National strategic advocacy to manage patients with inherited bleeding disorders in low and lower-middle income countries.

INTRODUCTION: Inherited bleeding disorders (IBDs) including hemophilia, von Willebrand disease, platelet disorders, mucocutaneous bleeding disorders and coagulation factor deficiencies are rarely found and under-recognized in low and lower-middle-income countries. Some patients succumbed to serious bleeding without diagnosis and treatment during childhood. AREA COVERED: Diagnosis, management, and prevention should be integrated into the existing health care system. Although some countries have not implemented appropriate health care infrastructure, an initiative plan should be set up by cooperation of experienced experts and health care providers. Identification of patients with IBDs should be started in the antenatal setting to search for females at risk of carrier state. The investigations include bleeding assessment, mixing venous clotting time, coagulogram, coagulation factor assay and mutation detection. Genotypic analysis is helpful for confirming the definite diagnosis, carrier detection as well as prenatal diagnosis for females at risk of bearing an offspring with severe bleeding manifestations. Management involves replacement therapy ranging from blood component to virus-inactivated factor concentrate. Appropriate research is an essential backbone for improving patients' care. EXPERT OPINION: Effective national strategic advocacy to manage patients with IBDs requires intensive collaboration among policy makers, health care providers, patients, and family members.

Bombardier Blood (2020): Un documental más allá de la enfermedad / Bombardier Blood (2020): A Documentary beyond the Illness

Si bien la hemofilia era conocida como una enfermedad que perturbaba solo a las familias reales de Europa, actualmente afecta a uno de cada 5.000 y a uno de cada 30.000 varones recién nacidos vivos tanto para la de Tipo A como B, respectivamente. La hemofilia es un trastorno de la coagulación sanguínea que afecta principalmente a varones por su carácter de herencia recesiva ligada al X, siendo su manifestación principal las hemorragias que pueden llegar a ser mortales si no son tratadas correctamente. En Bombardier Blood (2020) de Patrick James Lynch, un documental enfocado al recorrido de Chris Bombardier, una persona hemofílica cuyo sueño es escalar las siete cumbres más altas del mundo, incluyendo en su paso el monte Everest en el Himalaya. El documental además de destacar los aspectos médicos sobre esta enfermedad hace ver los diferentes estilos de vida de acuerdo a su localización, las normativas y sistemas de salud que los rige y como esto incide en el diagnóstico, seguimiento y tratamiento. (AU)

While hemophilia was considered a disease that disturbed only the royal families of Europe, it currently affects one in 5.000 and one in 30.000 live newborn males for both Type A and B, respectively. Hemophilia is a blood clotting disorder that mainly affects men due to its character of recessive inheritance linked to X, its main manifestation hemorrhaging that can become fatal if they are not treated correctly. Bombardier Blood (2020) by Patrick James Lynch is a documentary focused on the journey of Chris Bombardier, a hemophilic person whose dream is to climb the seven highest summits in the world, including Mount Everest in the Himalayas. The documentary, in addition to highlighting the medical aspects of this disease, shows the different lifestyles according to their location, the regulations and health systems that govern them, and how these affect diagnosis, monitoring, and treatment. (AU)

Preoperative diagnosis and management of inherited bleeding disorders in female adolescents and adults.

Although inherited bleeding disorders (IBDs) affect both females and males, this review of the preoperative diagnosis and management of IBDs focuses on genetic and gynecologic screening, diagnosis and management of affected and carrier females. A PubMed literature search was conducted, and the peer-reviewed literature on IBDs was evaluated and summarized. Best-practice considerations for screening, diagnosis and management of IBDs in female adolescents and adults, with GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) evidence level and ranking of recommendation strength, are presented. Health care providers need to increase their recognition of and support for female adolescents and adults with IBDs. Improved access to counselling, screening, testing and hemostatic management is also required. Patients should be educated and encouraged to report abnormal bleeding symptoms to their health care provider when they have a concern. It is hoped that this review of preoperative IBD diagnosis and management will enhance access to women-centred care to increase patients' understanding of IBDs and decrease their risk of IBD-related morbidity and mortality.

Molecular basis of rare congenital bleeding disorders.

Rare bleeding disorders (RBDs), including factor (F) I, FII, FV, FVII, combined FV and FVIII (CF5F8), FXI, FXIII and vitamin-K dependent coagulation factors (VKCF) deficiencies, are a heterogeneous group of hemorrhagic disorder with a variable bleeding tendency. RBDs are due to mutation in underlying coagulation factors genes, except for CF5F8 and VKCF deficiencies. FVII deficiency is the most common RBD with >330 variants in the F7 gene, while only 63 variants have been identified in the F2 gene. Most detected variants in the affected genes are missense (>50% of all RBDs), while large deletions are the rarest, having been reported in FVII, FX, FXI and FXIII deficiencies. Most were located in the catalytic and activated domains of FXI, FX, FXIII and prothrombin deficiencies. Understanding the proper molecular basis of RBDs not only can help achieve a timely and cost-effective diagnosis, but also can help to phenotype properties of the disorders.

Outcome of Surgical Interventions and Deliveries in Patients with Bleeding of Unknown Cause: An Observational Study.

BACKGROUND: The most optimal management for patients with bleeding of unknown cause (BUC) is unknown, as limited data are available. OBJECTIVE: Evaluate management and outcome of surgical procedures and deliveries in patients with BUC. MATERIALS AND METHODS: All patients ≥12 years of age, referred to a tertiary center for a bleeding tendency, were included. Bleeding phenotype was assessed and hemostatic laboratory work-up was performed. Patients were diagnosed with BUC or an established bleeding disorder (BD). Data on bleeding and treatment during surgical procedures and delivery following diagnosis were collected. RESULTS: Of 380 included patients, 228 (60%) were diagnosed with BUC and 152 (40%) with an established BD. In 14/72 (19%) surgical procedures major bleeding occurred and 14/41 (34%) deliveries were complicated by major postpartum hemorrhage (PPH). More specifically, 29/53 (55%) of the BUC patients who underwent surgery received prophylactic treatment to support hemostasis. Despite these precautions, 4/29 (14%) experienced major bleeding. Of BUC patients not treated prophylactically, bleeding occurred in 6/24 (25%). Of pregnant women with BUC, 2/26 (8%) received prophylactic treatment during delivery, one women with and 11 (46%) women without treatment developed major PPH. CONCLUSION: Bleeding complications are frequent in BUC patients, irrespective of pre- or perioperative hemostatic treatment. We recommend a low-threshold approach toward administration of hemostatic treatment in BUC patients, especially during delivery.

Challenges and concerns of patients with congenital bleeding disorders affected by coronavirus disease 2019.

Coronavirus disease 2019 (COVID-19) is a new medical challenge for all individuals, especially for those with underlying disorders, such as congenital bleeding disorders (CBDs). Therefore, the pandemic might significantly change the behaviour of patients with CBDs and results in some challenges. In the present study, we assessed the main challenges of COVID-19 infection to patients with CBDs. Data were collected from medical files and interviews of patients with CBDs who had COVID-19 infection. Follow-ups were performed on patients who had active severe acute respiratory syndrome coronavirus 2 infection between April and October 2020. All patients were interviewed by an expert in order to collect the pertinent data. Some questions were about patients' preventive behaviors and feelings prior to infection, and some were about the consequences of infection on patients' replacement therapy and bleeding management. Among 25 patients, infection and death of loved ones (n: 7, 28%), and their own (n: 5, 20%) or family members' (n: 1, 4%) infection, and the resulting economic burden (n: 2, 8%) were main concerns. Six patients experienced depression during the pandemic. The pandemic caused all severely affected patients but one (n: 11, 92%) to abandon replacement therapy. However, two received on-demand therapy after exacerbation of their bleeding. Only one (25%) of four patients on prophylaxis received in-home therapy, whereas the others (75%) abandoned prophylaxis. It seems that COVID-19 infection has great consequences on the lives of patients with CBDs, causing some to take dangerous actions, such as abandonment of their treatment. Healthcare systems, and healthcare providers, should have an appropriate strategy for management of patients with CBDs that prevents infection and provides timely replacement therapy.

Practical Recommendations for Treatment of Dental Patients with Congenital Bleeding Disorders during the Covid-19 Pandemic: A Narrative Review.

At the end of 2019, a new disease -COVID-19-was identified, and a few months later, the World Health Organization announced a pandemic. It is now known that SARS-CoV-2 is highly contagious and most confirmed infections are mild to moderate. The situation is particularly difficult for dentists due to the high risk of virus transmission in the dental surgery. Complications including, but not limited to, problems with the respiratory and cardiovascular systems have been reported in patients with SARS-CoV-2. Several changes in the coagulation system, such as lower platelet numbers or increased prothrombin time, as well as increased D-dimer and fibrinogen, were observed. This review is intended to systematize the knowledge on the treatment of patients with congenital bleeding disorders (CBD) during the SARS-CoV-2 pandemic. Extensive literature research was conducted into COVID-19 and the general medical and dental treatment of patients with CBD. Case studies, research results and recommendations of international societies were used in the study. The results of this research are presented in the form of recommendations for the treatment of patients with coagulopathies. It should be remembered that the impact of COVID-19 on the health condition of patients with CBD is unknown to date.

Congenital Bleeding Disorders amid the COVID-19 pandemic: Open questions and recommendations.

This article reviews the current knowledges of congenital bleeding disorders (CBD) amid the COVID-19 pandemic. It appears that CBD is not associated with higher risk of getting COVID-19 and so the prevalence of COVID-19 among them seems not higher compared to the general population. In absence of specific therapeutic recommendations, it is essential to make a correct assessment of the risk of haemorrhage/thrombosis. Based on expert opinion, strategies for outpatient management include adherence to prescribed regimens, telemedicine, and communication about COVID-19 in patients with CBD. More data should be also collected to better characterize the impact of COVID-19 on patients with CBD. The current findings encourage further studies to determine the prevalence of SARS-CoV2 infection in CBD patients to understand more fully the burden of this novel pathogen and to develop adequate preventive measures against this infection.

The impact of foetal restrictions on mode of delivery in women with inherited bleeding disorders.

OBJECTIVES: Management of pregnancy in women with congenital bleeding disorders (CBD) is challenging and requires understanding of risks conferred to both the mother and the foetus. Some elements of labour management are considered to increase the risk of neonatal bleeding and are not recommended for neonates at risk of a significant bleeding disorder. The impact of these restrictions on obstetric outcomes in women with CBD is unknown. METHODS: We retrospectively reviewed obstetric outcomes in a large cohort of women with CBD attending a specialised obstetric/haematology antenatal clinic over a 6-year period. RESULTS: Ninety-four pregnancies in 76 women with a wide variety of CBDs were assessed. Foetal precautions were recommended in the majority of cases (88%). Twenty (21.2%) were delivered by elective Caesarean section (CS), predominantly for obstetric indications. Of the 63 women who laboured with foetal precautions in place, 6 (10%) had a CS that was performed because of these precautions. There was no neonatal bleeding but primary postpartum haemorrhage (PPH) occurred in 12.2% of women. CONCLUSIONS: These data show that foetal precautions in labour recommended for women with CBDs will influence mode of delivery in approximately 10% of cases. This is important information for counselling these women about labour and delivery.

Managing Preoperative Hemostasis in Patients with Inherited and Acquired Bleeding Disorders.

Inherited and acquired bleeding disorders pose significant hemostatic challenges for surgery. Patients at particular risk of bleeding include those with inherited bleeding disorders such as hemophilia, von Willebrand disease, and platelet function defects; those on antiplatelet agents or anticoagulants; and those with acquired conditions such as immune thrombocytopenic purpura, liver disease, or renal impairment. Each has its own specific challenges and close collaboration between the anesthetic, surgical, and hematology teams is crucial. Optimizing surgical hemostasis for patients at risk involves attention to detail, with careful preoperative planning, meticulous surgical technique, prompt identification of complications and judicious use of hemostatic agents and blood components. This article gives an overview of the bleeding risks involved and therapeutic options to overcome them.

Home therapy for inherited bleeding disorders in South Africa: Results of a modified Delphi consensus process.

BACKGROUND: Optimal care of patients with inherited bleeding disorders requires that bleeding episodes are treated early, or still better prevented, through extension of patient care beyond hospital-based treatment to home-based therapy. In South Africa (SA), adoption of home therapy is variable, in part owing to lack of consensus among healthcare providers on what constitutes home therapy, which patients should be candidates for it, how it should be monitored, and what the barriers to home therapy are. OBJECTIVES: To conduct a modified Delphi process in order to establish consensus on home therapy among haemophilia healthcare providers in SA. METHODS: Treaters experienced in haemophilia care were invited to participate in a consensus-seeking process conducted in three rounds. In round 1, provisional statements around home therapy were formulated as questions and collated in a structured list. In rounds 2 and 3, evolving versions of the questionnaire were administered to participants. Consensus was defined as ≥70% agreement among the participants. RESULTS: The panel composition included an equal number of physicians and non-physicians. The participation rate was 100% through all three consensus rounds. The group reached consensus for 92% of the statements. Consensus of 100% was reached on starting home therapy in paediatric patients, requiring all patients on home therapy to sign informed consent and indemnity, and providing round-the-clock support for patients on home therapy. CONCLUSIONS: The home therapy consensus statements in this report have the potential to translate to policy on home therapy and to guide the initiation, practice and evaluation of home therapy programmes in SA.

[Heavy menstrual bleeding in teenage girls and women with inherited bleeding disorders]. / Ménométrorragies de l'adolescente et de la jeune femme ayant un trouble héréditaire de l'hémostase.

Menometrorrhagia is a frequent bleeding symptom in young women, and may be related to an inherited bleeding disorder. If there is no gynecological etiology, hemostasis tests are required. The early medical management of these teenage girls is important, especially when a bleeding disorder is known. The bleeding risk of the first periods may then be anticipated. Afterwards, the objective of the treatment is to keep the bleeding symptoms under control: anti-fibrinolytic treatment, specific replacement therapy for bleeding disorder and hormonal treatment. This management requires a multidisciplinary medical team, mainly hematologist and gynecologist, all along the genital lifespan, from the first periods to the desire for pregnancy.

MÉNOMÉTRORRAGIES DE L'ADOLESCENTE ET DE LA JEUNE FEMME AYANT UN TROUBLE HÉRÉDITAIRE DE L'HÉMOSTASE Les ménométrorragies constituent une symptomatologie hémorragique fréquente de la jeune femme. Elles peuvent être en lien avec un trouble de l'hémostase, qu'il faut savoir dépister en l'absence de cause gynéco-obstétricale. La prise en charge précoce des jeunes filles est essentielle, notamment quand le diagnostic d'anomalie de l'hémostase est établi. Il est important d'annoncer le risque hémorragique potentiel pour permettre d'anticiper les premières règles. Ensuite, la prise en charge consiste à maîtriser l'abondance des règles : traitement antifibrinolytique, traitement substitutif spécifique du trouble de l'hémostase et traitement hormonal. Cette prise en charge doit être multidisciplinaire, associant l'hématologue et le gynécologue, des premières règles de l'adolescente au désir de grossesse des jeunes femmes.

Updated Australian consensus statement on management of inherited bleeding disorders in pregnancy.

INTRODUCTION: There have been significant advances in the understanding of the management of inherited bleeding disorders in pregnancy since the last Australian Haemophilia Centre Directors' Organisation (AHCDO) consensus statement was published in 2009. This updated consensus statement provides practical information for clinicians managing pregnant women who have, or carry a gene for, inherited bleeding disorders, and their potentially affected infants. It represents the consensus opinion of all AHCDO members; where evidence was lacking, recommendations have been based on clinical experience and consensus opinion. MAIN RECOMMENDATIONS: During pregnancy and delivery, women with inherited bleeding disorders may be exposed to haemostatic challenges. Women with inherited bleeding disorders, and their potentially affected infants, need specialised care during pregnancy, delivery, and postpartum, and should be managed by a multidisciplinary team that includes at a minimum an obstetrician, anaesthetist, paediatrician or neonatologist, and haematologist. Recommendations on management of pregnancy, labour, delivery, obstetric anaesthesia and postpartum care, including reducing and treating postpartum haemorrhage, are included. The management of infants known to have or be at risk of an inherited bleeding disorder is also covered. CHANGES IN MANAGEMENT AS A RESULT OF THIS STATEMENT: Key changes in this update include the addition of a summary of the expected physiological changes in coagulation factors and phenotypic severity of bleeding disorders in pregnancy; a flow chart for the recommended clinical management during pregnancy and delivery; guidance for the use of regional anaesthetic; and prophylactic treatment recommendations including concomitant tranexamic acid.

The 1st WFH Gene Therapy Round Table: Understanding the landscape and challenges of gene therapy for haemophilia around the world.

In this first in a series of round table meetings, the 1st World Federation of Hemophilia Gene Therapy Round Table was convened to initiate a global dialogue on the expected challenges and opportunities that a disruptive therapy, such as gene therapy, will bring to the haemophilia community. Perspectives from key stakeholder groups, including healthcare professionals, regulators, payors, people with hemophilia and pharmaceutical industry representatives, were sought in the identification of the key issues we expect to face. Didactic presentations and open discussion covered the clinical development of gene therapy in haemophilia; regulatory perspectives of gene therapy; making informed decisions; accessibility, affordability and pricing of gene therapy; and ethical issues of gene therapy clinical trials. These were followed by small group work. This manuscript outlines the key issues identified and the path forward.

Conhecimento dos cirurgiões-dentistas em atendimento de pacientes com coagulopatias hereditárias / Knowledge of dentists in the care of patients with hereditary coagulopathies

Objetivo: verificar o conhecimento dos cirurgiões-dentistas que trabalham nas Unidades Básicas de Saúde (UBS) com Equipes de Saúde Bucal (ESB) modalidade I, no município de Campina Grande, sobre o atendimento odontológico de pacientes com coagulopatias hereditárias. Sujeitos e método: por meio de questionário autoaplicável, foi feita uma entrevista com os cirurgiões-dentistas do município em questão para analisar os seus conhecimentos. Participaram da pesquisa 24 profissionais que se encaixaram nos critérios de inclusão e responderam de forma adequada o questionário com questões objetivas, sendo que os participantes foram orientados a assinalar somente uma alternativa para cada questionamento. Resultados: a maioria dos profissionais é formada há mais de 10 anos. A média de acertos das respostas foi de 50%. Em relação aos achados clínicos que determinam a possível presença de distúrbio hemorrágico, 44% afirmaram que são: púr-pura, sangramento gengival espontâneo e hemartrose. Os pacientes considerados de risco elevado para o tratamento odontológico foram: pacientes sem distúrbios hemorrágicos revelados, mas com exames complementares alterados; pacientes em tratamento com AAS; e pacientes em tratamento com anticoagulante por via oral. A maioria (68%) não considera a utilização de sugadores de saliva como risco para sangramento bucal. Os procedimentos odontológicos que os profissionais não se sentem seguros a executar, nesse tipo de paciente, foram: exodontias (88%); tratamento periodontal cirúrgico (76%); raspagem e alisamento coronoradicular (RACR) (28%); anestesia do nervo alveolar inferior ou outros (24%); tratamento endodôntico (20%); e anestesia infiltrativa (8%). Conclusão: os dados obtidos na pesquisa mostraram que o conhecimento dos cirurgiões-dentistas das UBS do município de Campina Grande não é satisfatório, havendo dúvidas sobre a maioria dos tratamentos odontológicos direcionados aos pacientes com coagulopatias hereditárias. (AU)

Objective: this study aimed to determine the knowledge of dentists working in UBS with ESB mode I in the city of Campina Grande on Patients with hereditary Coagulopathies. Through self-administered questionnaire, own and without exclusion criteria, an interview was conducted with dental surgeons of the municipality concerned to analyze their knowledge of the relevant topic. By itself and without exclusion criterion an interview was made with the dentists concerning to analyze their knowledge about hereditary coagulopathies. Subjects and method: the participants were 24 dentists which fit the inclusion criteria and responded adequately to the questionnaire which contained objective questions, and the respondents were asked to point out only one alternative of each questioning. Results: most of them were graduated over 10 years. The mean score was 50% of the questionnaire. In relation to clinical findings that determine the possible presence of bleeding disorder, 44% said they are: purple spontaneous gingival bleeding and hemarthrosis; patients considered at high risk for dental treatment were patients without bleeding disorders disclosed but with altered exams; patients being treated with ASA; and patients treated with anticoagulant orally. Most dentists (68%) do not consider the use of saliva-sucking as a risk for oral bleeding. Dental procedures that professionals do not feel safe running in those patients were: extractions (88%); surgical periodontal treatment (76%); RACR (28%); anesthesia of nerve alveolar inferior or other (24%); endodontic treatment (20%); and infiltrative anesthesia (8%). Conclusion: the data obtained from the survey showed that knowledge of dentists from Campina Grande municipality is not satisfactory and there is doubt on most dental treatments targeted to patients with inherited bleeding disorders. (AU)