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Inhibitor Patients (inhibitor + patient)
Selected AbstractsIdentifying and managing inhibitor patients requiring orthopaedic surgery , the multidisciplinary team approachHAEMOPHILIA, Issue 2005C. LUDLAM Summary., Until recently, surgery in haemophilia patients with inhibitors was strongly contraindicated and was therefore often not even contemplated. Inhibitor patients entering the surgical arena face unique challenges; the most frequently encountered problem during surgical intervention is bleeding, and thrombosis is occasionally observed. The activated prothrombin complex concentrate, FEIBATM, and recombinant activated factor VII (rFVIIa) are available as haemostatic cover during surgery. The use of rFVIIa enables inhibitor patients to undergo orthopaedic surgery with an expectation of success, and results are generally good. An organized team approach is critical to this success. However, further information is required to enable different procedures to be optimized in terms of both outcome and safety. [source] Cost minimization analysis to compare activated prothrombin complex concentrate (APCC) and recombinant factor VIIa for haemophilia patients with inhibitors undergoing major orthopaedic surgeriesHAEMOPHILIA, Issue 5 2009P. O. BONNET Summary., Benefits of bypassing agents for maintaining haemostasis in major surgeries have been described in the literature; however, their use has a substantial economic impact. This study assessed the cost of FEIBA, an activated prothrombin complex concentrate and recombinant factor VIIa (rFVIIa) when used in inhibitor patients undergoing major surgeries. After reviewing published literature, a cost minimization model was developed describing dosing regimens recommended and used during major surgeries for FEIBA (pre-operative: 75,100 U kg,1; postoperative: 75,100 U kg,1 q 8,12 h days 1,5 and 75,100 U kg,1 q 12 h days 6,14) and rFVIIa (pre-operative: 90 ,g kg,1; intra-operative: 90 ,g kg,1 q 2 h; postoperative: 90 ,g kg,1 q 2,4 h days 1,5 and 90 ,g kg,1 q 6 h days 6,14). Using a 75 kg patient and US prices, total drug cost was calculated for three scenarios: use of FEIBA or rFVIIa alone and a third case combining rFVIIa pre- and intra-operative and FEIBA throughout a 14-day postoperative period. Dosage amounts of modelled bypassing agents were similar to cases in the literature. Using FEIBA instead of rFVIIa would decrease total drug cost by >50% and save over $400 000 per surgery. Sequential use of both bypassing agents would increase total drug cost by 9% when compared with FEIBA alone, but would remain >40% lower than rFVIIa alone. Univariate sensitivity analyses confirmed robustness of results. As large amounts of bypassing agents are necessary for patients with inhibitors to undergo major surgeries, cost is a major consideration. Use of FEIBA alone or in combination with rFVIIa has emerged as a cost-saving approach. [source] Identifying and managing inhibitor patients requiring orthopaedic surgery , the multidisciplinary team approachHAEMOPHILIA, Issue 2005C. LUDLAM Summary., Until recently, surgery in haemophilia patients with inhibitors was strongly contraindicated and was therefore often not even contemplated. Inhibitor patients entering the surgical arena face unique challenges; the most frequently encountered problem during surgical intervention is bleeding, and thrombosis is occasionally observed. The activated prothrombin complex concentrate, FEIBATM, and recombinant activated factor VII (rFVIIa) are available as haemostatic cover during surgery. The use of rFVIIa enables inhibitor patients to undergo orthopaedic surgery with an expectation of success, and results are generally good. An organized team approach is critical to this success. However, further information is required to enable different procedures to be optimized in terms of both outcome and safety. [source] Prophylactic recombinant factor VIIa in haemophilia patients with inhibitorsHAEMOPHILIA, Issue 3 2005G. Young Summary., Prevention of bleeding, especially into joints, with prophylactic factor infusions is the most effective treatment for severe haemophilia patients. Approximately 15,30% of patients with factor VIII deficiency and 3,5% of patients with factor IX deficiency develop neutralizing antibodies (inhibitors) to factor precluding their use. Such patients often have significant bleeding complications including life- and limb-threatening bleeds and severe joint disease. Prophylaxis for such patients is not generally considered because of the fact that the standard (bypassing) agents for such patients are not as effective as natural factor replacement, because of concerns for thrombotic complications and also because of the very high cost of bypassing agents. We treated two patients with high titre inhibitors with prophylactic recombinant factor VIIa (rFVIIa). The first patient was treated as a result of development of a target joint and to reduce the use of agents that can lead to anamnesis of his inhibitor. The second patient had multiple severe bleeds and was hospitalized 20% of the time over a 2-year period. He had a very poor quality of life. Both patients had shown good responses previously to rFVIIa for treatment of bleeds. Both patients had an outstanding response to prophylaxis albeit at a very high cost. Prophylaxis with rFVIIa can be an effective approach in select inhibitor patients with severe complications related to bleeding. [source] Central venous lines in haemophiliaHAEMOPHILIA, Issue 2003R. Ljung Summary., Infections and technical problems are the most frequent complications when using implantable central venous access devices in patients with haemophilia. There are two major experiences reported concerning infections in noninhibitor patients: one is approximately 0.2 infections per 1000 days and the other approximately 1.0 (0.7,1.6) per 1000 days. Infections are more frequent in inhibitor patients and approximately one infection per 6,12 months of use can be expected. The figures are low for clinically apparent thrombosis in the larger series on record, but routine venograms were not carried out in most of these series. In studies where this has been done, a high frequency of abnormalities on venograms has been seen in some but not in others. The final decision to use a central line has to take into account the medical goal, the patient's bleeding tendency, the social situation and the expected risk of complications at the particular haemophilia centre. Some of the complications may be reduced by adequate aseptic measures both during implantation and in subsequent use, and by clear basic routines for surveillance of the systems and repeated education of the users. [source] Porcine factor VIII in the treatment of high-titre inhibitor patientsHAEMOPHILIA, Issue 2002M.B. Garvey Development of an inhibitor against factor VIII (FVIII) is an important complication of haemophilia. It occurs in approximately 25,30% of patients with haemophilia A [1]. FVIII inhibitors may also occur as autoantibodies. The latter occur in nonhaemophiliacs and, although rare (occurring in approximately one per million of the population), are frequently associated with life-threatening bleeding. Inhibitors are considered low level if they are < 5 Bethesda Units (BU) or high level if they are > 10 BU. The former usually remain low and rarely give anamnestic response, the latter do so frequently. Despite various approaches to their management, the presence of inhibitors remains a major cause of morbidity and mortality. The effectiveness of porcine FVIII (pFVIII) in treating patients with both auto- and alloantibodies to FVIII has been well demonstrated when adequate circulating levels of FVIII are obtained [2,10]. However, pFVIII therapy may give rise to antibodies to the pFVIII and the utility of this treatment in the presence of high levels of porcine antibody is less well recognized and understood. Nonetheless, pFVIII under these circumstances may be useful in a select group of patients where management is difficult. [source] Impact of polymorphisms of the major histocompatibility complex class II, interleukin-10, tumor necrosis factor-, and cytotoxic T-lymphocyte antigen-4 genes on inhibitor development in severe hemophilia AJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 12 2009A. PAVLOVA Summary.,Background: Approximately 25% of severe hemophilia A (HA) patients develop antibodies to factor VIII protein. Patients: In the present case-controlled cohort study, 260 severely affected, mutation-type-matched HA patients were studied for association of human leukocyte antigen (HLA) class II molecules and polymorphisms in the genes encoding interleukin-10 (IL-10), tumor necrosis factor-, (TNF-,) and cytotoxic T-lymphocyte antigen-4 (CTLA-4) and development of inhibitors. Results: Our results demonstrate a higher frequency of DRB1*15 and DQB1*0602 alleles as well as of the haplotype DRB1*15/DQB1*0602 in inhibitor patients [odds ratio (OR) 1.9; P < 0.05]. In TNF-,, the A allele of the ,308G>A polymorphism was found with higher frequency in the inhibitor cohort (0.22 vs. 0.13, OR 1.80). This finding was more pronounced for the homozygous A/A genotype (OR 4.7). For IL-10, the ,1082G allele was observed more frequently in patients with inhibitors (0.55 vs. 0.43; P = 0.008). The functional cytokine phenotype was determined for the first time, on the basis of the genetic background, and this showed that 12% of patients with inhibitors were high-TNF-,/high-IL-10 producers, as compared with 3% of non-inhibitor patients (OR 4.4). A trend for a lower frequency of the A allele of the CT60 polymorphism in CTLA-4 was found in inhibitor patients (0.42 vs. 0.50). Conclusions: In conclusion, the reported data clearly highlighted the participation of HLA molecules in inhibitor formation in a large cohort of patients. The higher frequencies of the ,308G>A polymorphism in TNF-, and ,1082A>G in IL-10 in inhibitor patients confirmed the earlier published data. The CT60 single-nucleotide polymorphism in CTLA-4 is of apparently less importance. [source] Comparative immunogenicity of recombinant B domain-deleted porcine factor VIII and Hyate:C in hemophilia A mice presensitized to human factor VIIIJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 4 2004E. T. Parker Summary., Hyate is a commercial plasma-derived porcine factor (F)VIII concentrate that is used in the treatment of patients with inhibitory antibodies to FVIII. OBI-1 is a recombinant B domain-deleted form of porcine FVIII that is in clinical development for the same indication. Hemophilia A mice were presensitized with human FVIII to simulate clinical inhibitory antibody formation and then were randomized to receive OBI-1 or Hyate:C in a comparative immunogenicity trial. OBI-1 or Hyate:C were given in a series of four intravenous injections at weekly intervals at doses of 1, 10, or 100 U kg,1. Inhibitory antibodies to porcine FVIII were not detected by Bethesda assay in most of the mice given OBI-1 or Hyate:C at doses of 1 or 10 U kg,1, but were identified in 81% and 94% of mice given 100 U kg,1 of OBI-1 or Hyate:C, respectively. There was no significant difference between OBI-1 and Hyate:C in inhibitory antibody formation at any dose, although there was a trend toward a lower Bethesda titer in OBI-1-treated mice at 10 U kg,1 (P = 0.09). Total anti-FVIII antibodies to Hyate:C and OBI-1 were also measured by ELISA using immobilized purified plasma-derived porcine FVIII and OBI-1, respectively, as antigens. At the 10 and 100 U kg,1 doses, the mean anti-FVIII response was higher in Hyate:C-treated-mice than in OBI-1-treated mice (P = 0.02 and P = 0.004, respectively). The results using this model suggest that OBI-1 may be less immunogenic and safer than Hyate:C in FVIII inhibitor patients. [source] The concept of recombinant factor VIIa megadose for treating bleeding episodes in high-titer inhibitor patients with hemophilia: toward an expanding indication?JOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 3 2003C. Negrier No abstract is available for this article. [source] | ||||||||||