Anaphylactic Reaction After Replacement Therapy In Haemophilia B Patient with Inhibitor to Factor IX

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 4662-4662
Author(s):  
Rosanna Scaraggi ◽  
Paola Giordano ◽  
Cosimo Pietro Ettorre ◽  
Giuseppe Malcangi ◽  
Renato Marino ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Anaphylactic Reaction ◽  
Conflicts Of Interest ◽  
Therapeutic Option ◽  
Factor Ix ◽  
Careful Monitoring ◽  
Haemophilia B ◽  
Bleeding Management ◽  
Post Traumatic ◽  
The Right

Abstract Abstract 4662 Replacement therapy is a very hard challenge in haemophilia B with inhibitor. We describe the case of a child with severe haemophilia B and with a family history positive for development of inhibitor to factor IX (FIX) and for occurrence of allergic reaction after replacement therapy. Genetic analysis demonstrated an almost complete deletion of FIX gene. The child received replacement therapy first in his life when he was 5 years old because of the occurrence of a large haematoma of the left thigh. He was treated with recombinant FIX concentrate at the dosage of 30 IU/kg daily for three days and no inhibitor to FIX was evidenced after this therapy. Two months later the patient was treated with a single dose of recombinant FIX concentrate at the same dosage for the occurrence of a post-traumatic joint bleeding of the right knee. An inhibitor towards FIX (1.7 B.U.) was detected two weeks after this treatment and confirmed in a subsequent analysis performed after ten days (1.4 B.U.). One month later the patient was hospitalized for a post traumatic hemarthrosis of the right shoulder. In this occasion it was planned to treat the patient with recombinant FIX under careful monitoring in intensive care unit considering of the inhibitor. After the slow endovenous infusion of 200 IU of recombinant FIX concentrate we stopped immediately the administration because the child presented cough, mild respiratory failure, tachycardia, tongue and lips oedema, lips cyanosis, diffuse vasodilatation, psychomotor agitation. He received also hydrocortisone, antihistaminic by intramuscular injection and oxygen by facial mask. The presence of inhibitor towards FIX and anaphylactic reaction occurrence preclude forever any replacement therapy with FIX both recombinant and plasmatic (PCC and/or aPCC). After this episode the patient needed another hospitalization for a tonsil bleeding with severe anaemization. We treat him with recombinant activated FVII (rFVIIa) first at the dosage of 270 mcg/kg in bolus, and after at the dosage of 90 mcg/kg every three hours for one day with complete bleeding remission. We encourage the careful monitoring of inhibitor towards FIX in haemophilic B patients especially with large FIX gene deletion. It could prevent severe anaphylactic reaction during replacement therapy. Considering the previous anaphylactic reaction, in this child rFVIIa represents the only therapeutic option for bleeding management. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Phase 1-2 Clinical Trial of a Recombinant AAV5 Vector Containing the Human FIX Gene in Patients with Severe or Moderately Severe Haemophilia B

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5948-5948 ◽  
Author(s):  
Wolfgang A. Miesbach ◽  
Christian Meyer ◽  
Bart Nijmeijer ◽  
Florence Salmon ◽  
Nadina Grosios ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Replacement Therapy ◽  
Research Funding ◽  
Factor Ix ◽  
Activity Level ◽  
Severe Haemophilia ◽  
Haemophilia B ◽  
Commercial Scale ◽  
Number Of Patients ◽  
History Of

Abstract Gene therapy has been successfully used in a research setting in a limited number of patients with severe haemophilia B, primarily using vectors based on adeno-associated virus (AAV) serotype 2 and 8. Several research groups and companies are exploring new developments to improve current treatment strategies to eventually make gene therapy available for a larger number of patients. Pre-existing immunity to AAV capsid proteins may limit the availability of such therapies to small sub-groups of patients. A low prevalence of natural neutralizing antibodies against AAV5 compared with other serotypes has been demonstrated (Calcedo et al., Clin Vaccine Immunol 2009, 18:1586-1588). We use a recombinant AAV5 containing the codon optimized human factor IX gene (AAV5-hFIX), using a baculovirus production process that allows commercial scale manufacturing of the AAV5-hFIX drug product. Human FIX expression levels in macaques treated i.v. with AAV5-hFIX at a dose of 5 × 10^12 gc/kg were high enough to expect therapeutic effect on the haemophiliac phenotype in haemophilia B patients. Such levels were achieved in humans during AAV8-hFIXco clinical study (Nathwani et al., NEJM 2011, 365:2357-2365). hFIX levels in dose-escalating GLP toxicity studies in cynomolgus monkeys and mice showed linear dose responses using doses up to 1 × 10˄14 and 2.3 × 10^14 cg/kg, respectively, and no specific safety concerns. In human studies with AAV5 containing the human porbilinogen deaminase (PBGD) gene, administered in doses up to 2 x 10^13 gc/kg to patients with acute intermittent porphyria, no safety concerns were raised (D’Avola et al., ASGCT, Washington DC, 2014). Importantly, in this study no liver enzyme perturbations were observed following administration of AAV5. The primary objective of the proposed study is to investigate the safety of systemic administration of AAV5-hFIX to adult patients with severe or moderately severe haemophilia B. The multicentre trial has an open-label, uncontrolled, single-dose, dose-ascending design and consists of two cohorts. The study population consists of male patients, aged ≥18 years, with severe or moderately severe haemophilia B and a severe bleeding phenotype [i.e. known FIX deficiency with plasma FIX activity level <1% (severe), or plasma FIX activity level ≥1% and ≤2% (moderately severe) and currently on prophylactic FIX replacement therapy for a history of bleeding, or currently on on-demand therapy with a current or past history of frequent bleeding defined as four or more bleeding episodes in the last 12 months, or chronic haemophilic arthropathy. Patients should have had more than 150 previous exposure days of treatment with FIX protein. Subjects are allocated to one of two cohorts with the following planned dose levels: Cohort 1 (5 subjects) with AAV5-hFIX 5.0 × 10^12 gc/kg and Cohort 2 (5 subjects) with AAV5-hFIX 2.0 × 10^13 gc/kg. Key efficacy assessments include factor IX plasma levels, the need for FIX replacement therapy, incidence of spontaneous bleedings and health-related quality of life measurements. In conclusion, AAV5-hFIX produced in commercial scale represents a novel approach to gene therapy of haemophilia B. Disclosures Miesbach: uniQure: Consultancy; Bayer: Research Funding; Baxter: Research Funding; CSL Behring: Research Funding; Biotest: Research Funding; Octapharma: Research Funding. Meyer:uniQure B. V.: Employment. Nijmeijer:uniQure B. V.: Employment. Salmon:uniQure B. V.: Employment. Grosios:uniQure B. V.: Employment. Petry:uniQure B. V,: Employment. Leebeek:uniQure B. V.: Consultancy; CSL Behring: Research Funding; Baxter: Research Funding.

scholarly journals The Efficacy of Ultrasound Joint Examination for the Management in Patients with Hemophilia

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5027-5027
Author(s):  
Shiho Nishimura ◽  
Keita Tomioka ◽  
Maiko Shimomura ◽  
Yoko Mizoguchi ◽  
Shinobu Sasaki ◽  
...  
Keyword(s):  
Early Detection ◽  
Replacement Therapy ◽  
Conflicts Of Interest ◽  
Bone Erosion ◽  
Joint Damage ◽  
Factor Ix ◽  
Joint Effusion ◽  
Clotting Factors ◽  
Prophylactic Regimen ◽  
Joint Examination

Abstract The regular prophylactic replacement therapy with clotting factors has significantly reduced the arthropathy in patients with hemophilia. Early detection of the signs of joint damage is important to prevent the progressive joint damage. For the early detection, we have introduced the regular ultrasound (US) joint examination in patients with hemophilia from 2014 based on the hemophilia early arthropathy detection with ultrasound (Head-US) scanning protocol. US examination has been performed at the time of annual comprehensive clinic in Hiroshima University Hemophilia Center. Forty-five patients aged 1 to 33 years were enrolled and more than 280 joints were evaluated in this study. US joint examination was performed within 30 minutes without the sedation in all aged children. Abnormal findings, such as cartilage changes, subchondral bone erosion, synovial hypertrophy and/or joint effusion were observed in 8 out of 45 patients. The replacement therapy with clotting factors of all 8 patients aged 13 to 33 years was an insufficient prophylaxis during early childhood. The residual 37 patients aged less than 15 years have relatively followed the prophylactic treatment. The prophylactic regimen has been individually determined based on the trough levels of factor IX concentration in plasma for hemophilia B and pharmacokinetics of factor VIII using MyPKFitR for hemophilia A patients, respectively. The result suggests the importance of the careful prophylactic replacement therapy considering the factor concentration in plasma. Four patients aged 4, 5, 18, and 19 years, respectively, suffered from painful and/or swollen joint episodes from 2014 to 2018. Urgent US examination without the use of any sedatives revealed ankle, knee, or hip joint bleeding in each case. According to the replacement therapy for breakthrough bleeding, hemoarthropathy was accessed by consecutive examination of US. These results suggest that US joint examination could be necessary for the early detection of joint damage and for appropriate treatment of hemoarthropathy. Collectively, utilization of US examination would be essential for the management through the life in patients with hemophilia. Disclosures No relevant conflicts of interest to declare.

Assessment Levels of Factor VIII and IX Inhibitors in Patients with Hemophilia in North West of Iran: What Is the Main Reason of Low Inhibitor Titer and Rate in Our Patients?

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4662-4662
Author(s):  
Roya Dolatkhah ◽  
Ali Akbar Movasaghpour Akbari ◽  
Iraj Asvadi Kermani ◽  
Zohreh Sanaat ◽  
Azim Rezamand ◽  
...  
Keyword(s):  
Factor Viii ◽  
Hemophilia A ◽  
Conflicts Of Interest ◽  
Factor Ix ◽  
Haemophilia A ◽  
Inhibitor Development ◽  
Haemophilia B ◽  
On Demand ◽  
Viii And Ix

Abstract Abstract 4662 Introduction Today, the development of inhibitors against Factor VIII (FVIII) and Factor IX (FIX) is seen as the most serious complication of haemophilia A and B therapy. Recent studies on the role of the causative haemophilic mutation, race and ethnicity, family history of inhibitors and the possible influence of HLA genotype in inhibitor formation have revealed new and exciting insights. That is challenging conventional thinking about inhibitor development risk and type of factor products, recombinant or plasma-derived. The use of recombinant factor concentrates has revolutionized the treatment of severe factor VIII and IX deficiency. One of the most important complications is the development of antibodies (Inhibitors). Material and Methods Ninety two patients with haemophilia A and 12 patients with Haemophilia B have been studied. Confirmatory tests including one stage FVIII and FIX assay has been performed using STA Deficient FVIII and FIX, an immune-depleted plasma intended in plasma by analyzers of the STA line suitable with these reagents (Diagnostica Stago,France).Presence of Factor VIII and IX inhibitors have been tested by Bethesda Assay. All of the patients use mostly plasma-derived factor products, and on-demand treatment. Results Among 92 haemophilia A patients, FVIII levels were between 0.14–14.40 IU/dl (mean 2.91 ± 2.62), FIX levels were between 0.17 to 4.37 IU/dl (mean 1.53 ± 1.38) in12 haemophilia B patients. PT activity was 68.7–134 (mean 101.05 ± 15.13), APTT was 28.90 – 102 (mean 60.66 ± 13.50). FVIII inhibitor levels were between 0–1.14 BU (mean 0.04 ± 0.20) in 5 severe Hemophilia A patients (5.45%) and FIX Inhibitor levels were between 0–0.65 BU (mean 0.10 ± 0.23) in 2 Hemophilia B patients. Discussion Alloantibodies (inhibitors) against FVIII or FIX represent a major complication in patient care because they render classical substitution therapy ineffective. Inhibitors occur at a frequency of 20–30% in severe and 3–13% with mild or moderate haemophilia A, and 3% in haemophilia B, respectively. An alternative pathomechanism may underlie inhibitor development in patients with mild hemophilia A. Although it has been reported that inhibitors in patients with mild haemophilia are related to periods of intensive treatment or surgery, this has never been properly studied in children with severe haemophilia. The low inhibitor rate with Low Titers in our patients may be demonstrate the role of type of factor products, recombinant or plasma-derived, which in this study was mostly use of plasma-derived factor products, and on-demand treatment. Also detailed evaluation of major risk factors of development of Factor VIII and IX inhibitors in our patients is required. Disclosures: No relevant conflicts of interest to declare.

Anaphylactic response to factor IX replacement therapy in haemophilia B patients: complete gene deletions confer the highest risk

Haemophilia ◽  
1999 ◽  
Vol 5 (2) ◽  
pp. 101-105 ◽  
Author(s):  
E. C. THORLAND ◽  
J. B. DROST ◽  
J. M. LUSHER ◽  
I. WARRIER ◽  
A. SHAPIRO ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Factor Ix ◽  
Gene Deletions ◽  
Haemophilia B ◽  
Anaphylactic Response

Adult-to-Adult Living-Donor Liver Transplantation

Swiss Surgery ◽  
2003 ◽  
Vol 9 (5) ◽  
pp. 227-236 ◽  
Author(s):  
Majno ◽  
Mentha ◽  
Berney ◽  
Bühler ◽  
Giostra ◽  
...  
Keyword(s):  
Liver Transplantation ◽  
Living Donor ◽  
Living Donor Liver Transplantation ◽  
Therapeutic Option ◽  
Donor Liver ◽  
Donor Liver Transplantation ◽  
Multidisciplinary Program ◽  
First Case ◽  
Living Donor Transplantation ◽  
The Right

Living donor liver transplantation is a relatively new procedure in which the right side of the liver is harvested in a healthy donor and transplanted into a recipient. After the first case in 1994, over 3000 cases have been done worldwide. This review summarizes the reasons why the procedure is needed, describes its main technical aspects, highlights the boundaries in which it can be done safely, summarizes the current experience worldwide and describes the main points of the program in our unit. We argue that living-donor transplantation is a viable alternative to a long time on the waiting list for several patients, and it can be performed safely and successfully provided that all precautions are undertaken to minimize the risks in the donor and to increase the chances of a good outcome in the recipients. If these prerequisites are met, and within the framework of a structured multidisciplinary program, we believe that living-donor liver transplantation should be funded by health insurances as a recognized therapeutic option.

Performances of an Artificial Reagent for the One-stage Factor IX Assay

1975 ◽  
Vol 33 (03) ◽  
pp. 547-552 ◽  
Author(s):  
L Meunier ◽  
J. P Allain ◽  
D Frommel
Keyword(s):  
Human Plasma ◽  
Factor Ix ◽  
Severe Haemophilia ◽  
Normal Human Plasma ◽  
Haemophilia B ◽  
One Stage ◽  
Normal Human ◽  
The One

SummaryA mixture of adsorbed normal human plasma and chicken plasma was prepared as reagent for factor IX measurement using a one-stage method. The substrate was found to be specific for factor IX. Its performances tested on samples displaying factor IX activity ranging from <l%–2,500% compared favorably with those obtained when using the plasma of severe haemophilia B patients as substrate.

Sign in / Sign up

Export Citation Format

Share Document