• Klíčová slova
• HEMOPHILIA *,
• MeSH
• hemofilie A * MeSH
• lidé MeSH
• nedostatek faktoru XI * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• Klíčová slova
• EYE/diseases *, HEMOPHILIA/complications *,
• MeSH
• hemofilie A komplikace   MeSH
• lékařství * MeSH
• lidé MeSH
• oční nemoci * MeSH
• oftalmologie * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Hemophilia is the most spread hereditary bleeding disorder with severe bleeding symptoms. Although the number of hemophiliacs is below 0.1 per thousand in population, the care of these patients consumes a lot of financial expenditures, especially for treatment in appearance of inhibitor. Management of hemophilia is best provided by specialist in a hemophilia treatment centre. However, all physicians can meet the patients with hemophilia in urgent situation or with their chronic problems. The aim of this article is to give an overview of this disease from pathophysiology, clinical manifestation and diagnosis (including prenatal) to treatment. We describe most frequent complications of hemophilia treatment, particularly management of inhibitor.

• MeSH
• hemofilie A * komplikace   diagnóza   farmakoterapie   patofyziologie   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• anglický abstrakt MeSH
• časopisecké články MeSH
• přehledy MeSH

• Klíčová slova
• HEMOPHILIA *, RESPIRATORY INSUFFICIENCY *,
• MeSH
• hemofilie A * MeSH
• insuficience plicnice * MeSH
• lékařství * MeSH
• lidé MeSH
• obstrukce dýchacích cest * MeSH
• respirační insuficience * MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

• Klíčová slova
• HEMOPHILIA *,
• MeSH
• dědičné koagulopatie * MeSH
• hemofilie A * MeSH
• lékařství * MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The next frontier in hemophilia A management has arrived. However, questions remain regarding the broader applicability of new and emerging hemophilia A therapies, such as the long-term safety and efficacy of non-factor therapies and optimal regimens for individual patients. With an ever-evolving clinical landscape, it is imperative for physicians to understand how available and future hemophilia A therapies could potentially be integrated into real-life clinical practice to improve patient outcomes. Against this background, nine hemophilia experts from Central European countries participated in a pre-advisory board meeting survey. The survey comprised 11 multiple-choice questions about current treatment practices and future factor and non-factor replacement therapies. The survey questions were developed to reflect current unmet needs in hemophilia management reflected in the literature. The experts also took part in a follow-up advisory board meeting to discuss the most important unmet needs for hemophilia management as well as the pre-meeting survey results. All experts highlighted the challenge of maintaining optimal trough levels with prophylaxis as their most pressing concern. Targeting trough levels of ≥30-50 IU/L or even higher to achieve less bleeding was highlighted as their preferred strategy. However, the experts had an equal opinion on how this could be achieved (i.e., more efficacious non-factor therapies or factor therapy offering broader personalization possibilities such as targeting trough levels to individual pharmacokinetic data). In summary, our study favors personalized prophylaxis to individual pharmacokinetic data rather than a "one-size-fits-all" approach to hemophilia A management to maintain optimal trough levels for individual patients.

• Klíčová slova
• ABR – annualized bleed rate, BPAs – bypassing agents, BU – Bethesda units, EHL – extended half-life, FVIII/IX – factor VIII/IX, ITI – immune tolerance induction, PPX – prophylaxis, QoL – quality of life, SHL – standard half-life, TFPI – tissue factor pathway inhibitor, TGA – thrombin generation assays, WFH – World Federation of Hemophilia, aPCC – activated prothrombin complex concentrates, extended half-life, hemophilia, mHJHS – modified Haemophilia Joint Health Score, pd – plasma-derived, prophylaxis, r – recombinant, rFVIIIFc – recombinant FVIII Fc fusion protein, rFVIIIpeg – recombinant pegylated FVIII, siRNA – small interfering RNA,
• MeSH
• hemofilie A * farmakoterapie   prevence a kontrola   MeSH
• krvácení prevence a kontrola   MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Evropa MeSH

• Klíčová slova
• HEMOPHILIA *,
• MeSH
• hemofilie A * MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Hemophilia A is an X-linked bleeding disorder caused by a quantitative or qualitative defect of coagulation factor VIII. Since factor VIII has been cloned and several intragenic and linked DNA polymorphisms discovered, DNA analysis is an accepted and commonly used method for carrier testing in hemophilia A. Both a direct method using detection of mutation and an indirect method based on linkage between the disease and DNA polymorphism are used for this purpose. In this study, DNA samples of 110 hemophilia A patients from 99 families were screened for factor VIII gene mutation using Southern blot analysis; in seven families, mutations were detected. In 13 females from six families with identified mutation, the direct diagnosis of carriers was performed. Four intragenic (BclI, XbaI, BglI and MspI in F8C locus) and two linked polymorphisms (TaqI in DXS52 locus and BglII in DXS15 locus) were studied in members of 47 hemophilia A families. BclI-XbaI-BglI haplotypes were analyzed in 90 unrelated X chromosomes. Eighteen out of 31 females (58%) were heterozygous for at least one intragenic polymorphism, and 29 out of 31 females (94%) were heterozygous for at least one intra- or extragenic polymorphism tested. Carrier diagnosis was made in 15 out of 25 possible carriers (60%) based on intragenic and in an additional 3 out of 25 (12%) only on linked polymorphism.

• MeSH
• detekce genetických nosičů MeSH
• faktor VIII genetika   MeSH
• haplotypy MeSH
• hemofilie A genetika   MeSH
• lidé MeSH
• mutace * MeSH
• mutační analýza DNA MeSH
• polymorfismus délky restrikčních fragmentů * MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• faktor VIII MeSH

The treatment of hemophilia A has progressed amazingly in recent years. Emicizumab, a bispecific-humanized monoclonal antibody, is able to improve coagulation by bridging activated factor IX and factor X. Emicizumab is administered subcutaneously and much less often compared to factor VIII products. It has low immunogenicity, does not require dose adjustment, and can be administered regardless of the presence of factor VIII inhibitors. Thrombin generation assays but not factor VIII activity are indicated to guide and monitor the treatment. Emicizumab has enabled the conversion of patients with severe forms into patients with milder forms of hemophilia A. It has reduced the number of bleeding episodes compared to both on-demand and prophylactic substitution therapy and has an excellent safety profile. Gene therapy can elevate factor VIII plasma levels for many years after a single treatment course, could offer long-term protection from bleeding episodes, and minimize or eliminate the need for substitutive treatment with factor VIII concentrates. Gene therapy can provoke an immune response, manifested by an increase in common liver enzymes, that require immunotherapy. Long term monitoring is necessary to identify possible adverse effects. Future objectives are: the development of an ideal viral vector, the possibility of its re-administration, the use of gene therapy in hemophiliac children, and determining whether it can be successfully used to induce immune tolerance to factor VIII ceteri paribus. The future will determine the place of each type of treatment and group of patients for which it is indicated.

• Klíčová slova
• adeno-associated viral vector, emicizumab, hemophilia A, lentiviral vector, valoctocogene roxaparvovec,
• MeSH
• dítě MeSH
• faktor X terapeutické užití   MeSH
• genetická terapie MeSH
• hemofilie A * farmakoterapie   MeSH
• lidé MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• faktor X MeSH

Acquired hemophilia A (AHA), a rare bleeding disorder caused by neutralizing autoantibodies against coagulation factor VIII (FVIII), occurs in both men and women without a previous history of bleeding. Patients typically present with an isolated prolonged activated partial thromboplastin time due to FVIII deficiency. Neutralizing antibodies (inhibitors) are detected using the Nijmegen-modified Bethesda assay. Approximately 10% of patients do not present with bleeding and, therefore, a prolonged activated partial thromboplastin time should never be ignored prior to invasive procedures. Control of acute bleeding and prevention of injuries that may provoke bleeding are top priorities in patients with AHA. We recommend treatment with bypassing agents, including recombinant activated factor VII, activated prothrombin complex concentrate, or recombinant porcine FVIII in bleeding patients. Autoantibody eradication can be achieved with immunosuppressive therapy, including corticosteroids, cyclophosphamide and rituximab, or combinations thereof. The median time to remission is 5 weeks, with considerable interindividual variation. FVIII activity at presentation, inhibitor titer and autoantibody isotype are prognostic markers for remission and survival. Comparative clinical studies to support treatment recommendations for AHA do not exist; therefore, we provide practical consensus guidance based on recent registry findings and the authors' clinical experience in treating patients with AHA.

• MeSH
• autoprotilátky MeSH
• faktor VIII MeSH
• hemofilie A * diagnóza   farmakoterapie   MeSH
• krvácení MeSH
• lidé MeSH
• prasata MeSH
• rituximab terapeutické užití   MeSH
• vyšetření krevní srážlivosti MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoprotilátky MeSH
• faktor VIII MeSH
• rituximab MeSH