Introduction: Hemophilia is an inheritance bleeding disorder that classified into different types based on mutations in the genes encoding coagulation factors. The inheritability of A and B types is recessive X-linked but the deficiency or dysfunction of coagulation factor VIII is related to the A and deficiency or absence of coagulation factor IX caused the B type. In comparison hemophilia B is often considered less severe than hemophilia A. Hemophilia A is the most common type. The rare one is the Hemophilia C that is due to the lack of factor XI, and the other rare kind is parahemophilia, caused by the lack of factor V. These can diagnose by determining the levels of the coagulation factors and the presentation levels of inhibitor factors. Three subtypes are available for the hemophilia A and B based on diagnostic levels of FVIII and IX activity is made severe, moderate and mild classes for each one exclusively. Since the hemophilia A is more common, in this review is tried to understand the basis of this disorder and discuss the novel methods of curing it. Nowadays the diagnosis and treatments are done by the molecular biology techniques.
Methods: This information is gathered by searching in the google scholar, one of the most popular research engines, in purpose for finding novel and up to date treatments in hemophilia since 2019. These searches were based on different types of hemophilia and hemophilia treatment in case of "molecular revolution", Bispecific "antibodies, "emicizumab therapy".
Results: As usual, human being always wants to find the best ways for curing diseases, so it’s obvious that we have different methods in hemophilia treatment. The oldest using method was substitutive treatment by intravenous administration of factor VIII (FVIII) concentrates. Nowadays so many techniques have applied, the important point is that any method has its own advantages and disadvantages. And it needs to be suitable for the specific condition in each patient, because they could have had the other disorders beside hemophila in their body. So, recently, a lot of advances have expanded the therapeutic options for people with hemophilia, such as nonfactor therapies (emicizumab, fitusiran, and anti-tissue factor pathway inhibitor antibodies), extended half-life (EHL) products, gene therapy, RNA interference, even stem cell usage.
Conclusion: Disruptive molecular therapies have diversified the hemophilia therapy completely. The classic treatments have issues in efficacy, cost, availability, and side effects including the development of neutralizing antibodies. One of the nonfactor therapies, emicizumab, the first and only approved and increasingly accessible treatment option for hemophilia A, is a bispecific antibody that its structure is manufactured through genetic recombination, chemical conjugation or quadromas. Emicizumab mimics the action of factor VIII (FVIII) and it binds to both FIXa and FX inducing FXa generation in the early (extrinsic) stages. The most effective time of this bispecific antibody is for prophylaxis especially early in life due to avoid joints’ damage that may cause repeated hemarthrosis. One usage of Bypassing agents is helping to restore haemostasis in inhibitor patients. In case of prophylaxis, emicizumab is administered subcutaneously once a week, reduced the number of bleeding episodes in patients with inhibitors significantly. The emicizumab does not need to be activated by thrombin so, intrinsic pathway-based laboratory tests, including activated clotting time and activated partial thromboplastin time, clotting times with emicizumab and so on used for measuring the efficiency of it. The latency persistence of emicizumab depends on different situations in patients and their physical activity, it has to be under consideration by different kinds of tests. In severe cases of hemophilia A, the combination of high-dose FVIII therapy, the classic method, and bypassing agents like emicizumab needs to employed. The problem of using this method back to inadequacy and lack of scope for required tests equipment in the world and needs to be more accessible for patients. This method requires a basis knowledge to be taught to patients and make them aware. These kinds of treatments, bispecific antibodies are going to be developed in the future and become more available that can make an enormous effect in many disorders.