A High Purity Factor VIII/vWF Complex Concentrate Is Effective in the Management of Mild Hemophillia A with Inhibitors: A Case Report.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3959-3959
Author(s):  
Srivasavi Dukka ◽  
Susan Kaye ◽  
John Ashcroft ◽  
Anita Hill ◽  
Liakat A. Parapia
Keyword(s):  
Quality Of Life ◽  
Case Report ◽  
Factor Viii ◽  
Immune Tolerance ◽  
High Purity ◽  
Low Dose ◽  
Clinical Parameters ◽  
Factor Viii Activity ◽  
Inhibitor Development

Abstract Introduction: Inhibitor development in Mild Haemophilia A (MHA) is an uncommon complication, occurring in approximately 15% of MHA patients. Risk factors associated with the development of inhibitors in MHA include change in recombinant factor VIII (rFVIII), intensive replacement therapy, immunological challenges and missense mutations in the FVIII gene, including Tyr2105Cys mutation on exon 22. Only few reports have addressed the therapeutic options to eradicate these inhibitors, either by immune tolerance or immunosuppressive protocols. Patient: We present a case report of a 36-year-old MHA patient (original factor VIII activity of 17.5% (10–20%) with a Tyr2105Cys mutation. He developed a low titre inhibitor after intensive exposure to rFVIII to cover for spinal epidural steroid injection, switch of recombinant product (full length rFVIII to B-domain deleted rFVIII) and intensive antiviral treatment (pegylated interferon and ribavarin) for Hepatitis C. His quality of life was very poor due to recurrent spontaneous bleeds - ecchymoses, haematomas and haemarthroses. His baseline factor VIII activity dropped to 1% with an initial inhibitor titre of 2.6 BU and factor VIII recovery of less than 25%. Results: The patient responded positively when started on an immune tolerance protocol with a low dose of high purity FVIII/vWF complex concentrate. All clinical parameters improved two weeks after commencing 50 IU/kg on alternate days of the high purity FVIII/vWF product. FVIII recovery levels improved to 50% and he was asymptomatic in terms of bleeding manifestations for the following 17 weeks. Inhibitor titres stabilised at 3.5 BU. Recently, the recovery levels dropped to 26% and the frequency of bleeds increased, necessitating treatment with additional doses. The immune tolerance dose of the high purity FVIII/vWF was increased to 100IU/kg/day. Haemostatic and clinical parameters again recovered (factor VIII recovery levels of 43%) with no further spontaneous bleeds. Conclusions: The use of recombinant factor VIII, especially high intensity replacement may pose a risk of inhibitor development and bleeding complications during the management of MHA patients with Tyr2105Cys mutation. An immune tolerance protocol with FVIII/vWF concentrate is effective in the management of MHA patients with inhibitors and can improve the quality of life soon after the start of the treatment. There is no anamnestic response observed. Though low dose immune-tolerance protocol may be effective, the benefits may be short-lasting, necessitating treatment with high daily dose protocol.

scholarly journals “You’re only a carrier” – women and the language of haemophilia

2021 ◽  
Vol 8 (1) ◽  
pp. 128-132
Author(s):  
Steve Chaplin ◽  
Kate Khair
Keyword(s):  
Quality Of Life ◽  
Factor Viii ◽  
Strong Evidence ◽  
18Th Century ◽  
Joint Damage ◽  
Gene Variant ◽  
Factor Viii Activity ◽  
Impaired Quality

Abstract Women who have the gene variant for haemophilia are labelled solely as ‘carriers’ unless they have a factor VIII activity of ≤40%. This term, which describes an individual who can pass on a disorder but are themselves unaffected, reflects a legacy that extends from the 18th century to the present day. There is strong evidence that women labelled as carriers experience heavy periods, joint damage, pain and impaired quality of life. The label ‘carrier’ does not recognise this burden and is associated with guilt, stigma and difficulty accessing care. People living with a long-term disorder should now be described using person-first terminology and it is common to see the term ‘people with haemophilia’. The term ‘carrier’ should be limited to its application in genetics and not used as a catch-all label for women with haemophilia.

Immune Tolerance Resulting in a Dramatic Clinical Improvement in a High-Responding Inhibitor Hemophilia A Patient Using Immunosuppression with Mycofenolate Mofetil and a Factor VIII Concentrate Containing Von Willebrand Factor.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3220-3220
Author(s):  
Thierry Lambert ◽  
Cécile Goujard ◽  
Anne Rafowicz ◽  
Benoît Guillet ◽  
Yacine Taoufik ◽  
...  
Keyword(s):  
Quality Of Life ◽  
Factor Viii ◽  
Clinical Improvement ◽  
Von Willebrand Factor ◽  
Immune Tolerance ◽  
Hemophilia A ◽  
Inhibitor Level ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract A 40 year-old Caucasian patient with severe familial hemophilia A (FVIII <1%) related to an intron 22 inversion developed at the age of 2 a high-responding inhibitor. His elder brother also suffers from hemophilia A with high-responding inhibitor. Until 2000, the patient had been treated either using activated prothrombin complex concentrates (Autoplex® and Feiba®) or factor VIII (FVIII) concentrates of human (1983) and porcine origin (1992), resulting respectively in an inhibitor level rise at 360 Bethesda Units (BU) and 1800 BU. Between 2000 and 2003, the patient received exclusively recombinant activated Factor VII (NovoSeven®), and his inhibitor levels stabilized at a plateau of 15–20 BU. Between 2000 and 2003, several life or function threatening bleeding episodes occurred, such as hematomas of the iliopsoas muscles, spinal cord hematoma with transient paraplegia. Furthermore, due to hemarthroses the patient was confined to a wheelchair. Given the major impact of the inhibitor on the patient’s functional prognosis, life expectancy and quality of life, immune tolerance (IT) treatment was initiated, despite the high risk of failure (initiation 36 years after inhibitor onset, historical peak titer at 1800 BU, persistence of a plateau of 15–20 BU despite the absence of any stimulation with FVIII within the 3 last years). It started with an immunosuppressive drug, mycofenolate mofetil (Cellcept®) first given in may 2003 (no effect alone on inhibitor titer) and then in November 2003, infusions of a FVIII concentrate rich in von Willebrand factor, Factane® (LFB, Les Ulis, France) using 12,000 IU/day (150 IU/kg) of FVIII. The inhibitor peaked at 520 BU on D19 and was 0.5 BU by May 2004. Thus, the FVIII dosage was progressively reduced to 7000 IU/day. In July 2005, 24 hours after a 7000 IU FVIII infusion, inhibitor level was 0.7 BU, the residual FVIII level was 0.04IU/ml with a recovery of FVIIIc of 1.37%/IU/kg infused and a half-life of 4.9 hours. No significant change in the immunophenotype of peripheral blood lymphocytes was observed during this course. The patient’s quality of life was dramatically improved, with no hospitalization required and no bleeding episode observed within the 16 last months. The patient can now stand and has returned to his previous social activities. These preliminary results show that this IT treatment, performed despite a high theoretical risk of failure, resulted in this patient in a dramatic clinical improvement, even though biological criteria of success have not yet been achieved. The respective roles of the type of FVIII concentrate, and of immunosuppression remain to be assessed, as well as the cost/benefit analysis on a longer follow-up period.

Prophylactic Use of rFVIIa in a Young Hemophilia A Patient with Factor VIII Inhibitor.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 4068-4068
Author(s):  
Annie Borel-Derlon ◽  
Mounia Slaoui ◽  
Philippe Gautier ◽  
Patricia Guillon
Keyword(s):  
Quality Of Life ◽  
Factor Viii ◽  
Immune Tolerance ◽  
Hemophilia A ◽  
Factor Viia ◽  
High Dose ◽  
Factor Viii Inhibitor ◽  
On Demand ◽  
Viii Inhibitor

Abstract The prevention of bleeding by prophylaxis regimen particularly for joint rehabilitation, could be considered a more effective treatment for hemophilia patients. In hemophiliacs with factor VIII inhibitor (F VIII inh) prophylaxis is not generally proposed because the bypassing agents for these patients may be less effective than F VIII concentrates. We report the regimen and results of a 6 months rFVIIa (Recombinant factor VIIa) prophylaxis, in a young hemophilia A patient (4 years old), with F VIII inh and immune tolerance induction (ITI) treatment and compared, with rFVIIa, the on demand treatment results for the 6 months prior to prophylaxis. After 2 years of a high dose regimen ITI, the FVIII inh titer was less than 50 BU and the immune tolerance treatment remains on going. Due to the development of a right knee target joint the rFVIIa prophylaxis was decided as an active rehabilitation approach to prevent the development of chronic arthropathy as well as to improve the quality of life of the child. During the 6 months period, prior to the initiation of rFVIIa prophylaxis 22 bleeds occurred i.e., 9 right knee hemarthrosis and 13 other joint bleedings and hematoma including elbow, wrist, ankle, foot, arm and chest. These bleeds were all treated with rFVIIa with a dose ranging from 100 to 200 μg/kg depending on the severity of the episodes and the duration of treatment ranged from 1 to 8 days. After 6 recurrent right knee hemarthrosis, a lavage of the joint was performed and prophylaxis with rFVIIa was subsequently initiated. A 120 μg/kg rFVIIa injection was performed 3 times a week concomitantly with the ITI treatment infusion and just before the physiotherapy course. During the 6 months of prophylaxis regimen we observed 9 bleeds with 3 major post traumatic bleedings which were treated by one 200 μg/kg/day rFVIIa injection which was resolved in one to three days. This prophylaxis treatment was effective for the arthropathy evolution and permitted the patient to return to school on a regular basis compared to the previous year. The total dose of on demand rFVIIa treatment used before prophylaxis was 458 mg/6 months. This amount decreased by 25% during the six months of prophylaxis with rFVIIa to reach 343 mg. The results of this significant observation led us to conclude that rFVIIa could be effectively used as prophylactic treatment in patients with FVIII inh and administered safely via a portacath device even in cases of high doses, as demonstrated in this young patient. This prevention approach resulted in a decrease of bleeding episodes, injections, and a significant improvement in the quality of life.

scholarly journals Effect of tertiary prophylaxis with low-dose factor VIII in quality of life in adult patients with severe hemophilia A

2019 ◽  
Vol 10 (3) ◽  
pp. 88
Author(s):  
PrakasKumar Mandal ◽  
Abhijit Phukan ◽  
Amrita Bhowmik ◽  
Debasis Gantait ◽  
Prantar Chakrabarti
Keyword(s):  
Quality Of Life ◽  
Factor Viii ◽  
Low Dose ◽  
Hemophilia A ◽  
Adult Patients ◽  
Severe Hemophilia ◽  
Dose Factor

Low-dose immune tolerance induction in hemophilia A patients with inhibitors

Blood ◽  
1995 ◽  
Vol 86 (3) ◽  
pp. 983-988 ◽  
Author(s):  
EP Mauser-Bunschoten ◽  
HK Nieuwenhuis ◽  
G Roosendaal ◽  
HM van den Berg
Keyword(s):  
Factor Viii ◽  
Immune Tolerance ◽  
Low Dose ◽  
Hemophilia A ◽  
Tolerance Induction ◽  
Immune Tolerance Induction ◽  
Inhibitor Development ◽  
Two Factors ◽  
Inhibitor Level ◽  
Dose Factor

Abstract In patients with hemophilia A and inhibitory alloantibodies against factor VIII, various dosage schedules are used to obtain immune tolerance. In this study, we have evaluated the results of 13 years of low-dose immune tolerance induction and factors that are predictive of a positive result. The effect of immune tolerance induction in relation to age at inhibitor development, number of exposure days, age at start of therapy, maximum inhibitor titer, factor VIII products involved, and virologic status were determined. We evaluated 24 patients with severe hemophilia A and inhibitors who were treated with regular infusions with low-dose (25 U/kg every other day) factor VIII to obtain immune tolerance. In 21 of 24 patients (87%), immune tolerance induction was successful. The response time was determined by two factors: the highest inhibitor level and the age at inhibitor development. In patients with maximum inhibitor levels of less than 40 Bethesda units (BU)/mL, immune tolerance was obtained sooner than in patients with inhibitor levels exceeding 40 BU/mL (P = .005). Patients in whom an inhibitor developed before the age of 2.5 years also tended to have a quick immune response (P = .014). Immune tolerance with low-dose factor VIII is often successful in hemophilia A patients with inhibitors. Young children and patients with maximum inhibitors of less than 40 BU/mL show a relatively rapid response.

scholarly journals Low-dose immune tolerance induction in hemophilia A patients with inhibitors

Blood ◽  
1995 ◽  
Vol 86 (3) ◽  
pp. 983-988 ◽  
Author(s):  
EP Mauser-Bunschoten ◽  
HK Nieuwenhuis ◽  
G Roosendaal ◽  
HM van den Berg
Keyword(s):  
Factor Viii ◽  
Immune Tolerance ◽  
Low Dose ◽  
Hemophilia A ◽  
Tolerance Induction ◽  
Immune Tolerance Induction ◽  
Inhibitor Development ◽  
Two Factors ◽  
Inhibitor Level ◽  
Dose Factor

In patients with hemophilia A and inhibitory alloantibodies against factor VIII, various dosage schedules are used to obtain immune tolerance. In this study, we have evaluated the results of 13 years of low-dose immune tolerance induction and factors that are predictive of a positive result. The effect of immune tolerance induction in relation to age at inhibitor development, number of exposure days, age at start of therapy, maximum inhibitor titer, factor VIII products involved, and virologic status were determined. We evaluated 24 patients with severe hemophilia A and inhibitors who were treated with regular infusions with low-dose (25 U/kg every other day) factor VIII to obtain immune tolerance. In 21 of 24 patients (87%), immune tolerance induction was successful. The response time was determined by two factors: the highest inhibitor level and the age at inhibitor development. In patients with maximum inhibitor levels of less than 40 Bethesda units (BU)/mL, immune tolerance was obtained sooner than in patients with inhibitor levels exceeding 40 BU/mL (P = .005). Patients in whom an inhibitor developed before the age of 2.5 years also tended to have a quick immune response (P = .014). Immune tolerance with low-dose factor VIII is often successful in hemophilia A patients with inhibitors. Young children and patients with maximum inhibitors of less than 40 BU/mL show a relatively rapid response.

Misophonia: An Evidence-Based Case Report

2020 ◽  
Vol 29 (4) ◽  
pp. 685-690
Author(s):  
C. S. Vanaja ◽  
Miriam Soni Abigail
Keyword(s):  
Quality Of Life ◽  
Case Report ◽  
Case History ◽  
Pure Tone ◽  
Physiological Responses ◽  
Evidence Based ◽  
Management Option ◽  
Pure Tone Audiogram

Purpose Misophonia is a sound tolerance disorder condition in certain sounds that trigger intense emotional or physiological responses. While some persons may experience misophonia, a few patients suffer from misophonia. However, there is a dearth of literature on audiological assessment and management of persons with misophonia. The purpose of this report is to discuss the assessment of misophonia and highlight the management option that helped a patient with misophonia. Method A case study of a 26-year-old woman with the complaint of decreased tolerance to specific sounds affecting quality of life is reported. Audiological assessment differentiated misophonia from hyperacusis. Management included retraining counseling as well as desensitization and habituation therapy based on the principles described by P. J. Jastreboff and Jastreboff (2014). A misophonia questionnaire was administered at regular intervals to monitor the effectiveness of therapy. Results A detailed case history and audiological evaluations including pure-tone audiogram and Johnson Hyperacusis Index revealed the presence of misophonia. The patient benefitted from intervention, and the scores of the misophonia questionnaire indicated a decrease in the severity of the problem. Conclusions It is important to differentially diagnose misophonia and hyperacusis in persons with sound tolerance disorders. Retraining counseling as well as desensitization and habituation therapy can help patients who suffer from misophonia.

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