scholarly journals Results of a randomized phase III/IV trial comparing intermittent bolus versus continuous infusion of antihaemophilic factor (recombinant) in adults with severe or moderately severe haemophilia A undergoing major orthopaedic surgery

Haemophilia ◽  
2021 ◽  
Author(s):  
Ingrid Pabinger ◽  
Vasily Mamonov ◽  
Jerzy Windyga ◽  
Werner Engl ◽  
Jennifer Doralt ◽  
...  
Keyword(s):  
Continuous Infusion ◽  
Orthopaedic Surgery ◽  
Phase Iii ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Intermittent Bolus ◽  
Major Orthopaedic Surgery

F VIII Inhibitors in Haemophilia A Patients after Continuous Infusion of Factor VIII Concentrates.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 3100-3100
Author(s):  
Ch. von Auer ◽  
J. Oldenburg ◽  
M. von Depka ◽  
C. Escuriola-Ettinghausen ◽  
W. Kreuz ◽  
...  
Keyword(s):  
Factor Viii ◽  
Continuous Infusion ◽  
Orthopaedic Surgery ◽  
Coagulation Factor ◽  
Haemophilia A ◽  
Missense Mutations ◽  
Factor Viii Concentrates ◽  
Coagulation Factor Concentrates ◽  
Major Orthopaedic Surgery ◽  
Mild Haemophilia

Abstract Continuous infusion (CI) of coagulation factor concentrates has been used since the early 1990s. Recent reports of the occurrence of an inhibitor (inh) after CI have raised concerns about this method of treatment. We conduct a retrospective study to investigate the development of inh after CI of FVIII concentrates in Germany. 99 haemophilia treating physicians in Germany were contacted and asked to answer a questionnaire. So far data of 13 departments have been reported and analyzed. Three of these 13 centers never conducted a CI, in 5 no inh were detected and in 5 haemophilia centers 10 patients with inh development after CI were registered. 5 of these patients were suffering from severe, 1 from moderate and 4 from mild haemophilia (age between 7 months and 57 years). Indications for treatment were major bleeds and surgical procedures. Plasma derived (6) and recombinant (4) factor concentrates were given in various infusion sets. Data concerning infused amount (4300 to >100000 IE), exposure days (1 to >100) and inh characteristic (alloantibodies, 3 LR, 7 HR) were collected. Regarding the genotype, we found 4 missense-mutations, 2 intron-22-inversions, 1 small deletion, 3 were unknown. In our own center we found no inh in 81 patients with major orthopaedic surgery and bolus infusion of factor VIII concentrate compared to 2 inh in 8 patients with major orthopaedic surgery and CI of FVIII. In conclusion we found only in 2 patients the typical gene mutation for inh development. Strikingly the inh developed very often in patients with mild haemophilia. These findings agree with published results. There might be an uncommon inh-pathomechanism due to CI or patients with mild haemophilia might exhibit a much higher prevalence of inhibitor development when treated with an “intensive FVIII-treatment” such as CI.

Prospective study of continuous infusion with Beriate® P in patients with severe haemophilia A undergoing surgery – a subgroup analysis

2014 ◽  
Vol 134 ◽  
pp. S43-S47 ◽  
Author(s):  
Günter Auerswald ◽  
Andrea Bade ◽  
Julia Johne ◽  
Kirstin Haubold ◽  
David Overberg ◽  
...  
Keyword(s):  
Prospective Study ◽  
Continuous Infusion ◽  
Subgroup Analysis ◽  
Haemophilia A ◽  
Severe Haemophilia

Continuous infusion of extended half-life factor VIII (efmoroctocog alpha) for surgery in severe haemophilia A

Haemophilia ◽  
2018 ◽  
Vol 24 (4) ◽  
pp. e280-e283
Author(s):  
I. C. L. Kremer Hovinga ◽  
R. E. G. Schutgens ◽  
P. R. van der Valk ◽  
L. F. D. van Vulpen ◽  
E. P. Mauser-Bunschoten ◽  
...  
Keyword(s):  
Factor Viii ◽  
Continuous Infusion ◽  
Half Life ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Life Factor

Safety and efficacy of sucrose-formulated full-length recombinant factor VIII: Experience in the standard clinical setting

2008 ◽  
Vol 99 (01) ◽  
pp. 52-58 ◽  
Author(s):  
Elena Santagostino ◽  
Albert Faradji ◽  
Alfonso Iorio ◽  
Jan van der Meer ◽  
Jørgen Ingerslev ◽  
...  
Keyword(s):  
Observational Study ◽  
Factor Viii ◽  
De Novo ◽  
Observation Time ◽  
Full Length ◽  
Recombinant Factor Viii ◽  
Phase Iii ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Safety And Efficacy

SummaryThe safety of full-length sucrose-formulated recombinant factor VIII (rFVIII-FS; KOGENATE® FS) for up to 24 months of use was evaluated in a postmarketing observational study in Europe. Long-term safety and efficacy data were available for 212 patients with severe haemophilia A, including 13 previously untreated patients (PUPs) and 12 patients with 1–19 exposure days (EDs). Patients accumulated a mean (± SD) of 187 (121) EDs to rFVIII-FS and received a total of 39,627 infusions, mainly for prophylaxis and for the treatment of 4,283 spontaneous or trauma-related bleeds during an average observation time of 710 (136) days. Of these bleeding episodes, 85.4% were successfully treated with one or two infusions of rFVIII-FS. Haemostasis was also evaluated during 46 minor to major surgical pro- cedures, and the response to infusion was “excellent” or “good” in all cases. FVIII inhibitor formation was observed in six patients (two de novo; four persistent or recurrent). The de novo cases represent 8.0% (2 of 25) of patients who reported 0–19 previous EDs at study entry. Four of the five patients who reported possible drug-related adverse effects developed inhibitors. The results of this observational study demonstrate the efficacy and safety of rFVIII-FS during normal clinical use in the treatment of patients with severe haemophilia A. Furthermore, these findings are consistent with those of previous phase III clinical studies with rFVIII-FS, particularly with regard to its efficacy and low incidence of inhibitor formation.

Benefit-to-harm ratio of thromboprophylaxis for patients undergoing major orthopaedic surgery

2014 ◽  
Vol 111 (02) ◽  
pp. 199-212 ◽  
Author(s):  
Jane Liang ◽  
David Bergqvist ◽  
Roger Yusen ◽  
Russell Hull
Keyword(s):  
Major Bleeding ◽  
Orthopaedic Surgery ◽  
Bleeding Event ◽  
Phase Iii ◽  
Number Needed To Treat ◽  
Vte Prophylaxis ◽  
Major Orthopaedic Surgery ◽  
Definition Of ◽  
Newer Anticoagulants ◽  
Number Needed To Harm

SummarySurgeons consider the benefit-to-harm ratio when making decisions regarding the use of anticoagulant venous thromboembolism (VTE) prophylaxis. We evaluated the benefit-to-harm ratio of the use of newer anticoagulants as thromboprophylaxis in patients undergoing major orthopaedic surgery using the likelihood of being helped or harmed (LHH), and assessed the effects of variation in the definition of major bleeding on the results. A systematic literature search was performed to identify phase II and phase III studies that compared regulatory authority-approved newer anticoagulants to the low-molecularweight heparin enoxaparin in patients undergoing major orthopaedic surgery. Analysis of outcomes data estimated the clinical benefit (number-needed-to-treat [NNT] to prevent one symptomatic VTE) and clinical harm (number-needed-to-harm [NNH] or the NNT to cause one major bleeding event) of therapies. We estimated each trial’s benefitto-harm ratio from NNT and NNH values, and expressed this as LHH = (1/NNT)/(1/NNH) = NNH/NNT. Based on reporting of efficacy and safety outcomes, most studies favoured enoxaparin over fondaparinux, and rivaroxaban over enoxaparin. However, when using the LHH metric, most trials favoured enoxaparin over both fondaparinux and rivaroxaban when they included surgical-site bleeding that did not require reoperation in the definition of major bleeding. The exclusion of bleeding at surgical site which did not require reoperation shifted the benefit-to-harm ratio in favour of the newer agents. Variations in the definitions of major bleeding may change the benefit-to-harm ratio and subsequently affect its interpretation. Clinical trials should attempt to improve the consistency of major bleeding reporting.

Efficacy and Safety of VTE Prophylaxis with Oral Rivaroxaban Compared to Fondaparinux or Low-Molecular Weight Heparin In a Large Cohort of Consecutive Patients Undergoing Major Orthopaedic Surgery

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 210-210
Author(s):  
Jan Beyer-Westendorf ◽  
Lars Donath ◽  
Jörg Lützner ◽  
Sebastian Werth ◽  
Oliver Radke ◽  
...  
Keyword(s):  
Orthopaedic Surgery ◽  
Low Molecular Weight Heparin ◽  
Phase Iii ◽  
Bleeding Complications ◽  
Low Molecular Weight ◽  
Severe Bleeding ◽  
Efficacy And Safety ◽  
Vte Prophylaxis ◽  
Superior Efficacy ◽  
Major Orthopaedic Surgery

Abstract Abstract 210 Efficacy and safety of VTE prophylaxis with oral rivaroxaban compared to fondaparinux or low-molecular weight heparin in a large cohort of consecutive patients undergoing major orthopaedic surgery. Aim: Patients undergoing major orthopaedic surgery (MOS) have a high risk of postoperative venous thromboembolism (VTE). Several types of pharmacological thromboprophylaxis are approved for this indication. In phase III VTE prevention trials in MOS, the new oral facor Xa inhibitor rivaroxaban proved superior efficacy over LMWH in preventing VTE without increasing bleeding complications. However, study populations consist of selected patients screened for strict exclusion criteria before randomisation. Little is known about efficacy and safety of rivaroxaban prophylaxis in large unselected cohorts of patients undergoing MOS in daily practice. Method: We retrospectively evaluated 5346 consecutive patients undergoing MOS at our centre between January 2005 and June 2011 for the rate of VTE events, bleeding complications and surgical revisions by review of patient charts, complication and transfusion databases and autopsy reports. All events were analyzed according to the type of thromboprophylaxis used. Results: Of the 5346 patients, 1055 patients received thromboprophylaxis with rivaroxaban (R; hospital standard since 2010), 1683 patients received LMWH (hospital standard 2005–2007), 2069 received fondaparinux (F; hospital standard 2007–2009) and 539 patients received other prophylaxis. Symptomatic VTE event rates for patients receiving R, F or LMWH were 2.5%, 5.5% and 3.9%, respectively (table 1). R was significantly more effective to prevent symptomatic VTE compared to F or LMWH, mostly due to significantly lower rates of distal VTE. Overall, the safety of VTE prophylaxis with R was superior over F or LMWH with significantly lower rates of surgical revisions (1.1%, 1.8% and 4.7%, respectively) and lower rates of severe bleeding complications (7.4%, 11.1% and 14.9%, respectively, which also was statistically significant. Conclusion: VTE prophylaxis with rivaroxaban is superior over prophylaxis with fondaparinux or LMWH with regard to the prevention of symptomatic VTE complications. Furthermore, rivaroxaban prophylaxis was also safer with regard to severe bleeding complications and surgical complications compared to fondaparinux or LMWH, which is in contrast to the results of large phase III trials and the current opinion, that superior efficacy of prophylaxis has the downside of higher bleeding complications. We conclude that real world patients undergoing MOS are different from study populations and may especially benefit from rivaroxaban prophylaxis with regard to both efficacy and safety. Disclosures: Beyer-Westendorf: Bayer Healthcare: Research Funding, Speakers Bureau.

Xyntha®is effective and safe in previously treated patients with severe haemophilia A: Final results of a pivotal phase III study

Haemophilia ◽  
2009 ◽  
Vol 15 (2) ◽  
pp. 635-635
Author(s):  
KATIA EVANS ◽  
ROBERT JANCO ◽  
CHANDRASEKHAR UDATA ◽  
AMANDA O’BRIEN ◽  
BROOKE HAYWARD ◽  
...  
Keyword(s):  
Phase Iii ◽  
Haemophilia A ◽  
Severe Haemophilia ◽  
Pivotal Phase ◽  
Phase Iii Study ◽  
Previously Treated Patients ◽  
Previously Treated
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