Moderate haemophilia A: Recommendations from a Spanish panel of experts.

Introduction: Diagnosing moderate haemophilia A (MHA) solely based on deficient FVIII protein levels limits its optimal management and delays the initiation of prophylaxis. Updating protocols and incorporating new variables into its diagnosis could prevent underestimating disease severity, avoiding early arthropathies and impairing patients' quality of life.

Aim: To propose recommendations to improve the comprehensive management of people with MHA.

Value contribution of etranacogene dezaparvovec gene therapy in moderately severe and severe haemophilia B through multi-criteria decision analysis.

Introduction: The value of gene therapies for haemophilia needs to be assessed holistically.

Aim: To determine the value of etranacogene dezaparvovec (ED) compared to current extended half-life (EHL) recombinant factors (rFIX), using multi-criteria decision analysis (MCDA).

Method: MCDA EVIDEM methodology adapted to orphan drugs was used, with nine quantitative criteria and four contextual criteria.

A post hoc comparative real-world analysis of HEAD-US score for joint health assessment of patients with severe haemophilia A and B in Spain.

Aim: Joint damage due to haemarthrosis can be effectively monitored with point-of care ultrasound using the Haemophilia Early Arthropathy Detection with US (HEAD-US) scoring system. A post hoc comparative analysis of the joint status of patients with severe haemophilia A (HA) or B (HB) was performed.

Methods: The databases of two observational, cross-sectional studies that recruited patients with HA or HB from 12 Spanish centres were analysed to compare the status of the elbows, knees and ankles in patients with severe disease according to treatment modality.

The Limitations and Unmet Needs of the Five Cornerstones to Guarantee Lifelong Optimization of Prophylaxis in Hemophilia Patients.

Prophylaxis to prevent bleeding is highly recommended for hemophilia patients. The development of new drugs and tools for modeling personalized prophylaxis provides the means for people with hemophilia to lead active lives with a quality of life comparable to that of nonhemophilic individuals. The choice of regimens must be made on a highly individual basis.

Applicability of the European Society of Cardiology Guidelines on the management of acute coronary syndromes to older people with haemophilia A - A modified Delphi consensus by the ADVANCE Working Group.

Introduction: As people with haemophilia (PWH) receive better treatment and live longer they are more likely to encounter cardiovascular disease (CVD) and other comorbidities. ESC guidelines for the acute management of patients presenting with acute coronary syndrome (ACS) are based on the non-haemophilia population.

Aim: To review the guidelines and propose relevant adaptations for PWHA without inhibitors who are treated with prophylaxis and present with ACS.

Activated prothrombin complex concentrate to treat bleeding events in acquired hemophilia A: BAHAS study.

Objective: Activated prothrombin complex concentrate (aPCC) is a bypassing agent indicated to treat bleeds in patients with acquired hemophilia A (AHA). Nevertheless, its efficacy and safety in the real-world setting have not often been addressed.

Methods: We report the experience of Spanish reference centers for coagulation disorders and from acquired hemophilia Spanish Registry (AHASR) from August 2012 to February 2021.

Clinical Efficacy and Safety of Fanhdi, a Plasma-Derived VWF/Factor VIII Concentrate, in von Willebrand Disease in Spain: A Retrospective Study.

Objective: To evaluate the efficacy and safety of a plasma-derived factor VIII concentrate containing von Willebrand Factor (pdVWF/FVIII) in standard clinical practice in von Willebrand Disease (VWD) patients.

Methods: A retrospective, multicentric, observational study of VWD patients treated with Fanhdi, a pdVWF/FVIII concentrate, from January 2011 to December 2017 was conducted at 14 centers in Spain. Efficacy and safety were evaluated for acute bleeding episodes, for prevention of bleeding in surgeries, and for secondary long-term prophylaxis.

Management of acquired hemophilia A: results from the Spanish registry.

The Spanish Acquired Hemophilia A (AHA) Registry is intended to update the status of AHA in Spain. One hundred and fifty-four patients were included and retrospectively followed for a median of 12 months. Patients were predominantly male (56.

New Inhibitors in the Ageing Population: A Retrospective, Observational, Cohort Study of New Inhibitors in Older People with Hemophilia.

Introduction: A second peak of inhibitors has been reported in patients with severe hemophilia A (HA) aged >50 years in the United Kingdom. The reason for this suggested breakdown of tolerance in the aging population is unclear, as is the potential impact of regular exposure to the deficient factor by prophylaxis at higher age. No data on hemophilia B (HB) have ever been reported.

Acute abdomen in the immunocompromised patient: WSES, SIS-E, WSIS, AAST, and GAIS guidelines.

Immunocompromised patients are a heterogeneous and diffuse category frequently presenting to the emergency department with acute surgical diseases. Diagnosis and treatment in immunocompromised patients are often complex and must be multidisciplinary. Misdiagnosis of an acute surgical disease may be followed by increased morbidity and mortality.

Matching-Adjusted Indirect Comparison of Efficacy and Consumption of rVIII-SingleChain Versus Two Recombinant FVIII Products Used for Prophylactic Treatment of Adults/Adolescents with Severe Haemophilia A.

Introduction: Given the relatively small number of patients with haemophilia A, head-to-head comparisons between recombinant FVIII (rFVIII) products are difficult to conduct. This study compared the efficacy and consumption of rVIII-SingleChain (lonoctocog alfa, AFSTYLA) with rAHF-PFM (octocog alfa, Advate) and rFVIIIFc (efmoroctocog alfa, Elocta), for the prophylaxis and treatment of bleeding episodes in previously treated adolescents/adults with severe haemophilia A, through a matching-adjusted indirect comparison (MAIC).

Methods: A systematic literature review identified published clinical trials for rAHF-PFM and rFVIIIFc.

Expert opinion paper on the treatment of hemophilia B with albutrepenonacog alfa.

Current guidelines recommend prophylactic treatment of hemophilia B with the missing coagulation factor IX, either with standard half-life or extended half-life products. Extended half-life products have half-lives three to six times longer than the former, allowing a reduction in the number of weekly injections and therefore, potentially impacting on treatment adherence and quality of life. Albutrepenonacog alfa is an extended half-life fusion protein of coagulation factor IX with recombinant human albumin, indicated for both on-demand and prophylactic treatment for bleeding in patients with hemophilia B of all ages.

Costs of the management of hemophilia A with inhibitors in Spain.

Introduction: Emicizumab is a first-in-class monoclonal antibody, recently authorized for the treatment of hemophilia A with inhibitors. This study aims to estimate the direct and indirect costs of the management of hemophilia A with inhibitors, in adult and pediatric patients, including the prophylaxis with emicizumab.

Methods: We calculated the costs of the on-demand and prophylactic treatments with bypassing agents (activated prothrombin complex concentrate and recombinant activated factor VII) and the emicizumab prophylaxis, from the societal perspective, over 1 year.

Ultrasound evaluation of joint damage and disease activity in adult patients with severe haemophilia A using the HEAD-US system.

Introduction: The Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) system and scoring scale has proven to be an accurate and time-efficient imaging method for identifying joint damage in patients with haemophilia.

Aim: Observational, multicentre, cross-sectional study conducted in 8 centres in Spain that assessed the joint status of adult patients with severe haemophilia A (SHA) using HEAD-US.

Methods: Joint status of the elbow, knee and ankle was evaluated in adults with SHA receiving on-demand (OD) treatment, or primary (PP), secondary (SP), tertiary (TP) or intermittent (IP) prophylaxis.

Health-related quality of life and health status in adolescent and adult people with haemophilia A without factor VIII inhibitors-A non-interventional study.

Introduction: Real-world data on health-related outcomes in persons with haemophilia A (PwHA) can provide useful information for improving patient care. The global, non-interventional study (NIS; NCT02476942) prospectively collected high-quality data in PwHA, including those without factor VIII (FVIII) inhibitors treated according to local routine clinical practice.

Aim: To report health-related quality of life (HRQoL) and health status of adult/adolescent PwHA without FVIII inhibitors.

Common Genetic Variants in ABO and CLEC4M Modulate the Pharmacokinetics of Recombinant FVIII in Severe Hemophilia A Patients.

The pharmacokinetic (PK) response of severe hemophilia A (HA) patients to infused factor VIII (FVIII) shows substantial variability. Several environmental and genetic factors are associated with changes in FVIII plasma levels and infused FVIII PK. Based on the hypothesis that factors influencing endogenous FVIII can affect FVIII PK, the contribution of single-nucleotide variants (SNVs) in candidate genes was investigated in 51 severe HA patients.

Hydroxyurea can be used in children with sickle cell disease and cerebral vasculopathy for the prevention of chronic complications? A meta-analysis.

We conducted a systematic review for evaluating the impact of hydroxyurea and chronic blood transfusion in children with sickle cell disease (SCD). A search was done in four databases from inception to 2017. Trials enrolling pediatric patients with SCD and cerebral vasculopathy with or without previous episode of stroke and that reported outcomes of occurrence of stroke and other events were included.

Joint status in Spanish haemophilia B patients assessed using the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) score.

Aim: The use of musculoskeletal ultrasound (MSK-US) following protocols for haemophilic arthropathy and the Haemophilia Early Arthropathy Detection with Ultrasound (HEAD-US) score can help standardize monitoring in haemophilia. This study evaluated the joint status (elbows, knees and ankles) of patients with haemophilia B (HB) in Spain using MSK-US and the HEAD-US score.

Methods: Haemophilia B patients ≥14 years old were included in this observational, multicentre, cross-sectional study, regardless of their clinical condition, HB severity and treatment received.

Presence of acute and chronic renal failure in patients with paroxysmal nocturnal hemoglobinuria: results of a retrospective analysis from the Spanish PNH Registry.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare, life-threatening blood disease. With the advent of eculizumab treatment, renal function has substantially improved, although no data from real-world clinical practice are available. An observational, retrospective, multicenter study was conducted in Spain on clinical data obtained from outpatient visits of patients with PNH (Spanish PNH Registry) who had experienced acute (ARF) or chronic (CRF) renal failure.

Acquired haemophilia: Epidemiology, clinical presentation, diagnosis and treatment.

The development of circulating autoantibodies able to inhibit some coagulation proteins induces severe or even life-threatening bleeding. This disorder is called acquired haemophilia. This is a rare disease, although its impact may be underestimated because of the lack of records, the lack of knowledge by many specialists, the complexity of the laboratory diagnosis and, finally, because of the fulminant clinical presentation that often precludes diagnosis.

[Spanish consensus statement for diagnosis and treatment of paroxysmal nocturnal haemoglobinuria].

Paroxysmal nocturnal haemoglobinuria (PNH) is an acquired clonal disorder of the haematopoietic progenitor cells due to a somatic mutation in theX-linked phosphatidylinositol glycan class A gene. The disease is characterized by intravascular haemolytic anaemia, propensity to thromboembolic events and bone marrow failure. Other direct complications of haemolysis include dysphagia, erectile dysfunction, abdominal pain, asthenia and chronic renal failure (65% of patients).

Patients with type 1 Gaucher disease in Spain: A cross-sectional evaluation of health status.

A multicentre, cross-sectional epidemiological survey was conducted to describe the health status of patients with type 1 Gaucher disease (GD1) in Spain. Patient data were collected retrospectively from clinical records. Therapeutic goals for seven clinical parameters were chosen as primary outcome measures.