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Factor X Deficiency HELP
Based on 135 articles published since 2010
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These are the 135 published articles about Factor X Deficiency that originated from Worldwide during 2010-2020.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4 · 5 · 6
1 Review Factor X Friuli Coagulation Disorder: Almost 50 Years Later. 2018

Girolami, Antonio / Cosi, Elisabetta / Santarossa, Claudia / Ferrari, Silvia / Girolami, Bruno / Lombardi, Anna Maria. ·1 Department of Medicine, University of Padua Medical School, Padua, Italy. · 2 Division of Medicine, Padua City Hospital, Padua, Italy. ·Clin Appl Thromb Hemost · Pubmed #28030967.

ABSTRACT: The story of factor X (FX) Friuli. Factor X Friuli was discovered in 1969 to 1970. However, the story of that disease was an international event since patients with this defect were studied in France and in Italy, and different diagnoses were reached-FVII; FX; combined prothrombin complex; and combined FII, FVII, and FX deficiencies. The diagnostic difficulties were due to the peculiar clotting pattern presented by these patients, namely, prolonged partial thromboplastin time, prolonged prothrombin time but normal Russell viper venom clotting time. Only suitable anti-FX antisera clarified the pattern. Altogether 12 homozygotes and 102 heterozygotes have been followed during 4 decades. Six homozygotes died, 2 of them due to HIV infection and 1 due to hepatitis B liver cirrhosis. The other 3 died of nontransfusion-related morbidity. Bleeding tendency has been moderate in agreement with the extrinsic or intrinsic system assay results-FX level of 4% to 5% is considered normal. Heterozygotes may present occasional bleeding manifestations usually during surgery or delivery. Molecular analysis have shown that the mutation responsible for the defect is a Pro343Ser substitution in exon 8. Chimeric FX Friuli mice have been useful in studying the effect of FX levels on embryonic or natal mortality of these animals. No new homozygote but several heterozygotes have been recently seen. The study of FX Friuli has revolutionized the diagnostic approach to FX deficiencies. The FX should be assayed by all assay systems. The FX Friuli has never been described in any other country, and all patients studied come from the Friuli Meduna River Valley.

2 Review [Acquired, non-amyloid related factor X deficiency: A first case associated with atypical chronic lymphocytic leukemia and literature review]. 2017

Boudin, L / Patient, M / Roméo, E / Bladé, J-S / Gisserot, O / de Jauréguiberry, J-P. ·Service de médecine interne- oncologie, hôpital d'instruction des armées Sainte-Anne, boulevard Sainte-Anne, 83000 Toulon, France; École du Val-de-Grâce, boulevard Port-Royal, 75005 Paris, France. · Service de médecine interne- oncologie, hôpital d'instruction des armées Sainte-Anne, boulevard Sainte-Anne, 83000 Toulon, France. · Service de médecine interne- oncologie, hôpital d'instruction des armées Sainte-Anne, boulevard Sainte-Anne, 83000 Toulon, France; École du Val-de-Grâce, boulevard Port-Royal, 75005 Paris, France. Electronic address: oncologie@sainteanne.org. ·Rev Med Interne · Pubmed #28110969.

ABSTRACT: INTRODUCTION: Acquired factor X deficiency is in most cases associated with AL amyloidosis. Acquired non-amyloid related factor X deficiency (DNAA-FX) has been exceptionally reported in the literature. CASE REPORT: We report the first case of acquired, non-amyloid related factor X deficiency associated with atypical chronic lymphoid leukemia in a 66-year-old patient with spontaneous hematomas. After therapeutic failure with polyclonal intravenous immunoglobulins, specific lymphoid malignancy treatment allowed symptoms and coagulation disorder resolution. CONCLUSION: DNAA-FX should be considered in case of bleeding events or coagulation disorders during low-grade hematological malignancies. Its occurrence can be considered as a treatment indication to prevent potentially fatal bleeding complications.

3 Review Plasma-derived human factor X concentrate for on-demand and perioperative treatment in factor X-deficient patients: pharmacology, pharmacokinetics, efficacy, and safety. 2017

Shapiro, Amy. ·a Indiana Hemophilia & Thrombosis Center , Indianapolis , IN , USA. ·Expert Opin Drug Metab Toxicol · Pubmed #27797267.

ABSTRACT: INTRODUCTION: Hereditary factor X (FX) deficiency is a rare autosomal recessive bleeding disorder characterized mainly by mild-to-severe bleeding into the mucous membranes, muscles or joints. Previously, treatment options for hereditary FX deficiency were limited mostly to products that may not specify FX content (i.e. fresh frozen plasma and prothrombin complex concentrates) and that have associated safety concerns. To meet the need for a single-factor replacement therapy specifically for use in FX-deficient patients, a high-purity, high-potency, human plasma-derived FX concentrate (pdFX; Coagadex®; Bio Products Laboratory, Elstree, UK) has been developed and approved for treatment of perioperative bleeding and on-demand treatment in FX-deficient patients. Areas covered: The pharmacology, efficacy, and safety of pdFX are discussed, with a review of preclinical studies and clinical trial data that led to regulatory approval of pdFX in the United States and Europe. Expert opinion: As the first single-factor replacement therapy indicated for hereditary FX deficiency, pdFX is a safe and efficacious treatment option in patients aged ≥12 years with hereditary FX deficiency. Clinical studies of pdFX provide a dosing regimen for use in cases of bleeding episodes, surgery, and prophylaxis. Further studies are ongoing regarding use of pdFX long term and in patients aged ≤12 years.

4 Review Advances in the treatment of bleeding disorders. 2016

Peyvandi, F / Garagiola, I / Biguzzi, E. ·Angelo Bianchi Bonomi Hemophilia and Thrombosis Center, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Luigi Villa Foundation, Milan, Italy. · Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy. ·J Thromb Haemost · Pubmed #27590165.

ABSTRACT: Historically, the bleeding episodes in subjects with coagulation disorders were treated with substitution therapy, initially with whole blood and fresh frozen plasma, and more recently with specific factor concentrate. Currently, patients with hemophilia have the possibility of choosing different effective and safe treatments, including novel extended half-life and alternative hemostatic drugs. The availability of novel extended half-life products could probably overcome current prophylaxis limitations, particularly in hemophilia B patients, by reducing the frequency of injections, achieving a higher trough level, and improving the quality of life of the patients. In addition, subcutaneous administration of alternative therapeutics would simplify prophylaxis in patients with hemophilia A and B with and without inhibitors. Regarding von Willebrand disease, a recombinant von Willebrand factor was recently developed to control bleeding episodes in patients with this disease, in addition to available von Willebrand factor/factor VIII concentrates. The management of patients affected by rare bleeding disorders (RBDs) is still a challenge, owing to the limited number of specific products, which are mainly available only in countries with high resources. Some improvements have recently been achieved by the production of new recombinant factor (F) XIII A subunit-derived and FX plasma-derived products for the treatment of patients affected by FXIII and FX deficiency. In addition, the development of novel alternative therapeutics, such as anti-tissue factor pathway inhibitor, ALN-AT3, and ACE910, for patients with hemophilia might also have a role in the treatment of patients affected by RBDs.

5 Review Intracranial Hemorrhage as the First Manifestation of Severe Congenital Factor X Deficiency in a 20-Month-Old Male: Case Report and Review of the Literature. 2016

Diesch, Tamara / von der Weid, Nicolas Xavier / Schifferli, Alexandra / Kühne, Thomas. ·Division of Paediatric Oncology/Haematology, University Children's Hospital Basel, Basel, Switzerland. ·Pediatr Blood Cancer · Pubmed #27098186.

ABSTRACT: Factor X deficiency (FXD) is a rare bleeding disorder, which can result in severe bleeding symptoms such as intracranial hemorrhage (ICH). The most common bleeding symptoms are epistaxis and gum bleeding. ICH is reported in 9-26% of all patients with FXD, mostly during the first month of life. Here, we present a rare case of a male presenting with ICH at the age of 20 months as the first manifestation of FXD. Secondary prophylaxis with factor X substitution once weekly prevented further bleeding.

6 Review Spectrum of factor X gene mutations in Iranian patients with congenital factor X deficiency. 2016

Dorgalaleh, Akbar / Zaker, Farhad / Tabibian, Shadi / Alizadeh, Shaban / Dorgalele, Saeed / Hosseini, Soudabeh / Shamsizadeh, Morteza. ·aDepartment of Hematology and Blood Transfusion, School of Allied Medical Sciences bCellular and Molecular Research Center, Iran University of Medical Sciences, Tehran cDepartment of Laboratory Medicine, Zabol University of Medical Sciences, Zabol dSchool of Nursing and Midwifery, Shahroud University of Medical Sciences, Shahroud eDepartment of Hematology and Blood Transfusion, School of Allied Medical Sciences, Tehran University of Medical Sciences, Tehran, Iran. ·Blood Coagul Fibrinolysis · Pubmed #26891460.

ABSTRACT: Congenital factor X deficiency is one of the most severe forms of rare bleeding disorders transmitted in autosomal recessive manner. According to the World Federation of Hemophilia survey, 153 patients with factor X deficiency (FXD) live in Iran, but a few studies have been performed to determine the precise distribution of FXD in different parts of the country and to assess molecular basis of this disorder in Iranian patients. This study was conducted to assess the spectrum of factor X gene mutation in Iranian patients with congenital FXD. All relevant English and Persian-language publications were searched (until 2015). Clinical presentations or molecular basis of nearly 90 Iranian patients were reported in different studies. Most of these studies focused on clinical presentations of patients, whereas molecular analyses were rarely performed. Most molecular studies found a diversity in factor X disease causing mutations in Iranian patients. Like other parts of the world, the majority of mutations in Iranian patients were missense mutations, but splice-site mutations were relatively common. Three extremely rare cases of combined factor X and factor VII deficiencies were observed in two cases of which this disorder resulted from different missense mutations in respective factor genes. A wide spectrum of factor X gene mutations was observed in Iranian patients with congenital FXD that revealed diversity in FXD gene mutations.

7 Review Complex history of the discovery and characterization of congenital factor X deficiency. 2015

Girolami, Antonio / Cosi, Elisabetta / Sambado, Luisa / Girolami, Bruno / Randi, Maria Luigia. ·Department of Medicine, University of Padua Medical School, Padua, Italy. · Division of Medicine, Padua City Hospital, Padua, Italy. ·Semin Thromb Hemost · Pubmed #25875733.

ABSTRACT: Factor X (FX) plays a pivotal role in blood coagulation. FX represents the point where all coagulation systems converge and, once activated, it converts prothrombin into thrombin. The discovery and definition of FX are based on the description between 1956 and 1957 about three patients and their families with a peculiar defect later demonstrated to be almost identical. These patients were an American (Mr. Stuart), a British (Ms. Prower), and a Swiss with Italian background (infant Delia B). We stated "almost identical" because immunological and molecular biology studies subsequently revealed that even though the basic clotting defect was identical, the FX protein level and the mutation were different in each case. Mr. Stuart had no FX protein in his plasma and the mutation was Val298Met (homozygote). Ms. Prower instead had a normal level of FX protein and the mutation was Arg287Trp + Asp282Asn (compound heterozygote). Unfortunately, the status of the Swiss patient in this regard is not known. Subsequent studies described a few major variants (FX Friuli, FX Melbourne, FX Padua, and other similar patients), which showed peculiar activation patterns (FX Friuli had a normal Russell viper venom clotting time; FX Melbourne was defective only in the intrinsic coagulation system; FX Padua, on the contrary, was defective only in the extrinsic coagulation system). All these studies have informed on the great heterogeneity and complexity of the FX defect. The story of the discovery and classification of FX deficiency has contributed considerably to our understanding of blood coagulation. The three original families and the families of the major variants, together with the researchers that discovered them, should be remembered with deep respect and gratitude.

8 Review [Acquired coagulation factor X deficiency: three cases report and literature review]. 2014

Liu, Wenjie / Xuan, Min / Xue, Feng / Yang, Renchi. ·State Key Laboratory of Experimental Hematology, Institute of Hematology & Blood Diseases Hospital, CAMS & PUMC, Tianjin 300020, China. ·Zhonghua Xue Ye Xue Za Zhi · Pubmed #25052608.

ABSTRACT: OBJECTIVE: To deepen the understanding of acquired coagulation factor X (F X) deficiency. METHODS: The clinical data of 3 patients were analyzed and related literature were reviewed. RESULTS: Case 1, a 57-year-old male, secondary to multiple myeloma and amyloidosis, was presented with spontaneous mucous hemorrhage with the level of FX:C 1.8%, which kept unchanged after chemotherapy with melphalan, glucocorticoid, and thalidomide, and died of primary disease progression. Case 2, a 41-year-old male with psoriasis, was presented with cerebral and retinal hemorrhage with the level of FX:C 26.8%. The signs of hemorrhage were alleviated after the supplement of folic acid, vitamin B12, and vitamin K, and transfusion with red blood cells, platelets, and fresh frozen plasma. Case 3, a 63-year-old female, associated with high level of lupus anticoagulant, was presented with repeated ecchymosis and haemarthrosis with the level of FX:C 6.1%, which was refractory to prothrombin complex concentrate, methyprednisolone, azathioprine, and rituximab. CONCLUSION: Acquired FX deficiency is a rare disorder with variable symptoms. The diagnosis relies on history of disease and laboratory test. Currently, there is no standardized treatment. The prognosis of acquired FX deficiency is mainly related to the underlying disease.

9 Review Fatal bleeding due to acquired factor IX and X deficiency: a rare complication of primary amyloidosis; case report and review of the literature. 2014

Ericson, Stephanie / Shah, Nihar / Liberman, Justin / Aboulafia, David M. ·Division of Internal Medicine, Virginia Mason Medical Center, Seattle, WA. · Division of Gastroenterology, Virginia Mason Medical Center, Seattle, WA. · Division of Hematology and Oncology, Virginia Mason Medical Center, Seattle, WA; Division of Hematology, University of Washington, Seattle, WA. Electronic address: hemdma@vmmc.org. ·Clin Lymphoma Myeloma Leuk · Pubmed #24290671.

ABSTRACT: -- No abstract --

10 Review Acquired, non-amyloid related factor X deficiency: review of the literature. 2012

Lee, G / Duan-Porter, W / Metjian, Ara D. ·Department of Medicine, DUMC 3422, Duke University MedicalCenter, Durham, NC 27710, USA. ara.metjian@duke.edu ·Haemophilia · Pubmed #23437437.

ABSTRACT: -- No abstract --

11 Review [A patient with AL amyloidosis and severe factor X deficiency has been in complete haematological remission with normal factor X activity for 7 years following high-dose chemotherapy. A case study and literature review]. 2010

Adam, Z / Matýková, M / Krejcí, M / Pour, L / Kissová, J / Slechtová, M / Chlupová, G / Stavarová, Y / Simonides, J / Penka, M / Mayer, J / Hájek, R. ·Interní hematoonkologická klinika Lékarské fakulty MU a FN Brno. z.adam@fnbrno.cz ·Vnitr Lek · Pubmed #20184115.

ABSTRACT: Disturbance of haemostasis and bleeding are rather frequent complications of AL amyloidosis. These are frequently caused by increased fragility of capillaries, thrombocyte function disorders and coagulation cascade defects. The most frequent coagulation disorder is decreased factor X activity. We describe a 34-year old female after hysterectomy for myomatous uterus and metrorhagia. Before the surgery, the attending physicians did not identify any pathological changes suggesting a need for further investigations or presence of AL amyloidosis. Post-surgery development was complicated by life-threatening diffuse haemorrhage. Extended investigations of coagulation cascade revealed reduction of factor X activity to 16%. Targeted histological examination of the resected uterus confirmed AL amyloid deposits consisting of kappa chains. The patient's bone marrow contained certain small level of multiplied kappa chains-expressing plasma cells (< 10%); monoclonal immunoglobulins IgG K and free kappa chains were identified in serum. At that time, the patient did not satisfy the then valid Durie-Salmon criteria for multiple myeloma and thus the patient was diagnosed with primary systemic AL amyloidosis. The patient's condition gradually improved following substitution therapy (Prothromplex, fresh frozen plasma and erythrocyte transfusion) and bleeding slowly ceased so that chemotherapy with VAD (vincristine, adriamycin and dexamethasone) was initiated 6 weeks after the surgery. A total of 8 chemotherapy cycles were administered and complete haematological remission was achieved after the 5th cycle. Administration of the 8 VAD chemotherapy cycles resulted in increased factor X activity; bleeding complications subsided completely, thereby decreasing the risk of life-threatening mucositis-associated haemorrhage. Consequently, tandem high-dose chemotherapy (melphalan 100 mg/m2) with autologous haematopoietic stem cells transplantation was added to the treatment plan. Treatment was completed at the beginning of 2003 and, from that time, the patient is on continuous maintenance therapy with interferon alpha. Seven years from the diagnosis and 6 years from the completion of treatment the patient is in complete haematological remission, with no signs of organic damage caused by AL amyloid and with normal factor X activity. Factor X activity increased at the time when complete haematological remission was achieved after 8 cycles of VAD chemotherapy to 42%, it reached 68% the second year following high-dose chemotherapy, 77% after 5 years and 85% after 7 years. We had considered administration of high-dose chemotherapy in the standard regimen, i.e. following 4 cycles of VAD chemotherapy, as too high risk in the described young female patient. Therefore, we administered 8 cycles of conventional chemotherapy and only after complete haematological remission and partial organ response (factor X activity increased to 42%) were achieved, we added tandem high-dose chemotherapy to the treatment. We thus achieved long-term (7-years so far) complete haematological and organ remission. Increase in factor X activity is explicit over the entire 7-year observational period. We recommend starting treatment of high-risk transplant patients with AL amyloidosis with traditional chemotherapy regimen and, in case of positive haematological and organ treatment response, we recommend re-examination of potential benefits and risks of high-dose chemotherapy with autologous transplantation.

12 Clinical Trial Acquired factor X deficiency in light-chain (AL) amyloidosis is rare and associated with advanced disease. 2019

Patel, Gina / Hari, Parameswaran / Szabo, Aniko / Rein, Lisa / Kreuziger, Lisa Baumann / Chhabra, Saurabh / Dhakal, Binod / D'Souza, Anita. ·Medical College of Wisconsin Medical School, Milwaukee, WI, USA. · Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA. · Division of Biostatistics, Institute for Health and Equity, Medical College of Wisconsin, Milwaukee, WI, USA. · Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA; Blood Research Institute, Blood Center of Wisconsin, Milwaukee, WI, USA. · Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, WI, USA. Electronic address: andsouza@mcw.edu. ·Hematol Oncol Stem Cell Ther · Pubmed #30879471.

ABSTRACT: INTRODUCTION: Systemic light chain (AL) amyloidosis can lead to an acquired coagulopathy secondary to acquired factor X (aFX) deficiency. However, it is not very clear who develops aFX deficiency in AL amyloidosis. METHODS: We therefore undertook this single centre, retrospective study to better characterize AL amyloidosis-associated aFX deficiency. RESULTS: Out of 121 AL patients who had FX testing at the time of their first evaluation at our institution, including 17 patients on warfarin at the time of testing, 10 out of 104 patients (9.6%) with systemic AL amyloidosis were found to have FX levels below 50%. Acquired FX deficiency was associated with advanced stage of AL amyloidosis and elevated cardiac biomarkers. Lower FX activity, advanced stage, and cardiac involvement by disease were associated with higher hazard of death on univariate analysis. On multivariate analysis, stage of AL amyloidosis was the only significant predictor of survival. Median survival time of patients with FX deficiency was 9.3 months compared to 118.4 months in those without. CONCLUSIONS: We conclude that while aFX deficiency is rare in systemic AL amyloidosis, it is a marker of advanced disease.

13 Clinical Trial Prophylactic treatment of bleeding episodes in children <12 years with moderate to severe hereditary factor X deficiency (FXD): Efficacy and safety of a high-purity plasma-derived factor X (pdFX) concentrate. 2018

Liesner, R / Akanezi, C / Norton, M / Payne, J. ·Haemophilia Comprehensive Care Centre, Great Ormond Street Hospital, London, UK. · Bio Products Laboratory Ltd, Elstree, UK. · Department of Paediatric Haematology, Sheffield Children's NHS Foundation Trust, Sheffield, UK. ·Haemophilia · Pubmed #29707881.

ABSTRACT: BACKGROUND: Hereditary factor X (FX) deficiency (FXD) affects 1:500 000-1:1 000 000 people worldwide. A novel, high-purity plasma-derived FX concentrate (pdFX) is available in the United States and European Union as replacement therapy for FXD, but data are scarce on pdFX use in children <12 years. AIM: This prospective, open-label phase 3 study assessed the safety, efficacy and pharmacokinetics of pdFX in children <12 years with moderate/severe FXD. METHODS: Subjects aged <12 years with basal plasma FX activity (FX:C) <5 IU/dL received pdFX as prophylactic and on-demand treatment, with doses adjusted to maintain FX:C > 5 IU/dL. After ≥26 weeks and ≥50 exposure days, investigators rated pdFX efficacy for preventing/decreasing bleeds. Secondary endpoints included number and severity of bleeds, trough FX:C and incremental recovery. Safety parameters were adverse events (AEs), inhibitor development and changes in laboratory parameters. RESULTS: The study enrolled 9 subjects (0-5 years, n = 4; 6-11 years, n = 5) with severe (n = 8) or moderate (n = 1) FXD. At end of study, investigators rated pdFX efficacy excellent for all subjects. Ten bleeds occurred (n = 3 subjects; 6 major, 3 minor, 1 unassessed for severity). Trough FX:C levels remained >5 IU/dL for all subjects after the last dose adjustment study visit. Mean incremental recovery was significantly lower for younger vs older subjects (1.53 vs 1.91 IU/dL per IU/kg; P = .001). All AEs were unrelated to treatment; no inhibitor development or clinically significant changes in laboratory parameters were observed. CONCLUSIONS: These results demonstrate the efficacy and safety of pdFX for treating children <12 years with moderate/severe hereditary FXD.

14 Clinical Trial Use of a High-Purity Factor X Concentrate in Turkish Subjects with Hereditary Factor X Deficiency: Post Hoc Cohort Subanalysis of a Phase 3 Study. 2018

Öner, Ahmet F / Celkan, Tiraje / Timur, Çetin / Norton, Miranda / Kavaklı, Kaan. ·Yüzüncü Yıl University Faculty of Medicine, Department of Pediatric Hematology, Van, Turkey. · İstanbul University Cerrahpaşa Faculty of Medicine, Department of Pediatric Hematology and Oncology, İstanbul, Turkey. · İstanbul Medeniyet University, Göztepe Training and Research Hospital, Clinic of Pediatric Hematology, İstanbul, Turkey. · Bio Products Laboratory Ltd., Elstree, Hertfordshire, United Kingdom. · Ege University Faculty of Medicine, Department of Pediatric Hematology, İzmir, Turkey. ·Turk J Haematol · Pubmed #29545231.

ABSTRACT: Hereditary factor X (FX) deficiency is a rare bleeding disorder more prevalent in countries with high rates of consanguineous marriage. In a prospective, open-label, multicenter phase 3 study, 25 IU/kg plasma-derived factor X (pdFX) was administered as on-demand treatment or short-term prophylaxis for 6 months to 2 years. In Turkish subjects (n=6), 60.7% of bleeds were minor. A mean of 1.03 infusions were used to treat each bleed, and mean total dose per bleed was 25.38 IU/kg. Turkish subjects rated pdFX efficacy as excellent or good for all 84 assessable bleeds; investigators judged overall pdFX efficacy to be excellent or good for all subjects. Turkish subjects had 51 adverse events; 96% with known severity were mild/moderate, and 1 (infusion-site pain) was possibly pdFX-related. These results demonstrate that 25 IU/kg pdFX is safe and effective in this Turkish cohort (ClinicalTrials.gov identifier: NCT00930176).

15 Clinical Trial Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in women and girls with hereditary factor X deficiency. 2018

Kulkarni, R / James, A H / Norton, M / Shapiro, A. ·Michigan State University, East Lansing, MI, USA. · Duke University, Durham, NC, USA. · Bio Products Laboratory Ltd, Elstree, UK. · Indiana Hemophilia and Thrombosis Center, Indianapolis, IN, USA. ·J Thromb Haemost · Pubmed #29460388.

ABSTRACT: Essentials Plasma-derived factor X concentrate (pdFX) is used to treat hereditary factor X deficiency. pdFX pharmacokinetics, safety and efficacy were assessed in factor X-deficient women/girls. Treatment success rate was 98%; only 6 adverse events in 2 subjects were possibly pdFX related. On-demand pdFX 25 IU kg SUMMARY: Background A high-purity, plasma-derived factor X concentrate (pdFX) has been approved for the treatment of hereditary FX deficiency, an autosomal recessive disorder. Objective To perform post hoc assessments of pdFX pharmacokinetics, safety and efficacy in women and girls with hereditary FX deficiency. Patients/Methods Subjects aged ≥ 12 years with moderate/severe FX deficiency (plasma FX activity of < 5 IU dL

16 Clinical Trial Experience of a new high-purity factor X concentrate in subjects with hereditary factor X deficiency undergoing surgery. 2016

Escobar, M A / Auerswald, G / Austin, S / Huang, J N / Norton, M / Millar, C M. ·University of Texas Health Science Center and Gulf States Hemophilia and Thrombophilia Center, Houston, TX, USA. · Klinikum Bremen-Mitte, Prof-Hess-Kinderklinik, Bremen, Germany. · St. George's Hospital University NHS Foundation Trust, London, UK. · University of California San Francisco Benioff Children's Hospital, San Francisco, CA, USA. · Bio Products Laboratory, Elstree, UK. miranda.norton@bpl.co.uk. · Centre for Haematology, Hammersmith Campus, Imperial College Academic Health Sciences Centre, Imperial College, London, UK. ·Haemophilia · Pubmed #27217097.

ABSTRACT: INTRODUCTION: Maintaining haemostasis in surgery is challenging for hereditary rare bleeding disorders in which multi-coagulation-factor concentrates are the only therapeutic option. Hereditary factor X (FX) deficiency affects 1:500 000 to 1:1 000 000 individuals, and no specific replacement FX concentrate has been available. A high-purity, plasma-derived FX concentrate (pdFX) has been developed for patients with hereditary FX deficiency. AIM: Our objective was to assess the safety and efficacy of pdFX in subjects with FX deficiency undergoing surgery. METHODS: Subjects with hereditary mild-to-severe FX deficiency (basal plasma FX activity [FX:C] <20 IU dL(-1) ) undergoing surgery received pdFX preoperatively to raise FX:C to 70-90 IU dL(-1) and postoperatively to maintain levels >50 IU dL(-1) until the subject was no longer at risk of bleeding due to surgery. Efficacy of pdFX was assessed by blood loss during surgery, requirement for blood transfusion, postoperative bleeding from the surgical or other sites, and changes in haemoglobin levels. Safety was assessed by adverse events (AEs), development of inhibitors, and clinically significant changes in laboratory parameters. RESULTS: Five subjects (aged 14-59 years) underwent seven surgical procedures (four major and three minor). Treatment duration was 1-15 days. For each procedure, pdFX treatment was assessed as "excellent" in preventing bleeding and achieving haemostasis. No blood transfusions were required, no AEs related to pdFX were observed, and no clinically significant trends were found in any laboratory parameters. CONCLUSION: These data demonstrate that pdFX is safe and effective as replacement therapy in five subjects with mild-to-severe FX deficiency undergoing surgery on seven occasions.

17 Clinical Trial Efficacy, safety and pharmacokinetics of a new high-purity factor X concentrate in subjects with hereditary factor X deficiency. 2016

Austin, S K / Kavakli, K / Norton, M / Peyvandi, F / Shapiro, A / Anonymous4480868. ·St. George's Haemophilia Centre, St. George's University Hospitals NHS Foundation Trust, London, UK. · Department of Pediatric Hematology, Children's Hospital, Ege University Faculty of Medicine, Izmir, Turkey. · Bio Products Laboratory, Elstree, UK. · Angelo Bianchi Bonomi Hemophilia & Thrombosis Center, Milan, Italy. · Department of Pathophysiology and Transplantation, Università degli Studi di Milano, Milan, Italy. · Indiana Hemophilia & Thrombosis Center, Indianapolis, IN, USA. ·Haemophilia · Pubmed #27197801.

ABSTRACT: INTRODUCTION: Hereditary factor X (FX) deficiency is a rare bleeding disorder affecting 1:500 000 to 1:1 000 000 of individuals. Until recently, no specific replacement factor concentrate was available. AIM: The aim of this study was to assess safety and efficacy of a new, high-purity plasma-derived FX concentrate (pdFX) in subjects with hereditary FX deficiency. METHODS: Subjects aged ≥12 years with moderate or severe FX deficiency (plasma FX activity <5 IU dL(-1) ) received 25 IU kg(-1) pdFX as on-demand treatment or short-term prophylaxis for 6 months to 2 years. Subjects assessed pdFX efficacy for each bleed; at end-of-study, investigators assessed overall pdFX efficacy. Blood samples for pharmacokinetic analysis were obtained at baseline and ≥6 months. Safety was assessed by adverse events (AEs), inhibitor development and changes in laboratory parameters. RESULTS: Sixteen enrolled subjects (six aged 12-17 years; 10 aged 18-58 years) received a total of 468 pdFX infusions. In the 187 analysed bleeds, pdFX efficacy was categorized as excellent, good, poor or unassessable in 90.9%, 7.5%, 1.1% and 0.5% of bleeds respectively; 83% of bleeds were treated with one infusion. For pdFX, mean (median; interquartile range) incremental recovery and half-life were 2.00 (2.12; 1.79-2.37) IU dL(-1) per IU kg(-1) and 29.4 (28.6; 25.8-33.1) h respectively. No serious AEs possibly related to pdFX or evidence of FX inhibitors were observed, and no hypersensitivity reactions or clinically significant trends were detected in laboratory parameters. CONCLUSION: These results demonstrate that a dose of 25 IU kg(-1) pdFX is safe and efficacious for on-demand treatment and short-term prophylaxis in subjects with moderate or severe hereditary FX deficiency.

18 Clinical Trial Pharmacokinetics of a high-purity plasma-derived factor X concentrate in subjects with moderate or severe hereditary factor X deficiency. 2016

Austin, S K / Brindley, C / Kavakli, K / Norton, M / Shapiro, A / Anonymous2910858. ·St. George's Haemophilia Centre, St. George's Hospital University NHS Foundation Trust, London, UK. · KinetAssist Ltd, Quothquan, UK. · Faculty of Medicine, Children's Hospital, Ege University, Izmir, Turkey. · Bio Products Laboratory Ltd., Elstree, UK. · Indiana Hemophilia & Thrombosis Center, Indianapolis, IN, USA. ·Haemophilia · Pubmed #26879266.

ABSTRACT: INTRODUCTION: Hereditary factor X (FX) deficiency affects 1:500 000 to 1:1 000 000 of individuals. There are few published data on the pharmacokinetics (PK) of FX for existing treatments for FX deficiency, and no specific replacement factor concentrate exists. A high-purity plasma-derived FX concentrate (pdFX) has been developed for use as replacement therapy in subjects with hereditary FX deficiency. AIM: This analysis assessed pdFX PK after a single 25 IU kg(-1) bolus dose in subjects with hereditary moderate or severe FX deficiency (plasma FX activity [FX:C] <5 IU dL(-1) ). METHODS: For a baseline PK assessment, blood samples were taken predose and at intervals up to 144 h (7 days) post dose. After ≥6 months of on-demand pdFX treatment and treatment of ≥1 bleed with pdFX, subjects underwent repeat PK assessment. Samples were assayed for plasma FX:C (measured using the clotting and chromogenic assays) and FX antigen. RESULTS: FX:C peaked at 0.4-0.5 h and subsequently declined over the course of 144 h with a biphasic decay curve. PK parameters observed at the baseline (n = 16) and repeat (n = 15) assessments were equivalent, therefore summary PK values were obtained by combining data from both visits (n = 31). The mean terminal half-life and incremental recovery of pdFX was 29.4 h and 2.00 IU dL(-1) per IU kg(-1) respectively. CONCLUSION: This is the most comprehensive PK study to date in subjects with hereditary FX deficiency. These results are consistent with the observed haemostatic efficacy of pdFX and provide the PK data required for the treatment of hereditary FX deficiency using pdFX replacement therapy.

19 Article Molecular mechanism of a novel Ser362Asn mutation causing inherited FX deficiency in a Chinese family. 2020

Zhang, Xialin / Chen, Kun / Wang, Gang / Zhang, Cuiming / Zhao, Bingni / Liu, Xiue / Qin, Xiuyu / Yang, Linhua. ·Department of Hematology, The Second Hospital of Shanxi Medical University, No. 382 Wuyi Road, Taiyuan, 030001, Shanxi, People's Republic of China. · Department of Hematology, The Second Hospital of Shanxi Medical University, No. 382 Wuyi Road, Taiyuan, 030001, Shanxi, People's Republic of China. yanglh5282@163.com. ·Int J Hematol · Pubmed #32285359.

ABSTRACT: Factor X (FX) deficiency is an inherited autosomal recessive bleeding disorder. Here, we analyzed a proband with FX deficiency in a Chinese family. Genetic analysis revealed that the proband and his affected sister was homozygous for c.1085G>A mutation, corresponding to a Ser362Asn substitution. In vitro expression experiments showed that the FX Ser362Asn mutation led to a significant reduction in activity levels in the culture medium. This Ser to Asn substitution may change the shape of the active site. Moreover, simulations of molecular dynamics indicated that the binding energy of the FX Ser362Asn to the substrate is higher than that of wild type and the side-chain conformation of the catalytic residue His276 (His42) is changed. This impairs the conformational switch of the protein from zymogen to proteinase, thus causing the functional defect of FX protein. Our findings suggest that the Ser362Asn substitution is a pathogenic mutation that causes inherited FX deficiency.

20 Article Successful Treatment of Life-threatening Bleeding Caused by Acquired Factor X Deficiency Associated with Respiratory Infection. 2020

Ichikawa, Satoshi / Saito, Kei / Fukuhara, Noriko / Tanaka, Yuya / Lee, Yoonha / Onodera, Koichi / Onishi, Yasushi / Yokoyama, Hisayuki / Fujiwara, Minami / Harigae, Hideo. ·Department of Hematology and Rheumatology, Tohoku University Hospital, Japan. ·Intern Med · Pubmed #32023586.

ABSTRACT: Acquired factor X deficiency (AFXD) is a very rare coagulation disorder. A 40-year-old man with no comorbidities suffering from a fever, malaise, and severe hemorrhagic symptoms, including massive hematuria, was emergently admitted. His platelet count was normal, but his prothrombin time and activated partial thromboplastin time were markedly prolonged, which was thought to be due to autoantibody against a coagulation factor in the common pathway. Despite severe massive hematuria resulting in transient renal failure, he was successfully treated with urgent immunosuppressive therapy. Computed tomography revealed bronchopneumonia, which improved with antibiotic administration. AFXD without evidence of amyloidosis was subsequently diagnosed.

21 Article Coagulation and fibrinolytic features in AL amyloidosis with abnormal bleeding and usefulness of tranexamic acid. 2020

Arahata, Masahisa / Takamatsu, Hiroyuki / Morishita, Eriko / Kadohira, Yasuko / Yamada, Shinya / Ichinose, Akitada / Asakura, Hidesaku. ·Department of Hematology, Kanazawa University Hospital, 13-1 Takaramachi Kanazawa, Ishikawa, 920-8641, Japan. rqxhf297@yahoo.co.jp. · Department of Hematology/Respiratory Medicine, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan. · Department of Clinical Laboratory Science, Graduate School of Medical Sciences, Kanazawa University, Kanazawa, Japan. · Department of Hematology, Kanazawa University Hospital, 13-1 Takaramachi Kanazawa, Ishikawa, 920-8641, Japan. · Department of Hematology, Toyama Prefectural Central Hospital, Toyama, Japan. · Department of Molecular Patho-Biochemistry and Patho-Biology, Yamagata University School, Yamagata, Japan. ·Int J Hematol · Pubmed #31897889.

ABSTRACT: Abnormal bleeding is sometimes observed in patients with immunoglobulin light chain (AL) amyloidosis. Although several theories have been proposed regarding the pathological causes of the bleeding tendency in AL amyloidosis, many lacked sufficient evidence and full consensus. We conducted a retrospective survey at a single institution to assess bleeding manifestations, methods for evaluating hematological abnormalities, and treatments for bleeding in patients with systemic AL amyloidosis over the past 13 years. The participants were 10 men and 14 women, aged 39-84 years (mean 65 years). The prevalence of bleeding was 29%. Prolonged prothrombin time (PT), elevated plasmin-α2-antiplasmin complex, and factor X deficiency were distinctive to the bleeding group. Two case studies showed that tranexamic acid was effective for treating this hematological condition. However, two patients with normal PT and activated partial thromboplastin time (APTT) also had a bleeding manifestation. The rates of administration of coagulation and fibrinolytic tests were relatively low in the non-bleeding group. Therefore, a close investigation concerning coagulation and fibrinolysis should be performed in every patient with AL amyloidosis regardless of the PT/APTT values. A more careful, comprehensive, and large-scale study is required to reinforce these findings.

22 Article Genetic analysis of a compound heterozygous patient with congenital factor X deficiency and regular replacement therapy with a prothrombin complex concentrate. 2020

Togashi, Tomoki / Nagaya, Satomi / Nagasawa, Masayuki / Meguro-Horike, Makiko / Nogami, Keiji / Imai, Yuta / Kuzasa, Kana / Sekiya, Akiko / Horike, Shin-Ichi / Asakura, Hidesaku / Morishita, Eriko. ·Department of Laboratory Sciences, School of Health Sciences, College of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan. · Department of Clinical Laboratory Science, Kanazawa University Graduate School of Medical Science, 5-11-80 Kodatsuno, Kanazawa, 920-0942, Ishikawa, Japan. · Department of Pediatrics, Musashino RedCross Hospital, Tokyo, Japan. · Advanced Science Research Center, Kanazawa University, Kanazawa, Japan. · Department of Pediatrics, Nara Medical University Hospital, Kashihara, Nara, Japan. · Department of Hematology, Kanazawa University Hospital, Kanazawa, Japan. · Department of Clinical Laboratory Science, Kanazawa University Graduate School of Medical Science, 5-11-80 Kodatsuno, Kanazawa, 920-0942, Ishikawa, Japan. eriko86@staff.kanazawa-u.ac.jp. · Department of Hematology, Kanazawa University Hospital, Kanazawa, Japan. eriko86@staff.kanazawa-u.ac.jp. ·Int J Hematol · Pubmed #31667683.

ABSTRACT: Congenital factor X (FX) deficiency is a rare bleeding disorder with an incidence of one in one million. The proband, a 2-year-old girl, exhibited easy bruising and a history of umbilical cord bleeding at birth. Prothrombin time (> 40 s) and activated partial thromboplastin time (65.0 s) were prolonged. Marked declines in FX activity (< 1%) and FX antigen levels (5%) were also observed. Genetic analysis of the proband identified two types of single-base substitutions, c.353G>A (p.Gly118Asp) and c.1303G>A (p.Gly435Ser), indicating compound heterozygous congenital FX deficiency. Genetic analysis of family members revealed that her father and older sister (5-year-old) were also heterozygous for p.Gly118Asp, and that her mother was heterozygous for p.Gly435Ser. To improve the bleeding tendency, the proband received regular replacement of 500 units of PPSB-HT, a prothrombin complex concentrate (PCC). Following continued regular replacement of 500 units of PPSB-HT once per week, the proband has exhibited no bleeding tendencies and no new bruises have been observed. There are no previous report of the use of PPSB-HT for regular FX replacement. Regular replacement therapy with PPSB-HT may be an effective method for preventative control of bleeding tendencies in FX deficiency.

23 Article Acquired factor X deficiency in a patient with multiple myeloma: a rare case highlighting the significance of comprehensive evaluation and the need for antimyeloma therapy for bleeding diathesis. 2019

Reynolds, Samuel Benjamin / Maghavani, Dhaval Pravinkumar / Hashmi, Hamza. ·Department of Internal Medicine, University of Louisville School of Medicine, Louisville, Kentucky, USA. · Department of Medicine, Grant Medical College and Sir JJ Group of Hospitals, Mumbai, Maharashtra, India. · Division of Medical Oncology and Hematology, University of Louisville, Louisville, Kentucky, USA. ·BMJ Case Rep · Pubmed #31527206.

ABSTRACT: Factor X deficiency is a rare bleeding disorder that can be associated with life-threatening bleeding events. Factor X deficiency can either be inherited or acquired. Acquired cases of factor X deficiency can be seen in patients with plasma cell dyscrasias as well as amyloidosis. Coagulopathy, with clinically relevant bleeding events, although rare, is not an unusual phenomenon for patients with systemic amyloidosis. However, clinically relevant bleeding in patients with symptomatic multiple myeloma, without associated amyloidosis, has not been reported in literature before. We present a rare case of multiple myeloma without concomitant amyloidosis that presented with life-threatening bleeding from acquired deficiency of factor X and responded remarkably to treatment for underlying multiple myeloma. This case not only highlights the diagnostic workup required in patients with factor X deficiency but also provides the principles of management of acquired coagulopathy in plasma cell dyscrasias.

24 Article Bortezomib-based treatment can improve factor X activity in immunoglobulin light-chain amyloidosis with factor X deficiency. 2019

Wu, Xia / Miao, Hui-Lei / Zhu, Tie-Nan / Feng, Jun / Zhang, Lu / Mao, Yue-Ying / Zhou, Dao-Bin / Cao, Xin-Xin / Li, Jian. ·Department of Hematology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences Beijing , PR China. ·Amyloid · Pubmed #31526149.

ABSTRACT: -- No abstract --

25 Article Immunoglobulin Light Chain Amyloidosis with Severe Liver Dysfunction Accompanied by Factor X Deficiency. 2019

Guo, Yong-Mei / Takahashi, Nagi / Miyabe, Ken / Yoshida, Makoto / Abe, Fumito / Yamashita, Takaya / Nara, Miho / Yoshioka, Tomoko / Ohashi, Kenichi / Goto, Akiteru / Takahashi, Naoto. ·Department of Hematology, Nephrology, and Rheumatology, Akita University Graduate School of Medicine, Japan. · Department of Cellular and Organ Pathology, Akita University Graduate School of Medicine, Japan. · Department of Pathology, Yokohama City University Graduate School of Medicine, Japan. ·Intern Med · Pubmed #31243220.

ABSTRACT: Severe hepatic failure is rarely a cause of death in patients with immunoglobulin light chain (AL) amyloidosis. We herein report a case of AL amyloidosis involving a bleeding tendency due to factor X deficiency and marked hepatic involvement of amyloidosis. The patient died due to severe liver dysfunction two weeks after admission. The diagnosis was confirmed histologically by AL-λ amyloidosis, with the liver and spleen as the main lesions, on an autopsy. As treatment-related toxicity is strong in advanced cases, appropriate treatments are required to improve the prognosis of AL amyloidosis with severe liver dysfunction.

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