Genetic predictors for FVIII inhibitors formation in a Greek population of children with severe haemophilia A exclusively treated with recombinant concentrates

Letter

Author: Spanou, Kleopatra ; Dettoraki, Athina ; Constantinidou, Niki ; Economou, Marina ; Pergantou, Helen ; Kapsimali, Zoey ; Liatsis, Emmanouil ; Michalopoulou, Aikaterini

The aim of the current paper is to present our work regarding genetic factors that may influence inhibitor development in previously untreated patients (PUPs) with severe hemophilia A.Based on our first cohort published in 2013, 36 addnl. patients were prospectively included, and genetic pathogenic variants responsible for HA were identified in all children(i.e.Inv-22 or Inv-1 detection and sequencing).A total of 88 Greek PUP children with severe HA(FVIII levels < 1μ /dL), aged from 12 mo to 18 years, diagnosed between 1998 and 2020 and exclusively treated with recombinant FVIII products were enrolled in this study.Patients with out history of FVIII-Inh were treated with early ( n = 28) [i.e.initiation < 2 years of age] or late prophylaxis( n = 20) [i.e. initiation ≥ 2 years of age].Regarding HLA class I and II genotyping there was a confirmation and enhancement of our previous results,with increased frequencies of DRB1*01:01 ( p = .073, OR = 4.9), and DQB1*05:01 ( p = .009, OR = 5.7) in Group I as compared to Group II, whereas HLA- DRB1*11:04 was detected in lower frequency in Group I ( p = .03, OR = 0.3).Concerning cytokine genotyping, the previously shown predominance of FVIII-Inh development in homozygotes for the haplotypes ACC and ATA of IL-10 polymorphisms was not confirmed in this study, despite the higher number of patients.This study that in Greek children with HA the knowledge of the pathogenic variants and the presence or absence of HLA alleles DRB1*01:01, DQB1*05:01, DRB1*11:04 may constitute a predictive factor of FVIII-Inh development and could contribute to the therapeutic management of the disease.

01 Apr 2023·Current Opinion in Anaesthesiology

Alternative blood products in trauma

Review

Author: Moon, Tiffany S ; Jan, Kathryn M ; Mohapatra, Shweta

Purpose of reviewHemorrhage and trauma-induced coagulopathy cause significant morbidity and mortality in trauma patients. Although blood products are the cornerstone of resuscitation, these resources are scarce, necessitating alternatives. This review examines the use of alternative blood products in trauma as well as the literature supporting their use.Recent findingsThere is no single true blood product alternative. In recent years, there has been great progress in understanding trauma-induced pathophysiology and blood component alternatives. Products such as tranexamic acid and prothrombin complex concentrate have become well established and are frequently utilized in trauma centers, and many more alternatives are still undergoing further research and development.SummaryStabilization of hemorrhage and resuscitation is priority in trauma-induced coagulopathy treatment. Alternative products such as tranexamic acid, recombinant factors, prothrombic complex concentrate, fibrinogen concentrates, and desmopressin may also be considered based on the clinical context. Viscoelastic hemostatic assays such as rotational thromboelastometry and thromboelastography can help guide these efforts. Following initial stabilization, additional interventions such as iron supplementation, erythropoietin stimulating agents, and vitamin D may help with chronic sequela.

01 Aug 2022·Immunologic Research

Association of hepatitis B vaccine response to vitamin D supplementation and ultraviolet B (UVB) exposure during different time intervals in experimental animals

Article

Author: Maher, Al-Shaimaa ; Youssry, Sara ; Ghoneim, Hossam ; Shalaby, Thanaa

Abstract The implications of vitamin D deficiency on the immune system have become clearer in recent years, being associated with less immune response following HBV vaccine. We aimed to elucidate the effect of vitamin D supplementation and UVB exposure on short- and long-term performance of hepatitis B vaccine. Forty-five male rabbits were randomly divided into 3 groups that were immunized with recombinant HBsAg. The first group (group I) represented a negative control group, whereas group III rabbits were administered with commercially available 1,25 (OH)2 vitamin D as an alternative for UVB exposure in group II. Results showed that vitamin D concentrations were significantly higher in UVB exposed group compared to both negative control and vitamin D-supplemented groups during short- and long-time intervals. In addition, means of anti-HBsAg isotypes’ levels and anti-HBsAg IgG avidity% were significantly higher in negative control group compared to other groups during short- and long-time intervals. Moreover, vitamin D serum concentration was positively correlated with anti-HBsAg IgG level and avidity % in both negative control and vitamin D-supplemented groups, while it was negatively correlated with anti-HBsAg IgM level in negative control group. It can be concluded from the above results that UVB radiation may have both augmenting and suppressive effects and that circulating serum vitamin D concentration may have a positive association with premium immune modulation following HBV vaccination.

100 Deals associated with Recombinant erythropoietin(Cadila Pharmaceuticals Ltd.)

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Anemia	Phase 3	IN	Cadila Pharmaceuticals Ltd.	01 Dec 2006

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