176 results on '"Congenital Bleeding Disorder"'
Search Results
2. Congenital Bleeding Disorders: Diagnosis and Management
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Dorgalaleh, Akbar, Daneshi, Maryam, Dabbagh, Ali, Crookston, Kendall P., and Dorgalaleh, Akbar, editor
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- 2023
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3. Hereditary Coagulation Disorders
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Malviya, Sanjana A., Deng, Yi, Nikolaidis, Melissa, Scher, Corey S., editor, Kaye, Alan David, editor, Liu, Henry, editor, Perelman, Seth, editor, and Leavitt, Sarah, editor
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- 2021
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4. Known Bleeding Disorders for Surgery
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Escobar, Miguel A., Nguyen, Trinh, Montanez, Natalie A., and Teruya, Jun, editor
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- 2021
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5. Diagnostic Challenges in Children With Congenital Bleeding Disorders: A Developing Country Perspective.
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Khaliq, Sehar
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HEMOPHILIA , *DIAGNOSTIC errors , *VON Willebrand disease ,DEVELOPING countries - Abstract
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. [ABSTRACT FROM AUTHOR]- Published
- 2021
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6. Congenital Bleeding Disorders
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Dorgalaleh, Akbar, Rad, Fariba, and Dorgalaleh, Akbar, editor
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- 2018
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7. Traumatic intracranial hemorrhage in pediatrics: Implications of factor XIII deficiency and consumptive coagulopathy in abusive head trauma evaluation.
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López, Arianexys Aquino, Cohen, Clay T., Small, Amanda, Lam, Fong Wilson, and Bachim, Angela N.
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INTRACRANIAL hemorrhage , *BLOOD coagulation disorders , *CONGENITAL disorders , *LITERATURE reviews , *BRAIN injuries , *UTERINE hemorrhage , *SKULL fractures - Abstract
For infants that present with intracranial hemorrhage in the setting of suspected abusive head trauma (AHT), the standard recommendation is to perform an evaluation for a bleeding disorder. Factor XIII (FXIII) deficiency is a rare congenital bleeding disorder associated with intracranial hemorrhages in infancy, though testing for FXIII is not commonly included in the initial hemostatic evaluation. The current pediatric literature recognizes that trauma, especially traumatic brain injury, may induce coagulopathy in children, though FXIII is often overlooked as having a role in pediatric trauma-induced coagulopathy. We report an infant that presented with suspected AHT in whom laboratory workup revealed a decreased FXIII level, which was later determined to be caused by consumption in the setting of trauma induced coagulopathy, rather than a congenital disorder. Within the Child Abuse Pediatrics Research Network (CAPNET) database, 85 out of 569 (15 %) children had FXIII testing, 3 of those tested (3.5 %) had absent FXIII activity on qualitative testing, and 2 (2.4 %) children had activity levels below 30 % on quantitative testing. In this article we review the literature on the pathophysiology and treatment of low FXIII in the setting of trauma. This case and literature review demonstrate that FXIII consumption should be considered in the setting of pediatric AHT. [ABSTRACT FROM AUTHOR]
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- 2024
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8. An investigational RNAi therapeutic targeting antithrombin for the treatment of hemophilia A and B
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Machin N and Ragni MV
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congenital bleeding disorder ,clotting factor ,fitusiran ,mRNA ,novel bypass ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Nicoletta Machin, Margaret V Ragni Department of Medicine, University of Pittsburgh, Hemophilia Center of Western Pennsylvania, Pittsburgh, PA, USA 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. Keywords: congenital bleeding disorder, clotting factor, fitusiran, mRNA, novel bypass
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- 2018
9. Known Bleeding Disorders for Surgery
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Escobar, Miguel A., Nguyen, Trinh, and Teruya, Jun, editor
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- 2016
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10. Congenital Bleeding Disorders
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Martinez, Maria, Graf, Lukas, Tsakiris, Dimitrios A., Marcucci, Carlo Enrique, editor, and Schoettker, Patrick, editor
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- 2015
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11. A Life-threatening Cardiomyopathy following Port-a-Cath Infection under Immune Tolerance Therapy
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Wiegand, G., Rauch, R., Effenberger, W., Brackmann, H.-H., Hofbeck, M., Scharrer, Inge, editor, and Schramm, Wolfgang, editor
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- 2003
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12. Characterization of Portuguese Haemophilia patients based on the National Registry Data
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Carlos Ferreira, Beatriz Sousa Santos, and Leonor Teixeira
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congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Computer science ,Incidence (epidemiology) ,Haemophilia A ,020206 networking & telecommunications ,02 engineering and technology ,Disease ,Haemophilia ,medicine.disease ,language.human_language ,hemic and lymphatic diseases ,0202 electrical engineering, electronic engineering, information engineering ,medicine ,language ,General Earth and Planetary Sciences ,020201 artificial intelligence & image processing ,Haemophilia B ,National registry ,Portuguese ,Intensive care medicine ,Congenital Bleeding Disorder ,General Environmental Science - Abstract
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.
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- 2021
13. Rare post-operative complications in a previously undiagnosed Congenital Factor X deficiency patient.
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Hassan, MOHD NAZRI, Abbas Ahmed, SUHAIR, Wan Abd Rahman, WAN SURIANA, Zulkafli, ZEFARINA, Husin, AZLAN, and Abdullah, WAN ZAIDAH
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Factor X (FX) deficiency is a rare autosomal recessive congenital bleeding disorder. The clinical presentation is among the most severe among the rare coagulation defects. Thus, majority of diagnosed patients will receive factor replacement therapy before surgical manipulation. However, the diagnosis of FX deficiency may be overlooked because it is a rare entity. This is a case report of a 15-year-old male patient who was diagnosed with FX deficiency after developing post-operative complications. With regular fresh frozen plasma infusion given, the patient responded well and recovered. However, had he been diagnosed earlier pre-operatively, the post-operative complication could have been prevented. Therefore, pre-operative coagulation screening should be performed in patients with significant bleeding history in both emergency and elective situations to prevent surgical morbidity related to post-operative bleeding. [ABSTRACT FROM AUTHOR]
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- 2016
14. Recombinant vs plasma-derived von Willebrand factor to prevent postpartum hemorrhage in von Willebrand disease
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Nicoletta Machin and Margaret V. Ragni
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Adult ,medicine.medical_specialty ,030204 cardiovascular system & hematology ,Hemophilia A ,Thrombosis and Hemostasis ,03 medical and health sciences ,0302 clinical medicine ,Von Willebrand factor ,Hemophilias ,Pregnancy ,hemic and lymphatic diseases ,von Willebrand Factor ,Von Willebrand disease ,Humans ,Medicine ,Congenital Bleeding Disorder ,Retrospective Studies ,Gynecology ,biology ,business.industry ,Postpartum Hemorrhage ,Retrospective cohort study ,Hematology ,medicine.disease ,Bleeding diathesis ,von Willebrand Diseases ,030220 oncology & carcinogenesis ,biology.protein ,Female ,business ,Body mass index ,Postpartum period - Abstract
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.
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- 2020
15. Multivessel Percutaneous Coronary Intervention in a Patient With Bernard-Soulier Syndrome
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Osman Faheem, Arsalan Hamid, Mohammad Khurshid, Bilal Hussain, and Anila Rashid
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0301 basic medicine ,medicine.medical_specialty ,Acute coronary syndrome ,CAD, coronary artery disease ,medicine.medical_treatment ,stenting ,Case Report ,030105 genetics & heredity ,CAD - Coronary artery disease ,Bernard–Soulier syndrome ,03 medical and health sciences ,0302 clinical medicine ,Clinical Case ,PCI - Percutaneous coronary intervention ,hemic and lymphatic diseases ,Internal medicine ,medicine ,Diseases of the circulatory (Cardiovascular) system ,antiplatelets ,DES, drug-eluting stent ,BSS, Bernard-Soulier syndrome ,Congenital Bleeding Disorder ,bleeding disorder ,PCI, percutaneous coronary intervention ,business.industry ,percutaneous coronary intervention ,Percutaneous coronary intervention ,medicine.disease ,Bernard-Soulier syndrome ,DAPT, dual-antiplatelet therapy ,Thrombosis ,RC666-701 ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,030217 neurology & neurosurgery - Abstract
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…
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- 2020
16. Molecular and clinical profile of type 2 von Willebrand disease in Iran: a thirteen-year experience
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Mohammad Said Enayat, Mohammad Jazebi, F. Ala, Maryam Rassoulzadegan, Mehran Bahraini, Shadi Tabibian, Akbar Dorgalaleh, and Mahmood Shams
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Male ,medicine.medical_specialty ,Time Factors ,Ecchymosis ,von Willebrand Disease, Type 2 ,Iran ,Hemorrhagic disorder ,Miscarriage ,03 medical and health sciences ,symbols.namesake ,0302 clinical medicine ,Untranslated Regions ,Internal medicine ,medicine ,Von Willebrand disease ,Humans ,Congenital Bleeding Disorder ,Menorrhagia ,Sanger sequencing ,Hematology ,business.industry ,Exons ,medicine.disease ,Introns ,Epistaxis ,030220 oncology & carcinogenesis ,Mutation ,symbols ,Female ,Molecular Profile ,medicine.symptom ,Gingival Hemorrhage ,business ,030215 immunology - Abstract
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.
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- 2020
17. Diagnostic Challenges in Children With Congenital Bleeding Disorders: A Developing Country Perspective
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Sehar Khaliq
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Pediatrics ,medicine.medical_specialty ,Hematology ,Adolescent ,business.industry ,Developing country ,General Medicine ,medicine.disease ,Hemophilia A ,Thrombocytopenic purpura ,Bernard–Soulier syndrome ,von Willebrand Diseases ,Internal medicine ,Child, Preschool ,medicine ,Von Willebrand disease ,Humans ,Haemophilia B ,Pakistan ,Disease management (health) ,Diagnostic Errors ,business ,Congenital Bleeding Disorder ,Child ,Developing Countries - Abstract
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.
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- 2021
18. How to use a coagulation screen
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Christine Macartney, Mark Gilmore, Sarah Kapur, and Andrew Thompson
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medicine.medical_specialty ,Screening test ,Sample (material) ,Contusions ,Hemorrhage ,030204 cardiovascular system & hematology ,Easy Bruising ,03 medical and health sciences ,0302 clinical medicine ,030225 pediatrics ,Clinical information ,medicine ,Humans ,Intensive care medicine ,Congenital Bleeding Disorder ,education ,Child ,education.field_of_study ,Hematologic Tests ,business.industry ,Sampling error ,Blood Coagulation Disorders ,Pediatrics, Perinatology and Child Health ,Coagulation screen ,Blood Coagulation Tests ,business - Abstract
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.
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- 2021
19. Addressing the impact of SARS-CoV-2 infection in persons with congenital bleeding disorders: The Italian MECCOVID-19 study
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Coluccia A., Marchesini E., Giuffrida A. C., Rivolta G. F., Ricca I., Zanon E., Luciani M., De Cristofaro R., Coppola A., Rocino A., Ambaglio C., Borchiellini A., Bonetti E., Caimi T. M., Carulli C., Contino L., Cultrera D., D'Attilio E., Delios G., Feola G., Giordano P., Giuffrida G., Grandone E., Lassandro G., Linari S., Margaglione M., Marino R., Molinari A. C., Napolitano M., Nichele I., Notarangelo L. D., Pasca S., Piscitelli L., Pollio B., Quintavalle G., Radossi P., Santoro C., Santoro R. C., Schiavulli M., Sottilotta G., Speciale V., Tagliaferri A., Valdre L., Coluccia A., Marchesini E., Giuffrida A.C., Rivolta G.F., Ricca I., Zanon E., Luciani M., De Cristofaro R., Coppola A., Rocino A., Ambaglio C., Borchiellini A., Bonetti E., Caimi T.M., Carulli C., Contino L., Cultrera D., D'Attilio E., Delios G., Feola G., Giordano P., Giuffrida G., Grandone E., Lassandro G., Linari S., Margaglione M., Marino R., Molinari A.C., Napolitano M., Nichele I., Notarangelo L.D., Pasca S., Piscitelli L., Pollio B., Quintavalle G., Radossi P., Santoro C., Santoro R.C., Schiavulli M., Sottilotta G., Speciale V., Tagliaferri A., and Valdre L.
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Adult ,Inherited ,Male ,Pediatrics ,medicine.medical_specialty ,2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,congenital bleeding disorders ,congenital bleeding disorder ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,haemophilia ,Hemorrhage ,Haemophilia ,Letter to the Editors ,SARS‐CoV‐2 ,Young Adult ,Blood Coagulation Disorders, Inherited ,COVID‐19 ,COVID-19 ,epidemiology ,observational study ,SARS-CoV-2 ,Aged ,Child, Preschool ,Disease Management ,Female ,Humans ,Italy ,Middle Aged ,Epidemiology ,medicine ,Young adult ,Disease management (health) ,Child ,Preschool ,Letter to the Editor ,Genetics (clinical) ,business.industry ,Hematology ,General Medicine ,Blood Coagulation Disorders ,medicine.disease ,Observational study ,business - Abstract
congenital bleeding disorders
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- 2021
20. Hereditary Coagulation Disorders
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Melissa Annette Nikolaidis, Yi Deng, and Sanjana A. Malviya
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medicine.medical_specialty ,Hematology ,business.industry ,Perioperative ,medicine.disease ,Bleeding diathesis ,Coagulation ,Internal medicine ,Hemostasis ,medicine ,Coagulopathy ,business ,Intensive care medicine ,Congenital Bleeding Disorder ,Coagulation Disorder - Abstract
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.
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- 2021
21. Outcomes for studies assessing the efficacy of hemostatic therapies in persons with congenital bleeding disorders
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Stacy E. Croteau, Robert F. Sidonio, Camila C. Aquino, Alfonso Iorio, Nigel S. Key, Christine L. Kempton, Victoria Borg Debono, Federico Germini, Amy L. Dunn, Guy Young, and Drashti Pete
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medicine.medical_specialty ,MEDLINE ,Hemorrhage ,CINAHL ,PsycINFO ,Disease ,030204 cardiovascular system & hematology ,Haemophilia ,Hemophilia A ,Hemostatics ,03 medical and health sciences ,0302 clinical medicine ,Quality of life (healthcare) ,medicine ,Humans ,Intensive care medicine ,Congenital Bleeding Disorder ,Genetics (clinical) ,Hemostasis ,business.industry ,Hematology ,General Medicine ,medicine.disease ,Clinical trial ,Quality of Life ,business ,030215 immunology - Abstract
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.
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- 2020
22. Perioperative considerations in a girl with Glanzmann thrombasthenia. Case report
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Carolina López Pérez and Alexander Trujillo Mejía
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medicine.medical_specialty ,biology ,business.industry ,Perioperative ,030204 cardiovascular system & hematology ,Critical Care and Intensive Care Medicine ,Platelet membrane glycoprotein ,Surgery ,03 medical and health sciences ,0302 clinical medicine ,Anesthesiology and Pain Medicine ,Platelet transfusion ,Recombinant factor VIIa ,Hemostasis ,medicine ,biology.protein ,Platelet ,Congenital Bleeding Disorder ,business ,Tranexamic acid ,030215 immunology ,medicine.drug - Abstract
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.
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- 2020
23. Critical Review of the Pivotal Studies of Four rFVIII Products for the Treatment of Hemophilia A Patients: The Role of Octocog Alfa
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Lucia Sara D'Angiolella, Matteo Nicola Dario Di Minno, Paolo Cortesi, Lorenzo G. Mantovani, and Angelo Claudio Molinari
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Clotting factor ,lcsh:R5-920 ,Pediatrics ,medicine.medical_specialty ,education.field_of_study ,business.industry ,Population ,Gold standard ,Hemophilia ,Recombinant factor VIII ,Kovaltry® ,Critical review ,Haemophilia ,medicine.disease ,law.invention ,Clinical trial ,critical review ,recombinant factor viii ,Randomized controlled trial ,law ,hemophilia ,Octocog alfa ,Medicine ,kovaltry® ,lcsh:Medicine (General) ,business ,education ,Congenital Bleeding Disorder - Abstract
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.
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- 2020
24. RasGRP2 Structure, Function and Genetic Variants in Platelet Pathophysiology
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Matthias Canault, Marie-Christine Alessi, Centre recherche en CardioVasculaire et Nutrition = Center for CardioVascular and Nutrition research (C2VN), Aix Marseille Université (AMU)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de Recherche pour l’Agriculture, l’Alimentation et l’Environnement (INRAE), Laboratoire d'hématologie biologique [Hôpital de la Timone - Hôpital Nord - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), and Prémilleux, Annick
- Subjects
Male ,0301 basic medicine ,[SDV]Life Sciences [q-bio] ,Review ,030204 cardiovascular system & hematology ,Bioinformatics ,Shelterin Complex ,lcsh:Chemistry ,0302 clinical medicine ,Guanine Nucleotide Exchange Factors ,Medicine ,Platelet ,lcsh:QH301-705.5 ,Spectroscopy ,platelet ,inherited platelet disorder 1. RasGRPs General Description Cell Signal Transduction Is a Finely Regulated Process That Relies on Several Control Hubs ,[SDV.MHEP] Life Sciences [q-bio]/Human health and pathology ,RasGRP2 ,Structure function ,General Medicine ,Pathophysiology ,3. Good health ,Computer Science Applications ,[SDV] Life Sciences [q-bio] ,Child, Preschool ,Female ,Rap1 ,Guanine nucleotide exchange factor ,Signal Transduction ,Blood Platelets ,Telomere-Binding Proteins ,inherited platelet disorder ,Hemorrhage ,Platelet Glycoprotein GPIIb-IIIa Complex ,Catalysis ,Inorganic Chemistry ,03 medical and health sciences ,[SDV.MHEP.CSC]Life Sciences [q-bio]/Human health and pathology/Cardiology and cardiovascular system ,Humans ,Physical and Theoretical Chemistry ,Congenital Bleeding Disorder ,Molecular Biology ,business.industry ,Organic Chemistry ,Genetic variants ,Infant ,030104 developmental biology ,lcsh:Biology (General) ,lcsh:QD1-999 ,Blood Platelet Disorders ,business ,Function (biology) ,[SDV.MHEP]Life Sciences [q-bio]/Human health and pathology - Abstract
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.
- Published
- 2020
25. Clinical significance of slightly reduced von Willebrand factor activity (30–50 IU/dL)
- Author
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Bernadeta Ceglarek and Ksenia Bykowska
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,biology ,business.industry ,Mucocutaneous zone ,Gene mutation ,medicine.disease ,Gastroenterology ,Von Willebrand factor ,hemic and lymphatic diseases ,Internal medicine ,Internal Medicine ,biology.protein ,medicine ,Von Willebrand disease ,Clinical significance ,Family history ,Congenital Bleeding Disorder ,business ,Pathological ,circulatory and respiratory physiology - Abstract
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 (
- Published
- 2020
26. A Cross-Sectional Study of Women and Girls with Congenital Bleeding Disorders: The American Thrombosis and Hemostasis Network Cohort
- Author
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Dunlei Cheng, Michael Recht, Kristina M. Haley, Robert F. Sidonio, Roshni Kulkarni, and Shirley M. Abraham
- Subjects
Adult ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Cross-sectional study ,Population ,Hemorrhage ,030204 cardiovascular system & hematology ,Cohort Studies ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,Von Willebrand disease ,Medicine ,Humans ,Congenital Bleeding Disorder ,education ,Child ,Menorrhagia ,Aged ,Data Management ,Retrospective Studies ,Aged, 80 and over ,education.field_of_study ,business.industry ,Infant ,Retrospective cohort study ,General Medicine ,Blood Coagulation Disorders ,Middle Aged ,medicine.disease ,Thrombosis ,United States ,von Willebrand Diseases ,Cross-Sectional Studies ,Hemostasis ,Child, Preschool ,Cohort ,Female ,business ,030215 immunology - Abstract
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.
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- 2020
27. Epidemiology of Congenital Bleeding Disorders: a Nationwide Population-based Korean Study
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Hoi Soo Yoon, Min Jin Kim, Ja Min Byun, Taemi Youk, Young Jin Kim, Yujin Han, Jae Hee Lee, Jongha Yoo, and Tae Sung Park
- Subjects
Adult ,Male ,medicine.medical_specialty ,Pediatrics ,Adolescent ,Databases, Factual ,Epidemiology ,Population ,Population based ,Hemophilia A ,Hemophilia B ,Young Adult ,03 medical and health sciences ,Blood Coagulation Disorders, Inherited ,0302 clinical medicine ,Republic of Korea ,Health insurance ,medicine ,Von Willebrand disease ,Humans ,Oncology & Hematology ,030212 general & internal medicine ,Congenital Bleeding Disorder ,Child ,education ,education.field_of_study ,Korea ,business.industry ,Incidence ,Infant, Newborn ,Infant ,General Medicine ,Middle Aged ,medicine.disease ,von Willebrand Diseases ,Nationwide ,Child, Preschool ,Female ,Original Article ,business - Abstract
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
- Published
- 2020
28. An investigational RNAi therapeutic targeting antithrombin for the treatment of hemophilia A and B
- Author
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Nicoletta Machin and Margaret V. Ragni
- Subjects
0301 basic medicine ,Clotting factor ,Gene knockdown ,business.industry ,congenital bleeding disorder ,mRNA ,Antithrombin ,Review ,Hematology ,Perioperative ,030204 cardiovascular system & hematology ,Pharmacology ,clotting factor ,fitusiran ,Clinical trial ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,RNA interference ,Hemostasis ,Concomitant ,medicine ,novel bypass ,business ,medicine.drug - 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.
- Published
- 2018
29. Emergencies in Hemophilia
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Michael W. Dunn, Gary Woods, and Amy L. Dunn
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medicine.medical_specialty ,Bleeding episodes ,Factor replacement ,business.industry ,Medical evaluation ,Emergency department ,030204 cardiovascular system & hematology ,Acute bleeding ,Inhibitory antibodies ,03 medical and health sciences ,0302 clinical medicine ,Pediatrics, Perinatology and Child Health ,Emergency Medicine ,Medicine ,Hematologist ,business ,Congenital Bleeding Disorder ,Intensive care medicine ,030215 immunology - Abstract
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.
- Published
- 2018
30. No. 163-Gynaecological and Obstetric Management of Women With Inherited Bleeding Disorders
- Author
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Christine Derzko, Michèle David, Christine Demers, and Joanne Douglas
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Canada ,Pediatrics ,medicine.medical_specialty ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,03 medical and health sciences ,Blood Coagulation Disorders, Inherited ,0302 clinical medicine ,Pregnancy ,medicine ,Von Willebrand disease ,Humans ,Congenital Bleeding Disorder ,Desmopressin ,Contraindication ,Hysterectomy ,postpartum bleeding ,business.industry ,Pregnancy Complications, Hematologic ,Obstetrics and Gynecology ,Delivery, Obstetric ,medicine.disease ,Surgery ,030220 oncology & carcinogenesis ,Female ,business ,Tranexamic acid ,Blood sampling ,medicine.drug - Abstract
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).
- Published
- 2018
31. Gene Therapy for Hemophilia: Progress to Date
- Author
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John C. Chapin and Paul E. Monahan
- Subjects
0301 basic medicine ,Genetic enhancement ,Transgene ,Population ,Hemophilia A ,Hemophilia B ,03 medical and health sciences ,Pharmacotherapy ,Immune system ,Humans ,Medicine ,Pharmacology (medical) ,Congenital Bleeding Disorder ,education ,Pharmacology ,education.field_of_study ,biology ,business.industry ,Genetic Therapy ,General Medicine ,Dependovirus ,Clinical trial ,030104 developmental biology ,Immunology ,biology.protein ,Antibody ,business ,Biotechnology - Abstract
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.
- Published
- 2017
32. Peginterferon α-2a and ribavirin treatment of patients with haemophilia and hepatitis C virus infection: a single-centre study of 367 cases.
- Author
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Alavian, Seyed-Moayed, Tabatabaei, Seyed Vahid, Keshvari, Maryam, Behnava, Bita, Miri, Seyyed Mohammad, Elizee, Pegah Karimi, and Lankarani, Kamran Bagheri
- Subjects
- *
HEPATITIS C virus , *HEMOPHILIA , *HIV , *RIBAVIRIN , *BODY weight , *THERAPEUTICS - Abstract
Background/aims: Chronic hepatitis C virus infection (HCV) is a major comorbidity in patients with haemophilia. Peginterferon alpha and ribavirin is current standard anti-HCV thrapy but there is little information about safety and efficacy of peginterferon α-2a and ribavirin combination therapy in these patients. Material and methods: In an open-label single-treatment arm cohort study, 367 haemophilia patients seronegative for hepatitis B and human immunodeficiency virus markers and chronically infected with HCV (HCV RNA>50 IU/ml for at least 6 months) received 180 μg of Pegasys® and 800–1200 mg of ribavirin according to body weight. Genotypes 1 and 4, mixed and untypable infections were treated for 48 weeks, while genotypes 2 and 3 were treated for 24 weeks. The efficacy of therapy was expressed as sustained virological response (SVR). Results: Two hundred and twenty-five subjects [61%, 95% confidence interval (CI) 56–66] achieved SVR, 66 patients relapsed and 30 subjects did not respond and nine patients developed breakthrough during treatment. In a multivariate logistic regression model, age<24 odds ratio (OR)=1.8 (95% CI 1.1–3.1), genotype non-1 OR=1.8 (95% CI 1.1–3.2), BMI<25 OR=2.1 (95% CI 1.3–3.3) and HCV RNA<600 000 IU/ml OR=1.7 (95% CI 1.1–3.2) were independent predictors of SVR. Eight patients discontinued the treatment because of persistent neutropaenia and 22 subjects were dropped out because of intractable side effects. Furthermore, two patients died during treatment and five were lost to follow-up after treatment cessation. Conclusions: Peginterferon alpha-2a in combination with weight-based ribavirin has SVR rate of 51% for genotype 1 and 71% for genotype non-1 infections in haemophilia patients. Age<24, BMI<25, viral load<600 000 IU/ml and genotype non-1 are the major determinants of SVR achievement in these patients. [ABSTRACT FROM AUTHOR]
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- 2010
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33. Clinical outcome of interferon and ribavirin combination treatment in hepatitis C virus infected patients with congenital bleeding disorders in Iran.
- Author
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RAHMANI, M., TOOSI, M. N., GHANNADI, K., LARI, G. R., JAZEBI, M., RASOULZADEGAN, M., and ALA, F.
- Subjects
- *
INTERFERONS , *HEPATITIS C virus , *VIRAL hepatitis , *RIBAVIRIN , *ANTINEOPLASTIC agents , *NEUTROPENIA - Abstract
Hepatitis C virus (HCV) infection is a major cause of morbidity and mortality in patients with inherited bleeding disorders. The results of interferon and ribavirin combination therapy have been reported in a limited number of clinical trials on these patients. Peginterferon is a costly treatment. Conventional interferon and ribavirin therapy is still the main available and affordable antiviral therapy in some countries. The goal of this study was to assess the effectiveness and safety of interferon alfa-2b plus ribavirin in HIV seronegative, non-alcoholic, non-cirrhotic, naïve subjects with congenital coagulopathy. Between May 2003 and August 2007, 103 haemophiliacs were treated consecutively with standard inclusion and exclusion criteria, with interferon alfa-2b (PDferon B®) 3MIU three times a week subcutaneously plus ribavirin, for 24–48 weeks, with appropriate dose adjustments. They were all scheduled to have serial visits and laboratory tests. Among 7(6.8%) female and 96(93.2%) male haemophiliacs, 11(10.68%) cases did not complete the study because of psychological side effects. With intent-to-treat analysis, end-of-treatment response was 63.1%, and sustained virological response (SVR) was 56.3%. There was a significant correlation between SVR and genotype, baseline HCV viral load, rapid virological response, early virological response and BMI. A decrease in the haemoglobin level of two patients required ribavirin dose reduction. One developed thrombocytopenia at the end of treatment, but none had neutropenia. Hypothyroidism was observed in two patients. Interferon plus ribavirin combination therapy in HCV-infected haemophilic patients is well tolerated and treatment outcomes appear to be similar to those seen in the general population. [ABSTRACT FROM AUTHOR]
- Published
- 2009
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34. The Evaluation and Management of Neonatal Coagulation Disorders.
- Author
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Saxonhouse, Matthew A. and Manco-Johnson, Marilyn J.
- Abstract
Neonatal hemostatic abnormalities can present diagnostic and therapeutic challenges to the physician. Developmental deficiencies and/or increases of certain coagulation proteins, coupled with acquired or genetic risk factors, can result in a hemorrhagic or thromboembolic emergency. The timely diagnosis of a congenital hemorrhagic or thrombotic disorder can avoid significant long-term sequelae. However, due to the lack of randomized clinical trials addressing the management of neonatal coagulation disorders, treatment strategies are usually empiric and not evidence-based. In this chapter, we will review the neonatal hemostatic system and will discuss the most common types of hemorrhagic and thrombotic disorders. Congenital and acquired risk factors for hemorrhagic and thromboembolic disorders will be presented, as well as current treatment options. Finally, suggested evaluations for neonates with either hemorrhagic or thromboembolic problems will be reviewed. [Copyright &y& Elsevier]
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- 2009
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35. Recombinant factor XIII prophylaxis is safe and effective in young children with congenital factor XIII‐A deficiency: international phase 3b trial results
- Author
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Michael Williams, Andrew M. Will, Lotte Jacobsen, Bryce A. Kerlin, Aida Inbal, May-Lill Garly, and Susan L. Kearney
- Subjects
Male ,Pediatrics ,medicine.medical_specialty ,Time Factors ,medicine.medical_treatment ,030204 cardiovascular system & hematology ,Drug Administration Schedule ,03 medical and health sciences ,0302 clinical medicine ,Pharmacokinetics ,Fibrinolysis ,medicine ,Humans ,Factor XIII deficiency ,Adverse effect ,Congenital Bleeding Disorder ,Bleeding episodes ,Factor XIII ,Coagulants ,business.industry ,Head injury ,Age Factors ,Infant ,Hematology ,medicine.disease ,Factor XIII Deficiency ,Recombinant Proteins ,Treatment Outcome ,Child, Preschool ,Female ,Factor XIIIa ,business ,030215 immunology ,medicine.drug - Abstract
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
- Published
- 2017
36. Current and future approaches to overcoming the challenges of hemophilia treatment personalization
- Author
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K. N. Steinitz-Trost, Jennifer Doralt, and Alessandro Gringeri
- Subjects
medicine.medical_specialty ,business.industry ,Health Policy ,Alternative medicine ,030204 cardiovascular system & hematology ,Precision medicine ,Digital health ,Unmet needs ,Personalization ,03 medical and health sciences ,0302 clinical medicine ,Paradigm shift ,medicine ,Pharmacology (medical) ,Dosing ,Intensive care medicine ,Congenital Bleeding Disorder ,business ,Pharmacology, Toxicology and Pharmaceutics (miscellaneous) ,030215 immunology - Abstract
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...
- Published
- 2017
37. Transjugular liver biopsy is a safe and effective intervention to guide management for patients with a congenital bleeding disorder infected with hepatitis C.
- Author
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Dawson, M. A., McCarthy, P. H., Walsh, M. E., McLean, C. A., Thomson, K., Roberts, S., and Street, A. M.
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BIOPSY , *LIVER , *HEPATITIS C virus , *HEMORRHAGE , *DISEASES , *MORTALITY , *PATIENTS - Abstract
Abstract The prevalence of hepatitis C virus (HCV) infection in adult patients with a congenital bleeding disorder (CBD) approaches 95% and is a major cause of morbidity and mortality. Histological examination of the liver remains the cornerstone of management decisions in patients without a CBD. The reluctance to perform liver biopsies in patients with a CBD has been a major limitation in the management of these patients. We are currently the only haemophilia centre in Australasia performing liver biopsies in patients with a CBD for the purpose of guiding prognostic and therapeutic decisions. We report here the results of our centre's experience with transjugular liver biopsy (TJLB) in patients with a CBD. An adequate specimen for histological assessment was attained from all of the patients. There were no major complications recorded. Patients were hospitalized for ≤ 48 h for haemostasis prophylaxis. The diagnostic specimen obtained from patients was integral in guiding their future management. We suggest that with a coordinated multidisciplinary approach, TJLB can be performed in patients with a CBD. (Intern Med J 2005; 35: 556–559) [ABSTRACT FROM AUTHOR]
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- 2005
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38. Interest of transjugular liver biopsy in adult patients with haemophilia or other congenital bleeding disorders infected with hepatitis C virus.
- Author
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Stieltjes, Natalie, Ounnoughene, Nadra, Sava, Emilie, Paugy, Patricia, Roussel-Robert, Valérie, Rosenberg, Arielle R., Terris, Benoit, Salmon-Céron, Dominique, and Sogni, Philippe
- Subjects
- *
HEPATITIS C , *PROGNOSIS , *HISTOLOGY , *LIVER biopsy , *HEMOPHILIA , *HEPATITIS C virus , *POLYMERASE chain reaction , *HIV , *HOSPITAL care - Abstract
Liver histology is important for prognosis and treatment strategy in patients with hepatitis C. We report a 10-year experience of transjugular liver biopsy (TJLB) in patients with haemophilia and other congenital bleeding disorders (CBD) in terms of safety, efficiency and therapeutic consequences. TJLB was proposed to patients who were regularly followed for CBD, and were hepatitis C virus (HCV) positive by polymerase chain reaction. Patients with inhibitors or who were human immunodeficiency virus (HIV) positive with CD4 cells <0·2 × 109/l or with evidence of liver failure were excluded. TJLB was performed during a short hospitalization with factor replacement. Between 1992 and 2002, 88 TJLB were performed in 69 of 151 adult HCV patients (39% HIV positive). CBD was haemophilia A in 68% and haemophilia B in 24%. Few mild adverse events were recorded. Histology was assessable in 78 of 88 procedures (89%). Twenty-nine (37%) cases demonstrated minimal change (METAVIR A ≤ 1 and F ≤ 1). Extended fibrosis or cirrhosis was recorded in 23 procedures (26%), all in patients whose infection period was longer than 20 years. No relationship between liver histology, HIV status or HCV genotype was found. TJLB appears to be safe and useful in HCV patients with CBD. One-third of patients had minimal histological changes and could avoid systematic anti-HCV treatment. [ABSTRACT FROM AUTHOR]
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- 2004
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39. Transjugular liver biopsy is safe and diagnostic for patients with congenital bleeding disorders and hepatitis C infection.
- Author
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DiMichele, D.M., Mirani, G., Canchis, P. Wilfredo, Trost, D.W., and Talal, A.H.
- Subjects
- *
BIOPSY , *HEMORRHAGE , *HEMOPHILIA , *BLOOD coagulation factors - Abstract
Summary. The prevalence of chronic hepatitis C virus (HCV) infection among patients with severe congenital bleeding disorders is as high as 98%. Advances in HCV treatment currently result in sustained virological response rates of ≥50%. Recent recommendations have reaffirmed that liver biopsy, which provides a direct histological assessment of liver inflammation and fibrosis, is still important for accurate diagnosis and therapeutic decision making. Percutaneous liver biopsy is a simple, standardized procedure that can be performed rapidly and relatively inexpensively, and has been safely performed in patients with congenital coagulopathies. However, the safety and efficacy of the transjugular approach (transjugular liver biopsy, TJLB), recommended for patients with acquired coagulopathies, has only been minimally studied in the congenital bleeding diathesis population. We now report our institutional experience with TJLB in 13 such adult patients (mean age 33 years) with severe/mild haemophilia A/B (10); von Willebrand disease (1); factor V deficiency (1) and factor XIII deficiency (1). Data were collected by retrospective chart review and the TJLB was performed according to institutional protocol as described. Haemostasis prophylaxis was given for 1–5 days. Patients were hospitalized for ≤48 h and all tolerated the procedure without bleeding. Three patients experienced self-limited abdominal discomfort; one episode was accompanied by transient transaminaemia. Diagnostic specimens were obtained from all patients and were instrumental in the therapeutic decision-making process. We suggest that with a co-ordinated multidisciplinary approach to care, TJLB is a safe, effective and potentially cost-effective alternative to the percutaneous approach in the congenital bleeding disorders population. [ABSTRACT FROM AUTHOR]
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- 2003
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40. Hemophilia A in Afghanistan, the first report
- Author
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Akbar Dorgalaleh, Shadi Tabibian, Sayad Hamid Mousavi, and Hoda Motlagh
- Subjects
Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Pediatrics ,medicine.medical_specialty ,Adolescent ,Central asia ,Clinical manifestation ,Disease ,030204 cardiovascular system & hematology ,Hemophilia A ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Hemarthrosis ,Medicine ,Humans ,Family history ,Congenital Bleeding Disorder ,Child ,Factor VIII ,business.industry ,Incidence (epidemiology) ,Afghanistan ,Hematology ,General Medicine ,medicine.disease ,Coagulation ,Health Resources ,Blood Coagulation Tests ,business ,030215 immunology - Abstract
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.
- Published
- 2019
41. Acute Myelogenous Leukemia With Trisomy 8 and Concomitant Acquired Factor VII Deficiency
- Author
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Jonathan Bowen, Leila Moosavi, Jeffrey A Coleman, Arash Heidari, and Everardo Cobos
- Subjects
Myeloid ,Epidemiology ,Factor VII Deficiency ,Trisomy ,Case Report ,Trisomy 8 ,Gastroenterology ,vitamin K ,Acquired Factor VII Deficiency ,0302 clinical medicine ,Medicine ,Safety, Risk, Reliability and Quality ,Cancer ,Pediatric ,lcsh:R5-920 ,Leukemia ,cytogenetic abnormality ,Hematology ,Leukemia, Myeloid, Acute ,030220 oncology & carcinogenesis ,Pair 8 ,Female ,lcsh:Medicine (General) ,Safety Research ,Human ,Chromosomes, Human, Pair 8 ,lcsh:RB1-214 ,Adult ,medicine.medical_specialty ,acute myelogenous leukemia ,Antineoplastic Agents ,Acute ,Chromosomes ,Sepsis ,03 medical and health sciences ,Myelogenous ,Rare Diseases ,Clinical Research ,trisomy 8 ,Internal medicine ,lcsh:Pathology ,Humans ,Congenital Bleeding Disorder ,business.industry ,Autoantibody ,Induction chemotherapy ,medicine.disease ,Brain Disorders ,business ,030215 immunology - Abstract
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.
- Published
- 2019
42. Comprehensive care for hemophilia and other inherited bleeding disorders
- Author
-
David Page
- Subjects
Clotting factor ,medicine.medical_specialty ,Factor VIII ,business.industry ,Hematology ,Hepatitis C ,Disease ,History, 20th Century ,medicine.disease ,Hemophilia A ,Hemophilia B ,History, 21st Century ,Factor IX ,von Willebrand Diseases ,Infectious disease (medical specialty) ,hemic and lymphatic diseases ,Von Willebrand disease ,medicine ,Humans ,Hematologist ,Congenital Bleeding Disorder ,Intensive care medicine ,business ,medicine.drug - Abstract
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.
- Published
- 2019
43. Masculinity Challenges for Men With Severe Hemophilia
- Author
-
Kenneth Reinicke, Ida Stjerne Søgaard, and Sarah Mentzler
- Subjects
adolescent men ,Adult ,Male ,Health (social science) ,men’s health ,media_common.quotation_subject ,Social Stigma ,lcsh:Medicine ,Hemophilia A ,Danish ,03 medical and health sciences ,Fathers ,Qualitative analysis ,Age groups ,hemophilia ,Adaptation, Psychological ,Humans ,Lack of knowledge ,Interpersonal Relations ,Congenital Bleeding Disorder ,Qualitative Research ,media_common ,Masculinity ,030505 public health ,05 social sciences ,lcsh:R ,Public Health, Environmental and Occupational Health ,Middle Aged ,dialogue workshop ,language.human_language ,Negotiation ,Social Perception ,050903 gender studies ,language ,Original Article ,0509 other social sciences ,0305 other medical science ,Psychology ,Men's Health ,Qualitative research ,Clinical psychology ,qualitative methods - Abstract
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.
- Published
- 2019
44. Total hip arthroplasty for a woman with hemophilia A -case report
- Author
-
Akio Kanda, Itaru Morohashi, Kazuo Kaneko, Atsuhiko Mogami, and Osamu Obayashi
- Subjects
Clotting factor ,Pediatrics ,medicine.medical_specialty ,congenital, hereditary, and neonatal diseases and abnormalities ,business.industry ,Usually asymptomatic ,Case Report ,General Medicine ,03 medical and health sciences ,0302 clinical medicine ,Coagulation ,030220 oncology & carcinogenesis ,hemic and lymphatic diseases ,Medicine ,Childbirth ,030211 gastroenterology & hepatology ,Surgery ,business ,Congenital Bleeding Disorder ,Hemophilia A carrier ,Total hip arthroplasty - Abstract
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.
- Published
- 2019
45. Epidemiology and Treatment of Patients with Haemophilia in Austria-Update from the Austrian Haemophilia Registry
- Author
-
Werner Streif, Michael Grundbichler, Christoph Male, Rudolf Schwarz, Clemens Feistritzer, Karl Zwiauer, Wolfgang Muntean, Peter Neumeister, Katharina Thom, Alexander Hörbst, Neil Jones, Judit Rejtő, Sylvia Reitter-Pfoertner, Stefan Oberbichler, Sylvia Kepa, Ingrid Pabinger, and Gerhard Schuster
- Subjects
Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Pediatrics ,Adolescent ,Hepatitis C virus ,Haemophilia A ,Population ,HIV Infections ,Hemorrhage ,030204 cardiovascular system & hematology ,Haemophilia ,medicine.disease_cause ,Hemophilia A ,Severity of Illness Index ,03 medical and health sciences ,Young Adult ,0302 clinical medicine ,hemic and lymphatic diseases ,Epidemiology ,medicine ,Prevalence ,Humans ,Haemophilia B ,Registries ,education ,Congenital Bleeding Disorder ,Child ,Aged ,Aged, 80 and over ,education.field_of_study ,business.industry ,Infant ,Hematology ,Middle Aged ,medicine.disease ,Combined Modality Therapy ,Hepatitis C ,Austria ,Child, Preschool ,Cohort ,Female ,business ,030215 immunology - Abstract
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.
- Published
- 2018
46. Scope assisted ankle arthrodesis in a young male with hemophilic arthritis: A case study
- Author
-
Kevin Nguyen, Devon Consul, and Christopher F. Hyer
- Subjects
Clotting factor ,congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,business.industry ,Ankle arthrodesis ,Disease ,Hemophilic Arthritis ,Surgery ,medicine.anatomical_structure ,hemic and lymphatic diseases ,Medicine ,Ankle ,Complication ,business ,Congenital Bleeding Disorder ,Young male - Abstract
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.
- Published
- 2021
47. Generation of induced pluripotent stem cell GZLSL-i001-A derived from urine-derived cells of Hemophilia A patient with Inv22 mutation
- Author
-
Diyu Chen, Xiaoxia Guo, Nengqing Liu, Yinghong Yang, Xiaofang Sun, Yingjun Xie, Juan Zeng, Bing Song, Yi Cheng, Yuanshuai Li, Bangzhu Chen, Lina He, Dian Lu, and Yanting Xue
- Subjects
Male ,0301 basic medicine ,Induced Pluripotent Stem Cells ,Urine ,Biology ,Hemophilia A ,medicine.disease_cause ,Cell Line ,03 medical and health sciences ,0302 clinical medicine ,Plasmid ,medicine ,Humans ,Induced pluripotent stem cell ,Congenital Bleeding Disorder ,lcsh:QH301-705.5 ,Mutation ,Factor VIII ,Oncogene ,Electroporation ,Cell Biology ,General Medicine ,Introns ,030104 developmental biology ,lcsh:Biology (General) ,Coagulation ,Cancer research ,030217 neurology & neurosurgery ,Developmental Biology - Abstract
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.
- Published
- 2020
48. Men, Masculinities, and Hemophilia
- Author
-
Shannon Jackson, John L Oliffe, Laszlo Kalmar, Leanne M. Currie, and Deborah Gue
- Subjects
Adult ,Male ,congenital, hereditary, and neonatal diseases and abnormalities ,Health (social science) ,Psychotherapist ,media_common.quotation_subject ,lcsh:Medicine ,Context (language use) ,Disease ,030204 cardiovascular system & hematology ,Hemophilia A ,Haemophilia ,03 medical and health sciences ,0302 clinical medicine ,hemic and lymphatic diseases ,Adaptation, Psychological ,medicine ,Humans ,030212 general & internal medicine ,Congenital Bleeding Disorder ,Qualitative Research ,Depression (differential diagnoses) ,Defense Mechanisms ,media_common ,Masculinity ,Clotting factor ,Depression ,business.industry ,lcsh:R ,Public Health, Environmental and Occupational Health ,Middle Aged ,medicine.disease ,Men's Health ,business ,Clinical psychology ,Qualitative research - Abstract
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.
- Published
- 2016
49. Von Willebrand factor for menorrhagia: a survey and literature review
- Author
-
Margaret V. Ragni, Lynn M. Malec, Nicoletta Machin, Anne T. Neff, Peter A. Kouides, Andra H. James, B. A. Konkle, Donald Brambilla, Craig M. Kessler, and Claire S. Philipp
- Subjects
congenital, hereditary, and neonatal diseases and abnormalities ,medicine.medical_specialty ,Pediatrics ,Databases, Factual ,030204 cardiovascular system & hematology ,Haemophilia ,Article ,03 medical and health sciences ,0302 clinical medicine ,Von Willebrand factor ,hemic and lymphatic diseases ,Antifibrinolytic agent ,von Willebrand Factor ,medicine ,Von Willebrand disease ,Humans ,Deamino Arginine Vasopressin ,Desmopressin ,Congenital Bleeding Disorder ,Menorrhagia ,Genetics (clinical) ,Gynecology ,biology ,business.industry ,Hematology ,General Medicine ,medicine.disease ,Antifibrinolytic Agents ,female genital diseases and pregnancy complications ,Clinical trial ,von Willebrand Diseases ,Tranexamic Acid ,biology.protein ,Female ,business ,Tranexamic acid ,Contraceptives, Oral ,030215 immunology ,medicine.drug - Abstract
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.
- Published
- 2016
50. FREQUENCY AND DEGREE OF CHRONIC ARTHROPATHY IN HEMOPHILIA A PATIENTS ON PROPHYLACTIC AND ON-DEMAND TREATMENT
- Author
-
Dragana Drašković and Miodrag Vučić
- Subjects
musculoskeletal diseases ,medicine.medical_specialty ,Elbow ,lcsh:Medicine ,030204 cardiovascular system & hematology ,Knee Joint ,Hemophilia A ,Industrial and Manufacturing Engineering ,03 medical and health sciences ,0302 clinical medicine ,on-demand treatment ,Internal medicine ,medicine ,Congenital Bleeding Disorder ,030222 orthopedics ,Hematology ,business.industry ,lcsh:R ,hemophilic arthropathy ,Regimen ,medicine.anatomical_structure ,Shoulder joint ,prophylaxis ,Ankle ,business ,Complication - Abstract
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.
- Published
- 2016
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