The Italian registry of therapeutic apheresis in SISTRA: Year of activity 2022.

Therapeutic apheresis refers to a group of extracorporeal blood processing procedures used in the treatment of a variety of systemic diseases. These complex procedures are burdened by adverse reactions related to both procedures and underlying medical conditions. Given the importance of centralizing the collection and the analysis of information on therapeutic apheresis, the Italian National Blood Center (NBC), at the request of the Italian Scientific Society of Hemapheresis and Cell Manipulation (SIdEM), implemented the Italian Registry of Therapeutic Apheresis (IRTA) including it in the Information System of Transfusion Services (SISTRA), coordinated by the NBC. In 2022, a total of 34,702 therapeutic apheresis procedures was carried out in 8,781 patients, including paediatric patients, with an average of 3.9 procedures per patient. The 2022 IRTA data indicate that the patient with hematological and/or neurological disorders mainly turns to the apheresis centers. These results confirm the IRTA data from years 2020 and 2021. In the hematological field, the apheresis centers supply hematopoietic stem cells collection for autologous transplantation as well as mononuclear cell collection for extracorporeal photopheresis. With regard to the neurological field, myasthenia, chronic inflammatory demyelinating polyneuropathy and Guillain-Barré syndrome along with other neurological pathologies related to immune disorders are the most treated. In conclusion, this manuscript presents 2022 activity data of IRTA providing institutions and scientific societies with a wide range of information including type and number of therapeutic procedures, adverse events and patients' outcome.

Association between ABO blood groups and SARS-CoV-2 infection in blood donors of Puglia region.

This is an observational multicentric cross-sectional study aiming at assessing the association between ABO blood groups and SARS-CoV-2 seroprevalence among the blood donors in Puglia region. Data on ABO and Rh blood groups and demographic characteristics were obtained from Blood Bank Information System. All donors were screened for SARS-CoV-2 IgG antibodies. Comparison of seroprevalence among blood groups and the association between the recorded variables and seroprevalence were evaluated. A total of 35,709 donors from 22 centers were included, with a seroprevalence of 6.8%. The distribution of ABO phenotypes was blood type O (46.8%), A (34.0%), B (14.7%), and AB (4.5%). Among the 2416 donors reactive for SARS-CoV-2 IgG, the prevalent phenotype was blood type O (43.1%), followed by A (37.7%), B (14.2%), and AB (5%). The seroprevalence of phenotype A and AB was 7.5%, followed by B (6.5%) and O (6.2%). According to the adjusted analysis, there was an increase in seroprevalence in groups A and AB, compared to group O, and an increase in males compared to females. A possible effect modification was observed after stratifying for sex (p = 0.0515). A significantly lower prevalence of blood type O was found compared to A and AB, whereas no association was observed between Rh factor and seroprevalence. We hypothesized that the A antigen present in blood type A and AB can play a role in the binding of SARS-CoV-2 to ACE2 receptors, resulting in an increased risk of infection. Furthermore, natural anti-A/anti-B antibodies produced in group O could block viral adhesion to cells and explain a lower risk of infection.

The Italian registry of therapeutic apheresis: year of activity 2021.

In 2019, the Italian National Blood Center (NBC), at the request of the Italian Scientific Society of Haemapheresis and Cell Manipulation (SIdEM), included the Italian Registry of Therapeutic Apheresis (IRTA) in the Information System of Transfusion Services (SISTRA), whose activity is coordinated by the NBC. The IRTA provides institutions and scientific societies with a wide range of information including therapeutic procedures and outcomes of treated patients. The Italian National Health Service offers therapeutic apheresis for patients with various conditions, but it is mainly the patient with haematological and/or neurological disorders who turns to the apheresis centres as evidenced by the activity data of 2021. In the haematological field, the apheresis centres mainly supply haematopoietic stem cells for autologous or allogeneic transplantation as well as mononuclear cell collection for extracorporeal photopheresis (ECP), a therapeutic approach of II line in post-transplant Graft versus Host Disease. The activity of 2021 in the neurological field confirms the data of 2019, the pre-pandemic year, and indicates that myasthenia, chronic inflammatory demyelinating polyneuropathy and Guillain-Barré syndrome along with other neurological pathologies related to immune disorders are the diseases in which apheresis procedures are most used. In conclusion, the IRTA is a valuable tool for monitoring the activity of apheresis centres carried out at a national level and above all for providing an overall picture of how the use of this therapeutic tool evolves and changes over time.

The Italian registry of therapeutic apheresis enters the information system of transfusion services - SISTRA.

The National Blood Centre (NBC) at the request of the Italian Scientific Society of Haemapheresis and Cell Manipulation (SIdEM) has funded and developed a software dedicated to the collection of data related to therapeutic apheresis procedures, known as the Italian Registry of Therapeutic Apheresis (IRTA). Although on a voluntary basis, participation in the registry was widespread. The data collected includes type and number of procedures, patients treated and their outcomes, and reported adverse events to the procedures. For the years 2019 and 2020, the therapeutic apheresis procedure was widely used in the field of haematology, transplantation and rheumatology and was mainly associated with mild adverse events, thus showing a high level of safety. In addition to allowing the competent institution to monitor an important activity in the transfusion medicine field, the Registry is a new starting point for collaboration between transfusion centres distributed throughout the national territory and could encourage the design of major clinical trials.

Obstetric outcomes in pregnant COVID-19 women: the imbalance of von Willebrand factor and ADAMTS13 axis.

BACKGROUND: Thrombotic microangiopathy has been invoked as one of the most important mechanisms of damage in COVID-19 patients. Protease ADAMTS13 is a marker of microangiopathy responsible for controlling von Willebrand multimers size. Von Willebrand factor/ADAMTS13 ratio has been found impaired in COVID-19 patients outside pregnancy. METHODS: We prospectively investigated 90 pregnant women admitted to two tertiary academic hospitals in Italy with a laboratory-confirmed diagnosis of SARS-CoV-2 infection. Demographic, clinical information and routine laboratory data were collected at the hospital admission and until discharge. We investigated whether vonWillebrand /ADAMTS13 axis imbalance is a predictor of adverse outcomes. Logistic regression analysis, which controlled for potential confounders, was performed to evaluate the association between laboratory parameters and clinical outcomes. RESULTS: Most women (55.6%) were parae, with median gestational age at admission of 39 weeks. At hospital admission, 63.3% were asymptomatic for COVID-19 and 24.4% showed more than one sign or symptom of infection. Nulliparae with group O showed Willebrand / ADA MTS-13 ratios significantly lower than non-O, whereas in multiparae this difference was not observed. Logistic regression showed that ratio von Willebrand to ADAMTS13 was significantly and independently associated with preterm delivery (OR 1.9, 95%CI 1.1-3.5). CONCLUSION: This study shows an imbalance of vonWillebrand /ADAMTS13 axis in pregnant women with COVID-19, leading to a significantly higher and independent risk of preterm delivery. Monitoring these biomarkers might support decision making process to manage and follow-up pregnancies in this setting.

Correlation between In Vitro Neutralization Assay and Serological Tests for Protective Antibodies Detection.

Serological assays are useful in investigating the development of humoral immunity against SARS-CoV-2 in the context of epidemiological studies focusing on the spread of protective immunity. The plaque reduction neutralization test (PRNT) is the gold standard method to assess the titer of protective antibodies in serum samples. However, to provide a result, the PRNT requires several days, skilled operators, and biosafety level 3 laboratories. Therefore, alternative methods are being assessed to establish a relationship between their outcomes and PRNT results. In this work, four different immunoassays (Roche Elecsys® Anti SARS-CoV-2 S, Snibe MAGLUMI® SARS-CoV-2 S-RBD IgG, Snibe MAGLUMI® 2019-nCoV IgG, and EUROIMMUN® SARS-CoV-2 NeutraLISA assays, respectively) have been performed on individuals healed after SARS-CoV-2 infection. The correlation between each assay and the reference method has been explored through linear regression modeling, as well as through the calculation of Pearson's and Spearman's coefficients. Furthermore, the ability of serological tests to discriminate samples with high titers of neutralizing antibodies (>160) has been assessed by ROC curve analyses, Cohen's Kappa coefficient, and positive predictive agreement. The EUROIMMUN® NeutraLISA assay displayed the best correlation with PRNT results (Pearson and Spearman coefficients equal to 0.660 and 0.784, respectively), as well as the ROC curve with the highest accuracy, sensitivity, and specificity (0.857, 0.889, and 0.829, respectively).

Use of low-molecular weight heparin, transfusion and mortality in COVID-19 patients not requiring ventilation.

It is still debated whether prophylactic doses of low-molecular- weight heparin (LMWH) are always effective in preventing Venous Thromboembolism (VTE) and mortality in COVID-19. Furthermore, there is paucity of data for those patients not requiring ventilation. We explored mortality and the safety/efficacy profile of LMWH in a cohort of Italian patients with COVID-19 who did not undergo ventilation. From the initial cohort of 422 patients, 264 were enrolled. Most (n = 156, 87.7%) received standard LMWH prophylaxis during hospitalization, with no significant difference between medical wards and Intensive Care Unit (ICU). Major or not major but clinically relevant hemorrhages were recorded in 13 (4.9%) patients: twelve in those taking prophylactic LMWH and one in a patient taking oral anticoagulants (p: n.s.). Thirty-nine patients (14.8%) with median age 75 years. were transfused. Hemoglobin (Hb) at admission was significantly lower in transfused patients and Hb at admission inversely correlated with the number of red blood cells units transfused (p < 0.001). In-hospital mortality occurred in 76 (28.8%) patients, 46 (24.3%) of whom admitted to medical wards. Furthermore, Hb levels at admittance were significantly lower in fatalities (g/dl 12.3; IQR 2.4 vs. 13.3; IQR 2.8; Mann-Whitney U-test; p = 0.001). After the exclusion of patients treated by LMWH intermediate or therapeutic doses (n = 32), the logistic regression showed that prophylaxis significantly and independently reduced mortality (OR 0.31, 95% CI 0.13-0.85). Present data show that COVID-19 patients who do not require ventilation benefit from prophylactic doses of LMWH.

Position paper on the preparation of immune plasma to be used in the treatment of patients with COVID-19.

Passive immunotherapy with plasma derived from patients convalescent from SARS-CoV-2 infection can be a promising approach in the treatment of COVID-19 patients. It is important that Blood Establishments are prepared to satisfy requests for immune plasma by defining the requirements applicable to plasma donors and the standards for preparation, qualification, storage, distribution and control of use of the product. This position paper is aimed to give recommendations on biological characteristics of a plasma preparation from convalescent donors and to support the evaluation of this therapeutic approach in more rigorous investigations.

Anemone study: prevalence of risk factors for superficial vein thrombosis in a large Italian population of blood donors.

Knowledge of the distribution of risk factors for superficial thrombosis (SVT) in low-risk population is fundamental to improve the prevention of the disease in each individual and high-risk settings of patients. Exact frequency data for the low-risk population are scarce, but could be useful for optimal use of prophylactic strategies against venous thrombosis. Blood donors represent a low-risk population, because are healthier than the general population. The objective of this study was to assess the prevalence of vein thrombosis, particularly SVT, and associated risk factors in a low-risk population such as blood donors. In this multicentre cross-sectional study, donors from six Italian blood banks responded to a self-administered questionnaire. The enrolment lasted from 1st June 2017 to 30th July 2018. History of vein thrombosis was referred by 89 (0.76%) individuals, (49 men) with an age-dependent effect. The prevalence reached 2.9% in women and 0.8% in men aged ≥ 49 years, with a significant difference only for women. After controlling for potential confounders, a significant and independent association was found between a history of vein thrombosis and age (OR: 1.03, 95%CI 1.01-1.05), varicose veins (OR: 15.8, 95%CI 7.7-32.6), plaster cast/bed rest (OR: 2.3, 95% CI 1.0-5.3) and transfusion (OR: 5.1, 95% CI 1.3-19.5). This study shows that low-risk individuals share the same risk factors for SVT as patients in secondary care. It also suggests that transfusion confers an increased risk of SVT in healthy population.

Management of Patients Taking Oral Anticoagulants Who Need Urgent Surgery for Hip Fracture.

The number of hip fractures in anticoagulated patients is predicted to increase, due to people living longer. However, evidence regarding urgent perioperative management of elderly patients with hip fracture who take oral anticoagulants (vitamin K antagonists or direct oral anticoagulants) is scarce. In this article, the authors present a narrative review of the evidence to date supporting the urgent management of hip fracture in anticoagulated elderly patients. They discuss the complexity of managing the high risk of procedure-related bleeding and, at the same time, the high risk of thromboembolism. The role of a bridging procedure and the best strategy of anticoagulation reversal are also reviewed. Further studies are required to improve the evidence in urgent surgery, especially in frail elderly patients.

Validation of PLASMIC score and follow-up data in a cohort of patients with suspected microangiopathies from Southern Italy.

Severe ADAMTS13 deficiency (activity < 10%) is pathognomonic of thrombotic thrombocytopenic purpura. ADAMTS13 testing is time-consuming and unavailable in many hospitals. Recently, a seven-variables score named PLASMIC score, has been developed to stratify acute patients, based on their risk of having a severe ADAMTS13 deficiency. We present the application of this score in a cohort of patients referred to our Center. From 2012 to 2017, 42 patients with suspected thrombotic microangiopathies from 6 Centers were referred to Hemostasis and Thrombosis Center of "Casa Sollievo della Sofferenza" Hospital/Research Institute for ADAMTS13 testing. For all patients, relevant medical and laboratory information were collected. To obtain the statistical measure of the discriminatory power of PLASMIC scoring system, the Area Under the Curve Receiver Operating Characteristic (AUC ROC) was calculated. We were able to calculate the PLASMIC score in 27 out of 42 patients; we found a good discrimination performance of the score with a resulting AUC value of 0.86 (95% CI 0.71-1.0; p = 0.015). All patients but one with a high risk PLASMIC score (6-7) showed a severe deficiency. Among patients belonging to the intermediate risk (PLASMIC score 5) group, 2 showed normal ADAMTS13 activity and 2 levels below 10%. In none of the patients in the low risk group (PLASMIC score 0-4), a severe ADAMTS13 deficiency was found. Present results confirm and extend previous data regarding the predictive value of the PLASMIC score. Indeed, it shows a good diagnostic performance and can be useful for decision makers to properly and promptly define the better therapeutic approach.

Navigating anemia and anticoagulation in elderly patients undergoing orthopedic surgery: strategies for preventing complications and implementing treatments.

BACKGROUND: Elderly populations face an increased risk of anemia, leading to elevated transfusion requirements during surgery, especially major orthopedic procedures. Anemia itself increases the risk of thromboembolic events, thus compounding complications in elderly individuals. Polypharmacy and the prevalent use of oral anticoagulants (OAC), particularly for atrial fibrillation, contribute to bleeding risks in this population. Data available in the literature on the peri-operative management of anemia in patients taking OAC is limited and often heterogeneous. MATERIALS AND METHODS: This narrative case-based review focuses on the peri-operative management of elderly patients on OAC undergoing major orthopedic surgery. PubMed/Medline was used to search for relevant literature. RESULTS: With reference to two cases, we critically evaluate the literature, and focus on risk factors, and preventive and therapeutic strategies as fundamental tools to reduce bleeding and correct anemia as soon as possible in elderly patients undergoing major orthopedic surgery. DISCUSSION: Peri-operative management of these patients, especially those on OAC, requires a balanced approach considering bleeding and thrombotic risks. Intravenous iron therapy and tranexamic acid emerge as valuable strategies in minimizing transfusion requirements and optimizing patients' outcomes.

Posterior maxillary segmental osteotomy for the implant reconstruction of a vertically deficient ridge: a 3-year clinical report.

A vertically deficient posterior maxillary edentulous ridge in conjunction with sinus pneumatization or extensive horizontal bone resorption presents significant challenges for implant placement and restoration with an implant-supported fixed prosthesis. Various surgical techniques have been reported for the reconstruction of the vertically deficient posterior maxilla: guided bone regeneration, sinus elevation, block and/or particulate grafting with barrier membranes, and distraction osteogenesis. This clinical report describes the technique, the management of intrasurgical complications, and the 3-year follow-up results of augmenting the vertically deficient posterior maxilla with a segmental osteotomy prior to rehabilitation with an implant-supported fixed prosthesis.

Plerixafor added to chemotherapy plus G-CSF is safe and allows adequate PBSC collection in predicted poor mobilizer patients with multiple myeloma or lymphoma.

We evaluated the safety and efficacy of plerixafor, subsequent to disease-specific chemotherapy followed by granulocyte-colony stimulating factor (G-CSF), in 37 multiple myeloma (MM) or lymphoma patients, who were candidates for autologous stem cell transplantation (ASCT) predicted as poor mobilizers (PMs). Patients were identified as predicted PMs according to the history of a previously failed mobilization attempt or the presence of ≥1 factors predicting an unsuccessful harvest, such as advanced disease, prior extensive radiotherapy, or prolonged treatment, with stem cell poisons, advanced age, or extensive bone marrow involvement. Plerixafor (0.24 mg/kg) was administered subcutaneously for up to 3 consecutive days while continuing G-CSF for 9 to 11 hours before the planned apheresis. Plerixafor administration was safe and no significant adverse events were recorded. We observed a median 4-fold increase (range: 1.4-32) in the number of circulating CD34(+) cells following plerixafor compared with baseline CD34(+) cell concentration (from a median of 5 cells/µL, range: 1-32, to a median of 32 cells/µL, range: 6-201). Twenty-seven of the 37 patients (14 of 17 with MM and 13 of 20 with lymphoma) had ≥2×10(6) CD34(+) cells/kg collected in 1-3 apheretic procedures. Of the 27 patients rescued with plerixafor, 24 (13 MM, 11 lymphoma) have been transplanted with plerixafor-mobilized peripheral blood stem cells, showing a rapid and durable hematologic recovery. Our results suggest that the addition of plerixafor to G-CSF after disease-oriented chemotherapy is safe and allows for a satisfactory harvest in order to perform a safe ASCT, in a relevant proportion of lymphoma and MM patients considered to be PMs.

Blood supply, transfusion demand and mortality in Italian patients hospitalised during nine months of COVID-19 pandemic.

BACKGROUND: We describe blood supply and usage from March to December 2020 in two research medical hospitals in the Apulia region of Italy: Research Hospital "Casa Sollievo della Sofferenza" (Centre 1) and University Hospital of Bari (Centre 2). MATERIALS AND METHODS: We performed a retrospective observational study of blood component transfusions in the first eight months of the pandemic: 1st March-31st December 2020. We assessed the number of hospitalised patients who were transfused, the number and type of blood components donated and the number and type of blood components transfused in different care settings. RESULTS: Blood donations were lower in 2020 than in 2019, with a significant reduction in red blood cells (RBC) transfused (-29% in 2020 vs 2019) and fewer transfusions in 2020 in the Internal Medicine departments (-67% and -44% in Centres 1 and 2, respectively) and Intensive Care Units (ICUs) (-53% and -54% in Centres 1 and 2, respectively). The overall number of fatalities was significantly lower in 2020 than in 2019; the proportion of fatalities in men was significantly higher in 2020 than in 2019 (53.9% and 41.5%, respectively; p=0.000). Among COVID-19 patients (n=645), 427 (66.2%) were transfused in Infectious Disease departments and the remaining in ICUs. The fatality rate was 14.3% in COVID patients transfused in Infectious Disease departments and 22.5% in those transfused in ICUs. Kaplan-Meier analysis showed 30- and 60-day mortality was significantly higher in patients transfused in 2020 compared to those transfused in 2019. Fatalities were mostly observed in COVID-19 patients. DISCUSSION: Present data may be helpful in understanding the trend of collection and use of blood supplies during periods of pandemic. The implementation of a Patient Blood Management programme is essential to maintain sufficient blood supplies and to keep track of clinical outcomes that represent the most important goal of transfusion.