Gianluca Gessoni

Background: Iron deficiency anaemia is a major public health problem. Oral iron is generally recommended as first-line treatment because it is inexpensive and easily administered, but its use may be limited by gastrointestinal adverse effects, poor adherence, or inadequate absorption. Intravenous (IV) iron is an effective alternative when oral treatment is ineffective or poorly tolerated, or when rapid iron repletion is required. High-dose IV iron formulations may reduce the number of outpatient visits required to complete treatment. Materials and Methods: We retrospectively evaluated patients receiving IV iron therapy in seven outpatient clinics managed by the Department of Transfusion Medicine of the Province of Venice (North-East Italy) between January 2020 and December 2025. Ferric carboxymaltose (FCM) 100 mg and 500 mg and ferric derisomaltose (FDI) 1000 mg were used. An Activity-Based Costing (ABC) analysis was performed considering the cost of the iron preparation, the number of IV administrations and the associated healthcare and estimated non-healthcare costs required to complete a treatment cycle. A separate Patient Blood Management (PBM) analysis estimated the number of red blood cell (RBC) units and associated costs that would have been required under a predefined hypothetical transfusion scenario. Results: During the study period, 29,614 IV iron administrations were recorded in 13,683 patients. The mean number of administrations required to complete a treatment cycle was 9.1 with FCM 100 mg, 1.9 with FCM 500 mg and 1.1 with FDI 1000 mg, corresponding to approximately 79% and 88% reductions in outpatient visits compared with FCM 100 mg, respectively. The mean cost per treatment cycle was €1820.91 for FCM 100 mg, €444.79 for FCM 500 mg and €342.21 for FDI 1000 mg. Under the predefined hypothetical transfusion scenario, 5149 RBC units would have been required for patients with haemoglobin concentrations of <80 g/L or 81–90 g/L, corresponding to an estimated cost of €2,067,323.50. No RBC transfusions were recorded in the available Department of Transfusion Medicine of the District of Venice (DIMT) outpatient database during the study period. Conclusions: In this real-world outpatient network, the use of high-dose IV iron formulations was associated with substantially fewer outpatient visits and lower estimated treatment-cycle costs than low-dose FCM. The reduction in the number of administrations may also increase outpatient treatment capacity and facilitate the management of iron deficiency within a PBM-oriented model. The estimated RBC requirements and associated costs should be interpreted as a hypothetical scenario rather than as observed transfusion avoidance or realised cost savings.

Background: Thrombosis is a multifactorial condition in which inherited thrombophilic abnormalities, acquired haemostatic disturbances, and other clinical factors may coexist and contribute to thrombotic susceptibility. Because multiple abnormalities can occur within the same individual, their relative and combined associations with previous thrombosis require integrated evaluation, particularly when inherited thrombophilia and antiphospholipid antibody profiles are considered together. Aims: To characterise the integrated thrombophilic phenotype associated with previous thrombosis, identify abnormalities retaining an independent association after multivariable adjustment, and investigate the contribution and heterogeneity of antiphospholipid antibodies (aPL). Study Design: Analytical re-analysis of a previously assembled observational case-control cohort. Methodology: We re-analysed 623 subjects, comprising 292 individuals with previous thrombosis and 331 thrombosis-free consanguineous controls. A complete univariate screen was followed by Firth penalised logistic regression. The primary non-aPL model included age modelled with a 4-df natural cubic spline, sex, antithrombin deficiency, factor V Leiden (FVL) carrier status and factor II G20210A carrier status. Aggregate antiphospholipid antibody positivity (APA), ≥1 positive non-LAC aPL assay, seven individual non-LAC aPL specificities and cumulative aPL burden were analysed separately. Results: In the primary non-aPL model, FVL carrier status was associated with previous thrombosis (adjusted OR 3.40, 95% CI 2.32–4.99; P<.001), as was factor II G20210A carrier status (OR 5.29, 95% CI 2.88–9.71; P<.001) and antithrombin deficiency (OR 4.31, 95% CI 1.13–16.49; P=.033). Aggregate APA positivity showed an adjusted OR of 7.53 (95% CI 4.61–12.31; P<.001), while ≥1 positive non-LAC aPL assay showed an adjusted OR of 7.58 (95% CI 4.60–12.48; P<.001). Six of seven individual non-LAC aPL specificities remained significant after false-discovery-rate correction. Conclusion: Previous thrombosis was associated with an integrated pattern of inherited and acquired thrombophilic abnormalities. FVL and factor II G20210A were the principal inherited associations, while antithrombin deficiency and the antiphospholipid phenotype provided additional information. The aPL findings support a multimarker interpretation rather than attribution of the thrombotic phenotype to a single antibody specificity.

Background: In contemporary healthcare systems, the sustainability of complex care models increasingly depends on the transition toward decentralized frameworks. Community-based transfusion therapy have emerged as a strategic approach to ensure continuity of care for frail and chronically ill patients. This study reports the experience of outpatient transfusion therapy in a large area of northeastern Italy over a five-year period (2020–2024). Materials and Methods: Multiple operational settings were evaluated, including home transfusions, community hospitals, nursing homes, and outpatient clinics. Activity volumes recorded between 2020 and 2024 were analyzed. A comparative cost analysis was conducted between transfusions delivered in community settings and those performed in hospital settings (inpatient and day hospital), as well as cases requiring access to emergency departments. Results: Red blood cell concentrates were the most frequently transfused blood component in the community setting. The total number of transfusions delivered in outpatient settings increased from 4,222 in 2020 to 4,789 in 2024 (+507 units; +12%). Over the study period, community-based transfusion activity increased from 11.1% to 12.9% of total transfusion procedures. The incidence of post-transfusion adverse events was slightly higher than that observed in the overall hospital population, with a greater proportion of transfusion-associated circulatory overload reactions. Cost analysis demonstrated superior cost-effectiveness of community-based transfusion therapy compared with hospital-based care across the evaluated settings. Conclusions: Transfusion services delivered within, nursing homes, and community care centers represent a key component of a resilient, patient-centered healthcare system. Integration between the community network and specialized hospital services ensures the maintenance of hospital-level safety standards in decentralized settings. Consolidation of this model is essential to safeguard the right to health and the dignity of care, positioning transfusion medicine as a flexible and effective proximity-based service.

Background: Iron-deficient anemia (IDA) in pregnant women is a significant health issue globally. Oral iron supplementation is the primary treatment for IDA during pregnancy. For women who do not respond to or cannot tolerate oral iron treatment, intravenous (IV) iron preparations may offer a viable therapeutic option in the third trimester of pregnancy. Ferric carboxymaltose (FCM; Ferinject^®) is an IV iron preparation that allows rapid administration of high single doses of iron with a favorable safety profile. This study evaluated the potential impact of FCM therapy on fetal well-being by recording cardiotocography (CTG) before, during, and after iron infusions. Materials and Methods: We examined 105 women with IDA in the third trimester of pregnancy. During the initial evaluation, each patient was assessed for complete blood count, iron metabolism, B12, folates, hemoglobinopathies, CRP, kidney and liver function, and glucose levels. Each subject received intravenous ferric carboxymaltose (FCM), 500 mg. The study focused on the maternal and fetal safety of FCM infusion. The primary endpoint for maternal safety was the observation of adverse effects of iron infusion. For fetal safety, the primary endpoint was the assessment of CTG. Results: We considered 105 women, comprising 101 singleton and 4 twin pregnancies. The median hemoglobin (Hb) at initial observation was 95 g/L and 117 g/L post-therapy. Regarding maternal safety, side effects were observed during or after FCM infusion in four subjects; three cases involved local symptoms, while one case included nausea and skin rash. Concerning fetal safety, 100% of the cardiotocography records were deemed “normal” using the Dawes–Redman criteria. Conclusions: In conclusion, FCM proved effective in treating anemia in this clinically complex population of pregnant women in the third trimester and appeared safe in this cohort, though larger prospective studies are warranted.

Aims: In this paper the authors discuss a rare case of alloimmunization following a hematopoietic stem cell transplant (HSCT) with minor RhD incompatibility between a RhD+ recipient and a RhD- (with anti-D) haploidentical donor. Materials and Methods: The patient (O RhD+) had AML and in second remission received a PBSC transplant from haploidentical stem cells from her mother (O RhD- with anti-D). This was therefore a minor RhD incompatibility. Results: Engraftment was normal. A positive DAT test was observed early. A high-titre positivity for IAT was subsequently observed. Conclusions: We reported a very rare case of donor-derived anti-D alloimmunization after a HSCT wuth minor RhD incompatibility. In our opinion the main points of interest in this case lie in the rapid rise in anti-D titre to an extremely high level (1/525,288) and its subsequent slow decline. This is a unique aspect of the case. Moreover the case highlights the importance of closely monitoring the immune and hematological status of patients who have undergone an allogeneic HSCT, especially when there is RhD incompatibility between the donor and recipient.

Background: Today, in Western countries, patients with allo-antibodies to high-frequency antigens or with complex antibody mixtures represent one of the most significant challenges in transfusion medicine. Another important aspect is the prevention of allo-immunization of patients who lack high-frequency antigens. In these conditions, the availability of a bank of a rare red blood cell group, supported by a database of donors subjected to extensive erythrocyte typing (preferably using erythrogenomic study), can constitute a resource of great value. Materials and Methods: Repeat Caucasian blood donors of group A or O, with selected Rh phenotypes (CCDee, ccDEE, ccdee, ccDee), aged under 52 years, were considered for typing. Moreover, we selected all non-Caucasian repeat blood donors for typing. For extended phenotyping and genotyping we adopted commercial methods supplied by Grfols and Werfen, respectively. For cryopreservation, we selected a high glycerol method in −80 °C electric freezer; blood unit processing was performed using a Haemonetics ACP 215 automated cell processor with close circuit devices. Results: We considered the five patients as follows: PA was massively transfused for a road trauma, developed multiple allo-antibodies (anti-D, anti-k), and required compatible blood units for an elective cardiac surgery; PB was a pregnant woman with anti-Coa (a high frequency antigen) monitored during pregnancy and in which it was necessary to proceed with the transfusion of the newborn; PC was a poly-transfused patient with myelo dysplastic syndrome who developed multiple allo-antibodies (anti-k, anti-CW, anti-Lea) and required continuous supportive therapy, including the procurement of compatible units and the implementation of therapeutic actions in an attempt to reduce the transfusion requirement using luspatercept; PD was a patient with sickle cell disease. They had a Fy (null) genotype, making it very difficult to find compatible units; and PE was interesting for the complexity of the immunohematological and erythrogenomic study performed to characterize a recipient with a rare phenotype and thus allow the transfusion of compatible units, preventing allo-immunization. Discussion: In this report, we have maintained a narrative approach. Starting with five patients representing as many clinical situations as possible, we have illustrated the approach followed for the immune-hematological study and the choices made to try to guarantee effective and safe transfusion therapy.

The ongoing demand for reliable, cost-effective, and scalable diagnostic solutions during the COVID-19 pandemic emphasized the need for innovative production platforms. In this study, we present a plant-based molecular farming (PMF) strategy for the production of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein fused with an Fc region (RBDw-Fc). The RBDw-Fc antigen was transiently expressed in the Nicotiana benthamiana plant, achieving high yields and purity. Its functionality was assessed through antigen–antibody binding assays. The purified antigen was subsequently employed in the development of a rapid diagnostic blot assay capable of screening plasma EDTA samples from pre- and post-vaccinated as well as pre- and post-infected individuals, demonstrating high sensitivity and specificity. Our results show that the RBDw-Fc-based assay is effective for SARS-CoV-2 detection and offers considerable advantages in terms of production speed, scalability, and cost efficiency compared to traditional systems, such as cell-culture-based production. The assay delivers accurate results in just a few minutes, making it particularly suitable for clinical and resource-limited settings. This study highlights the versatility of PMF as a platform for producing high-quality reagents, with promising applications beyond SARS-CoV-2 diagnostics. The RBDw-Fc antigen-based method provides a model for the rapid, economical, and flexible development of screening tools for emerging infectious diseases and future pandemics.

The ongoing demand for reliable, cost-effective, and scalable diagnostic solutions during the SARS-CoV-2 pandemic has highlighted the need for innovative production platforms. Here, we present a plant-based molecular farming (PMF) strategy for the production of the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein fused with Fc (RBDw-Fc). The RBDw-Fc antigen was transiently expressed in Nicotiana benthamiana plant, achieving high yields and purity. Antigen-antibody binding assays were used to assess its functionality. The purified antigen was used to develop a rapid diagnostic blot assay to screen both pre and post vaccinated and pre and post infected plasma EDTA samples with high sensitivity and specificity. Our results demonstrate that the RBDw-Fc-based assay is effective for SARS-CoV-2 detection, and offers significant advantages in terms of production speed, scalability, and cost-efficiency compared to traditional systems, such as cell-culture-based production. This kind of diagnostic test deliver accurate results in just few minutes, enhancing its applicability in clinical and resource-limited settings. This study highlights the versatility of PMF as a platform for producing high-quality reagents, with potential applications beyond SARS-CoV-2 diagnostics. The RBDw-Fc antigen-based method offers a model for the development of rapid, economical, and adaptable screening tools for emerging infectious diseases and future pandemics.

Background: Extracorporeal photopheresis (ECP) consists of the collection of a patient’s peripheral blood mononuclear cells (MNCs) that, after incubation with a photosensitive molecule, are exposed to ultraviolet-A (UVA) and then reinfused into the patient. There are two methods for performing the ECP procedure: the “in-line” methods and the “off-line” methods. In the “in-line” method, all the phases of ECP (leukapheresis, photoactivation, and reinfusion) are achieved sequentially in extracorporeal circulation using a single instrument and a single sterile disposable kit without disconnection from the patient’s blood circulation. In this paper, we report our real-life experience with a recently licensed in-line ECP system proposed by Fresenius-Kabi. Methods: The ECP procedures (n = 211) were performed using an Amicus cell separator and a Phelix UV irradiator with Amicus software 4.51 and Phelix software 1.0. A targeted 2000 mL of whole blood (WB) was processed, and 1.5 J/cm² of UVA light was delivered to the collected mononuclear cells (MNCs). Results: From May 2023 to April 2024, we performed 211 ECP procedures in 11 patients with graft-versus-host disease (GvHD). The processed blood volume was between 1992 and 2000 mL, and the blood flow speed during the procedures was highly variable (from 30 to 50 mL/min), so the total duration of the procedure was quite variable (from 92 to 118 min). The collection efficiency (CE2) for mononuclear cells was always satisfactory (from 55% to 73%), with a minimal presence of RBCs and PLTs. Conclusions: In our experience, the Amicus system-based ECP procedure is safe and well tolerated as we observed only one side effect. The duration of the procedure was always under two hours. The collection efficiency (CE2) for MNCs was satisfactory, with minimal platelet and RBC product contamination.