42 research outputs found
Pharmacotherapy of haemophilia A
No full textINTRODUCTION: Haemophilia A is due to factor VIII (FVIII) deficiency. The main treatment is replacement therapy with FVIII concentrates. However, these concentrates carried a high risk of blood-borne viral infections and still have a high risk of inducing anti-FVIII inhibitors. AREAS COVERED: An overview of products available and therapeutic options for haemophilia A management in order to help in decision making. A literature search using Medline with the keywords: 'haemophilia', 'factor VIII', 'therapy', 'inhibitor', 'concentrate', 'bleeding', 'prophylaxis', 'on demand', 'plasma-derived', 'recombinant', 'coagulation factors', 'immunotolerance' was performed. The years 1960 - 2010 are included. EXPERT OPINION: Progress in management of patients with haemophilia A has allowed increased life expectancy and quality of life. There is evidence that prophylaxis prevents or, at least, slows down arthropathy development when started early in childhood. FVIII concentrates have achieved high levels of blood-borne pathogen safety. However, treatment is frequently complicated by development of FVIII-neutralizing inhibitors, which prevent control of bleeding and predispose to a high morbidity and mortality risk. Bypassing agents are effective in bleeding treatment in a high percentage of cases. Prophylaxis with bypassing agents and their use in combination are offering opportunities in management of inhibitor patients. More evidence is necessary to understand how to prevent and manage this complicatio
Ultrasonography of haemophilic arthropathy
No full textImaging is an essential tool for evaluation and monitoring of haemophilic arthropathy. Ultrasonography is increasingly used for joint assessment, due to its great sensitivity for soft tissue and relatively low cost. To assess the joint status and the role of ultrasonography in routine diagnosis and monitoring of joint disease in cohort haemophilic patients. Findings of patients with haemophilia, who routinely underwent ultrasonography were retrospectively evaluated to assess their joint status and the role of ultrasonography in routine diagnosis and monitoring of joint disease. Out of 325 joints examined (115 ankles, 210 knees), ultrasonography identified damages in 50% of ankles and 33% of knees in overall 111 patients, aged 7-80 years (median = 29 years). Synovial hypertrophy and cartilage abnormalities were the most frequent observations (88% and 76% in affected knees, respectively). Pristine joints were more frequently found in patients on primary prophylaxis, young age or no bleeding in the year prior to examination. Furthermore, no concordance was found between presence of joint changes at ultrasonography, and clinical joint status. Ultrasonography was shown to be able to detect joint damage involving soft tissues and bone surface. Its use might allow frequent monitoring of patients with haemophilia and early detection of arthropathy. For these reasons it might represent a valid tool in the routine management of haemophili
A prospective clinical trial of implantable central venous access in children with haemophilia
No full textTo assess the risks associated with the use of central venous ports in children with haemophilia, 15 HIV-negative patients were prospectively evaluated. Port insertion was required for immune tolerance in two inhibitor patients and continuous prophylaxis in 13 patients with severe factor VIII deficiency, for whom surgery was covered with recombinant factor VIII (rFVIII), then given daily at home until day 6. One inhibitor patient (titre 7BU/ml) received high-dose rFVIII by continuous infusion until day 3, followed by an immune tolerance treatment scheme; the other (titre 12 BU/ml) was given recombinant activated factor VII by continuous infusion until day 7. After training on the use of the port, all patients continued their infusion programme at home. All ports remained in place for a median period of 413d (range 125-509). The median number of entries into the port was 184 (range 53-567). Port-site haematoma and infection occurred in one patient on day 7 when an inhibitor became detectable (titre 12 BU/ml). An infectious complication occurred in another patient after 310d. The port infection rate was 0-42 per 1000 patient-days (0.33 per 1000 entries into the port). This protocol for port placement with short hospitalization appears feasible and safe
Safety and effectiveness of raltegravir in patients with haemophilia and anti-HIV multidrug resistance
No full textHighly active antiretroviral therapy (HAART) of HIV+ patients with haemophilia poses specific questions on safety and effectiveness because of long-lasting HIV infection, multidrug resistance, concomitant chronic liver disease and bleeding risk. Raltegravir belongs to a new class of drugs that inhibits HIV integrase and is known to have a good effectiveness and safety profile. The aim of this study was to evaluate safety and effectiveness of HAART with raltegravir in patients with haemophilia. HIV+ patients with haemophilia treated with raltegravir for ≥6 months were included in this retrospective study. Safety criteria were: occurrence of any adverse event, unexpected blood test abnormalities and increased consumption of coagulation factors. Effectiveness criteria were: no disease progression, viral load <40 HIV-RNA copies mL(-1) and increased or stable CD3+ CD4+ cell count above 200 cells cmm(-1) . Seven patients with HCV co-infection underwent treatment with raltegravir for a median of 20 months (min-max: 7-30). Before starting treatment with raltegravir, three patients had CD3+ CD4+ cell counts <200 cells cmm(-1) . The median viral load was 7547 copies mL(-1) (min-max: <40-37 807). During treatment, no new sign of disease progression was observed. All patients showed suppression of viral replication (<40 HIV-RNA copies mL(-1) ). CD3+ CD4+ cell counts showed a median increase of 152 cells cmm(-1) (min-max: 40-525). Two patients suffered from peripheral neuropathy, which was deemed as possibly associated with raltegravir. There was no evidence of increased bleeding frequency, modification of bleeding sites and lack of response to replacement therapy. Raltegravir-based HAART appeared to be effective and generally well-tolerated in patients with haemophilia, and it might represent a useful option in these patient
High prevalence of serum cryoglobulins in multitransfused hemophilic patients with chronic hepatitis C
No full textThe prevalence, clinical relevance, and risk factors of serum cryoglobulins in hemophilic patients with chronic hepatitis C virus (HCV) infection are unknown. We studied 135 consecutive hemophilic patients (median age, 31 years; range, 10 to 69 years) with chronic hepatitis C, exposed to the virus for 10 to 41 years. A total of 67 patients were coinfected with the human immunodeficiency virus (HIV), and 3 (2%) had signs of cirrhosis. Serum samples were tested for the presence of cryoglobulins, hepatitis B virus (HBV) markers, including HBV-DNA by hybridization assay, and antibody to HCV by enzyme immunoassay (EIA). Serum HCV-RNA was tested by polymerase chain reaction and typed with a hybridization technique. Samples were also tested for antitissue antibodies, immunoglobulins, rheumatoid factor, and C3 and C4 proteins of complement. Forty-two hemophiliacs (31%) circulated cryoglobulins (median levels, 166 mg/L; range, 66 to 480) predominantly type III (62%; and 29% type II). None of the patients had clinical signs or symptoms of systemic vasculitis. Cryoglobulinemic patients had more often serum HCV-RNA (95% v 80%, P < .05), rheumatoid factor (20% v 6%, P < .05), higher levels of IgG (2,354 ± 682 mg/dL v 1,928 ± 557 mg/dL, P < .0005) and IgM (323 ± 226 mg/dL v 244 ± 243 mg/dL, P < .05), and lower levels of serum C4 (19 ± 8 mg/dL v 24 ± 8 mg/dL, P < .05) than patients without cryoglobulins. The risk of producing cryoglobulins was greater for 114 patients circulating HCV-RNA than for 21 nonviremic patients (odds ratio [OR] = 4.9, 95% confidence interval [CI] = 1.1 to 22.0) and for the 31 patients with longer exposure to HCV (more than 26 years) than for the 24 patients with shorter (17 years or less) exposure (OR = 4.4 95% CI = 1.1 to 18.0). In conclusion a large number of multitransfused hemophiliacs with chronic HCV infection circulated serum cryoglobulins but none had clinical signs or symptoms of vasculitis. The risk of developing cryoglobulins parallels the duration of exposure to HCV
Long-term safety and feasibility of arteriovenous fistulae as vascular accesses in children with haemophilia : a prospective study
No full textInfectious and thrombotic complications limit the long-term use of subcutaneous ports as venous accesses for children with haemophilia. This study has evaluated for the first time the safety and feasibility of internal arteriovenous fistulae (AVF) as alternative accesses. During the 3-year study period, 27 severe haemophiliacs, 14 with factor VIII inhibitors (52%), underwent the creation of 31 proximal AVF in the forearm. Mild forearm haematomas were observed after five procedures (16%) in five patients who had or developed inhibitors after surgery. Inadequate AVF maturation was observed after five of 31 procedures (16%) in four children. AVF were first accessed after a median of 42 d and regularly used at home by 26 patients (96%) for a median follow-up period of 29 months. Thrombosis of a venous branch occurred in one AVF (3%) after 9 months of uncomplicated use in a child with inhibitor who spontaneously recovered from the symptoms and still used AVF for nine additional months. Mild symptoms, referable to distal ischaemia, were transiently reported by two children (7%) who needed no remedial intervention. This study demonstrates that the use of AVF in haemophiliacs enabled long-term treatment at home in all patients but one
Pendekatan Keadilan Restorasi Penyelesaian Kasus Kekerasan Dalam Rumah Tangga Pada Tingkat Penuntutan Berdasarkan Perja No 15 Tahun 2020
No full textKejaksaan mengeluarkan Peraturan Jaksa Agung Republik Indonesia Nomor 15 tahun 2020 tentang Penghentian Penuntutan Berdasarkan Keadilan Restoratif (selanjutnya ditulis Perja No. 15/2020). Adanya Perja No. 15/2020 yang memberikan kewenangan Jaksa untuk menghentikan penuntutan berdasarkan keadilan restoratif menjadi terobosan dalam penyelesaian tindak pidana. Penelitian ini membahas apakah bentuk pendekatan keadilan restoratif justice dapat diterapkan dalam penyelesaian kasus kekerasan dalam rumah tangga. Keadilan restoratif (restorative justice) merupakan pendekatan dalam penyelesaian tindak pidana yang saat ini kembali banyak disuarakan di berbagai negara. Melalui pendekatan keadilan restoratif, korban dan pelaku tindak pidana diharapkan dapat mencapai perdamaian dengan mengedepankan win-win solution, dan menitikberatkan agar kerugian korban tergantikan dan pihak korban memaafkan pelaku tindak pidana. Tindak pidana KDRT yang ditentukan dalam Pasal 44 ayat (1), Pasal 44 ayat (4), Pasal 45 ayat (1), Pasal 45 ayat (2) dan Pasal 49 UU Nomor 23 tahun 2004 tentang UU PKDRT dapat diselesaikan dengan menggunakan metode keadilan restoratif, jika memenuhi persyaratan sebagaimana ditentukan dalam Pasal 5 ayat (1 dan 6) jo. Pasal 7 ayat (1) jo. Pasal 10 ayat (4) Perja Nomor 15 tahun 2020 Tentang Penghentian Penuntutan Berdasarkan Keadilan Restoratif.
Penelitian ini bersifat Yuridis Normatif yaitu penelitian terhadap hukum positif dengan cara melakukan evaluasi terhadap kaidah hukum yang relevan. Bentuk pendekatan keadilan restoratif justice dapat diterapkan dalam penyelesaian kasus kekerasan dalam rumah tangga apabila memenuhi persyaratan untuk direstorative justic
Sequential combined bypassing therapy : a rescue option in refractory bleeds – the Italian experience
No full textBackground: Replacement therapy is ineffective in patients with high titre inhibitor and bypassing agents are required to induce clot formation. Unfortunately, whatever by-passing agent is initially used, some bleed (10-20%) cannot be controlled. A synergistic effect of sequential administration of two agents has been recently reported in patients who failed to respond to a single agent.
Methods: Sequentially combined bypassing therapy (SCT) was used in 2 children (8 and 14 year-old) and 2 adults (40 and 45 year-old) with haemophilia A and high-responding inhibitors, unresponsive to the single treatment with APCC and rFVIIa.
Results: The children were suffering from joint bleeds refractory to high doses of NovoSeven (up to 270 lg Kg-1every 2 h) and to high doses of FEIBA (up to 80 U Kg-1every 8 h). The adults had undergone major orthopaedic surgery (removal of knee prosthesis, knee arthrodesis), initially treated with NovoSeven up to 270 lg Kg-1every 2 h, with only an initial control (first 12-24 h), followed by significant bleed. One of these patients was switched to FEIBA 80 U Kg-1every 8 h without success. SCT was administered alternating one FEIBA dose (range 60-80 U Kg-18-12 h-1) to one NovoSeven dose (range 90-270 lg Kg-18-12 h-1). Complete bleeding control was achieved in 24-48 h. SCT was discontinued and patients underwent prophylaxis with FEIBA. No clinical adverse event was observed, but a rise of D-dimer levels occurred.
Conclusions: SCT can represent a valid rescue treatment of refractory bleeds. An international survey on combined by-passing therapy has recently started (www.intersectsurvey.org
Prospective cost-effectiveness study of regular continuous prophylactic replacement therapy in adults with severe hemophilia A
No full textBackground: Prophylaxis is effective in children with haemophilia. Adults with advanced haemophilic arthropathy can probably benefit from a continuous prophylactic replacement therapy (PRT), but no data are available on cost end efficacy.
Methods: A prospective study was designed to evaluate cost-effectiveness of PRT with a B-domain-deleted recombinant FVIII in adults with severe haemophilia, aged 18–60 years, with ‡18 bleeds in the previous year. PRT: 25 IU kg-1 of Refacto® 3 times a
week for 6 months. Bleeding rate and FVIII consumption was evaluated over the previous 6-month on-demand treatment (ODT) period and the PRT period. Medical costs were quantified adopting the perspective of the National Health Service. The incremental cost-effectiveness ratio (ICER) was calculated as ratio of cost and bleed difference of ODT and PRT. Confidence intervals (CIs) were generated by non-parametric bootstrap procedure. A cost-effectiveness plan and acceptability curve were created.
Results: Nineteen patients, aged 23–58 years (mean = 33.2) with a mean of 2.97 events/patient/ month (median = 1.67, range: 0.5–15) were enrolled. Bleeding frequency decreased to 0.48 events/ patient/ month. The incremental cost of PRT vs. ODT was
estimated to be € 11,619/patient/month (95% CI € 7,649–15,589) with an additional effect of 2.49 bleeds avoided/patient/month (1.06–3.93). The ICER was estimated to be € 5184 per bleed avoided (€1,071–9,297). The likelihood of PRT being cost-effective was 95% with a ceiling ratio of € 9000 per bleed avoided.
Conclusions: These findings showed PRT with Refacto® in adults with haemophilia is cost-effective, but it requires more resources than ODT. Our cost-effectiveness results can represent the reference for other similar evaluations
A prophylactic and therapeutic AIDS vaccine containing as a component the innocuous Tat toxoid
No full textExtracellular Tat can act as a viral toxin on uninfected cells of different tissues, including the CNS and the immune system, thus in order to immunize humans against Tat we have prepared a biologically inactivated but immunogenic Tat (Tat Toxoid). Tat Toxoid is not toxic in mice even at high doses. It triggers high levels of specific Tat Abs in the mouse and rabbit. Furthermore, in humans Tat Toxoid immunization was safe and induced in seronegatives persistent high levels of Tat Abs and in immunodeficient patients a significant rise of these specific Abs. Facing acute HIV-1 infection, the presence of high level of circulating Tat Abs promoted by Tat Toxoid vaccine should prevent Tat-induced immunosuppression and allow anti-HIV-1 cellular response to develop. As a consequence, early release of beta-chemokines could enhance host resistance towards HIV-1, and, in infected people, inhibit viral replication and evolution towards AID
