scholarly journals Tratamiento moderno de la hemofilia y el desarrollo de terapias innovadoras

2021 ◽  
Vol 62 (1) ◽  
pp. 73-95
Author(s):  
Arlette Ruiz-Sáez
Keyword(s):  
Factor Viii ◽  
Factor Ix ◽  
Terapia Génica ◽  
Hemofilia A

La hemofilia es una enfermedad hemorrágica resultante de mutaciones en el gen del factor VIII (F8) de la coagulación en el caso de la hemofilia A o en el gen del factor IX (F9) en el caso de la hemofilia B, siendo ambas formas indistinguibles clínicamente. El fenotipo clínico usualmente refleja la actividad del factor en plasma y la principal complicación del tratamiento es el desarrollo de aloanticuerpos neutralizantes. El tratamiento moderno de la hemofilia comienza a despuntarse en la década de 1970 con la disponibilidad de concentrados de factores de la coagulación de origen plasmático, el inicio de programas de profilaxis y el manejo multidisciplinario de la condición. Posteriormente, la producción de concentrados seguros, debidamente inactivados o de origen recombinante, facilitó la individualización de la terapia y el desarrollo de los agentes baipás mejoró el tratamiento de pacientes con inhibidores. Para todas esas opciones, la gran limitante ha sido la necesidad de frecuentes infusiones endovenosas por un tiempo indefinido. La biotecnología ha permitido el desarrollo de concentrados de factor VIII y IX de vida media plasmática extendida y a la producción de terapias novedosas, diferentes a la terapia de remplazo, que mejoran la coagulación o inhiben las vías anticoagulantes naturales. Por último, los progresos en la terapia génica como potencial cura de la condición generan grandes expectativas. Si bien estos avances ofrecen alternativas terapéuticas para pacientes con o sin inhibidores, aún están por definirse aspectos relacionados a sus indicaciones, monitorización y seguridad a corto y largo plazo.

scholarly journals Hematoma espontáneo del musculo psoas-ilíaco en pacientes con Hemofilia A: presentación de un caso y revisión de la literatura

2014 ◽  
Vol 6 (1) ◽  
pp. 73
Author(s):  
Jorge Luis Gutiérrez Cuesta ◽  
Diana Borré Naranjo ◽  
Mauricio Orozco Ugarriza
Keyword(s):  
Factor Viii ◽  
Factor Ix ◽  
Factor Xi ◽  
Hemofilia A

La Hemofilia es definida como la deficiencia genética de proteínas plasmáticas denominadas factores de la coagulación e implicadas en la hemostasia. Según el tipo de factor de coagulación alterado se clasifica la enfermedad en 3 tipos: Hemofilia A (Factor VIII), Hemofilia B (Factor IX) y Hemofilia C (Factor XI). Las manifestaciones clínicas de la Hemofilia A y B son similares y se diferencian en relación al grado de deficiencia del factor de la coagulación. Las manifestaciones clínicas de la Hemofilia A se caracterizan por sangrados periódicos, particularmente a nivel de las articulaciones (Hemartrosis) y músculos (Hematomas). Los episodios de hematomas musculares ocupan el segundo lugar después de la hemartrosis, la hemorragia en el musculo psoas-ilíaco es una compilación potencialmente grave y puede resultar en manifestaciones clínicas variadas.A continuación se describe el caso clínico de un paciente de sexo masculino con Hemofilia A leve que presentó hematoma espontáneo del músculo psoas-iliaco y se analizan los tiempos de tromboplastina activado, niveles de factor VIII, otros datos de ayuda diagnóstica y finamente, se hace una revisión de la literatura.

scholarly journals HAEMOPHILIA

2013 ◽  
Vol 4 (3) ◽  
Author(s):  
Diana S Purwanto
Keyword(s):  
Factor Viii ◽  
Prothrombin Time ◽  
Partial Thromboplastin Time ◽  
Activated Partial Thromboplastin Time ◽  
Factor Ix ◽  
Haemophilia A ◽  
Clotting Time ◽  
Serial Test ◽  
Faktor Viii ◽  
Hemofilia A

Abstrak: Hemofilia adalah kelainan perdarahan kongenital yang disebabkan oleh kekurangan faktor VIII (faktor antihemofilik) yang terkait dengan Hemofilia A, atau faktor IX (faktor Christmas) yang terkait dengan Hemofilia B. Kedua hemophilia diturunkan secara X-linked resesif, dan umumnya ditemukan pada laki-laki. Kami melaporkan kasus seorang anak berusia 4 tahun dengan riwayat memar, pendarahan berlebihan, disertai pembengkakan sendi yang nyeri dan hematoma otot, yang dicurigai mengidap hemofilia. Serial tes koagulasi dilakukan dengan hasil: jumlah trombosit, waktu perdarahan, prothrombin time (PT), thrombin clotting time (TCT), dan fibrinogen normal, sedangkan activated partial thromboplastin time (APTT) memanjang. Mixing studies dikoreksi ketika plasma normal dan adsorbed plasma ditambahkan ke plasma pasien, yang menunjukkan defisiensi faktor VIII merupakan penyebab hemofilia ini. Aktivitas faktor VIII 8% menegaskan suatu hemofilia A derajat ringan. Kata kunci: hemofilia, PT, APTT, mixing studies, faktor VIII.   Abstract: Haemophilia is a congenital bleeding disorder caused by a deficiency of factor VIII (antihaemophilic factor), which is related to haemophilia A, or factor IX (Christmast factor), associated with haemophilia B. Both X-linked are recessive, and males are affected mostly. In this case, a four year old boy, who had a history of excessive bruising and bleeding, also suffered from painful swelling of joints and muscle hematoma. He was diagnosed of suspected  haemophilia. A serial test of coagulation studies was performed. The results of platelet count, skin bleeding time, prothrombin time, thrombin clotting time, and fibrinogen were normal; whereas, the activated partial thromboplastin time was prolonged. The mixing studies were corrected when normal plasma and adsorbed plasma were added to the patient plasma, suggesting that the factor VIII deficiency was the cause of this haemophilia. The factor VIII activity was 8% which confirmed the evidence of mild haemophilia A. Keywords: haemophilia, PT, APTT, mixing studies, factor VIII.

scholarly journals Diagnóstico temprano de quiste hemofílico. Reporte de caso

Medicina ◽  
2017 ◽  
Vol 19 (2) ◽  
pp. 112-116
Author(s):  
Rocio Elizabeth Marin Panchez ◽  
Cristina Almeida Betty ◽  
Lorena Monserrate Coello ◽  
Teresa Rizzo Delgado
Keyword(s):  
Factor Viii ◽  
Factor Ix ◽  
Von Willebrand ◽  
Hemofilia A

 Los trastornos hereditarios de la coagulación con mayor incidencia en la edad pediátrica son la hemofilia A (deficiencia factor VIII), la hemofilia B o enfermedad de Christmas (deficiencia factor IX) y la enfermedad de Von Willebrand. Siendo la hemofilia una enfermedad de tipo hereditario ligado al cromosoma X que se manifiesta con ausencia o disminución de la función de los factores de coagulación (factor VIII y IX) que impide una correcta hemostasia y consecuentemente hemorragias tanto interna como externas. Existen varias complicaciones causadas por esta patología siendo la más infrecuente el quiste hemofílico. Por este motivo se presenta el caso clínico de un paciente de 14 años de edad con diagnóstico de hemofilia reciente y a pesar de recibir tratamiento específico persistió la tumoración a nivel gemelar izquierdo. El principal objetivo es dar a conocer la importancia del diagnóstico temprano junto al manejo multidisciplinario

Management of Haemophilia in Sweden

1976 ◽  
Vol 35 (03) ◽  
pp. 510-521 ◽  
Author(s):  
Inga Marie Nilsson
Keyword(s):  
Factor Viii ◽  
Total Population ◽  
Age Groups ◽  
Factor Ix ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Haemophilia B ◽  
Human Fraction ◽  
Mild Haemophilia

SummaryThe incidence of living haemophiliacs in Sweden (total population 8.1 millions) is about 1:15,000 males and about 1:30,000 of the entire population. The number of haemophiliacs born in Sweden in 5-year periods between 1931-1975 (June) has remained almost unchanged. The total number of haemophilia families in Sweden is 284 (77% haemophilia A, 23% haemophilia B) with altogether 557 (436 with A and 121 with B) living haemophiliacs. Of the haemophilia A patients 40 % have severe, 18 % moderate, and 42 % mild, haemophilia. The distribution of the haemophilia B patients is about the same. Inhibitors have been demonstrated in 8% of the patients with severe haemophilia A and in 10% of those with severe haemophilia B.There are 2 main Haemophilia Centres (Stockholm, Malmo) to which haemophiliacs from the whole of Sweden are admitted for diagnosis, follow-up and treatment for severe bleedings, joint defects and surgery. Minor bleedings are treated at local hospitals in cooperation with the Haemophilia Centres. The concentrates available for treatment in haemophilia A are human fraction 1-0 (AHF-Kabi), cryoprecipitate, Antihaemophilic Factor (Hyland 4) and Kryobulin (Immuno, Wien). AHF-Kabi is the most commonly used preparation. The concentrates available for treatment in haemophilia B are Preconativ (Kabi) and Prothromplex (Immuno). Sufficient amounts of concentrates are available. In Sweden 3.2 million units of factor VIII and 1.0 million units of factor IX are given per year. Treatment is free of charge.Only 5 patients receive domiciliary treatment, but since 1958 we in Sweden have practised prophylactic treatment of boys (4–18 years old) with severe haemophilia A. At about 5-10 days interval they receive AHF in amounts sufficient to raise the AHF level to 40–50%. This regimen has reduced severe haemophilia to moderate. The joint score is identical with that found in moderate haemophilia in the same age groups. For treatment of patients with haemophilia A and haemophilia B complicated by inhibitors we have used a large dose of antigen (factor VIII or factor IX) combined with cyclophosphamide. In most cases this treatment produced satisfactory haemostasis for 5 to 30 days and prevented the secondary antibody rise.

The Effect of Adrenaline Infusions on Blood Coagulation in Normal and Haemophilia B Dogs

1966 ◽  
Vol 15 (03/04) ◽  
pp. 349-364 ◽  
Author(s):  
A.H Özge ◽  
H.C Rowsell ◽  
H.G Downie ◽  
J.F Mustard
Keyword(s):  
Body Weight ◽  
Factor Viii ◽  
Factor Ix ◽  
Clotting Factor ◽  
Blood Ph ◽  
Order Of Magnitude ◽  
Dose Dependent ◽  
Generation Test ◽  
Plasma Activity

SummaryThe addition of trace amounts of adrenaline to whole blood in plasma in vitro increased factor VIII, factor IX and whole plasma activity in the thromboplastin generation test. This was dose dependent.Adrenaline infusions less than 22 (μg/kg body weight in normal dogs accelerated clotting, increased factor IX, factor VIII and whole plasma activity in the thromboplastin generation test and caused a fall in blood pH. In a factor IX deficient dog, there was no increase in factor IX activity. After adrenaline infusions, however, the other changes occurred and were of the same order of magnitude as in the normal. Adrenaline in doses greater than 22 μg/kg body weight did not produce as great an effect on clotting in normal or factor IX deficient dogs. The platelet count in the peripheral blood was increased following the infusion of all doses of adrenaline. These observations suggest that the accelerating effect of adrenaline on clotting is not mediated through increase in activity of a specific clotting factor.

A Survey of the Effectiveness of Prothrombin Complex Concentrates in Controlling Hemorrhage in Patients with Hemophilia and Anti-Factor VIII Antibodies

1980 ◽  
Vol 44 (01) ◽  
pp. 039-042 ◽  
Author(s):  
Philip M Blatt ◽  
Doris Ménaché ◽  
Harold R Roberts
Keyword(s):  
Factor Viii ◽  
Ad Hoc ◽  
Hemophilia A ◽  
Working Party ◽  
International Committee ◽  
Factor Ix ◽  
Prothrombin Complex Concentrates ◽  
Factor Viii Concentrates

SummaryThe treatment of patients with hemophilia A and anti-Factor VIII antibodies is difficult. Between July 1977 and June 1978, a survey was carried out by an ad hoc working party of the subcommittee on Factor IX concentrates of the International Committee on Thrombosis and Hemostasis to assess the effectiveness of Prothrombin Complex Concentrates in controlling hemorrhage in these patients. The results are presented in this paper and, although subjective, support the view that these concentrates are not as effective in patients with inhibitors as Factor VIII concentrates are in patients without inhibitors.

In Vitro Thrombogenicity Tests of Factor IX Concentrates

1979 ◽  
Vol 42 (05) ◽  
pp. 1355-1367 ◽  
Author(s):  
C V Prowse ◽  
A Chirnside ◽  
R A Elton
Keyword(s):  
Factor Viii ◽  
Partial Thromboplastin Time ◽  
Generation Time ◽  
Activated Partial Thromboplastin Time ◽  
Factor Ix ◽  
In Vitro Tests ◽  
Factor Viii Inhibitor ◽  
Factor Ixa ◽  
Viii Inhibitor

SummaryVarious factor IX concentrates have been examined in a number of in vitro tests of thrombogenicity. The results suggest that some tests are superfluous as in concentrates with activity in any of these tests activation is revealed by a combination of the non-activated partial thromboplastin time, the thrombin (or Xa) generation time and factor VIII inhibitor bypassing activity tests. Assay of individual coagulant enzymes revealed that most concentrates contained more factor IXa than Xa. However only a small number of concentrates, chiefly those that had been purposefully activated, contained appreciable amounts of either enzyme.

Molecular Weights of Factor VIII (AHF) and Factor IX (PTC) by Electron Irradiation

1962 ◽  
Vol 08 (02) ◽  
pp. 270-275 ◽  
Author(s):  
David L Aronson ◽  
John W Preiss ◽  
Michael W Mosesson
Keyword(s):  
Molecular Weight ◽  
Factor Viii ◽  
Electron Irradiation ◽  
Factor Ix ◽  
Molecular Weights

SummaryThe molecular weights of AHF (factor VIII) and of PTC (factor IX) have been estimated by their sensitivity to inactivation by 7 kilovolt electrons. The molecular weight of AHF was found to be 180 000 by this method and that of PTC was found to be 110 000.

Management of Haemophilia A with Antibodies - The Effect of Combined Treatment with Factor VIII, Hydrocortisone and Cyclophosphamide

1985 ◽  
Vol 54 (04) ◽  
pp. 776-779 ◽  
Author(s):  
U Hedner ◽  
L Tengborn
Keyword(s):  
Factor Viii ◽  
Combined Treatment ◽  
Factor Ix ◽  
Treatment Schedule ◽  
High Antibody ◽  
Anamnestic Response ◽  
Short Intervals ◽  
Low Responders ◽  
Antibody Levels ◽  
High Responders

SummaryImmune tolerance has by several methods been induced in haemophiliacs with antibodies. A conversion of “high responders” into “low responders” was previously reported after repeated moderate factor IX doses over periods of 7-10 days in combination with cyclophosphamide and steroids in two patients with haemophilia B and inhibitors. This paper reports similar results in a heamophilia A patient by giving factor VIII, cyclophosphamide, and steroids during relatively short periods of time (7-8 days). The anamnestic response markedly decreased already following the first treatment and never exceeded a level of 1 u/ml (˜ 3 BU/ml) even when boosted with ordinary factor VIII doses for only 3 days. It is concluded that the markedly decreased secondary antibody response is most probably the result of factor VIII given at short intervals (twice a day) for periods of up to about one week when given in combination with cyclophosphamide and steroids. The same effect may be achieved by other methods. The treatment schedule suggested in the present paper is, however, simple and avoids long periods of high antibody levels. Furthermore, the total factor VIII dose used is lower than suggested in most other treatment schedules, which makes the treatment substantially less expensive.

scholarly journals Gene Therapy in Hemophilia: Recent Advances

2021 ◽  
Vol 22 (14) ◽  
pp. 7647
Author(s):  
E. Carlos Rodríguez-Merchán ◽  
Juan Andres De Pablo-Moreno ◽  
Antonio Liras
Keyword(s):  
Gene Therapy ◽  
Adverse Events ◽  
Factor Viii ◽  
Coagulation Factor ◽  
Cost Savings ◽  
Factor Ix ◽  
Clotting Factors ◽  
Advanced Therapies ◽  
Potential Benefits

Hemophilia is a monogenic mutational disease affecting coagulation factor VIII or factor IX genes. The palliative treatment of choice is based on the use of safe and effective recombinant clotting factors. Advanced therapies will be curative, ensuring stable and durable concentrations of the defective circulating factor. Results have so far been encouraging in terms of levels and times of expression using mainly adeno-associated vectors. However, these therapies are associated with immunogenicity and hepatotoxicity. Optimizing the vector serotypes and the transgene (variants) will boost clotting efficacy, thus increasing the viability of these protocols. It is essential that both physicians and patients be informed about the potential benefits and risks of the new therapies, and a register of gene therapy patients be kept with information of the efficacy and long-term adverse events associated with the treatments administered. In the context of hemophilia, gene therapy may result in (particularly indirect) cost savings and in a more equitable allocation of treatments. In the case of hemophilia A, further research is needed into how to effectively package the large factor VIII gene into the vector; and in the case of hemophilia B, the priority should be to optimize both the vector serotype, reducing its immunogenicity and hepatotoxicity, and the transgene, boosting its clotting efficacy so as to minimize the amount of vector administered and decrease the incidence of adverse events without compromising the efficacy of the protein expressed.

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