0
selected
-
1.
Hemostatic therapy as a management strategy for acquired hemophilia: what does the future hold?
Franchini M, Schiavulli M, Liumbruno GM
Expert review of hematology. 2021;:1-8
Abstract
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.
-
2.
Enhanced Half-Life Recombinant Factor VIII Concentrates for Hemophilia A: Insights from Pivotal and Extension Studies
Di Minno MND, Di Minno A, Calcaterra I, Cimino E, Dell'Aquila F, Franchini M
Seminars in thrombosis and hemostasis. 2020
Abstract
The development of enhanced half-life recombinant factor VIII (EHL-rFVIII) concentrates has improved the management of hemophilia. Furthermore, the chance of maintaining higher trough levels has allowed higher protection from bleeding and, in turn, improved safely performance for certain types of physical activity. The first technology used to improve the pharmacokinetic profile of factor VIII (FVIII) was fusion with the Fc domain of immunoglobulin G. More recently, conjugation to hydrophilic polymers of polyethylene glycol (PEG) has been demonstrated to prolong plasma half-life of FVIII by means of a reduction in clearance of the molecule due to steric hindrance by PEG covering the protein. Here we report results of a systematic review of pivotal studies on EHL-rFVIII concentrates. Significant heterogeneity is observed among different studies on EHL-rFVIII concentrates, and direct comparisons should be avoided. The annualized bleeding rate has ranged between 1.2 and 1.9 in different EHL-rFVIII concentrates, with a progressive further decrease during extension phases of pivotal studies. Zero bleeding was reported by 40 to 45% of patients. Overall, the emerging treatment options seem to be highly effective and safe, associated with a decreased dosing interval to twice weekly or less, which reduces, but does not entirely eliminate, the burden of treatment. Overall, further information is needed from real-life settings to permit differentiation between EHL-FVIII concentrates and for individualizing treatment.
-
3.
Red blood cell alloimmunisation in transfusion-dependent thalassaemia: a systematic review
Franchini M, Forni GL, Marano G, Cruciani M, Mengoli C, Pinto V, De Franceschi L, Venturelli D, Casale M, Amerini M, et al
Blood transfusion = Trasfusione del sangue. 2019;17(1):4-15
-
-
-
Free full text
-
Editor's Choice
Abstract
BACKGROUND Chronic red blood cell transfusion is the first-line treatment for severe forms of thalassaemia. This therapy is, however, hampered by a number of adverse effects, including red blood cell alloimmunisation. The aim of this systematic review was to collect the current literature data on erythrocyte alloimmunisation. MATERIALS AND METHODS We performed a systematic search of the literature which identified 41 cohort studies involving 9,256 patients. RESULTS The prevalence of erythrocyte alloimmunisation was 11.4% (95% CI: 9.3-13.9%) with a higher rate of alloimmunisation against antigens of the Rh (52.4%) and Kell (25.6%) systems. Overall, alloantibodies against antigens belonging to the Rh and Kell systems accounted for 78% of the cases. A higher prevalence of red blood cell alloimmunisation was found in patients with thalassaemia intermedia compared to that among patients with thalassaemia major (15.5 vs 12.8%). DISCUSSION Matching transfusion-dependent thalassaemia patients and red blood cell units for Rh and Kell antigens should be able to reduce the risk of red blood cell alloimmunisation by about 80%.
PICO Summary
Population
Patients with transfusion-dependent thalassaemia (41 studies, n= 9,256).
Intervention
Systematic review on the prevalence of red blood cell alloimmunisation.
Comparison
Outcome
The prevalence of erythrocyte alloimmunisation was 11.4% with a higher rate of alloimmunisation against antigens of the Rh (52.4%) and Kell (25.6%) systems. Overall, alloantibodies against antigens belonging to the Rh and Kell systems accounted for 78% of the cases. A higher prevalence of red blood cell alloimmunisation was found in patients with thalassaemia intermedia compared to that among patients with thalassaemia major (15.5 vs. 12.8%).
-
4.
Assessing options for treating haemophilia with inhibitors
Farrugia A, Hermans C, Franchini M
Haemophilia. 2015;21((3)):307-9.
-
5.
Systematic review of the role of FVIII concentrates in inhibitor development in previously untreated patients with severe hemophilia a: a 2013 update
Franchini M, Coppola A, Rocino A, Santagostino E, Tagliaferri A, Zanon E, Morfini M, Italian Association of HemophiliaCenters Working Group
Seminars in Thrombosis & Hemostasis. 2013;39((7):):752-66.
Abstract
Nowadays, patients with hemophilia A receive a high standard of care; therefore, the most challenging complication of factor VIII (FVIII) replacement therapy has become the development of FVIII inhibitors, which render the concentrate infusion ineffective and expose patients to an increased risk of morbidity and mortality. Among environmental risk factors influencing inhibitor development, the type of FVIII products has always drawn the attention of investigators. Conflicting results are reported in the literature concerning rates of inhibitor development after either plasma-derived or recombinant FVIII concentrates. To help elucidate this controversial issue, we have performed a systematic review and meta-analysis of prospective studies evaluating the incidence of inhibitors in previously untreated patients with severe hemophilia A receiving plasma-derived or recombinant FVIII products. The quality of the studies was assessed using the Newcastle-Ottawa Scale (NOS), the STrenghtening the Reporting of OBservational studies in Epidemiology and an ad hoc quality score. Overall, 28 prospective studies, including 1,421 patients with hemophilia A, fulfilled our selection criteria and were included in the systematic review. No statistically significant differences were observed in the inhibitor incidence between plasma-derived and recombinant FVIII concentrates considering all (weighted means: 23%, 95% CI: 15-33% vs. 29%, 95% CI: 26-32%) and high titer (16%, 95% CI: 10-26% vs. 18%, 95% CI: 15-21%) inhibitors. Similarly, no significant differences were found in the inhibitor incidence among the different classes of recombinant products. In conclusion, the results of our meta-analysis show that the different types of FVIII products are not associated with different risks of inhibitor development. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.
-
6.
Thrombotic adverse events to coagulation factor concentrates for treatment of patients with haemophilia and von Willebrand disease: a systematic review of prospective studies
Coppola A, Franchini M, Makris M, Santagostino E, Di Minno G, Mannucci PM
Haemophilia. 2012;18((3):):e173-87.
Abstract
Thrombotic adverse events (AEs) after clotting factor concentrate administration are rare but the actual rate is unknown. A systematic review of prospective studies (1990-2011) reporting safety data of factor concentrates in patients with haemophilia A (HA), haemophilia B (HB) and von Willebrand disease (VWD) was conducted to identify the incidence and type of thrombotic AEs. In 71 studies (45 in HA, 15 HB, 11 VWD) enrolling 5528 patients treated with 27 different concentrates (20 plasma-derived, 7 recombinant), 20 thrombotic AEs (2 HA, 11 HB, 7 VWD) were reported, including two major venous thromboembolic episodes (both in VWD patients on prolonged replacement for surgery). The remaining thrombotic AEs were superficial thrombophlebitis, mostly occurring at infusion sites in surgical patients and/or during concentrate continuous infusion. The overall prevalence was 3.6 per 10(3) patients (3.6 per 10(4) for severe AEs) and 1.13 per 10(5) infusions, with higher figures in VWD than in haemophilia. Thrombotic AEs accounted for 1.9% of non-inhibitor-related AEs. Thrombosis-related complications occurred in 10.8% of patients with central venous access devices (CVADs) reported in six studies, the risk increasing with time of CVAD use. Data from prospective studies over the last 20 years suggest that the risk of thrombotic AEs from factor concentrate administration is small and mainly represented by superficial thrombophlebitis. These findings support the high degree of safety of products currently used for replacement treatment. Copyright 2012 Blackwell Publishing Ltd.
-
7.
Non-thrombotic-, non-inhibitor-associated adverse reactions to coagulation factor concentrates for treatment of patients with hemophilia and von Willebrand's disease: a systematic review of prospective studies
Franchini M, Makris M, Santagostino E, Coppola A, Mannucci PM
Haemophilia. 2012;18((3):):e164-72.
Abstract
In the last three decades there have been dramatic improvements in the availability and quality of treatment for people with inherited coagulation disorders. Indeed, the improvement of methods of purification and viral inactivation for plasma-derived coagulation factor concentrates first and then the development of products utilizing recombinant DNA technology have greatly improved the life expectancy of hemophiliacs, which has progressively become similar to that of males in the general population. Nowadays, the most frequent complication of factor replacement therapy for hemophilia is the development of inhibitors. However, no studies so far have systematically analysed the type and incidence of other adverse reactions following the administration of coagulation factor concentrates. The aim of this systematic review was to screen the published literature data to evaluate the types and frequencies of non-thrombotic-, non-inhibitor-associated adverse reactions to coagulation factor concentrates in patients with hemophilia A, hemophilia B and von Willebrand's disease. On behalf the European Haemophilia Safety Surveillance System (EUHASS), a systematic review of the prospective studies published in the last 20 years was performed using electronic databases and article references. Both severe and mild adverse events following infusion of coagulation factor concentrates are relatively rare in patients with inherited coagulation disorders; the most common events are of an allergic type. There are no differences in the rate of adverse events caused by plasma-derived or recombinant products. On the whole, these data confirm the high degree of safety of the products currently used for replacement therapy. Copyright 2012 Blackwell Publishing Ltd.
-
8.
Cumulative inhibitor incidence in previously untreated patients with severe hemophilia A treated with plasma-derived versus recombinant factor VIII concentrates: a critical systematic review
Franchini M, Tagliaferri A, Mengoli C, Cruciani M
Critical Reviews in Oncology-Hematology. 2012;81((1):):82-93.
Abstract
Inhibitor development represents currently the most serious and challenging complication of clotting factor replacement therapy. A number of studies have analyzed the impact of the type of factor VIII (FVIII) replacement therapy (plasma-derived versus recombinant concentrates) on inhibitor development in hemophilia A patients with conflicting results. In order to shed light on this controversial issue, we performed a systematic review and meta-analysis on the published prospective studies evaluating the incidence rate of inhibitors in previously untreated patients (PUPs) with severe hemophilia A. Data from a total of 800 patients enrolled in 25 prospective studies published between 1990 and 2007 were included in this review. The quality of the studies was evaluated using two different systems: the Newcastle-Ottawa Scale (NOS) and STrengthening the Reporting of OBservational studies in Epidemiology (STROBE). Overall, the inhibitor incidence rate did not differ significantly between recipients of plasma-derived and recombinant FVIII concentrates (weighted means: 21%; 95% CI, 14-30 versus 27%; 95% CI, 21-33). Similarly, high titer inhibitors did not differ significantly between patients treated with plasma-derived (weighted means: 14%; 95% CI, 8-25) or recombinant FVIII concentrates (weighted means: 16%; 95% CI, 13-20). Thus, the main conclusion of this systematic review performed using selective criteria is that the type of FVIII product (i.e. plasma-derived versus recombinant FVIII concentrates) does not seem to influence the inhibitor rate in PUPs with severe hemophilia A.
-
9.
The use of desmopressin in acquired haemophilia A: a systematic review
Franchini M, Lippi G
Blood Transfusion [Trasfusione Del Sangue]. 2011;9((4):):377-82.
-
10.
The use of desmopressin in congenital factor XI deficiency: a systematic review
Franchini M, Manzato F, Salvagno GL, Montagnana M, Lippi G
Annals of Hematology. 2009;88((10):):931-5.
Abstract
Factor XI (FXI) deficiency is a rare inherited coagulation disorder characterized by infrequent spontaneous bleeding, but increased risk of hemorrhagic complications especially after trauma or surgery. Treatment options for FXI-deficient patients include virus-inactivated fresh frozen plasma, plasma-derived FXI concentrates, and activated recombinant FVII. Inhibitors of fibrinolysis, such as tranexamic acid, and desmopressin (DDAVP) have also been used in these patients, especially in mild cases. The current knowledge on the use of the latter agent in this congenital bleeding condition is systematically reviewed here. Although limited, the available literature data suggest the potential role of DDAVP for either treatment of bleeding episodes or the prevention of postoperative bleeding in patients with milder FXI defects. However, these findings need to be supported by further trials on large population of patients.