and the susceptibility to severe complications from COVID-19, with a possible role of anti-T in driving the mechanism of the thrombotic tendency, as it was also correlated with an elevation in D-dimer levels.

T-activation polyagglutination can be caused by bacteria or viruses and has been associated with haemolytic anaemia. Coronavirus disease-19 (COVID-19) is also associated with haemolytic anaemia. The presented study aims to determine T activation polyagglutination in critically ill COVID-19 patients. Anti-T Arachis hypogaea lectin was incubated with the red blood cells of the COVID-19 patient and checked for agglutination. Thirty-four percent (34.3%) of COVID-19 patients in the intensive care unit (ICU) had potentially activated T cells and polyagglutinable red blood cells, as demonstrated by their cryptantigen exposure that caused agglutination. The study revealed a high prevalence of anti-T among ICU-admitted COVID-19 patients, suggesting that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) may cause transient T activation, polyagglutination in critically ill COVID-19 patients in vitro and possibly haemolysis in vivo.

Background: Foetal anaemia is caused by a severe pregnancy complication, haemolytic disease of the foetus and newborn. Intrauterine transfusions (IUTs) are performed to treat foetal anaemia in alloimmunised pregnant women. If left untreated hydrops can develop thereby reducing the chance of survival. Survival rates have improved but the procedure is not without complications. Procedure-related complications can be associated with early gestational age, hence delaying IUT could improve outcomes. This review aims to determine the effectiveness and safety of IUTs by examining survival and mortality rates, procedure-related complications with associated foetal mortality and the influence of hydrops. Study design and method: A systematic review was conducted by searching keywords in four scientific databases from January 2000 to April 2022. A meta-analysis was performed with the OpenMeta-Analyst software using an arcsine transformed proportion with the binary random-effects model and maximum likelihood method. Results: Fifteen studies were identified as eligible and used in the meta-analysis. The forest plots all showed statistically significant outcomes with heterogeneity of data. Results indicated a greater foetal survival rate with IUT to treat anaemic foetuses, a low foetal mortality rate, and low risk of procedure-related complications associated with foetal loss but a higher risk of foetal mortality when hydrops is present. Conclusion: The findings of this systematic review and meta-analysis provide evidence that IUT is a safe and effective treatment for foetal anaemia in the absence of hydrops when experienced personnel perform the procedure to minimise the risk of procedure-related complications.

AbstractRecent studies have identified autoimmune haemolytic anaemia (AIHA) as a haematopoietic stem cell transplant (HSCT) complication that represents a significant cause of morbidity and mortality for these patients. In order to understand this autoimmune phenomenon, emerging research has focused on the prognostic factors associated with the development of the disorder. These studies have identified numerous possible associations with often contrasting and conflicting results. A systematic review and meta‐analysis were performed in order to determine the effect of human leucocyte antigen (HLA) matching and donor relatedness on the risk of AIHA post‐HSCT. PubMed, SCOPUS and ProQuest were searched from 1 January 1995 to 1 August 2021 using a range of keywords. Meta‐analysis was performed using OpenMeta‐Analyst software using a random effects model and arcsine risk difference (ARD). Eight eligible articles were identified, and meta‐analysis showed an increased risk of AIHA in those who received HLA‐mismatched transplants (ARD −0.082; 95% confidence interval [CI] −0.157, −0.007;p = 0.031) and those who received donations from unrelated donor sources (ARD −0.097; 95% CI −0.144, −0.051;p < 0.001). Patients who receive HSCT from HLA‐matched and related donor sources have a reduced risk of developing AIHA. Healthcare practitioners should be mindful of the risk of AIHA, especially in those who receive HLA‐mismatched and unrelated donor‐sourced stem cells. While these findings provide further evidence for researchers investigating the pathogenesis of this HSCT complication, more studies are needed to fully understand the cause.

Background and Objectives Sickle cell disease (SCD) patients are commonly treated with red blood cell (RBC) transfusion. Pretransfusion tests commonly involve limited serological antibody testing. RBC alloimmunization to RBC antigens is a frequently encountered complication seen in chronically transfused patients. Genetic factors such as the human leukocyte antigen (HLA) are known to influence and regulate immune responses. HLAs are highly polymorphic and play an essential role in regulating immune responses, including RBC alloimmunization. The aim of this study was to conduct a systematic review and meta-analysis to evaluate the association between HLA Class II allelic polymorphisms with the possible risk of developing RBC alloantibodies. Materials and Methods Four databases were systematically searched for relevant studies between the years 2000 and 2021 following the PRISMA guidelines. Four articles met the eligibility and quality criterion, and three alleles, HLA-DRB1*04, HLA-DRB1*15 and HLA-DQB1*03, that were found to be potentially associated with an increased risk in alloantibody formation were included. Results The primary outcome measure was alloimmunization by RBC antigen exposure in multiply transfused SCD patients. The total estimate of alloimmunization of the SCD patients was 2.33 (95% CI, 1.58-3.44), demonstrating susceptibility to RBC alloantibody formation. Heterogeneity between the studies was insignificant, suggesting the differences associated with random sampling errors. The results showed that SCD patients carry an increased risk of producing RBC alloantibodies. Conclusion A strategy to prevent RBC alloimmunization is genotyping for genetically susceptible SCD patients receiving multiple transfusions. Early identification of genetic variants that can potentially increase the risk of RBC alloimmunization could aid in the screening process and selection of phenotypically matched RBC units.

Background: The hypercoagulability and thrombotic tendency in coronavirus disease 2019 (COVID-19) is multifactorial, driven mainly by inflammation, and endothelial dysfunction. Elevated levels of procoagulant microvesicles (MVs) and tissue factor-bearing microvesicles (TF-bearing MVs) have been observed in many diseases with thrombotic tendency. The current study aimed to measure the levels of procoagulant MVs and TF-bearing MVs in patients with COVID-19 and healthy controls and to correlate their levels with platelet counts, D-Dimer levels, and other proposed calculated inflammatory markers. Materials and Methods: Forty ICU-admitted patients with COVID-19 and 37 healthy controls were recruited in the study. Levels of procoagulant MVs and TF-bearing MVs in the plasma of the study population were measured using enzyme linked immunosorbent assay. Results: COVID-19 patients had significantly elevated levels of procoagulant MVs and TF-bearing MVs as compared with healthy controls (P<0.001). Procoagulant MVs significantly correlated with TF-bearing MVs, D-dimer levels, and platelet count, but not with calculated inflammatory markers (neutrophil/lymphocyte ratio, platelet/lymphocyte ratio, and platelet/neutrophil ratio). Conclusion: Elevated levels of procoagulant MVs and TF-bearing MVs in patients with COVID-19 are suggested to be (i) early potential markers to predict the severity of COVID-19 (ii) a novel circulatory biomarker to evaluate the procoagulant activity and severity of COVID-19.