A retrospective study assessing the characteristics of COVID-19 convalescent plasma donors and donations.

BACKGROUND: Although many trials are currently investigating the safety and efficacy of convalescent plasma (CP) in critically ill COVID-19 patients, there is a paucity of ongoing and published studies evaluating the CP donors' side. This retrospective study reports the first Italian experience on CP donors' selection and donations. METHODS: Patients aged 18-68 years who had recovered from COVID-19 at least 2 weeks previously were recruited between March 18 and June 30, 2020 in a study protocol at the Italian hospitals of Pavia and Mantova. RESULTS: During the study period, 494 of 512 donors recruited were judged eligible and underwent 504 plasmapheresis procedures. Eighty-five percent (437/512) of the CP donors were males. The average time between symptom recovery and CP donation was 36.6 (±20.0) days. Four hundred and eighty-eight plasmapheresis procedures (96.8%) were concluded and each unit was divided into two subunits (total 976) with an average volume of 316.2 (±22.7) mL. Ninety-three percent (460/494) of CP donors at the time of plasma donation had a neutralizing IgG titer ≥1:80. Plasmapheresis-related adverse reactions occurred in 2.6% (13/504) of cases; all the reactions were mild and none required therapeutic intervention. Donors' age and COVID-19 severity were positively associated with greater antibody responses. CONCLUSION: This study demonstrates the feasibility and safety of a pilot CP program conducted in Italy. The identification of factors (ie, age and severity of COVID-19) positively associated with higher neutralizing antibody titers at the time of donation may help to optimize the selection of CP donors.

COVID-19 vaccine-associated immune thrombosis and thrombocytopenia (VITT): Diagnostic and therapeutic recommendations for a new syndrome.

Very rare cases of thrombosis associated with thrombocytopenia have occurred following the vaccination with AstraZeneca COVID-19 vaccine. The aim of this concise review is to summarize the current knowledge on the epidemiologic and pathogenic mechanisms of this syndrome named vaccine-associated immune thrombosis and thrombocytopenia (VITT). A practical patient management section will also be dealt with using information available from national and international scientific societies as well as expert panels. A literature search on the VITT syndrome was carried out in PubMed using appropriate MeSH headings. Overall, 40 VITT cases have been reported. Continuous pharmacovigilance monitoring is needed to collect more data on the real incidence and the pathogenesis of VITT syndrome. Such information will also help us to optimize the management this rare but often clinically severe thrombotic condition associated with COVID-19 vaccination.

Inhibitors in Patients with Congenital Bleeding Disorders Other Than Hemophilia.

The most worrying complication of replacement therapy for severe hemophilia A and B is currently the occurrence of inhibitory alloantibodies against infused factor VIII and factor IX, respectively. Inhibitors compromise the management of hemorrhage in affected patients, with a considerable increase in complications, disability, and costs. While these alloantibodies have been extensively studied in the past years in hemophilia A and B, those occurring in patients with other inherited bleeding disorders are less well characterized and still poorly understood, mostly due to the rarity of these hemorrhagic conditions. This narrative review will deal with inhibitors arising in patients with inherited bleeding disorders other than "classical" hemophilia, focusing in particular on those developing in patients with congenital deficiency of coagulation factor V, factor VII, factor XI, and factor XIII.

An early start of West Nile virus seasonal transmission: the added value of One Heath surveillance in detecting early circulation and triggering timely response in Italy, June to July 2018.

In Italy, the 2018 West Nile virus transmission season started early with a high number of cases reported. One-Health surveillance, within the Italian West Nile national preparedness and response plan, detected viral circulation 9 days before symptom-onset of the first confirmed human case; triggering timely implementation of blood and transplant safety measures. This is an example of how functional coordination allows health authorities to use early warning triggers from surveillance systems to implement preventive measures.

The Role of ABO Blood Type in Thrombosis Scoring Systems.

In addition to their major role in transfusion medicine, there is increasing evidence that ABO blood group antigens (complex carbohydrate molecules widely expressed on the surface of red blood cells and several other cell types) are implicated in the development of a wide array of pathologic conditions. In particular, intense research has been dedicated over the last 50 years to the study of the association between non-O blood type and the risk of developing cardiovascular disorders. Several pathways have been hypothesized to explain this relationship, the most reasonable implying the influence of the ABO blood group on circulating plasma levels of von Willebrand factor, factor VIII, and several inflammatory cytokines. This narrative review summarizes the current knowledge on the role of ABO antigens in both venous and arterial thromboses, focusing on their association with clinical scoring systems evaluating thrombotic risk.

Human T-lymphotropic virus and transfusion safety: does one size fit all?

Human T-cell leukemia viruses (HTLV-1 and HTLV-2) are associated with a variety of human diseases, including some severe ones. Transfusion transmission of HTLV through cellular blood components is undeniable. HTLV screening of blood donations became mandatory in different countries to improve the safety of blood supplies. In Japan and Europe, most HTLV-infected donors are HTLV-1 positive, whereas in the United States a higher prevalence of HTLV-2 is reported. Many industrialized countries have also introduced universal leukoreduction of blood components, and pathogen inactivation technologies might be another effective preventive strategy, especially if and when generalized to all blood cellular products. Considering all measures available to minimize HTLV blood transmission, the question is what would be the most suitable and cost-effective strategy to ensure a high level of blood safety regarding these viruses, considering that there is no solution that can be deemed optimal for all countries.

West Nile Virus in Europe and Safety of Blood Transfusion.

West Nile virus (WNV) has become an increasing issue in the transfusion setting since 2002, when it was firstly shown in the USA that it can be transmitted through blood transfusion. Since then, several precautionary measures have been introduced in Europe in order to reduce the possible risk of transmission via transfusion/solid organ transplantation. In addition, the epidemiological surveillance has been tightened and the network for communication of human WNV cases strengthened. This review will focus on WNV circulation and the safety of blood in Europe.

Solvent/detergent plasma: pharmaceutical characteristics and clinical experience.

The solvent/detergent treatment is an established virus inactivation technology that has been industrially applied for manufacturing plasma derived medicinal products for almost 30 years. Solvent/detergent plasma is a pharmaceutical product with standardised content of clotting factors, devoid of antibodies implicated in transfusion-related acute lung injury pathogenesis, and with a very high level of decontamination from transfusion-transmissible infectious agents. Many clinical studies have confirmed its safety and efficacy in the setting of congenital as well as acquired bleeding disorders. This narrative review will focus on the pharmaceutical characteristics of solvent/detergent plasma and the clinical experience with this blood product.

Hemostasis, cancer, and ABO blood group: the most recent evidence of association.

Human ABO blood group antigens are expressed on the surface of red blood cells and a variety of human cells and tissues. However, an increasingly number of studies show that the ABO blood group, in addition to its fundamental role in transfusion medicine and in several other disciplines, has a causal role in predisposing to several human diseases, including hemostasis and neoplastic disorders, which will be the focus of this narrative review.

Proteomic analysis of venous thromboembolism: an update.

Venous thromboembolism is a complex, multifactorial disorder, the pathogenesis of which typically involves a variety of inherited or acquired factors. The multifactorial etiology of this disease and the partial correlation between genotype and prothrombotic phenotype limit greatly the value of genetic analysis in assessing thrombotic risk. The integration of several new 'omics' techniques enables a multifaceted and holistic approach to the study of venous thrombotic processes and pave the way to the search and identification of novel blood biomarkers and/or effectors of thrombus formation that can also be the possible future target of new anticoagulant and thrombolytic therapies for more personalized medicine. This review provides a comprehensive overview of the latest candidate proteomic biomarkers of venous thrombosis and of the proteomics studies relevant to its pathophysiology, some of which seem to confirm the existence of a common physiopathological basis for venous thromboembolism and atherothrombosis.

ABO blood group: old dogma, new perspectives.

Human blood group antigens are glycoproteins and glycolipids expressed on the surface of red blood cells and a variety of human tissues, including the epithelium, sensory neurons, platelets and the vascular endothelium. Accumulating evidence indicate that ABO blood type is implicated in the development of a number of human diseases, including cardiovascular and neoplastic disorders. In this review, beside its physiologic role in immunohematology and transfusion medicine, we summarize the current knowledge on the association between the ABO blood group and the risk of developing thrombotic events and cancers.

Intraoperative cell salvage in obstetrics: is it a real therapeutic option?

Obstetric hemorrhage is a leading cause of maternal and perinatal mortality worldwide. Intraoperative blood salvage is common practice in many surgical specialties but its safety in obstetrics is questioned for concerns on the risks of contamination of recovered blood with amniotic fluid (AF) and of maternal-fetal alloimmunization. However, the role of cell salvage as a blood-saving measure in obstetrics is progressively acquiring relevance thanks to the growing body of evidence regarding its quality and safety coming from over 800 documented procedures and more than 400 patients transfused with saved blood. Although the information about the outcomes of the patients treated and the allogeneic blood saving effect are still limited, modern cell savers remove most particulate contaminants and leukoreduction filtering of salvaged blood (SB) before transfusion adds further safety to this technique. Moreover, AF embolism is no longer regarded as an embolic disease and it is suggested that it is a rare anaphylactoid reaction to the fetal antigen. The contamination of the SB by fetal Rh-mismatched red blood cells (RBCs) can be dealt with using RhIG; ABO incompatibility tends to be a minor problem since ABO antigens are not fully developed at birth. Antibodies can be formed against other fetal RBC antigens, but it should also be noted that the risk of alloimmunization of the mother from allogeneic transfusion is probably even greater. Therefore, intraoperative cell salvage in obstetrics should be considered in patients at high risk for hemorrhage or in cases where allogeneic blood transfusion is difficult or impossible.

Convalescent Plasma for the Treatment of Severe COVID-19.

The COVID-19 pandemic in 2020 is one of the worst catastrophic events in human history. Several non-specific antiviral drugs have been tried to defeat the SARS-CoV-2, with mixed results. Convalescent plasma from patients who have recovered from COVID-19 is one of the specific biologic therapies being considered to treat SARS-CoV-2 infection. Preliminary studies have shown that convalescent plasma, containing antibodies able to neutralize SARS-CoV-2, is promising in blocking viral replication and improving patients' clinical symptoms. The results of several ongoing randomized controlled trials are, however, keenly awaited to definitively elucidate the safety and efficacy of this blood component in COVID-19. In this narrative review, we summarize the current evidence from the literature on the treatment of severe COVID-19 with convalescent plasma. A concise overview of the hypothesized mechanisms of action is also presented.

Potential mechanisms of action of convalescent plasma in COVID-19.

The COVID-19 pandemic will be remembered as one of the worst catastrophic events in human history. Unfortunately, no universally recognized effective therapeutic agents are currently available for the treatment of severe SARS-CoV-2 infection. In this context, the use of convalescent plasma from recovered COVID-19 patients has gained increasing interest thanks to the initially positive clinical reports. A number of mechanisms of action have been proposed for convalescent plasma, including direct neutralization and suppression of viremia, anti-inflammatory and immunomodulation effects and mitigation of the COVID-19-associated hypercoagulable state. These immune and non-immune mechanisms will be critically discussed in this narrative review.

Hemostatic therapy as a management strategy for acquired hemophilia: what does the future hold?

Introduction: Acquired hemophilia A (AHA) is a rare autoimmune disease caused by autoantibodies that bind and inactivate factor VIII (FVIII), predisposing to a potentially life-threatening bleeding.Areas covered: The main epidemiological, clinical, laboratory and therapeutic features of AHA are critically discussed. In particular, we focus on the hemostatic management of AHA patients analyzing the currently available treatment options and showing the latest data on the innovative hemostatic agents still under investigation. Authors searched the Medline and PubMed electronic databases for publication on AHA in the last twenty years.Expert opinion: While a rapid recognition of suspected cases of AHA is essential to make a correct diagnosis and appropriately and timely treat the hemorrhagic manifestations, the multidisciplinary approach to this challenging, rare and life-threatening bleeding disorder is of equal importance to improve patients' outcome. Although promising, the safety and efficacy of the clinical use of emicizumab in AHA needs to be validated by trials including an adequate number of patients, before registering the drug also for this indication.

The Three Pillars of COVID-19 Convalescent Plasma Therapy.

The new severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has spread rapidly around the world in the last year causing the coronavirus disease 2019 (COVID-19), which still is a severe threat for public health. The therapeutic management of COVID-19 is challenging as, up until now, no specific and efficient pharmacological therapy has been validated. Translating the experience from previous viral epidemics, passive immunotherapy by means of plasma from individuals recovered from COVID-19 has been intensively investigated since the beginning of the pandemic. In this narrative review, we critically analyze the three factors, named "pillars", that play a key role in determining the clinical effectiveness of this biologic therapy: the convalescent plasma, the disease (COVID-19), and the patients.