scholarly journals Hemofilia

Medicinus ◽  
2018 ◽  
Vol 6 (1) ◽  
Author(s):  
Michael Susanto ◽  
Andree Kurniawan
Keyword(s):  
Autosomal Recessive ◽  
Hemophilia A ◽  
Gene Mutations ◽  
Specific Inhibitor ◽  
Good Prognosis ◽  
Autoimmune Process ◽  
Clotting Factors ◽  
Hemophilic Arthropathy ◽  
Viii And Ix ◽  
Main Complication

Hemophilia A and B are X-linked recessive diseases that are caused by gene mutations in factors VIII adan IX of the blood clotting cycle. Hemophilia C is an autosomal recessive disease caused by a mutation in factor XI, and acquired hemophilia is largely is an autoimmune process. Hemophilia A and B cannot be distinguished clinically, and severe cases can cause bleeding in the joints and lead to chronic hemophilic arthropathy. The main treatment of hemophilia is infusions of factor VIII and IX, and DDAVP in less severe cases. The main complication that can rise from the use of clotting factors is the appearance of specific inhibitor antibodies that can neutralize the work of the factors. Severe cases of hemophilia A and B by itself carries a poor prognosis, but proper treatment throught the use of clotting factors can give a very good prognosis

Hemophilia therapeutics

2021 ◽  
Author(s):  
Moataz Dowaidar
Keyword(s):  
Gene Therapy ◽  
Bispecific Antibody ◽  
Hemophilia A ◽  
Blood Transfusions ◽  
Clotting Factors ◽  
Promising Alternative ◽  
Viii And Ix ◽  
The 1950S ◽  
The Cost

Hemophilia is a genetic hemorrhagic condition marked by uncontrollable and persistent bleeding following surgery or trauma. Hemophilia A is the more common of the two, affecting 1:5000 newborn males in the population. Injecting factor replacement treatments are the most common therapy for hemophilia. The drugs that replaced the clotting factors VIII and IX were developed in the 1950s and 60s. They have been used to treat blood transfusions since the mid-1970s. The development of a humanized bispecific antibody (emicizumab; ACE910) that binds to FIX and FX and replicates the action of FVIII was a key breakthrough in hemophilia therapy. The cost of maintaining this antibody is high, and the feasibility of developing antibodies against the reactant has yet to be determined. Gene therapy is a promising alternative.

Hemophilia

2016 ◽  
Author(s):  
Aric Parnes ◽  
Lisa Rotenstein
Keyword(s):  
Hemophilia A ◽  
Clinical Manifestations ◽  
Factor Ix ◽  
Hemophilia B ◽  
Bleeding Disorders ◽  
Clotting Factors ◽  
Acute Bleeding ◽  
Clotting Cascade ◽  
Viii And Ix

Hemophilia is a family of rare bleeding disorders characterized by deficiency of clotting factors. Hemophilia A is an inherited deficiency of factor VIII, whereas hemophilia B (Christmas disease) represents a deficiency of factor IX. Both hemophilia A and B are X-linked diseases, with hemophilia A accounting for 80 to 85% of cases and hemophilia B 15 to 20%. Although hemophilia has historically referred to deficiencies of factors VIII and IX, it is important to recognize that similar bleeding disorders can occur with other missing clotting factors, although this is far more rare. This review covers the definition, history, epidemiology, biology/genetics, clinical manifestations, diagnosis, differential diagnosis, treatment, complications, measures of quality of care, and prognosis of hemophilia, as well as future directions. Figures show the clotting cascade, the genetic makeup of severe hemophilia A, an algorithm for diagnosing hemophilia, and hemophilic arthropathy in a patient’s knees. Tables list severity in hemophilia A and B, treatment of acute bleeding in hemophilia A and B, frequency of dosing in acute bleeding, and treatment of acute bleeding with inhibitors. This review contains 4 highly rendered figures, 4 tables, and 59 references.

Hemophilia: An Updated Review

1995 ◽  
Vol 16 (8) ◽  
pp. 290-298
Author(s):  
Beverly Bell ◽  
David Canty ◽  
Michelle Audet
Keyword(s):  
Soft Tissues ◽  
Hemophilia A ◽  
Genetic Disorder ◽  
Von Willebrand Disease ◽  
Clotting Factors ◽  
Genetic Transmission ◽  
Viii And Ix ◽  
Recessive Disorders ◽  
Recessive Defect ◽  
Von Willebrand

Introduction Hemophilia is a genetic disorder that results in either an inactive or inadequate supply of a plasma protein needed for normal blood clotting. The two most common forms are hemophilia A and B, caused by a defect or deficiency in clotting factors VIII and IX, respectively. Both types are X-linked recessive disorders characterized by prolonged bleeding and hemorrhages, typically into joints and soft tissues. Hemophilia C is an autosomal recessive defect that results in a deficiency of factor XI. Marked by bleeding in mucous membranes, hemophilia C exhibits a somewhat different clinical pattern of hemorrhaging than hemophilia A or B but similar to that in von Willebrand disease. This review will focus on hemophilia A and B. Hemophilia has served as a model for the treatment of chronic illness through the comprehensive approach to care. If a child who has hemophilia is managed appropriately with early factor replacement therapy and attempts to avoid the long-term consequences of bleeding, the prospects for a long, full, and healthy life are very good. Epidemiology/Genetic Transmission The incidence of hemophilia A and B is about 15 to 20 per 100 000 males born worldwide and occurs in all races and socioeconomic groups. Hemophilia A, also known as "classical hemophilia," accounts for about 80% of cases of hemophilia, occurs in one of 10 000 male births, and affects about 17 500 individuals in North America.

Autosomal recessive congenital hereditary corneal dystrophy associated with a novel SLC4A11 mutation in two consanguineous Tunisian families

2021 ◽  
pp. bjophthalmol-2020-318204
Author(s):  
Zohra Chibani ◽  
Imen Zone Abid ◽  
Peter Söderkvist ◽  
Jamel Feki ◽  
Mounira Hmani Aifa
Keyword(s):  
Autosomal Recessive ◽  
Corneal Transplantation ◽  
Gene Mutations ◽  
In Silico Analysis ◽  
Corneal Dystrophy ◽  
Solute Carrier Family ◽  
Transporter Protein ◽  
Bicarbonate Transporter ◽  
Corneal Clouding ◽  
Solute Carrier

BackgroundAutosomal recessive congenital hereditary corneal dystrophy (CHED) is a rare isolated developmental anomaly of the eye characterised by diffuse bilateral corneal clouding that may lead to visual impairment requiring corneal transplantation. CHED is known to be caused by mutations in the solute carrier family 4 member 11 (SLC4A11) gene which encodes a membrane transporter protein (sodium bicarbonate transporter-like solute carrier family 4 member 11).MethodsTo identify SLC4A11 gene mutations associated with CHED (OMIM: #217700), genomic DNA was extracted from whole blood and sequenced for all exons and intron-exon boundaries in two large Tunisian families.ResultsA novel deletion SLC4A11 mutation (p. Leu479del; c.1434_1436del) is responsible for CHED in both analysed families. This non-frameshift mutation was found in a homozygous state in affected members and heterozygous in non-affected members. In silico analysis largely support the pathogenicity of this alteration that may leads to stromal oedema by disrupting the osmolarity balance. Being localised to a region of alpha-helical secondary structure, Leu479 deletion may induce protein-compromising structural rearrangements.ConclusionTo the best of our knowledge, this is the first clinical and genetic study exploring CHED in Tunisia. The present work also expands the list of pathogenic genotypes in SLC4A11 gene and its associated clinical diagnosis giving more insights into genotype–phenotype correlations.

The using of modular system (mega prosthesis) for hip, femur, and knee replacement in patient with severe hemophilia A.

2020 ◽  
Author(s):  
Г.В. Мишин ◽  
В.Ю. Зоренко ◽  
Е.Е. Карпов ◽  
Н.В. Садыкова ◽  
М.С. Сампиев ◽  
...  
Keyword(s):  
World Literature ◽  
Hemophilia A ◽  
Total Joint Replacement ◽  
Treatment Method ◽  
Modular System ◽  
Severe Hemophilia ◽  
Hemophilic Arthropathy ◽  
Hip Replacements ◽  
Significant Length ◽  
Late Stages

Представлен случай использования модульной эндосистемы (мега протеза), протезирующей коленный сустав, бедренную кость и тазобедренный сустав у больного с тяжелой формой гемофилии А. На поздних стадиях гемофилической артропатии оптимальным методом лечения является тотальное эндопротезирование пораженного сустава. Проведение таких операций у больных гемофилией возможно только на фоне заместительной гемостатической терапии. В большинстве случаев прибегают к использованию первичных эндопротезов, позволяющих максимально сохранить собственную костную ткань пациента. Десятилетняя выживаемость первичных эндопротезов коленного и тазобедренного суставов у пациентов с гемофилией составляет около 80%. В редких случаях использование первичных эндопротезов затруднено или невозможно в связи с недостаточным массивом костной ткани: асептическая нестабильность эндопротеза, перипротезный перелом, сильная деформация эпифизов бедренной и большеберцовой костей, гемофилическая псевдоопухоль бедренных и большеберцовых костей и др. В таких случаях требуется замещение дефекта костной ткани на значительном протяжении. Модульные эндопротезы (мега протезы, модульные эндосистемы) позволяют замещать частично или полностью диафизы костей. В мировой литературе описаны единичные случаи использования модульных эндосистем у больных гемофилией. The article presents a case of using a modular endosystem (mega prosthesis) that prosthetics the knee joint, femur and hip joint in a patient with severe hemophilia A. In the late stages of hemophilic arthropathy, the optimal treatment method is total joint replacement. Such operations in patients with hemophilia can only be performed with hemostatic replacement therapy. In most cases, primary endoprostheses are used to preserve the patient’s own bone tissue as much as possible. The 10-year survival rate of primary knee and hip replacements in patients with hemophilia is about 80%. In rare cases, the use of primary endoprostheses is difficult or impossible due to insufficient bone mass: aseptic loosening of the endoprosthesis, periprosthetic fracture, severe deformation of the femoral and tibial epiphyses, hemophilic pseudotumor of the femoral and tibial bones, etc. In such cases, it is necessary to replace the bone defect for a significant length. Modular endoprostheses (mega prostheses, modular endosystems) allow you to replace partially or completely the bone diaphysis. The world literature describes isolated cases of using modular endosystems in patients with hemophilia. It is interesting to share the experience of using a modular endosystem for hip, femur, and knee prosthetics in a patient with severe hemophilia A.

scholarly journals Coagulation Disturbances in Patients with Argininemia

2018 ◽  
Vol 140 (4) ◽  
pp. 221-225 ◽  
Author(s):  
Ertugrul Kiykim ◽  
Tanyel Zubarioglu ◽  
Mehmet Serif Cansever ◽  
Tiraje Celkan ◽  
Johannes Häberle ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Urea Cycle ◽  
International Normalized Ratio ◽  
Factor Ix ◽  
Factor Vii ◽  
Clotting Factor ◽  
Clotting Factors ◽  
Hepatic Involvement ◽  
Prolonged Aptt ◽  
Liver Transaminases

Background: Argininemia is an autosomal recessive urea cycle disorder (UCD). Unlike other UCD, hyperammonemia is rarely seen. Patients usually present in childhood with neurological symptoms. Uncommon presentations like neonatal cholestasis or cirrhosis have been reported. Although transient elevations of liver transaminases and coagulopathy have been reported during hyperammonemia episodes, a permanent coagulopathy has never been reported. Methods: In this retrospective study, coagulation disturbances are examined in 6 argininemia patients. All of the patients were routinely followed up for hepatic involvement due to argininemia. Laboratory results, including liver transaminases, albumin, prothrombin time (PT), international normalized ratio (INR), activated partial thromboplastin time (aPTT), and clotting factor levels, were assessed in all of the patients. Results: All of the patients had a prolonged PT and an increased INR, while none of the patients had a prolonged aPTT. Five patients had slightly elevated liver transaminases. A liver biopsy was performed in 1 patient but neither cirrhosis nor cholestasis was documented. Five of the 6 patients had low factor VII and factor IX levels, while other clotting factors were normal. Conclusions: Argininemia patients should be investigated for coagulation disorders even if there is no apparent liver dysfunction or major bleeding symptoms.

scholarly journals Therapeutic Potential of α-Synuclein Evolvability for Autosomal Recessive Parkinson’s Disease

2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Jianshe Wei ◽  
Gilbert Ho ◽  
Yoshiki Takamatsu ◽  
Eliezer Masliah ◽  
Makoto Hashimoto
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Therapeutic Potential ◽  
Gene Mutations ◽  
Mitochondrial Alteration ◽  
Rational Therapy ◽  
Ubiquitin Proteasome ◽  
Dominant Genes

The majority of Parkinson’s disease (PD) is sporadic in elderly and is characterized by α-synuclein (αS) aggregation and other alterations involving mitochondria, ubiquitin-proteasome, and autophagy. The remaining are familial PD associated with gene mutations of either autosomal dominant or recessive inheritances. However, the former ones are similar to sporadic PD, and the latter ones are accompanied by impaired mitophagy during the reproductive stage. Since no radical therapies are available for PD, the objective of this paper is to discuss a mechanistic role for amyloidogenic evolvability, a putative physiological function of αS, among PD subtypes, and the potential relevance to therapy. Presumably, αS evolvability might benefit familial PD due to autosomal dominant genes and also sporadic PD during reproduction, which may manifest as neurodegenerative diseases through antagonistic pleiotropy mechanism in aging. Indeed, there are some reports describing that αS prevents apoptosis and mitochondrial alteration under the oxidative stress conditions, notwithstanding myriads of papers on the neuropathology of αS. Importantly, β-synuclein (βS), the nonamyloidogenic homologue of αS, might buffer against evolvability of αS protofibrils associated with neurotoxicity. Finally, it is intriguing to predict that increased αS evolvability through suppression of βS expression might protect against autosomal recessive PD. Collectively, further studies are warranted to better understand αS evolvability in PD pathogenesis, leading to rational therapy development.

scholarly journals The Relationship between Hemophilia A Severity and Hemophilia Activities List

2021 ◽  
Author(s):  
Faizal Muhammad
Keyword(s):  
High Risk ◽  
Hemophilia A ◽  
Bleeding Event ◽  
Clinical Manifestations ◽  
Self Care ◽  
Daily Activities ◽  
Clotting Factors ◽  
Household Tasks ◽  
The Relationship ◽  
Lying Down

Hemophilia is a hereditary bleeding disorder due to clotting factors deficiency. Its clinical manifestations including spontaneous and recurrent joints and muscle bleeding. Thus, hemophilia can limit the patients’ daily activities. This study aims to assess the relationship of hemophilia A severity on daily activities and the Hemophilia Activities List (HAL). The research subjects were thirty men with hemophilia A aged 18 years old or older who went to the Hematology-Oncology Clinic of Dr. Moewardi General Hospital during February - September 2020. Standardized seven aspects of routine activities with high-risk for bleeding event were assessed using the HAL questionnaire including lying down/ sitting/ kneeling/ standing, functions of the legs, functions of the arms, use of transportation, self-care, household tasks, leisure activities and sports. Based on the frequency of activity difficulty due to hemophilia A, each average score of HAL aspect was categorized into never (100% - 76%); rarely (75% - 51%), sometimes (50% - 26%), and impossible (25% - 0%). Based on Factor VIII level, hemophilia A severity was categorized into mild, moderate, and severe. Spearman’s correlation test was used for statistical analysis. The result showed significant correlation (p < 0.05) on five aspects, including lying down/ sitting/ kneeling/ standing, functions of the legs, use of transportation, self-care, and household tasks. The aspects of arms functions and leisure sports activities were not significantly correlated (p > 0.05). Nevertheless, these two aspects showed positive sufficient (r = 0.330) and weak (r = 0.177) correlation respectively. Joint and muscle bleeding are an undeniable pathological event in hemophilia patients. Hemophilia A severity positively correlates with the bleeding event frequency in the essential routine musculoskeletal activities. According to the HAL questionnaire, it needs to be a concern for clinicians and patient education to prevent bleeding in any high-risk musculoskeletal activities.

Sign in / Sign up

Export Citation Format

Share Document