Massimo Franchini

• Head of Department at Azienda Ospedaliera Carlo Poma Mantova

In 2024, a novel recombinant of the Oropouche virus emerged as a potential threat. This virus has caused a significant outbreak in Brazil and Cuba, with imported cases subsequently reported in the USA and Europe. This review summarises the existing knowledge on the Oropouche virus, and discusses potential risk mitigation strategies for the transfus...

Background Prophylaxis with coagulation factor concentrates is the mainstay of treatment in severe hemophilia A and B. Data on bleeding rates in persons with congenital haemophilia B (PwcHB) receiving prophylaxis are inconsistent. Aim This systematic review and meta‐analysis were aimed at assessing bleeding outcomes, including annualised bleeding...

Chronic liver disease is a frequently encountered disorder and a major concern worldwide with a complex pathophysiology, which often affects the hemostatic system. Such alterations, which affect both primary and secondary hemostasis, are heterogenous, including pro-hemorrhagic (i.e., decreased coagulation factors, increased fibrinolysis, thrombocyt...

Acquired hemophilia A (AHA) is a rare acquired autoimmune disorder caused by autoantibodies against coagulation factor VIII (FVIII), which cause a hemorrhagic diathesis, not rarely of severe degree. Standard treatment consists of bleeding control with bypassing agents (recombinant activated factor VII and activated prothrombin complex concentrate)...

Historically, the aim of treatment for hemophilia, the congenital X-linked hemorrhagic disorder due to deficiencies of coagulation Factor (F) VIII (hemophilia A) or FIX (hemophilia B), has been the replacement through factor concentrates, whose regular administration (i.e., prophylaxis) has been shown to be highly effective in preventing bleeding c...

Italy was the first western country to be hit by the COVID-19 pandemic and has suffered nearly 200,000 deaths so far during the four years of the pandemic. In March 2020, Italy first deployed COVID-19 convalescent plasma (CCP) to treat hospitalized patients. Despite this initial effort, the proportion of COVID-19 patients treated with CCP during th...

Factor V (FV) is a glycoprotein that plays a pivotal role in hemostasis, being involved in coagulant and anticoagulant pathways. Congenital FV deficiency is a rare bleeding disorder with an incidence of 1 per million live births, considering the most severe homozygous form. FV deficiency is diagnosed using routine coagulation tests and FV activity...

Catastrophic thrombosis is a severe condition characterized by a hypercoagulable tendency, leading to multiple thromboembolic events in different blood vessels, usually within a short timeframe. Several conditions have been associated with the development of catastrophic thrombosis, including the catastrophic antiphospholipid syndrome, thrombotic a...

Introduction: Hemophilia B is a X-linked rare inherited bleeding disorder characterized by coagulation factor IX (FIX) deficiency. Therapy for hemophilia B is aimed at replacing the FIX deficiency by means of several plasma-derived or recombinant FIX products. The recent availability of recombinant FIX concentrates with a prolonged FIX half-life r...

Background: Sample size estimation is an essential step in the design of randomized controlled trials (RCTs) evaluating a treatment effect. Sample size is a critical variable in determining statistical significance and, thus, it significantly influences RCTs’ success or failure. During the COVID-19 pandemic, many RCTs tested the efficacy of COVID-1...

Pandemics are highly unpredictable events that are generally caused by novel viruses. There is a high likelihood that such novel pathogens belong to entirely novel viral families for which no targeted small-molecule antivirals exist. In addition, small-molecule antivirals often have pharmacokinetic properties that make them contraindicated for the...

Since the emergence of COVID-19 in 2020, an unprecedented range of therapeutic options has been studied and deployed. Healthcare providers have multiple treatment approaches to choose from, but efficacy of those approaches often remains controversial or compromised by viral evolution. Uncertainties still persist regarding the best therapies for hig...

Introduction: Acquired hemophilia A (AHA) is a rare hemorrhagic autoimmune disorder characterized by autoantibodies against coagulation factor VIII (FVIII). In approximately half of the cases AHA does not recognize any cause (idiopathic form), while in the other cases it may be triggered by autoimmune disorders, cancers, drugs, infections, or preg...

Influenzavirus is among the most relevant candidates for a next pandemic. We review here the phylogeny of former influenza pandemics, and discuss candidate lineages. After briefly reviewing the other existing antiviral options, we discuss in detail the evidences supporting the efficacy of passive immunotherapies against influenzavirus, with a focus...

Acquired hemophilia A (AHA) is a rare autoimmune bleeding disorder which can be life-threatening. AHA is due to autoantibodies against coagulation factor VIII. Disease onset may be idiopathic (approximately half of the cases) or triggered by autoimmune disorders, cancers, drugs, infections, or pregnancy. Besides treating the underlying disorder, sp...

Plasma collected from people recovered from COVID-19 (COVID-19 convalescent plasma, CCP) was the first antibody-based therapy employed to fight the pandemic. CCP was, however, often employed in combination with other drugs, such as the antiviral remdesivir and glucocorticoids. The possible effect of such interaction has never been investigated syst...

Tranexamic acid (TXA) is an important antifibrinolytic agent, which inhibits plasminogen activation and fibrinolysis. Several controlled randomized trials have investigated the role of TXA in preventing or decreasing blood loss across different surgical interventions or medical conditions characterized by excessive bleeding, consistently documentin...

Since late 2019, the new SARS-CoV-2 virus belonging to the Coronaviridae family has been responsible for COVID-19 pandemic, a severe acute respiratory syndrome. Several antiviral therapies, mostly derived from previous epidemics, were initially repurposed to fight this not rarely life-threatening respiratory illness. Among them, however, the only s...

Among the anti-Spike monoclonal antibodies (mAbs), the S-309 derivative sotrovimab was the most successful in having the longest temporal window of clinical use, showing a high degree of resiliency to SARS-CoV-2 evolution interrupted only by the appearance of the BA.2.86* variant of interest (VOI). This success undoubtedly reflects rational selecti...

This COVID‐19 outpatient randomized controlled trials (RCTs) systematic review compares hospitalization outcomes amongst four treatment classes over pandemic period, geography, variants, and vaccine status. Outpatient RCTs with hospitalization endpoint were identified in Pubmed searches through May 2023, excluding RCTs <30 participants (PROSPERO‐CR...

Since late 2019, COVID-19, a severe acute respiratory syndrome pandemic, was caused by the new SARS-CoV-2 virus belonging to the Coronaviridae family, . Several antiviral therapies, mostly derived from previous epidemics, were initially repurposed to fight this not rarely life-threatening respiratory illness. Among them, however, the only specific...

D-dimer, a soluble fibrin degradation product that originates from plasmin-induced degradation of cross-linked fibrin, is an important biomarker of coagulation activation and secondary fibrinolysis that is routinely used to rule out venous thromboembolism (VTE), to evaluate the risk of VTE recurrence as well as the optimal duration of anticoagulant...

Objective To examine the association of COVID-19 convalescent plasma transfusion with mortality and the differences between subgroups in hospitalized patients with COVID-19. Patients and Methods On October 26, 2022, a systematic search was performed for clinical studies of COVID-19 convalescent plasma in the literature from January 1, 2020, to Oct...

Among the host genetic factors playing a role in the susceptibility to infectious diseases, the ABO blood group system is of utmost importance. Following the first reports in early 2020, the association between ABO blood groups and SARS-CoV-2 infection or COVID-19 severity has been thoroughly investigated. The aim of this narrative review is to pro...

Background and objectives: COVID-19 convalescent plasma (CCP) has retained potency and clinical efficacy against SARS-CoV-2 and is currently of utmost value for seronegative immunocompromised patients. Since most of the effect is due to the vaccine boost of infection-elicited antibodies, there is a theoretical concern that the frequency of suitabl...

Recent 2022 SARS-CoV-2 Omicron variants, have acquired resistance to most neutralizing anti-Spike monoclonal antibodies authorized, and the BQ.1.* sublineages are notably resistant to all authorized monoclonal antibodies. Polyclonal antibodies from individuals both vaccinated and recently recovered from Omicron COVID-19 (VaxCCP) could retain new Om...

Purpose: Several case reports of acquired hemophilia A (AHA) following COVID19 vaccines were recently published. A possible increased incidence of AHA during the COVID19 vaccination campaign was also suggested. We aimed at generating evidence for the preliminary assessment of the association between AHA and COVID-19 vaccination through an ecologic...

COVID-19 convalescent plasma (CCP) is a safe and effective treatment for COVID-19 in immune compromised (IC) patients. IC patients have a higher risk of persistent infection, severe disease and death from COVID-19. Despite the continued clinical use of CCP to treat IC patients, the optimal dose, frequency/schedule, and duration of CCP treatment has...

With the striking advances in hemophilia care that materialized particularly in the last two decades, an increasing number of persons with hemophilia (PWH) have achieved a quality of life and life expectancy very close to that of unaffected individuals. With aging, a growing number of PWH develop age-related co-morbidities, including cancer and car...

Over the last three decades, the continuous evolution of recombinant factor VIII (rFVIII) concentrates for replacement treatment of hemophilia A, including recent extended half-life products, implies that patients may switch from one product to another, technologically more advanced, with the aim of improving treatment efficacy, safety, management...

IMPORTANCE. Many hospitalized patients with COVID-19 have been treated with convalescent plasma. However, it is uncertain whether this therapy lowers mortality and if so, if the mortality benefit is larger among specific subgroups, such as recipients of plasma with high antibody content and patients treated early in the disease course. OBJECTIVE. T...

Since December 2019, SARS-CoV-2 is ravaging the globe, currently accounting for over 660 million infected people and more than 6 [...]

Importance: Patients who are immunocompromised have increased risk for morbidity and mortality associated with coronavirus disease 2019 (COVID-19) because they less frequently mount antibody responses to vaccines. Although neutralizing anti-spike monoclonal-antibody treatment has been widely used to treat COVID-19, evolutions of SARS-CoV-2 have be...

Objectives Being COVID-19 convalescent plasma (CCP) a therapeutic option that can have a potential impact on the normalization of immunological parameters of COVID-19 affected patients, a detailed analysis of post-infusion immunological changes was conducted in CCP treated patients, aiming to identify possible predictive hallmarks of disease progno...

Background: The SARS-CoV-2 Omicron variants, dominating in the late 2022 COVID-19 waves, have acquired resistance to most neutralizing anti-Spike monoclonal antibodies authorized so far, and the BQ.1.* sublineages, dominant in the western countries, are notably resistant to all authorized monoclonal antibodies. Polyclonal antibodies from individual...

The latest SARS-CoV-2 variant of concern Omicron, with its immune escape from therapeutic anti-Spike monoclonal antibodies and WA-1 vaccine-elicited sera, demonstrates the continued relevance of COVID-19 convalescent plasma (CCP) therapies. Lessons learnt from previous usage of CCP suggests focusing on early outpatients and immunocompromised recipi...

Historically the therapeutic potential of polyclonal passive immunotherapies in viral diseases has been related to antiviral neutralizing antibodies, but there is also considerable evidence that non-neutralizing antibodies can translate into clinical benefit as well. In the setting of SARS-CoV-2 infection, we review here in vitro and in vivo eviden...

Background: COVID-19 convalescent plasma (CCP) is an important antiviral option for selected patients with COVID-19. Materials and methods: In this open-label, phase 2, clinical trial conducted from 30 April 2020 till 10 May 2021 in the Republic of North Macedonia, we evaluated the efficacy and safety of CCP in hospitalized patients. Treatment w...

Acquired hemophilia A (AHA), a rare but life-threatening disorder, most commonly occurs in older people and during pregnancy. During the coronavirus disease 2019 (COVID-19) vaccination campaign, an unexpected number of newly diagnosed AHA patients have been identified in clinical practice that were temporally related to COVID-19 vaccination. We pre...

Transitional medicine is defined as the branch of medicine which deals with the transition from the pediatric to adult healthcare system [...]

Immunosuppressed patients have increased risk for morbidity and mortality from COVID-19 because they less frequently mount antibody responses to vaccines and often cannot tolerate small-molecule antivirals. The Omicron variant of concern of SARS-CoV-2 has progressively defeated anti-Spike mAbs authorized so far, paving the way to a return to COVID-...

COVID-19 convalescent plasma (CCP) has been the only specific anti-viral therapy against SARS-CoV-2 available for more than one year. Following the negative results from most randomized controlled trials on its efficacy in COVID-19 hospitalized patients and the availability of anti-spike monoclonal antibodies (mAbs), the use of CCP has subsequently...

Background During pandemics, early outpatient treatments reduce the health system burden. Randomized controlled trials (RCTs) in COVID-19 outpatients have tested therapeutic agents, but no RCT or systematic review has been conducted comparing the efficacy of the main outpatient treatment classes to each other. We aimed in this systematic review of...

Background: Novel SARS-CoV-2 variants of concern (VOC) Delta and Omicron are able to escape some monoclonal antibody therapies, making again COVID-19 convalescent plasma (CCP) a potential frontline treatment. Study design/methods: In this study, we investigated the kinetics of anti-SARS-CoV-2 neutralizing antibodies (nAbs) against VOCs Delta and...

Introduction: The ongoing COVID19 pandemic represents an unprecedented opportunity to test the feasibility of monoclonal antibody (mAb) therapies against respiratory viruses. While many hurdles were easily predictable (e.g. time to develop, scalability, and economic sustainability), mAb cocktails (i.e. the combination of two mAbs) were finally dep...

In Winter 2020, Italy, and in particular the Lombardy region, was the first country in the Western hemisphere to be hit by the COVID-19 pandemic. Plasma from individuals recovered from COVID-19 (COVID-19 convalescent plasma, CCP) was the first therapeutic tool adopted to counteract the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2). I...

In this study, we reported the results of the one-year experience (April 2020–April 2021) on the compassionate use of CCP in patients hospitalized for severe COVID-19 at the city hospital of Mantua, Italy.

Convalescent plasma (CP) recurs as a frontline treatment in epidemics because it is available as soon as there are survivors. The COVID-19 pandemic represented the first large-scale opportunity to shed light on the mechanisms of action, safety, and efficacy of CP using modern evidence-based medicine approaches. Studies ranging from observational ca...

During the ongoing COVID-19 pandemic, serology has suffered several manufacturing and budget bottlenecks. Kode technology exposes exogenous antigens on the surface of cells; in the case of red blood cells, modified cells are called kodecytes, making antibody–antigen reactions detectable by the old-fashioned hemagglutination test. In this commentary...

Ischemic stroke risk in atrial fibrillation differs from patient to patient, depending on numerous variables. Many attempts have been made to translate this difference into simple numbers and to compare it to the hemorrhagic risk of anticoagulation. Different clinical scores have been studied to define a clear strategy. One score, the CHA2DS2-VASc...

Background: Regular treatment to prevent bleeding and consequent joint deterioration (prophylaxis) is the standard of care for persons with severe hemophilia A, traditionally based on intravenous infusions of the deficient clotting FVIII concentrates (CFCs). In recent years, extended half-life (EHL) CFCs and the non-replacement agent emicizumab, s...

Background: Acquired haemophilia A (AHA) is a rare bleeding disorder due to autoantibodies to coagulation factor VIII that may be secondary to autoimmune diseases, cancer, drugs, pregnancy, infections, or be idiopathic. Recurrent bleeding, often severe, mostly in muscles and soft tissues, and isolated prolonged activated partial thromboplastin tim...

COVID-19 convalescent plasma (CCP) was among the few frontline therapies used to treat COVID-19. After large randomized controlled trials (RCTs) relying on late use in hospitalized patients and/or low antibody titres failed to meet their predefined primary endpoint, the infectious disease community reduced usage of CCP in favour of monoclonal antib...

Background: Although several therapeutic strategies have been investigated, the optimal treatment approach for patients with coronavirus disease (COVID-19) remains to be elucidated. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of polyclonal intravenous immunoglobulin (IVIG) therapy in COVID-19. Methods: A sy...

The novel SARS-CoV-2 Omicron variant of concern (VOCs), with its escape from unboosted vaccines and monoclonal antibodies, is demanding for a return to COVID19 convalescent plasma therapies. Lessons learnt from previous usage of CCP suggests focusing on outpatients and using high nAb-titer units in early disease stages. In this systematic analysis,...

Von Willebrand disease, the most common inherited bleeding disorder that affects both males and females, is due to quantitative or qualitative defects of the multimeric glycoprotein von Willebrand factor, which cause mucous membrane bleeding but also soft tissue bleeding owing to the secondary deficiency of factor VIII. The aim of treatment is to c...

The accelerated SARS-CoV-2 evolution under selective pressure by massive deployment of neutralizing antibody-based therapeutics is a concern with potentially severe implications for public health. We review here reports of documented immune escape after treatment with monoclonal antibodies and COVID-19-convalescent plasma (CCP). While the former is...

Viral clearance is likely the best way to assess the efficacy of antibody-based therapies. Although antibodies can mediate a variety of effects that include modulation of inflammation, the demonstration of viral clearance provides an accessible and measurable parameter that can be used to evaluate efficacy and determine dosing. Therefore, it is imp...

Accelerated SARS-CoV-2 evolution under selective pressure by massive deployment of neutralizing antibody-based therapeutics is a concern with potentially severe implications for public health. We review here reports of documented immune escape after treatment with monoclonal antibodies and COVID19 convalescent plasma (CCP). While the former is main...

Purpose: Objective of this study was to assess the association between testosterone (T) levels and biochemical markers in a cohort of female patients admitted for SARS-CoV-2 infection in a respiratory intensive care unit (RICU). Methods: A consecutive series of 17 women affected by SARSCoV-2 pneumonia and recovered in the RICU of the Hospital of...

Convalescent plasma (CP) recurs as a frontline treatment in epidemics because it is available as soon as there are survivors. The COVID-19 pandemic represented the first large-scale opportunity to shed light into mechanisms of action, safety and efficacy of convalescent plasma using modern evidence-based medicine approaches. Studies ranging from ob...

Convalescent plasma (CP) from patients recovered from COVID-19 is one of the most studied anti-viral therapies against SARS-COV-2 infection. The aim of this study is to summarize the evidence from the available systematic reviews on the efficacy and safety of CP in COVID-19 through an overview of the published systematic reviews (SRs). A systematic...

Cancer is associated with an increased incidence of both venous thromboembolism (VTE) and arterial thrombosis (cardiovascular events and ischemic stroke). Cancer-associated arterial thrombotic events are less well studied than VTE, but increasingly recognized, particularly in specific malignancies and in association with specific anticancer therapi...

COVID-19 convalescent plasma (CCP) is currently under investigation for both treatment and post-exposure prophylaxis. The active component of CCP mediating improved outcome is commonly reported as specific antibodies, particularly neutralizing antibodies, with clinical efficacy characterized according to the level or antibody affinity. In this revi...

safety of convalescent plasma for covid-19

Background: In Italy, as in many developed countries, a decline in blood component (BC) consumption, especially red blood cells (RBC), has been described, but not studied at a national level. We, therefore, designed a nationwide survey to determine the main features of BC recipients and obtain a picture of the clinical use of BC for the first time...

The differences of the epidemiology (incidence, case-to-death rate, mortality, etc) of COVID-19 between USA and Italy are analyzed taking into account the social, economic and sanitary characteristics of the two countries, both severely hit be the pandemic; and the causes of the so many different behaviors of the disease in each of them are discuss...

Objective Coagulation and inflammatory parameters are mildly altered in children with SARS-CoV-2 (COVID-19) infection, and laboratory evidence of a proinflammatory and procoagulant state has been noted in multisystem inflammatory syndrome in children (MIS-C). It is not clear whether this pediatric condition is related to thrombotic events. With thi...

Fibrinolysis is a complex enzymatic process aimed at dissolving blood clots to prevent vascular occlusions. The fibrinolytic system is composed of a number of cofactors that, by regulating fibrin degradation, maintain the hemostatic balance. A dysregulation of fibrinolysis is associated with various pathological processes that result, depending on...

The treatment of COVID-19 is particularly critical in pregnant women, considering the potential teratogenic effects of antiviral agents and the immune-depression related with pregnancy. The aim of this review is to systematically examine the current evidence on the clinical use of convalescent plasma during pregnancy. The electronic databases Medli...

A brief unexplained resolved event (BRUE) is an event observed in a child under 1 year of age in which the observer witnesses a sudden, brief but resolved episode of change in skin color, lack of breathing, weakness or poor responsiveness. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of coronavirus disease-201...

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 pract...