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8
https://doi.org/10.29013/ELBLS-20-4-6-8
Asibi (Abu Shtiwi) Anas Dakar, 6th year student, Faculty of Medicine 2 of SUMP,"Nicolae Testemitanu", Chisinau, Republic of Moldova E-mail: alasibianas11@gmail.com Buruiana Sanda,
Associate Professor of the Department of Hematology
SUMP,"Nicolae Testemitanu" Chisinau, Republic of Moldova E-mail: sandaburuiana69@gmail.com
MANAGEMENT OF HEMOPHILIA A TREATMENT: PAST AND PRESENT
Abstract. Hemophilia A is the most common severe hereditary hemorrhagic disorder, caused by the deficiency of clotting factor VIII in the blood. The management of Hemophilia A treatment in different historical periods has been depending on level of knowledge about the disease, technological innovations and is constantly improving. Knowing the historical evolution of the treatment applied to patients with Hemophilia A will help us to select an individual therapeutic regimen for each patient.
Keywords: Hemophilia, treatment, clotting factor VIII.
1. Background 3. Results
Hemophilia, which means love (philia) of blood The management of Hemophilia A treatment in
(hemo), is the most common severe hereditary hem- different historical periods has been depending on
orrhagic disorder [1; 2]. Hemophilia A is usually an level of knowledge about the disease, technological
inherited condition and caused by the deficiency innovations and others. In the years 1950-1970 the
of clotting factor VIII in the blood. The estimated purpose of treatment was only to replace the level of
frequency of hemophilia is around 1 in 10000 live factor VIII in the blood by plasma transfusion, cryo-
births, and the number of people worldwide living precipitate [4; 5]. In 1964 Dr. Judith Graham Pool,
with hemophilia is about 400000. It presents in 1 in a scientist and researcher, made the important dis-
5000 live male births, whereas hemophilia B pres- covery that the fraction cryoprecipitate from plasma
ents in 1 in 30000 live male births [1; 3]. Over the (the precipitate left from thawing plasma contained
years, the treatment of Hemophilia has had multiple large amounts of FVIII). This cryoprecipitate could
changes that clearly favored the quality of treatment, be given to hemophilia A patients in relatively small
the quality of life of the patient with Hemophilia A. volumes to help with clotting during bleeding epi-
2. Study methods sodes. The shortage in supply led to treatment guide-
Electronic searches using Google scholar, lines including episodic therapy as an alternative for
PubMed, Cochrane Library were performed for prophylaxis [5]. Treatment to replace factor VIII
studies published in English and Romanian between with blood products has been shown to have many
2010-2020. side effects:
MANAGEMENT OF HEMOPHILIA A TREATMENT: PAST AND PRESENT
- increased rate of transfusion infections (viral B, C hepatitis, human immunodeficiency virus);
- increased rate of allergic reactions to blood components;
- plasma or cryoprecipitate was performed only in hospital conditions, so the patient had to travel to the hospital;
- difficult venous access in both, children and adults, which conditions low adherence to treatment;
- early invalidation of the patient due to frequent relapses of hemorrhage in the joint;
- decrease the quality of life of patients with Hemophilia A with economic impact.
The modern treatment of hemophilia A is considered to have started in the 1970 s, with the production of lyophilized plasma concentrates of coagulation factor VIII. This technological innovation greatly improved the quality and expectancy of life of people with hemophilia A as it enabled the widespread adoption of home replacement therapy with the early control bleeding episodes [5]. However, the treatment remained to be applied only in case of development of hemorrhagic complications.
The discovery in 1977 of the synthetic agent desmopressin provided a new, inexpensive and safe treatment for many patients with mild hemophilia A, which reduced the exposure to non-virus inactivated plasma-derived products.
The most important advance in this field was based on the rapid progress in DNA technology (following the cloning in 1982 of FVIII genes), which allowed the industrial production of recombinant FVIII [3; 5]. The treatment of hemophilia A may involve:
- home replacement therapy with the early control bleeding episodes;
- qualitative prophylactic treatment;
- management of bleeding episodes;
- treatment and rehabilitation of hemophilia synovitis;
- decreased rate of transfusion infections (viral B, C hepatitis, human immunodeficiency virus);
- increased the quality of life of patients with Hemophilia A;
- hemophilia treatment Centre network expanded.
But at the same time, negative effects were determined, such as:
- difficult venous access it remained a big problem, especially in home condition. A family member had to be taught to administer the intravenous factor VIII;
- frequent intravenous injections, which reduced adherence to treatment;
- short half-life of the synthetic factor;
- increased the risk of antibody formation to factor VIII.
This moment motivated the study of alternative treatment methods, such as: the creation of factor VIII preparations with a longer half-life, non-factoring agents, genetic treatment, the possibility of subcutaneous administration [6].
The treatment with non-factoring agents is given depending on whether or not antibodies have formed. In the case of Hemophilia A with inhibitors can be used: induction of immunological tolerance, Emici-zumab, recombinant coagulation factor VIIa (rFVIIa). In the case of Hemophilia A without inhibitors can be used: Emicizumab, substitution treatment with coagulation factor [7; 8]. It is recommended to increase the level of factor VIII by more than 12-15% [9].
Gene therapy means a technique of introducing a nucleic acid into a patient's cells in order to treat certain diseases [5]. There are methods that use viral vectors (biological nanoparticles), videlicet modified viruses and non-viral methods that are based on naked DNA complexes. Because hemophilia involves a genetic defect, viral vectors are used to deliver unmodified copies of genes into the patient's body. Non-viral methods are considered superior because they allow the production of proteins on a large scale and require a lower immune response from the host. Gene therapy in hemophilia A was evaluated in a study by BioMarine company.
The implementation of these treatment methods has a positive impact which is manifested by:
• Decreases the risk of possible bleeding;
• Preserving the structure and functionality of joints in children;
• Stopping the destruction of the joint in children and adults in whom arthropathy began to develop;
• Improving the quality of life [5; 8].
4. Conclusion
Based on the results of the literature review we can say that the modern treatment of patients with Hemophilia A should be applied not only during bleeding, but also prophylactically for the prevention of possible hemorrhages. The goal of treatment is to avoid any bleeding, which will increase the quality of life of these patients.
References:
1. WeyandA., Steven W. New therapies for hemophilia. Blood. 2019; 133(5): 389-398.
2. Castaman G., Matino D. Hemophilia A and B: molecular and clinical similarities and differences. Hae-matologica. 2019; 104(9): URL: https://doi.org/10.3324/haematol.2019.221093
3. Peyvandi F., Garagiola I., Young G. The past and future of haemophilia: diagnosis, treatments, and it complications. - Lancet. 2016; PubMed: PMID: 26897598.
4. Guidlinex for the management of haemophilia 2012.
5. Franchini M. The modern treatment of haemophilia: a narrative review. Blood Transfusion. 2013; 11(2): 178-182.
6. MASAC. Treatment Recommendations 2020. URL: https:/www.hemophilia.org/Researches Healthcare-Providers/Medical and Scientific
7. Kitazova T et. al. Factor VIIIa-mimetic cofactor activity of a bispecific antibody to factors IX/IXa and X/Xa, Emicizumab, depends on its ability to bridge the antigens. Thromb Haemost. 2017; 117(07): 1348-1357.
8. Young G. A multicenter open-label, phase 3 study of emicizumab prophilaxis in children with Haemophilia A with inhibitors. Blood. 2019; 134 (24): 2127-2138.
9. Jimenez-Yuste V et al. Achieving and maintaining an optimal throught level for prophilaxis in hemophilia: the past, the present and the future. Blood Transfusion. 2014; 12(3): 314-319.
