Search

Haemophilia is a chronic and rare congenital bleeding disorder requiring treatment for life. An updated registry of data on this disease is of paramount importance for documenting prevalence, planning care, and evaluating effectiveness of resources in any country. The study presented in this paper is aimed at characterizing Portuguese patients’ clinical condition and demography, as well as the replacement therapy used in their treatment, based on hemo@record data, a technological solution that supports the National haemophilia registry. The analysis of 110 patients records confirmed the high prevalence of haemophilia A (75.5%) compared with haemophilia B (11.8%) and a large incidence in the severe levels (or the existence of people with mild severity without diagnosis and, consequently, without proper treatment) promoting insight about the portrayal of haemophilia in Portugal. This study should be extended as the registry evolves fostering an ever more efficient management of resources and ultimately a better quality of care for people with haemophilia.

von Willebrand disease (VWD) is a congenital bleeding disorder characterized by deficient or defective von Willebrand factor (VWF). Among women with VWD, postpartum hemorrhage (PPH) is common. Treatment options at delivery include plasma-derived VWF (pdVWF) and recombinant VWF (rVWF). However, limited data are available regarding their efficacy. We conducted a retrospective observational study comparing PPH in women with VWD treated at the Hemophilia Center of Western Pennsylvania between 1 February 2017 and 31 January 2018 with either rVWF or pdVWF. We compared postpartum outcomes, including PPH frequency and estimated blood loss (EBL) at delivery. There were a total of 12 deliveries, 7 vaginal and 5 cesarean. At delivery and for 3 days postpartum, 6 women received 80 IU/kg of rVWF and 6 received 80 IU/kg of pdVWF, based on prepregnancy weight, insurance, and/or patient choice. Treatment groups had similar demographics, including median age (32.0 vs 27.0 years; P = .075), bleeding scores (3.0 vs 3.5; P = .734), and prepregnancy body mass index (29.0 vs 29.2 kg/m2; P = .691). PPH occurred in 3 (25.0%) of 12 deliveries, with no difference by treatment group (2 of 6 rVWF vs 1 of 6 pdVWF; P = 1.000) and no difference in EBL by treatment group (685 vs 462 mL; P = .384) or delivery type (vaginal, P = .722 vs cesarean, P = .531). In summary, PPH occurred in one-fourth of the deliveries in women with VWD, despite a higher dose (80 IU/kg) of rVWF or pdVWF. Future trials are needed to develop and assess novel strategies to prevent PPH in VWD.

Bernard-Soulier syndrome, a congenital bleeding disorder, can rarely present with atherosclerosis and thrombosis. Acute coronary syndrome in such patients present a unique challenge as no standard set of guidelines exist for successful treatment. (Level of Difficulty: Intermediate.), Graphical abstract, Bernard-Soulier syndrome, a congenital bleeding disorder, can rarely present with atherosclerosis and thrombosis. Acute coronary syndrome in such…

Type 2 von Willebrand disease (VWD) is the most common congenital bleeding disorder, with variable bleeding tendency and a complex laboratory phenotype. In the current study, we report the clinical and molecular profile of a large number of Iranian patients with type 2 VWD. All exons, intron-exon boundaries, and untranslated regions were sequenced by Sanger sequencing for direct mutation detection. All identified mutations were confirmed in family members and by relevant bioinformatics studies. A total of 136 patients with type 2 VWD were diagnosed, including 42 (30.9%), 32 (23.6%), 38 (27.9%), and 24 (17.6%) patients with type 2A, type 2B, type 2M, and type 2N, respectively. Epistaxis (49%), gum bleeding (30.2%), ecchymosis (23.2%), and menorrhagia (16.3%) were the most common clinical presentations, while miscarriage (2.3%) and umbilical cord bleeding (0.8%) were the rarest. Thirty mutations were identified within the VWF gene, nine (30%) being novel, with p.Arg1379Cys (n = 20), p.Val1316Met (n = 13), p.Arg1597Trp (n = 13), p.Arg1374Cys (n = 10), p.Ser1506Leu (n = 10), and p.Arg1308Cys (n = 9) the most common. Type 2 VWD is a hemorrhagic disorder with variable bleeding tendency and a heterogeneous molecular basis in patients in Iran.

Objectives To assess the frequency and characteristics of children with inherited bleeding disorders that were initially misdiagnosed, leading to inappropriate disease management. Methods This study was conducted at the Haematology/Pathology Department of Fauji Foundation Hospital, Rawalpindi, Pakistan, from August 2014 to August 2018. Children who were diagnosed with an inherited bleeding disorder but did not respond to initial therapy were reevaluated. Results In total, 62 children were diagnosed with a bleeding disorder. Of these, 27 were diagnosed with an inherited bleeding disorder and 35 with an acquired bleeding disorder. Of the 27 children with inherited bleeding disorders, 18% (n = 5) were misdiagnosed and treated inappropriately. The median age of the misdiagnosed patients was 9 years (range, 5-13 years). Three patients with Bernard-Soulier syndrome had been misdiagnosed as having immune thrombocytopenic purpura, 1 patient with von Willebrand disease had been misdiagnosed as having hemophilia A, and 1 patient with haemophilia B had been misdiagnosed as having hemophilia A. Conclusions There are chances of misdiagnosis and improper or invasive management if comprehensive laboratory evaluation and a thorough clinical evaluation are not performed in children with congenital bleeding disorders.

A coagulation screen is an important screening test when investigating a child who presents with easy bruising or bleeding. Interpretation of a coagulation screen can be challenging for clinicians. Evolution of the haemostasis system during childhood means normal ranges vary with age and needs to be interpreted alongside the clinical information. It is essential to consider preanalytical variables when interpreting a coagulation screen, and the reason for the investigation must always be considered. It is important that the sample is taken under optimal conditions, including sample technique, use of the correct bottle and prompt transport to the laboratory. An abnormal coagulation screen may indicate an underlying congenital bleeding disorder or an acquired bleeding disorder, or may be due to sampling error. Limitations of the coagulation screen are essential to be aware of, as some children with normal coagulation screen results may have bleeding disorders. Conversely, an abnormal coagulation screen does not always indicate a bleeding disorder.

congenital bleeding disorders

The most common inherited coagulopathies include hemophilia and Von Willebrand’s disease. The aim of this chapter is to highlight the less common disorders that result in defects in coagulation; these can be categorized according to abnormalities in primary, secondary, or tertiary hemostasis. Many of these conditions are associated with comorbidities that require surgical correction. Unexpected perioperative hemorrhage can be avoided by maintaining a high index of suspicion for bleeding diathesis. Routine laboratory testing in these patients may be normal and does not necessarily exclude a coagulation disorder, and hematology should be consulted early for further testing and guidance on perioperative management.

Introduction Management strategies and hemostatic treatments to achieve control of bleeding are relevant across many disease areas. Identification of primary outcomes for studies assessing hemostatic intervention was the objective of a National Heart, Lung and Blood Institute (NHLBI) sponsored multidisciplinary initiative. The aim of this report is to summarize the evidence reviewed, and the outcomes identified by the subgroup tasked to assess outcomes for inherited bleeding disorders. Methods The subgroup decided to focus on haemophilia, the prototypal congenital bleeding disorder and the one with the largest available body of evidence. MEDLINE, EMBASE and PsycINFO, The Cochrane Review, CINAHL, and Web of Science were searched for systematic and narrative reviews on outcomes used in haemophilia clinical trials. Three different clinical goals were identified as typical objectives of future research. Results Out of 1322 unique citations, 24 reviews published in the period 2002-2019 were included. We identified 113 outcome measures, categorized in 6 domains: health-related quality of life (HRQoL), comorbidities and mortality, overall physical functioning and participation, bleeding and hemostasis, joint health, and costs and resource use. Three different clinical goals were identified as typical objectives of future research: Episodic 'on demand' replacement therapy, prevention of bleeding (Prophylaxis), and long-term and overall impact of bleeding. For each of these scenarios, specific outcomes were recommended. Conclusions Primary outcomes for clinical trials assessing the efficacy of hemostatic treatment in achieving control, prevention and limiting long-term consequences of bleeding in inherited bleeding disorders are suggested, and their strength and limitations discussed.

Introduction: Glanzmann thromboasthenia is a rare congenital bleeding disorder caused by a mutation in platelet glycoprotein α-IIb and β3 encoding genes (ITGA2B; 607759 and ITGB3; 173470) in chromosomes 17q21.31 and 17q21.32 , respectively, which results in a qualitative or quantitative alteration of the platelet integrin αIIbβ3 (glycoprotein IIb/IIIa) receptor. Glanzmann thromboasthenia is classified as type I when less than 5% of glycoprotein αIIbβ3 is expressed, and as type II when more than 5% is expressed. Case presentation: Description of the perioperative management of a 13-year-old female patient with Glanzmann thromboasthenia who underwent endoscopic anterior bilateral ethmoidectomy. Management was centered on prophylactic platelet transfusion plus the use of tranexamic acid, as well as thromboelastographic determination of hemostasis. There were no bleeding complications during or after the procedure. Conclusions: Pediatric patients with Glanzmann thromboasthenia are at a high risk of perioperastive bleeding. Platelet transfusion is the best prophylactic and therapeutic alternative; however, even in the absence of anti-platelet antibodies, it may not be effective, and viscoelastic testing must be used for assessment during the surgical procedure in order to improve patient safety.

INTRODUCTION: Hemophilia A is a rare congenital bleeding disorder caused by a deficiency of clotting factor VIII (FVIII). The severe form of the disease is characterized by spontaneous bleeds, especially into the joints. Prophylaxis, based on regularly intravenous administration of the missing factor to avoid hemorrhages, represents the gold standard of treatment. In recent years, new products that significantly improve the treatment management options for patients with hemophilia have become available in the market. OBJECTIVE: To critically evaluate the pivotal studies of recombinant FVIII (rFVIII) products, approved in Europe within the first half of 2018 having obtained the indication for a prophylaxis dosing regimen based also on a twice weekly infusion frequency or even less, highlighting their limitations or strengths. METHODS: A systematic literature search was conducted, and several databases (PubMed and Embase) were consulted. RESULTS: Nine clinical trials involving patients with severe hemophilia A without inhibitor were included in this analysis. Four rFVIII products (Elocta ® , Biogen, Cambridge, MA, USA; Kovaltry ® , Bayer HealthCare Pharmaceuticals, Germany; Afstyla ® , CSL Behring GmbH, Germany; Adynovi ® , Baxalta Innovation GmbH, Austria) with different pharmacokinetic profiles were evaluated. The trials included in this analysis had different designs and heterogeneous methods were utilized to assess the study outcomes. The baseline characteristics of the patients enrolled in the studies were also often different and sometimes not adequately described. LEOPOLD II, a trial to compare prophylaxis to on-demand therapy with an unmodified rFVIII product (Kovaltry ® , octocog alfa), was the only completely randomized trial that enrolled a more critical patient population in terms of compromised joint condition than the other studies. Based on these side-by-side comparison, Octocog alfa reported similar efficacy, in terms of annualized bleeding rate, to the other rFVIII products, including extended half-life. CONCLUSIONS: Even without structural modifications, octocog alfa may be considered a useful treatment option for two times a week prophylaxis in a selected population of haemophilia patients.

RasGRP2 is calcium and diacylglycerol-regulated guanine nucleotide exchange factor I that activates Rap1, which is an essential signaling-knot in “inside-out” αIIbβ3 integrin activation in platelets. Inherited platelet function disorder caused by variants of RASGRP2 represents a new congenital bleeding disorder referred to as platelet-type bleeding disorder-18 (BDPLT18). We review here the structure of RasGRP2 and its functions in the pathophysiology of platelets and of the other cellular types that express it. We will also examine the different pathogenic variants reported so far as well as strategies for the diagnosis and management of patients with BDPLT18.

Von Willebrand disease (VWD) is the most common congenital bleeding disorder, with a clinical presentation of mucocutaneous and surgical bleeding varying from mild to severe. It is inherited in an autosomal dominant or autosomal recessive manner. The disease is caused by quantitative or qualitative deficiency of the von Willebrand factor (VWF) and is classified as type 1, 2 (2A, 2B, 2M, 2N), and 3. Although type 1 VWD is the most common form of VWD, the f ormal cutoff for diagnosis remains a subject of debate. In our paper, we present results of studies regarding the clinical and laboratory importance of a new type of bleeding disorder called low VWF. The new guidelines for VWD diagnosis and management suggested that patients with historically type 1 VWD should be divided into 2 subsets: type 1 VWD with a VWF antigen level (VWF:Ag) of less than 30 IU/dl or less than 40 IU/dl, in which about 80% of patients exhibited VWF gene mutations, and low VWF with a VWF:Ag level of 30 to 50 IU/dl or 40 to 50 IU/dl, in which the causative mutation is detected in merely 40% of patients and in most families, inheritance is not dependent on the locus of VWF on chromosome 12. Previously, moderately reduced VWF levels (30-50 IU/dl) were considered a risk factor for bleeding, but not a true bleeding disorder, and this condition was named low VWF. Recently, it was documented in a large group of patients with type 1 VWD and low VWF that bleeding score does not correlate with VWF:Ag and bleeding symptoms in type 1 VWD (

Introduction: The number of women and girls (WG) with bleeding disorders cared for at hemophilia treatment centers has increased dramatically over the last 30 years, owing to improved recognition of bleeding symptoms specific to WG. However, basic epidemiologic data of this population remain elusive. The ATHNdataset (American Thrombosis and Hemostasis Network) is a surveillance tool for people with bleeding disorders in the United States, providing demographic as well as bleeding symptom and treatment information. The aim of this study was to characterize the female cohort within the ATHNdataset. Methods: In this retrospective cohort study, the ATHNdataset was queried for demographic data, bleeding disorder diagnosis, bleeding symptoms, and treatment. Descriptive statistics were used. Results: As of December 31, 2017, 8,820 WG with a congenital bleeding disorder were enrolled in the ATHNdataset, comprising 24.5% of the entire ATHNdataset cohort (35,945). The most common reported diagnosis was von Willebrand disease (VWD), accounting for 62.9% of the population. Reproductive tract bleeding was reported in 15.8% of participants older than 15 years. Conclusions: The ATHNdataset describes the largest cohort of WG with bleeding disorders to date. VWD is the most common diagnosis in WG with bleeding disorders. Symptoms specific to WG, such as heavy menstrual bleeding, are underreported in this data set compared with other data sources. Ongoing efforts are needed to improve diagnosis, treatment, and surveillance of WG with bleeding disorders.

Background Except for data in the Korea Hemophilia Foundation Registry, little is known of the epidemiology of congenital bleeding disorders in Korea. Methods Data were obtained from the Korean Health Insurance Review and Assessment Service (HIRA) database. Results From 2010 to 2015, there were 2,029 patients with congenital bleeding disorders in the Korean HIRA database: 38% (n = 775) of these patients had hemophilia A (HA), 25% (n = 517) had von Willebrand disease (vWD), 7% (n = 132) had hemophilia B (HB), and 25% (n = 513) had less common factor deficiencies. The estimated age-standardized incidence rate (ASR) of HA and HB was 1.78–3.15/100,000 and 0.31–0.51/100,000, respectively. That of vWD was 1.38–1.95/100,000. The estimated ASR of HA showed increase over time though the number of new patients did not increase. Most patients with congenital bleeding disorders were younger than 19 years old (47.8%), and most were registered in Gyeonggi (22.1%) and Seoul (19.2%). Conclusion This is the first nationwide population-based study of congenital bleeding disorders in Korea. This study provides data that will enable more accurate estimations of patients with vWD. This information will help advance the comprehensive care of congenital bleeding disorders. We need to continue to obtain more detailed information on patients to improve the management of these diseases., Graphical Abstract

Fitusiran is an RNA interference therapeutic that targets antithrombin (AT) in the liver and interferes with AT translation by binding and degrading messenger RNA-AT, thereby silencing AT gene expression and preventing AT synthesis. In both preclinical and clinical studies, AT knockdown results in dose-dependent AT lowering when fitusiran is given weekly or monthly subcutaneously. In clinical trials, fitusiran dose escalation has resulted in improved thrombin generation and clinical hemostasis as measured by reduction in annualized bleed rate. Unlike currently licensed drugs, this improvement was not only in patients with hemophilia A but in also those with hemophilia B, with or without inhibitors. In dental and surgical procedures, fitusiran also provided perioperative hemostasis in association with AT lowering. Fitusiran is well tolerated, with minor local injection site reactions, but in one subject with severe hemophilia A, the concomitant use of daily high-dose factor VIII, inconsistent with trial guidance to avoid high, repeat doses of clotting factor, was associated with fatal thrombosis, suggesting the need for caution when using hemostatic agents in conjunction with fitusiran. Preclinical in vitro and in silico studies indicate improvement in thrombin generation in rare bleeding disorder plasmas, including in plasmas from patients with severe factors V, VII, and X deficiency, suggesting potential therapeutic benefit.

Hemophilia is a severe congenital bleeding disorder associated with both spontaneous and traumatic bleeding episodes that can require emergent medical evaluation. Many persons with hemophilia (PWH) utilize the emergency department for the initial management of acute bleeding events. Prompt administration of factor replacement products is crucial in controlling acute bleeds and minimizing potential associated morbidity. PWH who have inhibitory antibodies can be especially difficult to treat, as they often require by-passing agent therapies to obtain hemostatic control. Although consultation with an experienced hematologist is always warranted, initial management of acute complications in hemophilia is emergent, which necessitates emergency care providers to have a strong understanding of the current treatment principles in this complex condition.

Objective The prevalence of bleeding disorders, notably von Willebrand disease (vWD), among adult women with objectively documented menorrhagia is consistently reported to be 10% to 20% and is even higher in adolescents presenting with menorrhagia. Options Diagnostic tools and specific medical and, where appropriate, surgical alternatives to management are reviewed and evidence-based recommendations presented. Evidence A MEDLINE search of the English literature between January 1975 and November 2003 was performed using the following key words: menorrhagia, uterine bleeding, pregnancy, von Willebrand, congenital bleeding disorder, desmopressin/DDAVP, tranexamic acid, oral contraceptives, medroxyprogesterone, therapy, hysterectomy, anesthesia, epidural, spinal. Recommendations from other society guidelines were reviewed. Values The quality of evidence reported in this document has been described USing the Evaluation of Evidence criteria outlined in the Report of the Canadian Task Force on the Preventive Health Exam (Table 1).13 Recommendations 1.Inherited bleeding disorders should be considered in the differential diagnosis of all patients presenting with menorrhagia (II-2B). The graphical scoring system presented is a validated tool which offers a simple yet practical method that can be used by patients to quantify their blood loss (II-2B). 2.Because underlying bleeding disorders are frequent in women with menorrhagia, physicians should consider performing a hemoglobin/hematocrit, platelet count, ferritin, PT (INR) and APTT in women with menorrhagia. In women who have a personal history of other bleeding or a family history of bleeding, further investigation should be considered, including a vWD workup (factor VIII, vWF antigen, and vWF functional assay) (II-2B). 3.Treatment of menorrhagia in women with inherited bleeding disorders should be individualized (III-B). 4.An inherited bleeding disorder is not a contraindication to hormonal therapy (oral contraceptives [II-IB], depot medroxyprogesterone acetate (DMPA) [II-3B], danazol [II-2B], GnRH analogs [II-3B]) or local treatments (Ievonorgestrel-releasing IUS [II-IB]) and non-hormonal therapy (antifibrinolytic drug tranexamic acid [II-IB]) as well as desmopressin (II-IB). These therapies represent first line treatment. Blood products should not be used for women with mild bleeding disorders (III-A). 5.In women who no longer want to preserve their fertility, conservative surgical therapy (ablation) and hysterectomy may be options (III-B). Clinicians may consult the "SOGC Clinical Practice Guideline: Guidelines for the Management of Abnormal Uterine Bleeding" for an in-depth discussion of the available therapeutic modalities, both medical and surgical. To minimize the risk of intraoperative and post-operative hemorrhage, coagulation factors should be corrected preoperatively with post-operative monitoring (II-IB). 6.Girls growing up in families with a history of vWD or other inherited bleeding disorders should be tested premenarchally to determine whether or not they have inherited the disease to allow both the patient and her family to prepare for her first and subsequent menstrual periods (III-C). 7.In adolescents presenting with menorrhagia, an inherited bleeding disorder should be excluded (III-B). When possible, investigation should be undertaken before oral contraceptive therapy is instituted, as the hormonally induced increase in factor VIII and vWF may mask the diagnosis (II-B). 8.Pregnancy in women with inherited bleeding disorders may require a multidisciplinary approach. A copy of their recommendations should be given to the patient and she should be instructed to present it to the health care provider admitting her to the birthing centre. Women with severe bleeding disorders or with a fetus at risk for a severe bleeding disorder should deliver in a hospital (level three) or where there is access to consultants in obstetrics, anesthesiology, hematology, and pediatrics (III-C). 9.Vacuum extraction, forceps, fetal scalp electrodes, and fetal scalp blood sampling should be avoided if the fetus is known or thought to be at risk for a congenital bleeding disorder. A Caesarean section should be performed for obstetrical Indications only (II-2C). 10.Epidural and spinal anesthesia are contraindicated if there is a coagulation defect. There is no contraindication to regional anesthesia if coagulation is normalized. The decision to use regional anesthesia should be made on an individual basis (III-C). 11.The risk of early and late postpartum hemorrhage is increased in women with bleeding disorders. Women with inherited bleeding disorders should be advised aboutthe possibility of excessive postpartum bleeding and instructed to report this immediately (III-B). 12.Intramuscular injections, surgery, and circumcision should be avoided in neonates at risk for a severe hereditary bleeding disorder until adequate workup/preparation are possible (III-B).

Hemophilia is a congenital bleeding disorder that affects nearly half a million individuals worldwide. Joint bleeding and other co-morbidities are a significant source of debilitation for this population. Current therapies are effective but must be given lifelong at regular intervals, are costly, and are available to only about 25% of the hemophilia population living in resource-rich countries. Gene therapy for hemophilia has been in development for three decades and is now entering pivotal-stage clinical trials. While many different technology platforms exist for gene therapy, all current clinical trials for hemophilia employ adeno-associated vector (AAV)-based cell transduction. This small viral particle is capable of packaging modified F8 or F9 transgenes, can be generated robustly from cell lines, and transduces several relatively end-differentiated target tissues such as the liver with high efficiency. While pre-existing neutralizing antibodies to the AAV capsid are recognized to limit current therapy, other challenges have been identified in human studies that were not seen in preclinical studies. Both liver transaminase elevations and immune-mediated loss of transgene expression have been observed in clinical trials. Toll-like receptors, cytotoxic T cells, and other components of the immune response have been implicated in the loss of factor expression, but a full understanding of the immune response awaits clarification. Despite these challenges, many patients enrolled in gene therapy trials have attained long-term expression of factors VIII and IX. This emerging technology now represents a cure for the severe bleeding and joint damage associated with hemophilia.

SummaryBackground Factor XIII deficiency is a rare, severe congenital bleeding disorder. Monthly prophylaxis with recombinant factor XIII (rFXIII) has demonstrated favorable safety and efficacy in patients ≥6 years and may similarly benefit younger children. Objective To evaluate the long-term safety and efficacy of rFXIII in children

Introduction: Hemophilia is a rare congenital bleeding disorder that requires coagulation factor replacement therapy to treat or, better, to prevent life- and limb-threatening bleeding and its complications. Personalized treatment of patients with hemophilia is crucial for improving outcomes in an environment with increasing health budget constraints.Areas covered: Unmet needs for a more effective and efficient use of factor concentrates are examined. The current approach is described with its limits and recent improvements, i.e. pharmacokinetic assessments and dosing tools/models. Future approaches to personalization were researched in the literature and discussed, including biomarkers, genotyping, decision-making tools, goal attainment tools and digital health systems.Expert opinion: A paradigm shift in hemophilia management personalization is necessary in order to improve outcome and ensure long-term sustainability in a landscape of growing and aging patient populations, increasing expectations...

Hemophilia A is the most severe congenital bleeding disorder with estimated incidence of 1 per 5000 live male birth. Afghanistan located within south Asia and central Asia have a considerable number of patients with bleeding disorders that is accompanied by low government resources and limited diagnostic facilities. This study aimed to evaluate different aspects of hemophilia A in Afghanistan for the first time. This study was conducted on 167 patients with hemophilia A who were referred to hemophilia center of Kabul city. The diagnosis of the disease was performed based on standard questionnaire, evaluation of clinical manifestations and family history as well as laboratory assays. Diagnose of hemophilia A was confirmed by coagulation factor VIII (C: FVIII) assay. The mean age and mean age at diagnosis were 13.7 ± 2.4 and 1.4 ± 0.7 years, respectively. The mean FVIII level was 0.7 IU/dl. The most common clinical manifestation was hemarthrosis, which was detected in 80% of patients. According to geographical distribution, 42% of patients are residents of Kabul Province. About 41% of patients were Tajik, whereas 37% were Pashtun. In Afghanistan, as a country with low number of diagnosed patients with hemophilia A because of limited diagnostic and treatment facilities, high amount of investments are required in order to improve the quality and quantity of hemophilic patients.

Acquired isolated factor VII deficiency is a rare bleeding disorder and has been reported in 31 cases. This is in contrast to congenital factor VII deficiency, which while also infrequent is the most common rare congenital bleeding disorder. Acquired isolated factor VII deficiency has been described primarily in patients with solid malignancies, sepsis, and in the presence of anti-factor VII autoantibodies. We report a case of acute myelogenous leukemia with an associated trisomy 8 cytogenetic abnormality presenting with factor VII deficiency. The factor VII deficiency cleared after induction chemotherapy and with the disappearance of the cytogenetic and molecular abnormalities. We discuss a possible link between trisomy 8 and vitamin K metabolism, which might result in acquired factor VII deficiency in acute myelogenous leukemia.

The World Federation of Hemophilia (WFH) states in its Guidelines for the Management of Hemophilia, Second Edition [1], that people with hemophilia are best managed in a comprehensive care setting. That team is typically comprised of a core group including a hematologist, nurse coordinator, physiotherapist, social worker, specialized lab technologist and data manager, and as needed, by other specialists. Hemophilia is an X-linked congenital bleeding disorder caused by a deficiency of coagulation factor VIII (FVIII) in hemophilia A or factor IX (FIX) in hemophilia B. There are a number of other disorders that are now typically treated in these comprehensive care centers including von Willebrand disease (VWD), rare factor deficiencies (I, II, V, V & VIII, VII, X, XI and XIII), and inherited platelet function disorders. Models of comprehensive care delivery for hemophilia and other inherited bleeding disorders were first defined in the 1960s and have been in constant evolution ever since. Comprehensive care for hemophilia and other inherited bleeding disorders was made possible by the discovery of cryoprecipitate for the treatment of hemophilia A in the mid-1960s and, in the decade that followed, the development of lyophilized clotting factor concentrates. It was quickly realized that treatment at home was far preferable to frequent visits to Emergency Departments or out-patient. Tragically, the same clotting factor concentrates that revolutionized treatment and dramatically improved quality of life exposed thousands of people with hemophilia to HIV-AIDS and hepatitis C in the late 1970s and 1980s [2]. The model of comprehensive care was forced to add specialists in infectious disease and hepatology. At the same time, the crisis accelerated the development of recombinant FVIII and IX clotting factors; these entered the clinic in 1993 and 1997 respectively. The proven safety of both recombinant and plasma-derived products spurred on the expansion of prophylactic care to more patients. Today, with the success of a comprehensive care model that keeps patients out of the hospital (and out of sight), and promises a normal lifespan, there is an emerging impression among many health system managers that the problem of hemophilia is "solved." In 2019, however, even the best care and treatment remains highly burdensome and not entirely efficacious. Emerging innovative therapies are promising yet dramatically different in their modes of action, dosing and administration. Much of what has been learned in terms of management of the disease over the last 50 years may no longer be relevant. Rather than one type of treatment for all, there may well be many different therapies. Comprehensive care centres will not become obsolete. It will remain critically important that specialized staff be able to foster long-term relationships with patients and their families. Indeed, they will need to expand their knowledge and expertise in order to be able to continue to deliver the standards of care so carefully developed since the 1960s.

Hemophilia is a congenital bleeding disorder that mainly affects men. Men with severe hemophilia experience stigma because they are unable to live up to various ideals of masculinity. This study involves a qualitative analysis of how nine Danish men aged 40–54 years with severe hemophilia manage life as functionally impaired relative to their masculine identity. The analytical focus is on how the men manage on a daily basis, how they construct their identity as a result of the disorder, and the body’s importance in these identity negotiations. The source of their biggest defeat is that the disorder often prevents them from living up to social expectations about men as fathers. This results in a variety of management strategies that they apply to neutralize the stigma, allowing them to (a) distance themselves from the disorder in various practical and verbal ways and to (b) assume primary responsibility for managing the disorder, including internalizing being experts on the disorder. The results identify that men with severe hemophilia are frustrated by the lack of advice provided by the health sector. The article proposes initiatives that can be taken to address the lack of knowledge and to create a broader network of peers for men with hemophilia across varying age groups.

Hemophilia A is a congenital bleeding disorder caused by an X-linked hereditary pattern. Female hemophilia A carriers are usually asymptomatic, although some have far lower levels of clotting factor because more X chromosomes with the normal gene are switched off, a phenomenon referred to as "lyonization." During a medical checkup at our hospital, a 56-year-old Japanese woman with coxalgia was also diagnosed as an obligate hemophilia A carrier based on World Federation of Hemophilia criteria. She underwent total hip arthroplasty using blood product coagulation factor VIII to address her hemophilia. Immediate female relatives (mother, sisters, daughters) of a person with hemophilia should have their clotting factor levels checked, especially prior to any invasive intervention or childbirth, or if any symptoms occur.

The Austrian Haemophilia Registry collects epidemiological data on patients with haemophilia, on treatment modalities and potential side effects. The Registry covers more than 85% of the assumed total number of haemophilia patients in Austria. This report summarizes data on 753 patients: 84.3% (635) have haemophilia A and 15.7% (118) have haemophilia B. Patients' median age is 34 years (range: 1-93 years). Of the total cohort, 39.0% (294) patients have severe haemophilia, 11.3% (85) moderate haemophilia, and 49.4% (372) mild haemophilia. Of the patients with severe haemophilia, 38.4% (113) have been infected with hepatitis C virus (HCV) and 12.6% (37) are human immunodeficiency virus (HIV) positive. Overall, 10.6% (67) of patients with haemophilia A and 1.7% (2) of those with haemophilia B have had an inhibitor in their history. Among patients with severe haemophilia, 68.4% (201) receive prophylaxis and 28.6% (84) receive on-demand therapy. There are 65.0% (191) patients with severe haemophilia who are treated with recombinant products. In conclusion, most patients with severe haemophilia receive prophylactic treatment. HCV and HIV infections are still important issues in the Austrian haemophilia population.Das Österreichische Hämophilieregister sammelt epidemiologische Daten über Patienten mit Hämophilie, über die Behandlungsmodalitäten und über die möglichen Nebenwirkungen. Das Österreichische Hämophilie Register erfasst mehr als 85% der zu erwartenden Anzahl von Hämophilen in Österreich. Im Register sind 753 Patienten erfasst, von denen 84.3% (635) Hämophilie A und 15.7% (118) Hämophilie B haben. Das mediane Alter ist 34 Jahre (1–93). Es haben 39.0% (294) eine schwere, 11.3% (85) eine mittelschwere und 49.4% (372) eine leichte Hämophilie. Von den Patienten mit schwerer Hämophilie wurden 38.4% (113) mit HCV infiziert und 12.6% (37) sind HIV positiv. Insgesamt haben 10.6% (67) aller Patienten mit Hämophilie A und 1.7% (2) aller Patienten mit Hämophilie B einen Hemmkörper in ihrer Anamnese. Von den Patienten mit schwerer Hämophilie erhalten 68.4% (201) eine Prophylaxe und 28.6% (84) eine Bedarfsbehandlung. Von den Patienten mit schwerer Hämophilie erhalten 65.0% (191) ein rekombinantes Produkt. Zusammenfassend erhalten die meisten Patienten mit schwerer Hämophilie eine Prophylaxe. HCV und HIV Infektionen sind immer noch von großer Bedeutung für die österreichischen Hämophilie-Patienten.

Hemophilia is a congenital bleeding disorder caused by the absence or decrease of clotting factor VIII (Hemophilia A) or XI (Hemophilia B). When severe, this X-linked disease results in intra-articular bleeding which can progress to joint destruction. This is known to be the most common complication of severe uncontrolled hemophilia. We present a case of arthroscopic assisted ankle arthrodesis in a young male presenting with advanced ankle hemophilic arthritis. Our case report presents a unique pathology and the successful 1-year post-operative outcome that can be accomplished through surgical intervention and a multidisciplinary treatment approach.

Hemophilia A (HA), is a X-linked recessive congenital bleeding disorder, caused by deficiency of the coagulation factor VIII (FVIII) which is encoded by coagulation factor 8 (F8). HA affects 1 of every 5,000 males worldwide. The intron 22 inversion (Inv22) mutation of F8 causes about 45% of severe HA cases. Here, we generated induced pluripotent stem cells (iPSCs) from a HA patient with Inv22 mutation by electroporation of urine-derived cells (UCs) with episomal plasmids under feeder-free, virus-free, serum-free condition and without oncogene c-MYC. This iPSCs line could facilitate future applications of human iPSCs by provide a valuable cell model.

Hemophilia is a congenital bleeding disorder that predominantly affects men. Home intravenous replacement of missing clotting factor is the most effective treatment; however, the uptake of preventative treatment (also known as prophylaxis) varies among men with hemophilia. The purpose of the current qualitative study was to describe the connections between masculinities and men’s ( n = 11) experiences of hemophilia across varying age groups. The inductively derived findings revealed bleed-related joint pain as the primary prompt for men to treat or seek medical help. Many men reported experiencing a high number of bleed-related injuries in adolescence, particularly in high school, oftentimes as a result of engaging in idealized masculine physical activities. Though the limitations imposed by hemophilia were contested by most men early on in their lives, as men grow older more conservative approaches were employed both in terms of treatment and activity to reduce the potential for residual bleed-related disabilities. Overall, the results indicate that men with hemophilia may benefit from peer and professional education about recognition, prevention, and optimal treatment of bleeds. Furthermore, masculine ideals act as important context in which men navigate hemophilia management practices and may facilitate contesting or conceding behaviors. Masculine ideals of strength and control may be garnered to facilitate optimal hemophilia management practices.

Background von Willebrand disease (VWD) is the most common congenital bleeding disorder. In women, menorrhagia is the most common bleeding symptom, and is disabling with iron deficiency anaemia, high health cost and poor quality of life. Current hormonal and non-hormonal therapies are limited by ineffectiveness and intolerance. Few data exist regarding von Willebrand factor (VWF), typically prescribed when other treatments fail. The lack of effective therapy for menorrhagia remains the greatest unmet healthcare need in women with VWD. Better therapies are needed to treat women with menorrhagia. Methods We conducted a survey of US haemophilia treatment centres (HTCs) and a literature review using medical subject heading (MeSH) search terms ‘von Willebrand factor,’ ‘menorrhagia’ and ‘von Willebrand disease’ to assess the use of VWF in menorrhagia. Analysis was by descriptive statistics. Results Of 83 surveys distributed to HTC MDs, 20 (24.1%) provided sufficient data for analysis. Of 1321 women with VWD seen during 2011–2014, 816 (61.8%) had menorrhagia, for which combined oral contraceptives, tranexamic acid and desmopressin were the most common first-line therapies for menorrhagia, whereas VWF was third-line therapy reported in 13 women (1.6%). Together with data from 88 women from six published studies, VWF safely reduced menorrhagia in 101 women at a dose of 33–100 IU kg−1 on day 1–6 of menstrual cycle. Conclusions This represents the largest VWD menorrhagia treatment experience to date. VWF safely and effectively reduces menorrhagia in women with VWD. A prospective clinical trial is planned to confirm these findings.

Hemophilia A is the most common congenital bleeding disorder caused by a deficiency in coagulation factor VIII activity, characterized by a marked bleeding tendency. It is inherited recessively. The most common complication of the disease is chronic arthropathy. In the prophylactic treatment regimen, the subjects receive preventative F VIII infusions every second day or three times a week. In an on-demand regimen, bleeds are treated as they occur. Analysis of the frequency and degree of chronic hemophilic arthropathy in patients with moderate and severe hemophilia A. Analysis of involvement of individual joints, and their score values by the treatment regimen (prophylaxis vs. on-demand treatment.) The study included 23 patients - 15 patients on „on-demand“ regimen and 8 patients who had prophylaxis, all being treated at the Clinic of Hematology and Clinical Immunology, Clinical Center Niš. In the assessment of frequency of complications we used descriptive statistics: the number, proportion and mean. The comparison of arithmetic means of the two samples was performed using the t-test. The comparison of frequency values was performed using the chi-square test or Fisher’s test. In the group without prophylaxis, the knee and hip were the most commonly affected sites (73.33% and 53.33%), and in the group with prophylaxis, the elbow joint was mostly affected (37.50%). The knee was statistically more often affected in patients without prophylaxis compared to those on prophylaxis. The knee score had the highest value in both groups. It was statistically significantly higher in patients without prophylaxis compared to those on prophylaxis. The hip score was the second highest value in the examined groups, the third was the elbow joint score, followed by the ankle score, and the lowest score was observed for the shoulder joint. Elbow and ankle scores were statistically significantly higher in patients without prophylaxis compared to those on prophylaxis. Chronic arthropathy is the most common complication in patients with severe and moderate Haemophilia A, with maximum involvement of the knee joint in both groups of patients (with or without prophylaxis), but with a statistically significantly higher score in patients without prophylaxis.