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Hemophilia is a hemorrhagic disorder with a sex-linked inherited pattern, characterized by an inability to amplify coagulation due to a deficiency in coagulation factor VIII (hemophilia A or classic) or factor IX (hemophilia B). Sequencing of the genes involved in hemophilia has provided a description and record of the main mutations, as well as a...
Contexts in source publication
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... educational purposes, genetic defects in factor VIII can be divided into three groups: (1) genetic rearrangements, such as inversion of intron 22, which occurs in 45% of patients with severe hemophilia and is caused by homologous recombination between the 9.5 kb sequence and 2 extragenic homologous regions, and inversion of intron 1 that occurs in 1-2% of severe cases; (2) insertions or deletions of genetic sequences; and (3) single DNA base substitutions resulting in missense, nonsense, or frameshift mutations. Figures 1-3 describe the chromosomal abnormalities in HA depending on severity, showing predominance of point mutation, followed by deletions, duplications, and insertions. In HB patients, point mutations occur in most cases, followed by deletions, insertions, and duplications (Figs. ...
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... of CFC (age of first infusion, type, and intensity of treatment), and the infusion associated with warning or alarm signs. Peyvandi and Garagiola review summarizes the conclusions of the main publications regarding risk factors for the development of inhibitors in PwH A and highlighting type of FVIII product as the main environmental risk factor (Fig. 10) 51 ...
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... incidence for all types of inhibitors was 26.8% for pdFVIII and 44.5% with rFVIII and for high-responding inhibitors was 18.6% and 28.4%, respectively, documenting a significantly higher incidence of 87% for rFVIII. Some authors do not accept published results and have criticized methodological aspects on Figure 10. Environmental risk factors for the development of inhibitors in severe hemophilia A. Taken from Peyvandi and Garagiola, 2018 47 . ...
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... the intention of improving treatment of PwH, products with prolonged half-life and alternative mechanism of action have been designed to achieve adequate hemostasis and reduced immunogenicity 75 through: (1) CFC with extended half-life (EHL); (2) gene therapy; (3) specific antibodies that simulate the function of FVIII; and (4) molecules that modify the action of natural anticoagulants 76 . These are shown in figure 11 and briefly described below: ...
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... is similar to congenital hemophilia and depends on inhibitor levels in low (< 5 BU/mL) or high (> 5 BU/mL) titers. Figure 12 shows the diagnostic algorithm for AHA suggested by the Spanish group 88 . ...
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... in AHA exhibit a non-linear or type 2 FVIII inactivation pattern (as opposed to type 1 kinetics caused by characteristic alloantibodies in congenital hemophilia), causing a first phase of linear inactivation, followed by an equilibrium phase or "plateau" that allows residual detection of FVIII (Fig. 13). This mechanism causes residual FVIII levels to be unreliable for predicting the risk of bleeding. Therefore, even with relatively high levels of FVIII, the risk of bleeding is relevant if inhibitor titers are high in ...
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... 1 inhibition kinetics of FVIII activity ( Figure 13, black circles) is characteristic of alloantibodies in congenital hemophilia, it presents a linear pattern where a higher concentration of antibodies, greater neutralization capacity of FVIII. Type 2 kinetics ( Figure 13, triangles). ...
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... 1 inhibition kinetics of FVIII activity ( Figure 13, black circles) is characteristic of alloantibodies in congenital hemophilia, it presents a linear pattern where a higher concentration of antibodies, greater neutralization capacity of FVIII. Type 2 kinetics ( Figure 13, triangles). Characteristic of alloantibodies in congenital hemophilia, it presents a linear pattern where the greater the concentration of antibodies, the greater the neutralization of FVIII. ...
Context 9
... educational purposes, genetic defects in factor VIII can be divided into three groups: (1) genetic rearrangements, such as inversion of intron 22, which occurs in 45% of patients with severe hemophilia and is caused by homologous recombination between the 9.5 kb sequence and 2 extragenic homologous regions, and inversion of intron 1 that occurs in 1-2% of severe cases; (2) insertions or deletions of genetic sequences; and (3) single DNA base substitutions resulting in missense, nonsense, or frameshift mutations. Figures 1-3 describe the chromosomal abnormalities in HA depending on severity, showing predominance of point mutation, followed by deletions, duplications, and insertions. In HB patients, point mutations occur in most cases, followed by deletions, insertions, and duplications (Figs. ...
Context 10
... of CFC (age of first infusion, type, and intensity of treatment), and the infusion associated with warning or alarm signs. Peyvandi and Garagiola review summarizes the conclusions of the main publications regarding risk factors for the development of inhibitors in PwH A and highlighting type of FVIII product as the main environmental risk factor (Fig. 10) 51 ...
Context 11
... incidence for all types of inhibitors was 26.8% for pdFVIII and 44.5% with rFVIII and for high-responding inhibitors was 18.6% and 28.4%, respectively, documenting a significantly higher incidence of 87% for rFVIII. Some authors do not accept published results and have criticized methodological aspects on Figure 10. Environmental risk factors for the development of inhibitors in severe hemophilia A. Taken from Peyvandi and Garagiola, 2018 47 . ...
Context 12
... the intention of improving treatment of PwH, products with prolonged half-life and alternative mechanism of action have been designed to achieve adequate hemostasis and reduced immunogenicity 75 through: (1) CFC with extended half-life (EHL); (2) gene therapy; (3) specific antibodies that simulate the function of FVIII; and (4) molecules that modify the action of natural anticoagulants 76 . These are shown in figure 11 and briefly described below: ...
Context 13
... is similar to congenital hemophilia and depends on inhibitor levels in low (< 5 BU/mL) or high (> 5 BU/mL) titers. Figure 12 shows the diagnostic algorithm for AHA suggested by the Spanish group 88 . ...
Context 14
... in AHA exhibit a non-linear or type 2 FVIII inactivation pattern (as opposed to type 1 kinetics caused by characteristic alloantibodies in congenital hemophilia), causing a first phase of linear inactivation, followed by an equilibrium phase or "plateau" that allows residual detection of FVIII (Fig. 13). This mechanism causes residual FVIII levels to be unreliable for predicting the risk of bleeding. Therefore, even with relatively high levels of FVIII, the risk of bleeding is relevant if inhibitor titers are high in ...
Context 15
... 1 inhibition kinetics of FVIII activity ( Figure 13, black circles) is characteristic of alloantibodies in congenital hemophilia, it presents a linear pattern where a higher concentration of antibodies, greater neutralization capacity of FVIII. Type 2 kinetics ( Figure 13, triangles). ...
Context 16
... 1 inhibition kinetics of FVIII activity ( Figure 13, black circles) is characteristic of alloantibodies in congenital hemophilia, it presents a linear pattern where a higher concentration of antibodies, greater neutralization capacity of FVIII. Type 2 kinetics ( Figure 13, triangles). Characteristic of alloantibodies in congenital hemophilia, it presents a linear pattern where the greater the concentration of antibodies, the greater the neutralization of FVIII. ...
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Introduction: Haemophilia is a hereditary, chronic, and hemorrhagic disorder caused by a deficiency in coagulation factors. Long-term spontaneous bleeding of joints and soft tissues can seriously affect the quality of life of patients.
Objectives: The study aimed to assess the health-related quality of life of patients with haemophilia and associat...
Citations
Renal inflammatory myofibroblastic tumor (IMT) is an exceptionally uncommon occurrence. This report presented the first documented case of renal IMT coexisting with hemophilia A carrier status. A 52-year-old asymptomatic female was incidentally discovered to have a kidney mass during a routine computed tomography (CT) scan spanning a 5-month period. Ultrasonography and contrast-enhanced CT scan raised suspicion of a potential renal malignant tumor. Over 2 decades ago, the patient experienced significant bleeding during childbirth, and she possessed a 5-year history of rheumatoid arthritis. Following a radical surgical procedure, intravenous supplementation of factor VIII was administered during the perioperative period. Subsequent to strenuous defecation, the patient encountered hematuria. Continued coagulation factor supplementation led to alleviation of hematuria symptoms. The underlying causes and pathogenesis responsible for IMT remain unclear. IMT is often associated with rheumatoid arthritis, possibly suggesting a connection to its etiology. Surgical excision stands as the primary approach to treatment, with recurrence being an exceedingly rare event. In instances where hemophilia is a complicating factor, vigilant monitoring of coagulation function and appropriate coagulation factor supplementation is imperative.
A large group of countries constitute Latin American (LATAM) countries, where hemophilia care is as varied as the landscape of this region. To better understand the care provided to persons with bleeding disorders, especially hemophilia, a symposium was organized as part of the CLAHT Congress 2021 in Colombia to highlight the issues of hemophilia care and challenges faced by persons with hemophilia in four LATAM countries, Colombia, Peru, Argentina, and Mexico. A summary of the symposium is provided. Four clinicians highlighted the issues in their own country, the status, and the path forward to bring the standard of care to the international level in each of these countries. The geography of the country, the health infrastructure, and the resources available are obstacles in these countries to provide state‐of‐the‐art care to the bleeding disorder community. However, depending on the country, its infrastructure and the resources available, progress is being made to upend the care provided. Indeed, the care of persons with hemophilia has been greatly improved, including personalized prophylaxis. The information summarized here first emphasizes how the geography of a country and the different healthcare infrastructures play a major role in how care is offered. It also provides a path for other countries to evaluate these issues in their own realities. In parallel, these data provide hope to many developing countries; despite obstacles, strides can be made in the care of the bleeding disorder community.
