scholarly journals Secondary prophylaxis with anti-inhibitor coagulant complex (AICC) : from anecdote to reality.

2017 ◽  
Vol 4 (2) ◽  
pp. 37
Author(s):  
M. H. Solano ◽  
A. Linares ◽  
C. Sossa ◽  
C. Casas ◽  
M. Cortés ◽  
...  
Keyword(s):  
Health System ◽  
Developing Country ◽  
Hemophilia A ◽  
Secondary Prophylaxis ◽  
Severe Bleeding ◽  
Bleeding Events ◽  
Two Cities ◽  
Bleeding Episodes ◽  
Hemophilia Treatment Centers ◽  
System Objective

Background. Evidence of prophylaxis benefit in patients without inhibitors to reduce hemarthrosis and severe bleeding have not been demonstrate in patients with hemophilia A (HA) and inhibitors, however, we could assume the reduction in bleeding episodes. Several publications have shown good results of secondary prophylaxis with AICC agents to reduce safely the number of bleeding events. We report the results in hemophilia treatment centers of two cities in a developing country, with access difficulties related to the high cost of this therapy to the health system. Objective. To describe the frequency of hemarthrosis and other bleeding episodes in patients with HA and inhibitors under AICC (Feiba®) prophylaxis.

Severe Bleeding Events in Hemophilia Α Patients Receiving Emicizumab Prophylaxis

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 1126-1126
Author(s):  
Karen L. Zimowski ◽  
Glaivy M. Batsuli ◽  
Paulette Bryant ◽  
Jenny McDaniel ◽  
Kelly Tickle ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Hemophilia A ◽  
Severe Bleeding ◽  
Severe Hemophilia ◽  
Bleeding Events ◽  
Advisory Committees ◽  
Acute Bleeding ◽  
Fviii Activity ◽  
Bleeding Episodes

Introduction : Emicizumab is a novel humanized bispecific antibody that mimics the function of activated coagulation factor VIII (fVIII). It has significantly changed the management of patients with hemophilia A and inhibitors by achieving baseline hemostatic control. Based on the HAVEN studies, emicizumab markedly reduces annualized bleeding rates and is FDA-approved for prophylaxis in hemophilia A patients of all ages, regardless of inhibitor status. In the HAVEN2 interim analysis, only 3/57 pediatric patients receiving emicizumab prophylaxis required treatment for an acute bleeding event after a 9-week median observation time. We report 3 patients with severe hemophilia A and a history of inhibitors receiving emicizumab prophylaxis with severe or refractory bleeding episodes to highlight the importance of vigilance and surveillance of children with severe hemophilia A on emicizumab. Methods: This retrospective analysis includes patients between 0-21 years of age with severe hemophilia A (fVIII activity < 1%) receiving emicizumab prophylaxis and admitted for the management of an acute bleeding episode following emicizumab's FDA approval in November 2017. Patients were followed at the Pediatric Hemophilia Treatment Center at the Hemophilia of Georgia Center for Bleeding & Clotting Disorders of Emory and the St. Jude Affiliate Clinic at Novant Health Hemby Children's Hospital. Data collected included demographics, past medical history including inhibitor status, bleeding history, and treatment modalities, and details regarding the presentation, management, and outcome of acute severe bleeding events. Due to the nature of the study, descriptive statistics were primarily used for data analysis. Results: Three patients with severe hemophilia A receiving emicizumab prophylaxis were admitted for the management of 4 severe bleeding episodes. All patients had a history of a fVIII inhibitor. Three of the 4 bleeding episodes were trauma-induced while 1 occurred spontaneously. For the traumatic episodes, all patients presented with worsening symptoms approximately 1 week following the inciting event. All patients had a normal aPTT at the time of presentation, ruling out a significant anti-drug antibody (emicizumab level not available). A patient with a low-titer inhibitor developed an epidural hematoma following a trampoline injury and was treated with continuous infusion of recombinant factor VIII (rfVIII), adjusting the rate to achieve chromogenic fVIII activity of 100% for 14 days. Following 14 days, he was started on rfVIII 50 IU/kg Q12 hours with a goal fVIII activity of 50%. His rfVIII dosing interval was gradually weaned to every other day while in inpatient rehabilitation. As outlined in Table 1, the remaining 3 bleeding events were initially managed with recombinant activated factor VII (rfVIIa) dosed at 80-90 mcg/kg/dose with escalating frequency for an average of 8 days. However, due to lack of improvement, treatment was changed to low-dose activated prothrombin complex concentrates (aPCC; 10-15 IU/kg/dose Q12-24 hours for an average of 7 days). In all 3 of these events, the hematomas improved after treatment with aPCC. No patient experienced thrombotic microangiopathy, thrombosis, or had evidence of DIC while receiving these treatment regimens. Discussion/Conclusion: Pharmacokinetic analysis of emicizumab suggests that following the standard 4-week loading phase, trough plasma emicizumab concentrations obtained prior to a 1.5 mg/kg once weekly maintenance dose correlates with at least 10-15 IU/dL equivalent fVIII activity. This degree of thrombin generation should be sufficient to prevent severe spontaneous bleeding episodes in most patients. However it does not preclude significant trauma-induced bleeding or spontaneous bleeding in inhibitor patients. Based on our cases, providers should maintain a high index of suspicion for acute bleeding in patients receiving emicizumab prophylaxis. Serious bleeding events, although rare, may have a more insidious onset in patients receiving emicizumab. Furthermore, despite the baseline hemostasis achieved with emicizumab, acute bleeding events may still require aggressive therapy. Our cases suggest that low-dose aPCC or continuous infusion fVIII may be feasible options for treating acute bleeding events in patients with hemophilia A and inhibitors receiving emicizumab prophylaxis. Disclosures Zimowski: Pfizer: Research Funding; National Hemophilia Foundation: Other: Medical Loan Reimbursement, Research Funding. Batsuli:Octapharma: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Genetech: Membership on an entity's Board of Directors or advisory committees. Bryant:Novo Nordisk: Other: PI on Novo Nordisk sponsored Studies. McDaniel:Genentech: Membership on an entity's Board of Directors or advisory committees. Tickle:National Hemophilia Foundation: Research Funding. Meeks:Bayer: Membership on an entity's Board of Directors or advisory committees; Genentech: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Bioverativ: Membership on an entity's Board of Directors or advisory committees; Takeda-Shire: Membership on an entity's Board of Directors or advisory committees; HEMA Biologics: Membership on an entity's Board of Directors or advisory committees. Sidonio:Genetech: Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda-Shire: Membership on an entity's Board of Directors or advisory committees, Research Funding; Bioverativ: Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Grifols: Membership on an entity's Board of Directors or advisory committees, Research Funding; Biomarin: Membership on an entity's Board of Directors or advisory committees; Uniqure: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Kedrion: Research Funding.

Cost-effectiveness of prophylaxis against on-demand treatment in boys with severe hemophilia A in Iran

2009 ◽  
Vol 25 (4) ◽  
pp. 584-587 ◽  
Author(s):  
Aliasghar Ahmad Kia Daliri ◽  
Hassan Haghparast ◽  
Jahanara Mamikhani
Keyword(s):  
Cost Effectiveness ◽  
Chart Review ◽  
Prophylactic Treatment ◽  
Bleeding Event ◽  
Retrospective Chart Review ◽  
Third Party ◽  
Bleeding Events ◽  
On Demand ◽  
Bleeding Episodes ◽  
Hemophilia Treatment Centers

Objective: The aim of this study was to assess the incremental cost-effectiveness of on-demand versus prophylactic hemophilia therapy in Iran from a third-party payers’ perspective.Methods: A retrospective chart review of twenty-five type A hemophiliacs who were treated in three hemophilia treatment centers was conducted. The patients were boys 0–9 years old receiving one of two treatments: (i) prophylaxis with concentrate at clinic; (ii) concentrate at clinic as on-demand. Fourteen boys received on-demand infusions for bleeding events, and eleven boys received infusions prophylaxis. Data were extracted from documents in the hemophilia treatment centers during a period of approximately 6 months.Results: The patients receiving prophylactic treatment had fewer bleeding events each month (mean, 0.26 versus 2.74) but used more concentrate (225.31 versus 87.20 units/kg per month). Average monthly cost per patient in the prophylaxis group was approximately 1.9 times higher than in the on-demand group. Compared with on-demand infusion, prophylaxis costs 3,201,656 Rials (€213.45) per bleeding event prevented.Conclusion: Prophylactic care markedly reduces the number of bleeding episodes, but at considerable cost.

A Phase II Open-Label Study Evaluating Hemostatic Activity, Pharmacokinetics and Safety of Recombinant Porcine Factor VIII (OBI-1) in Hemophilia A Patients with Alloantibody Inhibitors Directed Against Human FVIII.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 783-783 ◽  
Author(s):  
Johnny Mahlangu ◽  
Tatiana A. Andreeva ◽  
Donald Macfarlane ◽  
Mark T. Reding ◽  
Christopher Walsh ◽  
...  
Keyword(s):  
Phase Ii ◽  
Hemophilia A ◽  
Dose Range ◽  
Vital Signs ◽  
Cross Reactivity ◽  
Bleeding Events ◽  
Open Label ◽  
Hemostatic Activity ◽  
Laboratory Variables ◽  
Bleeding Episodes

Abstract Development of inhibitors to human FVIII (hFVIII) is a significant complication in the reversal and prevention of bleeding events in hemophilia A patients. Porcine FVIII (pFVIII) possesses low cross reactivity to anti-hFVIII antibodies. OBI-1, a recombinant B-domain deleted pFVIII, has recently been tested in a Phase II trial in patients with congenital hemophilia A and inhibitors experiencing a non-life/non-limb threatening bleed. In patients with a measurable anti-pFVIII antibody titer, dosing was initiated with a loading dose (LD) followed by up to 8 doses of 50 to 150 U/kg of OBI-1 administered at 6 hour intervals until the bleed was controlled. The PK profile of OBI-1 was assessed for the first OBI-1 infusion of each patient. FVIII levels were measured 30 minutes after each infusion. Inhibitor titers were evaluated for a minimum of 6 months after the first OBI-1 infusion. A total of 25 bleeding episodes in 9 patients were treated successfully with OBI-1. The median time from bleeding onset to treatment was 7 hours (range: 3 20 hr). OBI-1 showed a cumulative efficacy of 72% after 1 injection, 84% after 2 injections or less, 92% after 3 injections or less, and 100% after 8 or less injections. In over 40 infusions, OBI-1 was well tolerated and no drug related SAEs were observed. One case of pruritus rated as mild was easily controlled with diphenhydramine. FVIII levels measured 30 minutes after each OBI-1 infusion ranged from < 0.5% to 226%. They were generally lower with higher anti-pFVIII titers although all bleeds were successfully controlled. Follow up inhibitor titers are still being monitored and final results will be presented and discussed. Other investigative parameters, including vital signs and laboratory variables did not show treatment related abnormalities. OBI-1 can be given as a short infusion. It was effective in controlling all bleeds which occurred in this study and was well tolerated. The results suggest that a LD is not needed with OBI-1 treatment, and in some instances patients may have been over treated. Given the promising results in this study, additional studies are planned to optimize dose range for OBI-1 and to confirm the long term safety and efficacy of OBI-1 in the treatment of bleeds in a larger cohort of individuals with hemophilia A complicated by the presence of hFVIII inhibitors.

Bypassing Agents in Children with Inhibitors: How Much Do We Use and How Much Is Too Much?

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1217-1217
Author(s):  
Deana Gordon ◽  
Michael Wang ◽  
Katherine Ruegg ◽  
Elizabeth Villalobos-Menuey ◽  
Marilyn J. Manco-Johnson
Keyword(s):  
Hemophilia A ◽  
Conflicts Of Interest ◽  
Factor Viia ◽  
High Titer ◽  
Tolerance Induction ◽  
Treatment Center ◽  
Severe Bleeding ◽  
Bleeding Events ◽  
Dose Frequency ◽  
Bypassing Agents

Abstract Abstract 1217 Background: Children with hemophilia A and high-titer inhibitors suffer frequent severe bleeding events and often respond to bypassing agents more poorly than adults resulting in increased dosing and cost. Aims: This study was conducted to determine the amount and variability of bypass agent therapy currently given to children with inhibitors at a large combined adult and pediatric hemophilia treatment center in comparison to treatment of adult inhibitor patients. Methods: All subjects were enrolled onto a single institution prospective inceptional cohort study of bleeding disorders with appropriate IRB-approved consent and assent. All children who developed high-titer inhibitors were treated with immune tolerance induction, and children treated with bypassing agents primarily represent difficult inhibitors. Data regarding treatment agents, dose and duration were extracted for 24 bleeding events in 6 children in comparison to comparable data on 26 bleeding events in 5 adults with high-titer inhibitors. Treatment decisions were made clinically by academic hematologists in consultation with hemophilia nurses, patients and parents based on perceived severity of bleeding events and therapeutic response. Treatment was given as recombinant factor VIIa (NovoSeven, N, n=28), prothrombin complex concentrates (FEIBA, F, n=10) or alternating doses of both (A, n=12). Median results for individual children and aggregated adult data are shown on Table 1. Children received seven times the treatment doses and duration compared with adults. In addition, children received both N and F for half of the bleeding events, while this was used for only one adult event. Treatment duration in children was not affected by initial dose or dose frequency of N (p > 0.05 for both). Bleeding events were severe and difficult to manage; significant long-term morbidity in these 6 children include ankle arthropathy in 3, elbow contracture following compartment syndrome in 2 and quadrucep pseudotumor in 1. Discussion: Children with hemophilia A and inhibitors experience bleeding episodes that are poorly responsive to both N and F, resulting in higher dosing, longer duration and enormous costs. Children require better inhibitor therapies. Clinical trials of new bypassing agents designed specifically for children are urgently needed. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Neonatal hemophilia: a rare presentation

2015 ◽  
Vol 7 (4) ◽  
Author(s):  
Nuno Ferreira ◽  
Elisa Proença ◽  
Cristina Godinho ◽  
Dulce Oliveira ◽  
Ana Guedes ◽  
...  
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Neonatal Period ◽  
Post Partum ◽  
Severe Bleeding ◽  
Factor Viii Activity ◽  
Bleeding Events ◽  
Rare Presentation ◽  
Increased Risk ◽  
Coagulation Study

Hemophilia A is a X-linked hereditary condition that lead to decreased factor VIII activity, occurs mainly in males. Decreased factor VIII activity leads to increased risk of bleeding events. During neonatal period, diagnosis is made after post-partum bleeding complication or unexpected bleeding after medical procedures. Subgaleal hemorrhage during neonatal period is a rare, severe extracranial bleeding with high mortality and usually related to traumatic labor or coagulation disorders. Subgaleal hemorrhage complications result from massive bleeding. We present a neonate with unremarkable family history and uneventful pregnancy with a vaginal delivery with no instrumentation, presenting with severe subgaleal bleeding at 52 hours of life. Aggressive support measures were implemented and bleeding managed. The unexpected bleeding lead to a coagulation study and the diagnosis of severe hemophilia A. There were no known sequelae. This case shows a rare hemophilia presentation reflecting the importance of coagulation studies when faced with unexplained severe bleeding.

Effects of “Primary Prophylaxis” and “On-Demand” Therapy on the Clinical Expression of Severe Hemophilia A in Children - Results of a Multicenter Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3146-3146
Author(s):  
Rosemarie Schobess ◽  
Karin Kurnik ◽  
Wolfhart Kreuz ◽  
Frauke Friedrichs ◽  
Anne Krumpel ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Bleeding Episode ◽  
Joint Damage ◽  
Primary Prophylaxis ◽  
Secondary Prophylaxis ◽  
Outcome Variable ◽  
Severe Hemophilia ◽  
On Demand ◽  
Imaging Results ◽  
Bleeding Episodes

Abstract Background: Patients with severe hemophilia A (HA) can either be treated by regular FVIII infusions twice or thrice per week (prophylaxis), or only in case of bleeding episodes (on-demand). Whereas prophylaxis reduces the number of bleeding episodes and may therefore prevent the development of hemophilic arthropathy, recommendations regarding age and dose at start of prophylactic regimens are still a matter of debate. The present cohort study was performed to investigate the role of “primary prophylaxis” versus “on-demand” therapy in HA children. The outcome variable was imaging-proven hemophilic joint damage. Methods: 42 children were initially treated with primary prophylaxis following the first bleeding episode, and were frequency-matched (year of birth, catchment area) to 67 patients receiving “on-demand” therapy with an early switch to “secondary prophylaxis”. Results: In multivariate analysis adjusted for the HA mutation type and the presence or absence of thrombophilia, the Pettersson score investigated at a median age of 12.5 years in joints with at least one documented bleeding episode was no significantly different between the two patient groups (p=0.944), and no statistically significant differences were found in patients with target joints (p=0.3), or in children in which synovitis had occurred (p=0.77). Imaging results obtained showed a substantial agreement (87.14%) beyond that expected by chance alone (42.4%) between local and central readers in the patients tested (kappa=0.77; Z= 17.27; p < 0.001). Conclusion: In cases with severe HA where primary prophylaxis is impossible, the procedure to switch from “on-demand” to early secondary prophylaxis can be achieved in the majority of young children affected. In addition, the needs of parents around the time of diagnosis of severe HA could be better addressed.

scholarly journals Prospective Evaluation of Bleeding Incidence in Fibrinogen Deficiency (PRO-RBDD Study)

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 207-207
Author(s):  
Roberta Palla ◽  
Marzia Menegatti ◽  
Marco Boscarino ◽  
Jan Blatny ◽  
Ondrej Zapletal ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Cumulative Incidence ◽  
Research Funding ◽  
Severe Bleeding ◽  
Bleeding Events ◽  
On Demand ◽  
Number Of Patients ◽  
Wide Range ◽  
Bleeding Episodes

Abstract BACKGROUND: Congenital fibrinogen disorders are rare diseases affecting either the quantity (afibrinogenaemia and hypofibrinogenaemia) or the quality (dysfibrinogenaemia) or both (hypodysfibrinogenaemia) of fibrinogen. Afibrinogenemia is associated with mild-to-severe bleeding, whereas hypofibrinogenemia is most often asymptomatic. Previously, our group (Peyvandi et al, JTH 2006) showed that in a group of 100 patients with afibrinogenemia and hypofibrinogenemia, the mean annual incidence of bleeding episodes was 0.7 on on-demand therapy (range 0-16.5) and 0.5 on prophylactic replacement therapy (range 0-2.6). Dys- and hypodysfibrinogenemia are commonly associated with bleeding, thrombosis, or both; however, most individuals are asymptomatic. Treatment of fibrinogen deficiency is challenging because the minimum amount of fibrinogen to prevent bleeding is unknown and because thromboembolism may occur in association with fibrinogen substitution therapy. Therefore a guideline for optimal treatment is not available yet. AIMS: The 3-year observational prospective study on rare bleeding disorders (PRO-RBDD) aimed at evaluating the incidence of bleeding episodes in patients with fibrinogen deficiency and the benefits and complication of current treatment regimens. METHODS: 17 Hemophilia Treatment Centers worldwide collected data in a web-based database at baseline (patient history) and at pre-specified time-points (every 6 months, follow up study); 146 patients (86 females/60 males) were recorded. Analysis was carried out on patients with available data on both antigen and activity levels. Bleeding incidence was calculated to evaluate number of bleeding episodes in patients on on-demand therapy. A survival analysis was also made to evaluate the cumulative incidence of the first bleeding requiring replacement therapy. Analysis was done using R v.3.3.1 (R Foundation for Statistical Computing, Vienna, Austria). RESULTS: Data on activity and antigen level were available on 96 patients (54 females/42 males), of whom 81 are currently on follow up. Twenty-one (26%) patients were afibrinogenemic, 17 (21%) hypofibrinogenemic, 36 (44%) dysfibrinogenemic and 7 hypodysfibrinogenemic (9%), according to standard classification. Patients were followed up for a median of 810 days (IQR: 728-916, min-max: 221-1215). In on-demand therapy, the bleeding incidence was 0.86 patient-year-1 (95%CI 0.57-1.15) in afibrinogenemia, 0.30 (95%CI 0.15-0.52) in hypofibrinogenemia, 0.14 (95%CI 0.06-0.25) in dysfibrinogenemia and 0.06 (95%CI 0.-0.27) in hypodysfibrinogenemia. At 1200 days of follow up, the bleeding cumulative incidence of the first bleeding treated with replacement therapy was 0.43 (95%CI 0.11-0.64) in afibrinogenemia, 0.30 (95%CI 0.05-0.49) in hypofibrinogenemia, 0.06 (95%CI 0.0-0.14) in dysfibrinogenemia and 0.14 (95%CI 0.0-0.37) in hypodysfibrinogenemia. Prophylaxis regimen (dosage range 50 - 666 mg/Kg/month) with fibrinogen concentrate was used only in one third of patients (6/21) with afibrinogenemia and it seems to reduce the median number of bleeding events per year [from 1 (min-max: 1-3/year) to 0.4 (min-max: 0-1.25)]. Only one allergic reaction and no thrombotic events were reported. CONCLUSION: The results of this prospective observational study on patients with fibrinogen deficiency showed that the bleeding incidence decreased accordingly to plasmatic fibrinogen levels. Preliminary data on a limited number of patients with afibrinogenemia showed a reduction of bleeding episodes even if a wide range of prophylaxis dosage has been used. A larger group of patients and a longer follow up period are required to evaluate the efficacy of prophylaxis and to find the optimal target level to prevent spontaneous major bleeding in afibrinogenemic patients. Disclosures Palla: Pfizer: Other: travel support . Menegatti:Pfizer: Other: travel support . Blatny:CSL Behring: Speakers Bureau. Halimeh:Bayer Healthcare GmbH: Research Funding, Speakers Bureau; Baxalta Innovations GmbH: Research Funding, Speakers Bureau; Biotest AG: Research Funding, Speakers Bureau; CSL Behring GmbH: Research Funding, Speakers Bureau; Novartis Pharma GmbH: Speakers Bureau; Novo Nordisk Pharma GmbH: Research Funding, Speakers Bureau; Octapharma GmbH: Research Funding, Speakers Bureau; LFB GmbH: Speakers Bureau; Pfizer Pharma GmbH: Research Funding, Speakers Bureau. Siboni:LFB: Speakers Bureau; Bayer: Speakers Bureau. Laros-Van Gorkom:Baxter: Research Funding; CSL Behring: Research Funding; Sanquin: Speakers Bureau. Schutgens:CSL Behring: Research Funding; Pfizer: Research Funding; Bayer: Research Funding; Baxalta: Research Funding; Novonordisk: Research Funding. De Moerloose:Bayer: Consultancy, Research Funding, Speakers Bureau; Baxalta: Consultancy, Research Funding, Speakers Bureau; LFB: Speakers Bureau; Stago: Speakers Bureau; Novonordisk: Consultancy, Research Funding, Speakers Bureau; LFB: Consultancy, Research Funding; Instrumentation Laboratory: Consultancy, Research Funding. Casini:CSL Berhing: Speakers Bureau; Bayer: Other: Travel support. Makris:CSL Behring: Consultancy; Novo Nordisk: Consultancy; Freeline Therapeutics: Consultancy; Bayer: Speakers Bureau; Biogen: Speakers Bureau; Grifols: Speakers Bureau. Chapin:Baxalta: Consultancy; CSL Behring: Consultancy; Novo Nordirsk: Consultancy; Alexion Pharmaceuticals: Consultancy; Apopharma: Consultancy; Bayer: Consultancy. Peyvandi:CSL Behring: Speakers Bureau; Novo Nordisk: Other: research funding paid to Luigi Villa Foundation, Research Funding, Speakers Bureau; Ablynx: Membership on an entity's Board of Directors or advisory committees, Other: research funding paid to Luigi Villa Foundation, Research Funding; Grifols: Speakers Bureau; SOBI: Speakers Bureau; Kedrion Biopharma: Consultancy, Other: research funding paid to Luigi Villa Foundation, Research Funding; LFB: Consultancy; Alexion: Other: research funding paid to Luigi Villa Foundation, Research Funding; Octapharma: Consultancy; Bayer: Speakers Bureau; Biotest: Other: research funding paid to Luigi Villa Foundation, Research Funding, Speakers Bureau.

scholarly journals Emicizumab in the treatment of hemophilia A

2020 ◽  
Vol 36 (81) ◽  
pp. 2007-2010
Author(s):  
Ivan Tijanić ◽  
Ivana Golubović ◽  
Miodrag Vučić ◽  
Miloš Tijanić
Keyword(s):  
Hemophilia A ◽  
Bleeding Events ◽  
Surgical Interventions ◽  
Hemostatic Activity ◽  
Adults And Children ◽  
Bleeding Episodes ◽  
Prophylactic Use ◽  
Bypassing Agents ◽  
Favorable Safety

Introduction: Despite substantial advances in the treatment of Hemophilia A with the use of concentrated factor VIII preparations during recent decades, bleeding episodes still occur from time to time. The development of inhibitors significantly reduces the efficacy of traditional replacement therapy, seriously increasing morbidity and mortality in these patients. Emicizumab (HEMLIBRA ®) is a chimeric bispecific humanized antibody that bridges activated FIX and FX and thus restores the function of missing activated FVIII. Aim: The aim of the study was to analyze the literature date of the effect of Emicizumab in the treatment of Hemophilia A. Results: Multicenter randomized studies called HAVEN have shown excellent results of this medication in the treatment of patients with Hemophilia A. FVIII inhibitors do not bind to or neutralize Emicizumab and therefore have no effect on the hemostatic activity of the drug. Emicizumab prophylaxis produced a significant reduction in treated bleedings of 79%, compared to with the group of patients on prophylaxis with bypassing agents, while the rate grew up to even 95% after longer observation. Other studies have also confirmed good treatment results and a favorable safety profile in both adults and children. In the cases of bleeding events or preparation for immediate surgical interventions, it is recommended to user FVII (NovoSeven) ® according to previous guidelines. Conclusion: The results of the prophylactic use of Emicizumabhave so far shown that it may be a revolutionary preparation that can significantly reduce bleeding episodes and improve the quality of life of patients with Hemophilia A. Nevertheless, further testing of this drug is required.

Coagulation Disorders in Thrombocythaemia, a Study of Seven Cases

1962 ◽  
Vol 07 (01) ◽  
pp. 114-128 ◽  
Author(s):  
Stefan Niewiarowski ◽  
Halina Zywicka ◽  
Zbigniew Latałło
Keyword(s):  
Liver Parenchyma ◽  
Platelet Factor 4 ◽  
Coagulation System ◽  
Severe Bleeding ◽  
Clotting Factors ◽  
Platelet Factor ◽  
Antiheparin Activity ◽  
Thromboplastic Activity ◽  
Bleeding Episodes ◽  
Routine Coagulation

SummaryThe blood coagulation system has been studied in 7 patients with thrombocythaemia. 4 of these patients had thrombocythaemia after splenectomy, 2 of them had thrombocythaemia associated with myeloid leukemia, and 1 thrombocythaemia associated with polycythaemia. Severe bleeding episodes were noted in 5 cases, 2 patients had only mild bleeding symptoms.Each patient was examined several times. The period of observations varied from 2 months to 3 years. Platelet count varied from 350 000 to 3 800 000 per mm3.Bleeding time and tourniquet test were normal in all cases. Routine coagulation and fibrinolysis studies did not reveale characteristic abnormalities in plasma clotting factors. A decrease of prothrombin complex components was observed in 4 cases. This disturbance was due to the coexisting injury of liver parenchyma or myeloid changes but not to an increase of platelets or to the abnormalities in the platelet system.An increase of antiheparin activity was found in the plasma of 4 patients. This activity is probably due to the escape of platelet factor 4 from destroyed or qualitatively changed platelets into plasma.Platelet clotting factors were investigated in isolated platelet suspensions, A significant decrease of platelet factor 1 was observed in all patients and a decrease of platelet factor 4 in 5 patients. In 2 cases platelet factor 4 increased. Platelet thromboplastic activity showed a great variety of disturbances in conformity with other workers observations.Recent views on the pathogenesis of bleedings in thrombocythaemia are discussed. On the basis of their own investigations the authors suggest that the significant disturbances of platelet function may contribute to the development of bleeding, and that the increase of antiheparin activity in plasma may produce hypercoagulability and favorize the formation of thrombi.

A Multicenter Study of Recombinant Factor VIII (RecombinateTM) in Previously Treated Patients with Hemophilia A

1997 ◽  
Vol 77 (04) ◽  
pp. 660-667 ◽  
Author(s):  
G C White ◽  
S Courter ◽  
G L Bray ◽  
M Lee ◽  
E D Gomperts ◽  
...  
Keyword(s):  
Hemophilia A ◽  
Recombinant Dna ◽  
Home Treatment ◽  
Pharmacokinetic Parameters ◽  
Pharmacokinetic Studies ◽  
Open Label ◽  
Treat Ment ◽  
Previously Treated Patients ◽  
Bleeding Episodes

SummaryA prospective, open-label multicenter investigation has been conducted to compare pharmacokinetic parameters of recombinant DNA-derived FVIII (rFVIII) and plasma-derived FVIII concentrate (pdFVIII) and to assess safety and efficacy of long-term home-treat- ment with rFVIII for subjects with hemophilia A. Following comparative in vivo pharmacokinetic studies, 69 patients with severe (n = 67) or moderate (n = 2) hemophilia A commenced a program of home treatment using rFVIII exclusively for prophylaxis and treatment of all bleeding episodes for a period of 1.0 to 5.7 years (median 3.7 years). The mean in vivo half-lives of rFVIII and pdFVIII were both 14.7 h. In vivo incremental recoveries at baseline were 2.40%/IU/kg and 2.47%/IU/kg, respectively (p = 0.59). The response to home treatment with rFVIII was categorized as good or excellent in 3,195 (91.2%) of 3,481 evaluated bleeding episodes. Thirteen patients received rFVIII for prophylaxis for twenty-four surgical procedures. In all cases, hemostasis was excellent. Adverse reactions were observed in only 13 of 13,591 (0.096%) infusions of rFVIII; none was serious. No patient developed an inhibitor to r FVIII.

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