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20 pages, 1705 KB  
Article
From Blood Count Parameters to ROP Risk: Early Hematological Predictors in Preterm Infants
by Laura Bujoreanu Bezman, Carmen Tiutiuca, Florin Ciprian Bujoreanu, Nicoleta Cârneciu, Mihaela Crăescu, Florentin Dimofte, Elena Niculeț and Aurel Nechita
Medicina 2025, 61(9), 1581; https://doi.org/10.3390/medicina61091581 - 1 Sep 2025
Viewed by 25
Abstract
Background and Objectives: Retinopathy of prematurity (ROP) persists as a major global cause of preventable childhood blindness. While early diagnosis and timely intervention can significantly mitigate visual loss, research is increasingly focused on identifying novel prognostic factors, with hematological markers emerging as [...] Read more.
Background and Objectives: Retinopathy of prematurity (ROP) persists as a major global cause of preventable childhood blindness. While early diagnosis and timely intervention can significantly mitigate visual loss, research is increasingly focused on identifying novel prognostic factors, with hematological markers emerging as a promising avenue for refining ROP risk prediction. This study aimed to assess the association of hemoglobin levels, red blood cell count, platelet count, and blood transfusions with the risk of developing ROP. Materials and Methods: We conducted a retrospective study involving 140 preterm infants (gestational age ≤ 34 weeks) admitted to a neonatal intensive care unit between 2021 and 2024. Hematological parameters were monitored sequentially during the first 28 days of life, and ROP screening was performed in accordance with international guidelines. Statistical analyses evaluated associations between hematological markers and the risk of developing ROP. Results: Anemia prevalence was significantly higher in infants who developed ROP (83.1%) compared with those who did not (60.3%), conferring an increased risk of ROP (OR = 3.239; p = 0.001). Red blood cell transfusions were linked to a higher likelihood of developing ROP (OR = 3.088; p = 0.001), while platelet transfusions showed a similar association (OR = 2.807; p = 0.027). Platelet counts were significantly lower on days 7, 14, and 21 in the ROP group, and thrombocytopenia was associated with an elevated risk of disease (OR = 3.542; p = 0.001). Conclusions: Early hematological imbalances (anemia, thrombocytopenia) and the requirement for blood product transfusions are significantly associated with an increased risk of ROP. Integrating the monitoring of these specific parameters into existing ROP screening protocols could enhance early identification of vulnerable preterm infants, enabling more targeted surveillance and potential preventative strategies. Full article
(This article belongs to the Special Issue Clinical Ophthalmology: Current Status and Future Challenges)
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27 pages, 10135 KB  
Article
Rotational Thromboelastometry (ROTEM) Hemostasis Profile in Pregnant Women with Preeclampsia and Their Offspring: An Observational Study
by Christos-Georgios Kontovazainitis, Dimitra Gialamprinou, Alexandra Fleva, Theodoros Theodoridis, Ilias Chatziioannidis, Christina Mitsiakou, Anastasia Banti, Elissavet Diamanti and Georgios Mitsiakos
Diagnostics 2025, 15(17), 2156; https://doi.org/10.3390/diagnostics15172156 - 26 Aug 2025
Viewed by 328
Abstract
Background/Objectives: Conventional Coagulation Tests (CCTs) fail to accurately reflect Preeclampsia’s (PE’s) coagulation status, disease progression, and hemostatic alterations. They do not differentiate between the normal hypercoagulability of healthy pregnancies and the pathological hypercoagulability associated with PE. Rotational Thromboelastometry (ROTEM) analyzes clot dynamics [...] Read more.
Background/Objectives: Conventional Coagulation Tests (CCTs) fail to accurately reflect Preeclampsia’s (PE’s) coagulation status, disease progression, and hemostatic alterations. They do not differentiate between the normal hypercoagulability of healthy pregnancies and the pathological hypercoagulability associated with PE. Rotational Thromboelastometry (ROTEM) analyzes clot dynamics from initiation through amplification and propagation to termination and fibrinolysis. However, their application in PE, particularly in neonates born to women with PE, is limited. We aimed to identify the hemostatic alterations in pregnant women with PE using ROTEMs that remain undetected by CCTs and to assess PE’s impact on neonatal hemostasis at birth. Methods: This was a single-center observational study (March 2022–March 2024) including 31 women with PE (34 newborns) and 45 pregnancies without PE (47 newborns). Maternal blood was collected intrapartum before placental delivery. Neonatal arterial samples were obtained within the first hour of life before vitamin K administration. ROTEM (Intrinsic (INTEM), Extrinsic (EXTEM), Fibrinogen (FIBTEM), Aprotinin (APTEM)), and CCTs were performed. Subgroup analyses considered PE severity and onset. ROC analyses examined discrimination for persistent maternal thrombocytopenia within 7 days of delivery and association with maternal platelet transfusion. Results: In preeclamptic women, the INTEM and FIBTEM assays were more affected, with higher Actual Clot Firmness (ACF) (p = 0.03, p = 0.04, respectively) and a higher Clot Formation Rate (CFR) (p = 0.03, p = 0.02, respectively). Hyperfibrinolysis was present (CT-APTEM < CT-EXTEM, MCF-APTEM > MCF-EXTEM). Clot Formation Time CFT-EXTEM was an indicator of maternal platelet transfusion (AUC = 0.81). Across EXTEM, INTEM, and APTEM, A10 (Amplitude at 10 min) and CFT showed good discrimination capability for maternal persistent thrombocytopenia within 7 days of delivery (AUCs 0.82–0.95). Neonates of women with PE presented lower ACF across all assays (INTEM p = 0.003; EXTEM p = 0.001; FIBTEM p = 0.01; APTEM p < 0.001), consistent across severity/onset subgroups. Conclusions: In this cohort, ROTEM identified maternal hypercoagulability with hyperfibrinolysis and neonatal hypocoagulability during the first hour of life. Several alterations were not reflected in CCTs. Further prospective studies should evaluate the role and clinical utility of combining ROTEM with CCTs for hemostatic monitoring in women with PE and their neonates. Full article
(This article belongs to the Special Issue Advancements in Maternal–Fetal Medicine: 2nd Edition)
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9 pages, 215 KB  
Article
Absence of Red Blood Cell Alloimmunization in Transfused Patients Receiving Daratumumab: Experience from a Single Center
by Lara Eritzpokhoff, Ernesto Talegón De La Fuente, Aida Carril Barcia, Pedro Asensi Cantó, Ines Gómez Segui, Mario Arnao Herraiz, Javier De La Rubia Comos and Pilar Solves Alcaina
J. Clin. Med. 2025, 14(16), 5754; https://doi.org/10.3390/jcm14165754 - 14 Aug 2025
Viewed by 364
Abstract
Background/Objectived: Daratumumab is an anti-CD38 monoclonal antibody used in the treatment of multiple myeloma. Its use interferes with the indirect antiglobulin test (IAT). Treatment of reagent red blood cells (RBCs) with dithiothreitol (DTT) is one of the most validated techniques to resolve this [...] Read more.
Background/Objectived: Daratumumab is an anti-CD38 monoclonal antibody used in the treatment of multiple myeloma. Its use interferes with the indirect antiglobulin test (IAT). Treatment of reagent red blood cells (RBCs) with dithiothreitol (DTT) is one of the most validated techniques to resolve this interference. The objective of this study is to evaluate the rate of alloimmunization in transfused patients receiving daratumumab and the occurrence of hemolytic transfusion reactions. Materials and Methods: We conducted a single-center, retrospective, descriptive analysis of all patients treated with daratumumab at our institution from October 2016 to April 2024. For daratumumab-treated patients requiring RBC transfusions, an IAT with DTT-pretreated RBCs (DTT-IAT) was performed using the automated Orthovision system. Transfusion was administered only with a previous negative DTT-IAT while respecting Rh and Kell phenotyping. We assessed the transfusion profile of our patient cohort, including their rates of alloimmunization before and after daratumumab initiation, as well as the incidence of hemolytic complications. Additionally, a literature review was performed on reported alloimmunization rates in daratumumab-treated patients. Results: Among all patients, 106 received RBC and/or platelet transfusions after starting daratumumab. Four had known pre-existing alloantibodies. None developed new alloantibodies or experienced hemolytic complications while receiving anti-CD38 therapy. There were four cases of false-positive DTT-IAT due to residual drug interference or technical variability, in which no alloantibodies or adverse transfusion reactions were detected. Conclusions: Patients receiving daratumumab exhibit a low risk of alloimmunization. This may be partly explained by adherence to Rh and Kell phenotyping and daratumumab’s immunosuppressive effects on alloantibody production. These results support the conclusion that an extended red blood cell phenotype or genotype before starting daratumumab could be omitted if a fast and reliable technique for pretransfusion testing (such as automated DTT-IAT) is available 24 h. Full article
16 pages, 1215 KB  
Review
Understanding Chemotherapy-Induced Thrombocytopenia: Implications for Gastrointestinal Cancer Treatment
by Supriya Peshin, Adit Dharia, Ehab Takrori, Jasmeet Kaur, Kannan Thanikachalam and Renuka Iyer
Curr. Oncol. 2025, 32(8), 455; https://doi.org/10.3390/curroncol32080455 - 14 Aug 2025
Viewed by 631
Abstract
Chemotherapy-induced thrombocytopenia (CIT) is a common yet underrecognized complication of systemic chemotherapy, particularly in gastrointestinal (GI) cancers. Despite progress in targeted and immune-based therapies, platinum-based and fluoropyrimidine regimens, especially oxaliplatin-containing protocols, remain standard in GI cancer treatment and are linked to high rates [...] Read more.
Chemotherapy-induced thrombocytopenia (CIT) is a common yet underrecognized complication of systemic chemotherapy, particularly in gastrointestinal (GI) cancers. Despite progress in targeted and immune-based therapies, platinum-based and fluoropyrimidine regimens, especially oxaliplatin-containing protocols, remain standard in GI cancer treatment and are linked to high rates of CIT. This complication often leads to treatment delays, dose reductions, and elevated bleeding risk. This review provides a comprehensive overview of the pathophysiology, clinical implications, and management strategies of CIT in GI malignancies. CIT arises from several mechanisms: direct cytotoxicity to megakaryocyte progenitors, disruption of the marrow microenvironment, thrombopoietin dysregulation, and immune-mediated platelet destruction. Platinum agents, antimetabolites, and immune checkpoint inhibitors can contribute to these effects. Oxaliplatin-induced CIT may occur acutely via immune mechanisms or chronically through marrow suppression. CIT affects 20–25% of solid tumor patients, with highest rates in those receiving gemcitabine (64%), carboplatin (58%), and oxaliplatin (50%). Within GI cancer regimens, FOLFOXIRI and S-1 plus oxaliplatin show higher CIT incidence compared to FOLFIRI and CAPIRI. Thrombocytopenia is graded by severity, from mild (Grade 1–2) to severe (Grade 3–4), and often necessitates treatment adjustments, transfusions, or supportive therapies. Current strategies include chemotherapy dose modification, platelet transfusion, and thrombopoietin receptor agonists (TPO-RAs) like romiplostim and eltrombopag. While platelet transfusions help in acute settings, TPO-RAs may preserve dose intensity and reduce bleeding. Emerging agents targeting megakaryopoiesis and marrow protection offer promising avenues for long-term management. Full article
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16 pages, 957 KB  
Article
The Influence of Blood Transfusion Indexed to Patient Blood Volume on 5-Year Mortality After Coronary Artery Bypass Grafting—An EuroSCORE II Adjusted Spline Regression Analysis
by Joseph Kletzer, Maximilian Kreibich, Martin Czerny, Tim Berger, Albi Fagu, Laurin Micek, Ulrich Franke, Matthias Eschenhagen, Tau S. Hartikainen, Mirjam Wild and Dalibor Bockelmann
J. Cardiovasc. Dev. Dis. 2025, 12(8), 287; https://doi.org/10.3390/jcdd12080287 - 28 Jul 2025
Viewed by 459
Abstract
Background: While timely blood transfusion is critical for restoring oxygen-carrying capacity after coronary artery bypass grafting (CABG), allogeneic blood product transfusions are independently associated with increased long-term mortality, necessitating a risk-stratified approach to balance oxygen delivery against immunological complications and infection risks. Methods: [...] Read more.
Background: While timely blood transfusion is critical for restoring oxygen-carrying capacity after coronary artery bypass grafting (CABG), allogeneic blood product transfusions are independently associated with increased long-term mortality, necessitating a risk-stratified approach to balance oxygen delivery against immunological complications and infection risks. Methods: We retrospectively analyzed 3376 patients undergoing isolated CABG between 2005 and 2023 at a single tertiary center. Patients who died during their perioperative hospital stay within 30 days were excluded. Transfusion burden was assessed both as the absolute number of blood product units (packed red blood cells, platelet transfusion, fresh frozen plasma) and as a percentage of calculated patient blood volume. The primary outcome was all-cause mortality at 5 years. Flexible Cox regression with penalized smoothing splines, adjusted for EuroSCORE II, was used to model dose–response relationships. Results: From our cohort of 3376 patients, a total of 137 patients (4.05%) received >10 units of packed red blood cells (PRBC) perioperatively. These patients were older (median 71 vs. 68 years, p < 0.001), more often female (29% vs. 15%, p < 0.001), and had higher preoperative risk (EuroSCORE II: 2.53 vs. 1.41, p < 0.001). After 5 years, mortality was 42% in the massive transfusion group versus 10% in controls. Spline regression revealed an exponential increase in mortality with transfused units: 14 units yielded a 1.5-fold higher hazard of death (HR 1.46, 95% CI 1.31–1.64), rising to HR 2.71 (95% CI 2.12–3.47) at 30 units. When transfusion was indexed to blood volume, this relationship became linear and more tightly correlated with mortality, with lower maximum hazard ratios and narrower confidence intervals. Conclusions: Indexing transfusion burden to the percentage of patient blood volume replaced provides a more accurate and clinically actionable predictor of 5-year mortality after CABG than absolute unit counts. Our findings support a shift toward individualized, volume-based transfusion strategies to optimize patient outcomes and resource stewardship in a time of limited availability of blood products. Full article
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8 pages, 855 KB  
Case Report
Severe Malaria Due to Plasmodium falciparum in an Immunocompetent Young Adult: Rapid Progression to Multiorgan Failure
by Valeria Sanclemente-Cardoza, Harold Andrés Payán-Salcedo and Jose Luis Estela-Zape
Life 2025, 15(8), 1201; https://doi.org/10.3390/life15081201 - 28 Jul 2025
Viewed by 486
Abstract
Plasmodium falciparum malaria remains a major cause of morbidity and mortality, particularly in endemic regions. We report the case of a 21-year-old male with recent travel to an endemic area (Guapi, Colombia), who presented with febrile symptoms, severe respiratory distress, and oxygen saturation [...] Read more.
Plasmodium falciparum malaria remains a major cause of morbidity and mortality, particularly in endemic regions. We report the case of a 21-year-old male with recent travel to an endemic area (Guapi, Colombia), who presented with febrile symptoms, severe respiratory distress, and oxygen saturation below 75%, necessitating orotracheal intubation. During the procedure, he developed pulseless electrical activity cardiac arrest, achieving return of spontaneous circulation after advanced resuscitation. Diagnosis was confirmed by thick blood smear, demonstrating P. falciparum infection. The patient progressed to multiorgan failure, including acute respiratory distress syndrome with capillary leak pulmonary edema, refractory distributive shock, acute kidney injury with severe hyperkalemia, and consumptive thrombocytopenia. Management included invasive mechanical ventilation, vasopressor support, sedation-analgesia, neuromuscular blockade, methylene blue, unsuccessful hemodialysis due to hemorrhagic complications, and platelet transfusions. Despite these interventions, the patient experienced a second cardiac arrest and died. This case highlights the severity and rapid progression of severe malaria with multisystem involvement, underscoring the critical importance of early diagnosis and intensive multidisciplinary management. It also emphasizes the need for preventive strategies for travelers to endemic areas and the development of clinical protocols to improve outcomes in complicated malaria. Full article
(This article belongs to the Section Medical Research)
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14 pages, 690 KB  
Article
Ibrutinib in Combination with Lenalidomide Revlimid/Dexamethasone in Relapsed/Refractory Multiple Myeloma (AFT-15)
by Yvonne Efebera, Vera Suman, Shira Dinner, Taylor O’Donnell, Ashley Rosko, John Mckay, Peter Barth, Patrick Hagen, Saad Usmani, Paul Richardson and Jacob Laubach
Cancers 2025, 17(15), 2433; https://doi.org/10.3390/cancers17152433 - 23 Jul 2025
Viewed by 468
Abstract
Background: Studies have suggested a synergism between lenalidomide (LEN) and ibrutinib (IBR) in multiple myeloma (MM). Both downregulate IRF4, a key target and master transcriptional factor regulating myeloma cell survival. Method: A 3 + 3 phase I trial was conducted to determine the [...] Read more.
Background: Studies have suggested a synergism between lenalidomide (LEN) and ibrutinib (IBR) in multiple myeloma (MM). Both downregulate IRF4, a key target and master transcriptional factor regulating myeloma cell survival. Method: A 3 + 3 phase I trial was conducted to determine the maximum tolerated dose (MTD) of IBR in combination with LEN + dexamethasone (DEX) in patients with relapsed/refractory (RR) MM who had at least one prior line of therapy. Three dose levels (DLs) were planned. The cycle length was 28 days. IBR was administered orally daily in doses of 560 mg on DL1-2 and 840 mg on DL3, LEN was administered orally on days 1–21 in doses of 15 mg on DL1 and 25 mg on DL2-3, and DEX was administered orally on days 1, 8, 15, and 22 in a dose of 40 mg if age < 75 years or in a dose of 20 mg if it was ≥75 years for DL1-3. Patients with a glomerular filtration rate (GFR) <60 but ≥30 mL/min were treated in accordance with the manufacturer’s instructions with LEN 10 mg. Dose-limiting toxicities (DLTs) included the following: grade 4 neutropenia lasting more than 5 days, thrombocytopenia, febrile neutropenia, nausea, vomiting or diarrhea; grade 3 thrombocytopenia with bleeding or platelet transfusion; and grade 3–4 hyperglycemia or a thrombotic/embolic event, and other nonhematologic toxicities. The overall response rate (ORR) was defined as the percentage of patients with a partial response (PR), very good partial response (VGPR), or complete response (CR) according to IMWG criteria on two consecutive evaluations at least 4 weeks apart. The clinical benefit rate (CBR) was defined as the percentage of patients with stable disease (SD) or a better outcome on two consecutive evaluations at weeks apart. Results: Fourteen patients (DL1: six patients; DL2: three patients; DL3: five patients) were registered for the study from March 2019 to May 2023, prior to its closure due to limited accrual. Thirteen patients are included in the summary of toxicities and response as one patient on DL3 halted participation prior to the start of the treatment. Two patients on DL3 were excluded from the determination of MTD: one having discontinued cycle 1 treatment due to COVID-19 infection and the another having mistakenly taken 280 mg/day of IBR instead of the assigned 840 mg/day dose during cycle 1. Only one patient developed a DLT, on DL1 with grade 3 non-viral hepatitis. The median number of cycles administered was 4 (range: 1–56). Severe toxicities reported included grade 4 lymphocytopenia (1), grade 4 thrombocytopenia (1), and grade 5 sepsis in the setting of PD (1). Disease responses included a VGPR on DL1 and CR on DL3. Thus, the ORR was 15.4% (90% CI: 2.8–41.0%). One patient on DL1 maintained SD for 4.6 years before discontinuing the treatment to undergo an alternative therapy. Another five patients maintained SD for ≥ 2 consecutive cycles. Thus, the CBR was 61.5% (90% CI: 35.5–83.4%). Conclusions: The combination of LEN with IBR in RR MM proved feasible, with manageable toxicities and the majority of discontinuations being due to disease progression. Full article
(This article belongs to the Special Issue Multiple Myeloma: Diagnosis and Therapy)
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22 pages, 8428 KB  
Article
Platelet and Fibrinogen Contribution to Clot Strength in Premature Neonates with Sepsis
by Dimitra Gialamprinou, Christos-Georgios Kontovazainitis, Abraham Pouliakis, Alexandra Fleva, Anastasia Giannakou, Elisavet Diamanti, Panagiotis Kratimenos and Georgios Mitsiakos
Children 2025, 12(7), 948; https://doi.org/10.3390/children12070948 - 18 Jul 2025
Viewed by 401
Abstract
Background/Objectives: Platelet transfusions are administered to preterm neonates with thrombocytopenia prophylactically to decrease their bleeding risk. The amplitude difference between the extrinsic rotational thromboelastometry (EXTEM) and the fibrinogen rotational thromboelastometry (FIBTEM) assays is considered an index of platelet contribution to clot strength, [...] Read more.
Background/Objectives: Platelet transfusions are administered to preterm neonates with thrombocytopenia prophylactically to decrease their bleeding risk. The amplitude difference between the extrinsic rotational thromboelastometry (EXTEM) and the fibrinogen rotational thromboelastometry (FIBTEM) assays is considered an index of platelet contribution to clot strength, guiding transfusion management. The difference in maximum clot elasticity (MCE) (namely the platelet contribution to clot elasticity—MCEplatelet) is considered highly accurate. Limited data exist to specify the contribution of platelets and fibrinogen in clot formation during sepsis in neonates with thrombocytopenia. We investigated the potential of MCFplatelet (platelet contribution to clot firmness) and MCEplatelet in reflecting platelet count and function in septic preterm neonates. We simultaneously assessed the contribution of both platelets and fibrinogen to clot strength during sepsis. Methods: We compared 28 preterm neonates with sepsis born (gestational age 24+1-34+3) with 30 healthy counterparts by using rotational thromboelastometry (ROTEM) and platelet flow cytometry. Results: MCEplatelet showed a higher association with platelet count in the sepsis group than MCFplatelet (R2 = 47.66% vs. R2 = 18.79%). MCEplatelet (AUC = 0.81) had better discrimination capability than MCFplatelet (AUC = 0.78) in platelet count <100 × 103/L. MCEplatelet was poorly associated with platelet function. The contribution of platelets was significantly lower (MCEplatelet = 84.03 vs. 89.21; p < 0.001) compared with fibrinogen (36.9 vs. 25.92; p < 0.001) in the sepsis group. Conclusions: MCEplatelet has a better predictive value than MCFplatelet. In clinical practice, the elasticity difference between EXTEM and FIBTEM may replace the amplitude difference. The higher contribution of fibrinogen in clot strength during neonatal sepsis results in higher MCF, even in neonates with thrombocytopenia. Full article
(This article belongs to the Section Pediatric Neonatology)
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13 pages, 354 KB  
Article
Clinical Impact of Viscoelastic Testing in Liver Transplantation: A Before-and-After Study of Transfusion Needs and Outcomes
by Iulian Buzincu, Mihaela Blaj, Eliza Isabela Bărbuță, Adi-Ionuț Ciumanghel, Irina Gîrleanu, Irina Ciumanghel, Ana-Maria Trofin, Vlad Nuțu, Alexandru Năstase, Ramona Cadar, Mihai Zabara, Vlad Carp, Beatrice Cobzaru, Corina Lupascu Ursulescu and Cristian Dumitru Lupașcu
J. Clin. Med. 2025, 14(14), 4882; https://doi.org/10.3390/jcm14144882 - 9 Jul 2025
Viewed by 677
Abstract
Background/Objectives: Liver transplantation (LT) is often complicated by severe bleeding and coagulopathy. Viscoelastic testing (VET) offers real-time, bedside assessment of coagulation and may improve transfusion management compared to standard tests. This study evaluates the clinical impact of VET implementation during liver transplantation [...] Read more.
Background/Objectives: Liver transplantation (LT) is often complicated by severe bleeding and coagulopathy. Viscoelastic testing (VET) offers real-time, bedside assessment of coagulation and may improve transfusion management compared to standard tests. This study evaluates the clinical impact of VET implementation during liver transplantation on bleeding, transfusion requirements, complications, and mortality in a single Eastern European tertiary transplant center. Methods: We conducted a single-center before-and-after study comparing patients undergoing LT before and after the implementation of VET. All procedures were performed by the same surgical and anesthetic team using a standardized protocol. Data were collected retrospectively for the Before VET group and prospectively for the After VET group. We compared transfusion requirements, bleeding, complications, and mortality. Results: A total of 59 patients were included, 22 in the After VET group and 37 in the Before VET group. VET implementation was associated with lower intraoperative blood loss (median 4000 mL vs. 6000 mL, p = 0.017) and reduced red blood cell (RBC) transfusion volume (670 mL vs. 1000 mL, p = 0.008). FFP (0.23 vs. 1.59 units, p = 0.007) and platelet use (0.68 vs. 1.81 units, p = 0.035) were also significantly lower in the VET group, while fibrinogen use was higher (3.00 g vs. 2.00 g, p = 0.036). No differences were observed in complication rates or mortality at 30 days and 1 year in this small before-and-after study. Conclusions: VET improved transfusion precision and individualized coagulation management during LT, leading to reduced use of blood products. These findings support the adoption of VET as a standard of care in LT protocols, as it may enhance patient safety, even though no differences in postoperative complications or mortality were observed. Full article
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9 pages, 194 KB  
Article
Perinatal Outcomes in Pregnancies Complicated by Maternal Thrombocytopenia: A Retrospective Cohort Study
by Woo Jeng Kim, In Yang Park and Sae Kyung Choi
J. Clin. Med. 2025, 14(13), 4524; https://doi.org/10.3390/jcm14134524 - 26 Jun 2025
Viewed by 467
Abstract
Background/Objectives: Maternal thrombocytopenia, affecting approximately 10% of pregnancies, may be physiological (e.g., gestational thrombocytopenia) or pathological (e.g., immune thrombocytopenic purpura, aplastic anemia, preeclampsia, systemic lupus erythematosus). While gestational thrombocytopenia is typically benign, its severity and etiology may impact maternal and neonatal outcomes. [...] Read more.
Background/Objectives: Maternal thrombocytopenia, affecting approximately 10% of pregnancies, may be physiological (e.g., gestational thrombocytopenia) or pathological (e.g., immune thrombocytopenic purpura, aplastic anemia, preeclampsia, systemic lupus erythematosus). While gestational thrombocytopenia is typically benign, its severity and etiology may impact maternal and neonatal outcomes. This study examined the association between severe and moderate thrombocytopenia during pregnancy and perinatal outcomes, focusing on maternal hemorrhage and neonatal thrombocytopenia. Methods: A retrospective analysis was conducted of 182 pregnant women with thrombocytopenia who delivered at Incheon St. Mary’s Hospital and Seoul St. Mary’s Hospital between 2009 and 2019. Participants were classified into two groups: severe thrombocytopenia (platelet count <50 × 109/L) and moderate thrombocytopenia (50–150 × 109/L). Maternal hemorrhagic outcomes, transfusion needs, and neonatal platelet counts were evaluated. Statistical analyses were performed using univariate methods. Results: Severe thrombocytopenia was associated with greater blood loss during delivery, increased transfusion requirements, and elevated neonatal thrombocytopenia rates. Moderate to severe thrombocytopenia was more frequently identified in neonates delivered by mothers with immune thrombocytopenic purpura than in those delivered by mothers with gestational thrombocytopenia. Conclusions: Both the severity and etiology of maternal thrombocytopenia significantly affect the risk of maternal hemorrhage and neonatal thrombocytopenia. Careful prenatal assessment is essential to optimize management and reduce complications. Full article
(This article belongs to the Special Issue AI in Maternal Fetal Medicine and Perinatal Management)
13 pages, 296 KB  
Article
Analysis of Massive Transfusion Protocol Utilization in Trauma Across Sociodemographic Groups
by Monique Arnold, Bharti Sharma, Matthew Conn, Kate Twelker, Navin D. Bhatia, George Agriantonis, Jasmine Dave, Juan Mestre, Zahra Shafaee and Jennifer Whittington
Medicina 2025, 61(7), 1133; https://doi.org/10.3390/medicina61071133 - 24 Jun 2025
Viewed by 665
Abstract
Background and Objectives: Blood shortages are a national crisis, creating dangerous scenarios for patients requiring the use of a massive transfusion protocol (MTP). A judicious use of blood products is critical to rescue salvageable patients while refraining from unnecessary MTP to save [...] Read more.
Background and Objectives: Blood shortages are a national crisis, creating dangerous scenarios for patients requiring the use of a massive transfusion protocol (MTP). A judicious use of blood products is critical to rescue salvageable patients while refraining from unnecessary MTP to save precious resources. This study examines effect of trauma characteristics, socioeconomic variables and markers of futility on the likelihood of activating and receiving MTP in the trauma setting. Materials and Methods: In this retrospective study, emergency department (ED) trauma activations from a database of an urban Level I trauma center were analyzed from 1 January 2017 to 30 June 2022, inclusive. In-ED mortality, RBC transfusion volumes during initial resuscitation, patient sociodemographic data, and trauma event factors were analyzed. The primary outcomes were the dichotomous outcomes of MTP activation and MTP transfusion. Univariable analyses and logistic regressions were conducted, with class balancing sensitivities applied to the multivariable regressions to adjust for imbalance in the data. p < 0.05 was considered statistically significant. Results: Among the 8670 trauma activations, there was a 0.3% in-ED mortality rate. MTP activation and MTP transfusion were associated with higher in-ED mortality rates (3.8% and 15.4%, respectively, compared to 0.2% without MTP). Younger patients, male patients, and Medicaid recipients were more likely to undergo MTP activation; Medicare patients were less likely. Penetrating trauma substantially increased the likelihood of both MTP activation (odds ratio (OR) 5.81) and transfusion (OR 3.63). The logistic regression models identified the presence of penetrating trauma, lower probability of survival, and age as the most important covariates. Models demonstrated high discriminatory value (area under the curve (AUC) of the receiver operating characteristic curve (ROC) of 0.876 for MTP activation, 0.935 for MTP transfusion) and precision (0.974 for activation, 0.994 for transfusion), with class balancing further improving model performance and precision scores. Conclusions: These results are significant as assessing the futility of MTP should be equitable, and future transfusion guidelines should consider salvageability in cases with a low probability of survival despite age and mechanism. Full article
(This article belongs to the Special Issue Trauma, Critical Care, and Acute Care Surgery)
21 pages, 1799 KB  
Review
Novel Roles and Therapeutic Approaches Linking Platelets and Megakaryocytes to Non-Hemostatic and Thrombotic Disease
by Ana Kasirer-Friede
Int. J. Transl. Med. 2025, 5(3), 25; https://doi.org/10.3390/ijtm5030025 - 22 Jun 2025
Viewed by 746
Abstract
Historically, pharmacological interventions aimed at platelets have targeted their canonical hemostatic and thrombotic roles. The therapeutic vision, however, has minimally embraced alternate mechanisms by which anucleate platelets, their parent cells, megakaryocytes, and cellular derivatives may be utilized to yield novel and effective therapies. [...] Read more.
Historically, pharmacological interventions aimed at platelets have targeted their canonical hemostatic and thrombotic roles. The therapeutic vision, however, has minimally embraced alternate mechanisms by which anucleate platelets, their parent cells, megakaryocytes, and cellular derivatives may be utilized to yield novel and effective therapies. Platelets contain storage granules rich in a wide variety of proteins, chemicals, growth factors, and lipid particles that can modulate the fate and activity of diverse cell types, and impact diseases not previously thought to have a platelet component. In this article, we will address unconventional platelet contributions to health and disease development. Recent studies indicate extensive platelet roles in neurodegeneration, insulin secretion, and bone marrow fibrosis, along with a recognition of platelets as immune cells in their own right, partially based on the presence of surface MHC, Toll-like receptors, and stored immunomodulatory molecules. Recent technological advances have produced iPS-derived gene-editable megakaryocytes (MKs) that have been differentiated to clinical-grade platelets for transfusion; however, such successes are still rare. Continued improvements in the standardization of cell isolation, iPS differentiation protocols, technology for the utilization of platelet derivatives, and platelet Omics will expand our understanding of underlying platelet and MK heterogeneity and direct novel therapeutic applications. Furthermore, additional roles for these cells as microniche sensors that monitor systemic pathology by endocytosing shed particles as they circulate through the vasculature will be explored. Taken together, novel insights into the many exciting potential uses of platelets outside of their canonical roles are on the horizon, and continued amelioration of existing protocols and enhanced understanding of communication pathways between platelets and specific cells will help expand opportunities for platelet-related clinical trials to yield improved health outcomes. Full article
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16 pages, 1445 KB  
Article
Enhanced Quinolone Resistance and Differential Expression of Efflux Pump nor Genes in Staphylococcus aureus Grown in Platelet Concentrates
by Carina Paredes, Que Chi Truong-Bolduc, Yin Wang, David C. Hooper and Sandra Ramirez-Arcos
Antibiotics 2025, 14(7), 635; https://doi.org/10.3390/antibiotics14070635 - 21 Jun 2025
Viewed by 747
Abstract
Background/Objective: Platelet concentrates (PCs) are used in transfusion medicine to treat bleeding disorders. Staphylococcus aureus, a predominant PC contaminant, has been implicated in several adverse transfusion reactions. The aim of this study was to investigate the impact of PC storage on [...] Read more.
Background/Objective: Platelet concentrates (PCs) are used in transfusion medicine to treat bleeding disorders. Staphylococcus aureus, a predominant PC contaminant, has been implicated in several adverse transfusion reactions. The aim of this study was to investigate the impact of PC storage on S. aureus resistance to quinolones, which are commonly used to treat S. aureus infections. Methods/Results: Four transfusion-relevant S. aureus strains (TRSs) were subjected to comparative transcriptome analyses when grown in PCs vs. trypticase soy broth (TSB). Results of these analyses revealed differentially expressed genes involved in antibiotic resistance. Of interest, the norB gene (encodes for the NorB efflux pump, which is implicated in quinolone resistance and is negatively regulated by MgrA) was upregulated (1.2–4.7-fold increase) in all PC-grown TRS compared to TSB cultures. Minimal Bactericidal Concentration (MBC) of ciprofloxacin and norfloxacin in PC-grown TRS compared to TSB showed increased resistance to both quinolones in PC cultures. Complementary studies with non-transfusion-relevant strains S. aureus RN6390 and its norB and mgrA deletion mutants were conducted. MBC of ciprofloxacin and norfloxacin and RT-qPCR assays of these strains showed that not only norB, but also norA and norC may be involved in enhanced quinolone resistance in PC-grown S. aureus. The role of norB in S. aureus virulence was also tested using the silkworm Bombyx mori animal model; lethal dose 50 (LD50) assays revealed slightly higher virulence in larvae infected with the wild-type strain compared to the norB mutant. Conclusions: The PC storage environment enhances quinolone resistance in S. aureus and induces differential expression of efflux pump nor genes. Furthermore, our preliminary data of the involvement of NorB in virulence of S. aureus using a silkworm model merit further investigation with other systems such as a mammal animal model. Our results provide mechanistic insights to aid clinicians in the selection of antimicrobial treatment of patients receiving transfusions of S. aureus-contaminated PCs. Full article
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9 pages, 866 KB  
Case Report
Bone Marrow Aplasia and Neutropenic Fever Following Azathioprine Dose Escalation in a TPMT-Deficient Patient with Crohn’s Disease and Psoriatic Arthritis—A CARE–Compliant Case
by Krzysztof Wroński, Michał Tadeusz Holecki, Natalia Boguszewska, Marzena Skrzypczak-Zielińska and Jerzy Tadeusz Chudek
Clin. Pract. 2025, 15(6), 114; https://doi.org/10.3390/clinpract15060114 - 19 Jun 2025
Viewed by 707
Abstract
Background: Myelotoxicity, usually manifested by moderate leukopenia (particularly neutropenia), is a well-known adverse drug reaction to azathioprine (AZA) therapy. Thiopurine methyltransferase (TMPT) and nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) genotyping are not routinely performed in patients starting AZA therapy [...] Read more.
Background: Myelotoxicity, usually manifested by moderate leukopenia (particularly neutropenia), is a well-known adverse drug reaction to azathioprine (AZA) therapy. Thiopurine methyltransferase (TMPT) and nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) genotyping are not routinely performed in patients starting AZA therapy due to their low cost-effectiveness. Additionally, the concomitant use of xanthine oxidase inhibitors and 5-aminosalicylates may slow the metabolism of 6-mercaptopurine. Case Description: We describe a case of a 26-year-old Caucasian man with Crohn’s disease and psoriatic arthritis treated with mesalazine and AZA (100 mg daily) who developed prolonged bone marrow aplasia and neutropenic fever after increasing the daily dose of AZA from 100 to 150 mg (from 44 to 66 mg/m2), without frequent total blood count monitoring. Discontinuation of AZA, multiple transfusions of red blood cells and platelet concentrate, filgrastim, empirical antibiotic therapy, and antiviral and antifungal prophylaxis were obtained after 11 days complete recovery of bone marrow aplasia. Methods: Genomic DNA genotyping of coding regions of TPMT (exons 2–9) and NUDT15 (exons 1–3). Results: Heterozygous alleles in the untranslated region (c.460G>A and c.719A>G) associated with TPMT deficiency and a benign variant (c.*7G>A) in the 3′-UTR of NUDT15 with no effect on enzyme activity were found. Conclusions: This case highlights the importance of monitoring the total blood count frequently during the first weeks of treatment with moderate-to-high doses of AZA. Furthermore, the interaction between AZA and mesalazine may play a significant role in the development of prolonged bone marrow aplasia. Full article
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14 pages, 443 KB  
Review
Platelet Transfusions: Current Practices and Emerging Alternatives in the United States
by Mark Friedman, Victoria Costa, Behnam Rafiee, Timothy Hilbert, Mansab Jafri and Ding Wen Wu
Life 2025, 15(6), 985; https://doi.org/10.3390/life15060985 - 19 Jun 2025
Viewed by 1506
Abstract
Platelet transfusions are a cornerstone of hemorrhage management in patients with thrombocytopenia or platelet dysfunction, yet their indications and dosing are largely based on expert opinion and low-quality evidence. This review offers a timely and comprehensive analysis of platelet transfusion practices in the [...] Read more.
Platelet transfusions are a cornerstone of hemorrhage management in patients with thrombocytopenia or platelet dysfunction, yet their indications and dosing are largely based on expert opinion and low-quality evidence. This review offers a timely and comprehensive analysis of platelet transfusion practices in the United States (U.S.), uniquely integrating clinical evidence, such as the pivotal PLADO trial, with emerging technological advancements. Using a holistic approach, this manuscript addresses not only conventional practices (such as dosing standards and storage methods), but also cutting-edge alternatives like cold-stored and freeze-dried platelets, pathogen reduction technologies, and synthetic platelet substitutes. By juxtaposing U.S. practices with international standards, it highlights inefficiencies in dosing and supply management, proposing actionable solutions like lower-dose transfusions and diversified platelet inventories. Furthermore, the manuscript’s exploration of whole blood-derived platelets and the ethical debate surrounding paid donors adds a forward-looking perspective. By examining these innovations alongside strategies to optimize supply, this work aims to provide a comprehensive overview of how transfusion medicine is adapting to meet clinical and logistical demands. Full article
(This article belongs to the Section Medical Research)
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