scholarly journals Haemostatic action of a topical foam-based patch (VELSEAL-T) in haemophiliac patients with external bleeding

2020 ◽  
Vol 7 (1) ◽  
pp. 78-84
Author(s):  
Anupam Dutta ◽  
Taniya Sarkar Dutta ◽  
Anup Kumar Das ◽  
Pranoy Dey
Keyword(s):  
Low Cost ◽  
Coagulation Factor ◽  
Northeast India ◽  
Factor Ix ◽  
Clotting Factor ◽  
Controlled Study ◽  
Efficacy And Safety ◽  
Medical College ◽  
Good Treatment Option ◽  
Time Required

AbstractIntroductionHaemophilia is an X-linked congenital bleeding disorder due to deficiency of coagulation factor VIII (in haemophilia A) or factor IX (in haemophilia B) caused by mutations of the respective clotting factor genes. Treatment involves the administration of an appropriate dose of factor concentrate, as soon as possible, in the event of any bleeding episode. In low-resource settings, such as Northeast India, where factor concentrates are not widely available, people with haemophilia (PwH) may bleed profusely even from trivial external injuries, warranting transfusion of blood or blood products. We previously reported on the use of a low cost, foam-based haemostatic patch to treat an external bleed in a single patient. In this study, we investigated its use to treat a range of external injuries in PwH presenting at Assam Medical College and Hospital.MethodOver 24 months, eligible PwH with external injuries attending our haemophilia clinic were treated with a topical haemostatic patch (VELSEAL-T) at the target bleeding site. The time to cessation of bleeding was recorded and the wound sites evaluated after haemostasis to monitor efficacy and safety.ResultsOut of 72 individuals with bleeding disorders who volunteered to participate, 59 cases of external bleeding in 48 PwH were eligible for inclusion in the study. Nine (15.3%) had aberration wounds, 24 (40.7%) cut wounds, 21 (35.6%) tooth and/or gum bleeding and five (8.4%) bleeding from puncture wounds. The average time required for achievement of haemostasis was 9.9 (±4.7) minutes. Aberration wounds required the least amount of time for haemostasis at 7.3 (±4.4) minutes. Cut wounds required a mean time of 8.5 (±2.9) minutes; puncture wounds required 9.0 (±3.1) minutes; gum bleeding required the longest time to achieve haemostasis with a mean of 12.7 (±5.6) minutes.ConclusionThe use of this topical haemostatic patch has been shown to be beneficial in the treatment of external injuries in PwH, and provides a good treatment option in resource-constrained areas. A larger controlled study would be helpful to further investigate its efficacy and safety.

scholarly journals Use of Seton in Management of High Variety of Anal Fistula

2017 ◽  
Vol 8 (2) ◽  
pp. 100-104
Author(s):  
Mohammad Noor A Alam ◽  
Sharmin Abbasi
Keyword(s):  
Anal Fistula ◽  
Low Cost ◽  
Dentate Line ◽  
Internal Opening ◽  
Efficacy And Safety ◽  
Medical College ◽  
Small Channel ◽  
A Prospective Study ◽  
Low Rate

Background: Anal fistula is an abnormal communicative small channel that has an internal opening and an external opening and connected by the primary track. Our study evaluate the effectiveness of seton in high variety anal fistula.Objectives: Evaluation the efficacy and safety of seton as surgical management of high anal fistula. Methods: This is a prospective study done on 57 patients in BIRDEM hospital and some other clinic of Dhaka city in 3 years period with high variety of anal fistula which is above the dentate line and were treated with seton .Outcome measured during follow up period were- successfully healed, recurrence, incontinence, percentage of complications and patients satisfaction.Result: Among 57 patients mean age was 38.2+_6.8 years. Overall outcome of the patients showed-fistula completely healed in 51 patients, incontinence occurred in 2 patients and recurrence occurred in 4 patients.Conclusion: Seton is relatively safe, effective and low cost for the management of high anal fistula with low rate of incontinence. It can therefore, be recommended as the standard of treatment for high variety fistula in ano.Anwer Khan Modern Medical College Journal Vol. 8, No. 2: Jul 2017, P 100-104

scholarly journals Biological Rationale for New Drugs in the Bleeding Disorders Pipeline

Hematology ◽  
2011 ◽  
Vol 2011 (1) ◽  
pp. 397-404 ◽  
Author(s):  
Patrick F. Fogarty
Keyword(s):  
Coagulation Factor ◽  
Coagulation Factors ◽  
Developed Countries ◽  
Factor Ix ◽  
New Drugs ◽  
Joint Disease ◽  
Novel Agents ◽  
Clotting Factor ◽  
Alternative Pathways ◽  
Long Acting

AbstractSince the introduction of replacement coagulation factor infusions for the treatment of hemophilia in the 1970s and subsequent improvements in the safety profile of available factor VIII (FVIII) and factor IX (FIX) concentrates, mortality among patients with hemophilia has improved considerably and now parallels that of the noncoagulopathic population in developed countries. Substantial morbidity, however, continues from the development of inhibitory antibodies, a recognized complication of clotting factor replacement; from infections and thrombosis complicating placement of central venous catheters, which are required in children with hemophilia due to frequent prophylactic infusions of coagulation factors with defined half-lives; and from disabling joint disease in individuals without access to costly prophylaxis regimens. In response to the need for long-acting, more potent, less immunogenic, and more easily administered therapies, an impressive array of novel agents is nearly ready for use in the clinical setting. These therapeutics derive from rational bioengineering of recombinant coagulation factors or from the discovery of nonpeptide molecules that have the potential to support hemostasis through alternative pathways. The number of novel agents in clinical trials is increasing, and many of the initial results are promising. In addition to advancing treatment of bleeding episodes or enabling adherence to prophylactic infusions of clotting factor concentrate, newer therapeutics may also lead to improvements in joint health, quality of life, and tolerability of iatrogenic or comorbidity-associated bleeding challenges.

Extravascular Clotting Factor Activity within Joint Tissues Protects Against Progression of Hemophilic Arthropathy.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 496-496 ◽  
Author(s):  
Junjiang Sun ◽  
Narine Hakobyan ◽  
Leonard A. Valentino ◽  
Paul E. Monahan
Keyword(s):  
Factor Viii ◽  
Coagulation Factor ◽  
Joint Capsule ◽  
Factor Ix ◽  
Clotting Factor ◽  
Needle Puncture ◽  
Factor Activity ◽  
Clotting Factors ◽  
Hemophilic Arthropathy ◽  
Human Factor Viii

Abstract Hemophilic arthropathy is the major morbidity of congenital factor VIII and IX deficiency. Therapies localized to hemophilic joints could provide adjunctive protection, in addition to that provided by systemic factor replacement. However, the ability of extravascular clotting factors to contribute to hemostatic protection within joint tissue is unknown. We hypothesized that replacing deficient factor VIII or IX within the injured joint capsule of mice with hemophilia A (FVIII −/ −) or hemophilia B (FIX −/ −), respectively, would decrease the progression of synovitis. We developed a bleeding model consisting of a unilateral knee joint capsule needle puncture to induce hemorrhage in hemophilic mice. Pathology of the joint at two weeks after the injury is graded 0 to 10 using a murine hemophilic synovitis grading system (Valentino, Hakobyan. Haemophilia, 2006). Hemostatically normal mice do not develop synovitis following this injury, but > 95% of FIX −/ − mice develop bleeding and synovitis with a mean grade of 3–4 or greater. Coincident with needle puncture, recombinant human coagulation factor doses ranging from 0 to 20 IU/kg body weight of factor IX or 0 to 25 IU/kg of factor VIII were instilled intraarticularly (I.A.). Comparison groups received the same injury and intravenous (I.V.) factor IX or VIII doses of 25 IU/kg to 100 IU/kg (n= 4–7 mice per study group). Joint bleeding phenotype of the two strains of mice was similar. Mice receiving only saline injection at the time of needle puncture developed mean synovitis scores of 5 ±0.5 in the FVIII −/ − mice and 6 ±0.5 in the FIX −/ − mice. Protection by human clotting factor in the mouse coagulation system was incomplete; mice receiving 100 IU/kg I.V. of factor VIII or factor IX developed synovitis scores of 2.6 ± 1.7 and 2.1 ± 0.2, respectively. In contrast, pathology grade of FVIII −/ − mice dosed with 25 IU/kg I.A. was 0.67 ± 0.3 (p = 0.05 for comparison of 25 IU/kg I.A. with 100 IU/kg IV); FIX−/ − mice receiving 20 IU/kg I.A. had synovitis scores of 0.45 ± 0.58 (p < 0.01 for comparison of 25 IU/kg I.A. with 100 IU/kg I.V.). We next ruled out the possibility that I.A. factor was entering the circulation, and via that route resulting in joint protection, either through technical error at the time of injection, or from a depot effect in the joint with late equilibration into the circulation. Additional groups of mice received factor VIII or IX intravenously at 100 IU/kg, or intraarticularly at 4 times the doses used in the hemarthrosis challenge (80 IU/kg FIX or 100 IU/kg FVIII), and factor activity assays were performed at 1, 4, 12, 24, and 48 hours. Expected circulation kinetics were seen following I.V. dosing; no increase in circulating factor VIII or IX activity were seen in the intraarticular dosing groups at any timepoint. In considering the potential immunogenicity of an intraarticular therapy approach for hemophilic joint therapy, factor VIII −/ − mice were treated with three doses of human factor VIII 100 IU/kg at five day intervals either I.V. or I.A. At two weeks after exposure, 5/5 I.V.-treated mice developed inhibitor antibodies with titers ranging 0.8–7.2 BU; 2/5 I.A.-treated mice had detectable low-titer antibodies (1.3 BU), indicating no greater immunogenicity in the I.A. model. Extravascular factor VIII and factor IX can contribute to protection against blood-induced joint deterioration; enhancing local tissue hemostasis with protein or gene therapy may prove a useful adjunct to systemic replacement.

scholarly journals Real World Data Analysis of Coagulation Factor IX Costs in Specific Patients with Hemophilia B Switching from Standard Half-Life to Extended Half-Life Products

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 4963-4963 ◽  
Author(s):  
Bartholomew J. Tortella ◽  
Patrick F. Fogarty ◽  
José Alvir ◽  
Margaret McDonald ◽  
Dean Spurden ◽  
...  
Keyword(s):  
Real World ◽  
Half Life ◽  
Coagulation Factor ◽  
Factor Ix ◽  
Hemophilia B ◽  
Clotting Factor ◽  
Real World Data ◽  
Replacement Product ◽  
Traumatic Bleeding ◽  
Factor Concentrate

Abstract Introduction: Hemophilia B, an X-linked genetic disease characterized by low clotting factor IX (FIX) levels, leads to spontaneous and traumatic bleeding in affected individuals. Intravenous FIX replenishment is administered to maintain adequate levels. The recent introduction of an extended half-life (EHL) FIX replacement product provided the opportunity to compare costs of care associated with treatment with an EHL product versus a standard half-life (SHL) product. Methods: The Truven Marketscan US claims database (Oct 2010 - Apr 2016) was used to identify factor concentrate charges for patients who had claims data for at least 3 months prior to and after switching from SHL to EHL products. Additionally, available data for up to 12 months pre- and post-switch on these identified patients were analyzed. Results: Thirteen patients, ranging from 3-64 years of age (median 18) were included in the analyses. Factor concentrate costs were higher after switch from SHL to EHL in each of the time periods examined (Table). Median costs were used since they were less influenced by isolated outliers and were similar to means in most cases. The median costs were 238% higher in the 3 months just after switching to the EHL product compared to the 3 months just prior to switching from the SHL product. Median costs were $51,881, $79,654, $75,695 and $61,515 in the 12-10, 9-7, 6-4 and 3-1 months prior to switch respectively compared to $173,515, $147,061, $149,971 and $207,973 in the corresponding quarterly month intervals post switch. Conclusion: This analysis of real world administrative data following individual patients through the switch from SHL to EHL products continuum suggests that switching from an SHL to an EHL product is associated with increased median factor costs throughout the 12 months following the switch, and that further analysis with larger numbers of patients should be explored. Disclosures Tortella: Pfizer Inc: Employment. Fogarty:Pfizer Inc: Employment. Alvir:Pfizer Inc: Employment. McDonald:Pfizer Inc: Employment. Spurden:Pfizer Inc: Employment. Pleil:Pfizer Inc: Employment.

Genetic Characterization of Hemophilia and Implications for Novel Therapies

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. SCI-9-SCI-9 ◽  
Author(s):  
David Lillicrap
Keyword(s):  
Gene Transfer ◽  
Phase I ◽  
Half Life ◽  
Genetic Characterization ◽  
Viral Vector ◽  
Conflicts Of Interest ◽  
Coagulation Factor ◽  
Factor Ix ◽  
Clotting Factor

Abstract Abstract SCI-9 The genes encoding factor VIII (FVIII) and factor IX (FIX) were cloned 25 years ago. Since then, substantial translational application of this knowledge has been witnessed. First, genetic analysis of hemophilia has enabled a detailed understanding of the types and patterns of mutation responsible for these conditions. This knowledge has provided important biological insights into the mechanisms underlying mutation generation and has also formed the basis for precise molecular diagnosis for hemophilia carriers and potentially affected fetuses. In addition, the hemophilic genotype is the best-characterized and strongest predictor for the development of inhibitor generation in previously untreated patients. The second benefit deriving from the genetic characterization of the hemophilias has been the production of recombinant coagulation factor concentrates. Over the past 20 years, the use of recombinant factor concentrates has increased dramatically and we are currently witnessing a flurry of activity to develop second-generation, enhanced concentrates. The major objective of these projects is to facilitate clotting factor prophylaxis through the production of concentrates whose half-lives are extended, thus reducing the frequency of factor administration. These endeavors are utilizing a variety of approaches, but most are focused on either chemical modification of the factors through polymer conjugates or the generation of fusion proteins with immunoglobulin or albumin to take advantage of the recycling function of the neonatal Fc receptor. The first wave of these new products is now undergoing early phase clinical studies, and while substantial benefits for FIX half-life extension appear achievable, FVIII half-life modification may be more challenging. Finally, molecular genetic knowledge of the hemophilias has resulted in the pursuit of strategies to utilize genetic approaches to effect long-term “cures” of the disease. These initiatives have resulted in several small phase I/II trials of viral vector-based gene transfer but have also formed the basis of mutation-specific therapies such as a translational read-through approach being undertaken in patients with nonsense mutations. Currently, two phase I/II trials are in progress with liver-directed AAV FIX gene transfer in which two different AAV serotypes are being evaluated. These studies follow on from two previous AAV clinical trials in which the major obstacle to clinical benefit appears to have been the host immune response to the vector. There is considerable interest in the outcomes of these new studies. Disclosures: No relevant conflicts of interest to declare.

Adeno-Associated Virus-Mediated Gene Transfer of Factor IX for Treatment of Hemophilia B by Gene Therapy

1999 ◽  
Vol 82 (08) ◽  
pp. 540-546 ◽  
Author(s):  
Roland Herzog ◽  
Katherine High
Keyword(s):  
Gene Therapy ◽  
Gene Transfer ◽  
Coagulation Factor ◽  
Factor Ix ◽  
Biologically Active ◽  
Hemophilia B ◽  
Clotting Factor ◽  
Severe Hemophilia ◽  
Dog Model ◽  
Life Threatening

IntroductionPatients with severe hemophilia have circulating blood coagulation factor VIII (hemophilia A) or factor IX (hemophilia B) levels below 1% of normal due to a genetic defect in the respective X-linked gene. The resulting bleeding disorder is characterized by spontaneous joint bleeds or, in a more life-threatening situation, into critical closed spaces, such as the intracranial or retroperitoneal space. Current treatment for hemophilia is based on intravenous infusions of clotting factor concentrates. These can be episode-based in response to bleeds (which does not prevent ongoing tissue damage nor the risk of a life-threatening bleed) or prophylactic (an expensive and not always practical alternative). The goal of a gene-based therapy is to introduce a functional clotting factor gene into a patient in order to provide a continuous supply of factor levels above 1%.1,2 Clinical endpoints for the efficacy of potential gene therapy trials for hemophilia are, therefore, well-defined and unequivocal.The relatively small size of the factor IX coding sequence (1.4 kb) and the fact that a number of cell types other than hepatocytes (which normally synthesize factor IX) are capable of producing biologically-active factor IX have contributed to the development of hemophilia B into an important model for the treatment of genetic diseases by gene therapy. The factor IX gene can be incorporated into a variety of vector systems. Various target tissues can be chosen for gene transfer as long as the secreted factor IX reaches the circulation and tight regulation of transgene expression is not required.3 Possibly most important in research on gene therapy for coagulation factor deficiencies, and genetic disorders in general, is the availability of a large animal model with severe disease. In this case, it is the well-characterized hemophilia B dogs maintained at the University of North Carolina at Chapel Hill. The animals contain a point-mutation in the portion of the factor IX gene encoding the catalytic domain. This mutation results in an absence of circulating factor IX antigen and, consequently, severe hemophilia B that closely mimics the human disease.4 Gene therapy strategies for hemophilia B have typically established a method of gene transfer, resulting in expression of factor IX in mice, and subsequently, attempted scale-up to the dog model. These investigations have established experiments in the hemophilic dog model as a critical step for the assessment of the efficacy of gene therapy protocols showing initial promise in mice. For example, reimplantation of primary myoblasts that had been transduced ex vivo with a retrovirus was successful in mice, but not in the canine model.5 Adenoviral gene transfer, characterized by varying success in mice, depending on the strain and dose used, has persistently resulted in high, but transient expression following intravenous infusion into dogs.6,7 Cellular immune responses and hepatotoxicity have limited the expression of factor IX from adenoviral vectors to just a few weeks. Repeat administration of the vector was complicated by the induction of neutralizing antibodies to viral particles in injected animals following the first administration. Retroviral gene transfer to hepatocytes was successful in long-term expression of factor IX in hemophilia B dogs but required a partial hepatectomy prior to infusion of the vector through the portal vein. The resulting expression levels were no higher than 0.1% of normal human factor IX levels.8

scholarly journals A COMPARATIVE STUDY OF HEMOPHILIA A VERSUS HEMOPHILIA B IN GOVERNMENT MEDICAL COLLEGE, KADAPA

2019 ◽  
Vol 3 (9) ◽  
Author(s):  
Dr. B. Naga Raja ◽  
Dr. G. Sobha Rani
Keyword(s):  
Hemophilia A ◽  
Factor Ix ◽  
Hemophilia B ◽  
Clotting Factor ◽  
Recessive Trait ◽  
Government Medical College ◽  
Clotting Factors ◽  
Blood Samples ◽  
Medical College ◽  
Blotting Paper

Introduction: Hemophilia is a genetic bleeding disorder caused by deficiency of clotting factor VIII (Hemophilia A) or Factor IX (Christmas disease) or Factor XI (Hemophilia C). Hemophilia is a X linked recessive trait with defective F8 an F9 genes in long arm of X chromosome. Hemophilia can also be acquired due to development of antibodies directed against the clotting factors. Aim: To compare the prevalence of Hemophilia A and Hemophilia B. Materials and Methods: The present study is done over a period of two years i.e., from 2016 to 2018. During the above period 130 cases were studied. Among these 112 cases (86.1%) were Hemophilia A and 18 cases (13.8%) were Hemophilia B. Requirement of materials: Capillary tubes, Blotting paper, Blood samples, Sprit and cotton. Results: In the present study we registered 130 cases of Hemophilia.  Among these 112 cases (86.1%) were Hemophilia A and 18 cases (13.8%) were Hemophilia B. Keywords: Blood sample, Hemophilia A, Hemophilia B, Kadapa

scholarly journals A transgender person with haemophilia

2018 ◽  
Vol 5 (1) ◽  
pp. 147-151
Author(s):  
Caroline Valk
Keyword(s):  
Factor Viii ◽  
Coagulation Factor ◽  
Factor Ix ◽  
Clotting Factor ◽  
Bilateral Mastectomy ◽  
Sex Reassignment Surgery ◽  
Haemophilia A ◽  
Cultural Changes ◽  
Transgender People ◽  
Specialist Doctor

Abstract Introduction: Transgender people face many obstacles to accessing healthcare but cultural changes are likely to increase provision of sex reassignment surgery in countries with sufficient resources. Haemophilia services traditionally focus on providing factor replacement therapy for males and should therefore understand how the care they provide can be adapted to meet the needs of transgender people. Haemophilia is an X-linked congenital bleeding disorder, caused by deficiency of coagulation factor VIII (haemophilia A) or factor IX (haemophilia B). The condition is passed on through carrier females, the majority of whom have a factor level high enough to allow for normal blood clotting. However, around 10% of carrier females are symptomatic and at risk of abnormal bleeding. Case presentation: This case report describes a person with mild haemophilia A who, on first presentation to the haemophilia service, stated he was a transgender person in transition to becoming a male. Haemophilia was diagnosed when heavy bleeding occurred following bilateral mastectomy approximately 25 years previously. He now requested phalloplasty. Management and outcome: Phalloplasty was performed at a hospital geographically separate from the haemophilia centre, requiring careful coordination between the two services. A haemophilia specialist nurse provided education and training about haemophilia and its management to the surgical nurses. Twenty-four-hour support was available from the nurse and a specialist doctor. Preparation and administration of clotting factor was the responsibility of the haemophilia nurse until the surgical team was confident in its use. Clotting factor replacement was managed using standard procedures, successfully maintaining factor VIII above a target level of 100% with a twice daily dose. Surgery went well, but wound healing was delayed, in part, due to persistent bleeding. Discussion: Close collaboration between the haemophilia and surgical teams provided effective prophylaxis of bleeding during a complex procedure that presented new challenges. Both services now have better understanding of the needs of transgender people.

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