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Bleeding Episodes (bleeding + episode)
Selected AbstractsPost-varicella thrombocytopenic purpuraACTA PAEDIATRICA, Issue 9 2010Achiya Amir Abstract Aims:, The aim of the study was to characterize the clinical course of post-varicella idiopathic thrombocytopenic purpura (ITP) and to asses the risk of acquiring ITP after varicella infection. Methods:, A retrospective study of all children diagnosed with ITP in a tertiary medical centre during 1998,2008. Findings were compared with the Intercontinental Childhood ITP Study Group database. The risk of acquiring ITP after a varicella infection was assessed. Results:, Ten children were diagnosed with post-varicella ITP. The incidence of post-varicella ITP was 1.9% amongst children diagnosed with ITP and 1.1% amongst children hospitalized for varicella. ITP was diagnosed, on average, 8.5 days after the onset of the varicella rash. The female-to-male ratio was 1:1.5. The average minimal platelet count was 9.5 × 109 platelets/L. Post-varicella ITP had an acute course in 80% of cases and a chronic course in the remaining 20%. Bleeding episodes occurred in three patients. During the follow-up period, 11 patients with previously diagnosed ITP developed varicella. The infection had no apparent affect on the platelet count of the children with acute ITP, but caused a relapse in 71% of the patients with chronic ITP. Conclusions: Post-varicella ITP has similar clinical features and course to non-varicella associated ITP. The calculated risk of ITP as a complication of varicella infections is approximately 1:25 000. [source] FEIBA® in treatment of acute bleeding episodes in patients with haemophilia A and factor VIII inhibitors: a retrospective survey in regional haemophilia centreHAEMOPHILIA, Issue 3 2009P. SMEJKAL Summary., FEIBA® (factor eight inhibitor by-passing activity) is used to achieve haemostasis in haemophiliacs with inhibitor. The aim of this study was to evaluate efficacy and consumption of the product in treatment of haemorrhages in haemophiliacs with factor VIII inhibitor, and determine factors that can influence the results of treatment. We used data from our haemophilia centre from years 2000,2008. Six haemophiliacs with factor VIII inhibitor were treated on demand with FEIBA® for 61 bleeding episodes (45 haemarthroses, six muscle bleeds, six other sites bleeds and four multiple sites bleeds). The median cumulative dose of FEIBA® per bleeding episode was 205 U kg,1. Bleeding was stopped in 96.7% (59 of 61) of events but re-bleeding occurred in 3 events (4.9%) within 48 h after cessation of bleeding. In home treatment (20 of 61) bleeding stopped in 90% (18 of 20) without recurrence and the median consumption per event was reduced to 153 U kg,1. Without the use of home treatment the median consumption was 250 U kg,1 per event and bleeding ceased definitely in 92.7% (38 of 41) of cases. The cumulative dose of FEIBA® was lower for three episodes with re-bleeding: median 96 U kg,1 but not in the two cases of ineffective treatment: 361 U kg,1. FEIBA® in management of bleeding episodes completely resolved the haemorrhage in 91.8% of events and in a further 4.9% if treatment was restarted. Using home treatment saved expenditure due to the lower cumulative dose needed for treatment of haemorrhage. [source] Domiciliary application of CryoCuff in severe haemophilia: qualitative questionnaire and clinical auditHAEMOPHILIA, Issue 4 2008A. I. D'YOUNG Abstract., The acute management of haemophilic bleeding episodesin the home setting is based on the concept of immediate factor replacement therapy and the PRICE regime , an acronym representing the concepts of Protection, Rest, Ice, Compression and Elevation [1,2]. Integral to this regime is the application of cold therapy, and yet little is known regarding the safe periods of application, or the relative safety of cryotherapy devices such as the CryoCuffÔ when used in the home setting by patients suffering from severe haemophilia and related bleeding disorders. This study examines the subjective patient response to the application of the CryoCuffÔ device in the home setting in terms of the effect on pain, joint swelling and the return to ,pre-bleed status' of the knee, ankle or elbow in patients with severe haemophilia A/B or type III von Willebrand's disease (VWD) immediately following haemarthrosis, and any potential adverse effects related to the device or recommended duration of application as stated in the PRICE guideline (Fig. 1). Twelve patients, either with severe haemophilia A/B or with VWD were recruited and asked to use the CryoCuffÔ device as part of the PRICE regime immediately following the onset of knee-, ankle- or elbow bleeds for the next one year. Each subject was then sent a qualitative questionnaire to determine subjective responses to the device. All patients reported that the application protocol was easy to follow, they were able to apply the device as per the PRICE regime and they were able to tolerate it for the recommended period. Whereas, all the patients felt that the device had a significant impact on alleviation of pain and return to pre-bleed status, 78% of the patients felt that the device led to a significant reduction in swelling around the affected joint. There was no conclusive evidence that the device resulted in any reduction in the amount of factor used to treat the acute bleeding episode, however, no patients reported any perceived delay in achieving haemostasis or required extra factor replacement therapy consequent to the usage of the device. No other adverse effects were reported by participants in this study. Figure 1. ,The qualitative participant questionnaire, given following 1 year of unsupervised use in the home setting immediately following the onset of the symptoms of haemarthroses. [source] Individualized duration of oral anticoagulant therapy for deep vein thrombosis based on a decision modelJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 12 2003R. Vink Summary.,Background:,The optimal duration of oral anticoagulant therapy for patients with a first episode of deep vein thrombosis (DVT) is still a matter of debate. However, according to the ACCP consensus strategy a limited stratification in treatment duration is advocated, i.e. 3 months for patients with a transient risk factor and 1 year or longer for patients with recurrent disease or a consistent risk factor such as thrombophilia or cancer. This consensus strategy is founded on the mean optimal duration of therapy obtained in large cohorts of patients and is mainly based on the risk of recurrent venous thromboembolism (VTE), with only minimal consideration for the patient's bleeding risk. Objective:,The aim of this study is to optimize the anticoagulant treatment strategy with vitamin K antagonists for the individual patient with DVT. Methods:,Based on an extensive literature study, a mathematical model was constructed to balance the risk of recurrent VTE against the risk of major hemorrhagic complications. The following parameters are incorporated in the model: baseline estimates and risk factors for recurrent VTE and bleeding, clinical course of DVT, and efficacy of treatment with vitamin K antagonists. With the use of these parameters, the risk for a recurrent VTE and a bleeding episode can be calculated for the individual patient. The optimal duration of anticoagulant therapy can be defined as the timepoint at which the benefit of treatment (prevention of VTE) is counterbalanced by its risk (bleeding). Results/conclusions:,How long a patient should receive anticoagulant treatment is a matter of balancing the benefits and risks of treatment. The model shows that the optimal treatment duration varies greatly from patient to patient according to the patient's unique bleeding and recurrence risk. [source] Occurrence and relapse of bleeding from duodenal ulcer: respective roles of acid secretion and Helicobacter pylori infectionALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 6 2001G. Capurso Background: Helicobacter pylori infection, gastric acid hypersecretion and NSAID consumption may cause peptic ulcer. Aim: To investigate the respective roles of H. pylori and acid secretion in bleeding duodenal ulcer. Patients and methods: A total of 99 duodenal ulcer patients were referred for evaluation of acid secretion: seven with Zollinger,Ellison Syndrome; 14 with hypersecretory duodenal ulcer, defined by the coexistence of elevated basal acid output and pentagastrin acid output; and 78 duodenal ulcer patients with normal acid output. All non-Zollinger,Ellison Syndrome patients were H. pylori -positive and cured of infection. All patients were followed-up for a 36-month period, to assess the occurrence of bleeding episodes. Results: Twenty-nine patients had at least one bleeding episode in the 4 years before the study. Bleeding was more frequent in males and in patients on NSAIDs. The mean basal acid output was not higher among bleeders. In the 21 patients (14 hypersecretory duodenal ulcer, seven Zollinger,Ellison Syndrome) with basal acid output > 10 meg/h and pentagastrin acid output > 44.5 meg/h, the risk of bleeding was higher (OR 6.5; 95% CI: 2,21). In the follow-up period, three out of 83 (3.3%) non-Zollinger,Ellison Syndrome patients had a H. pylori -negative duodenal ulcer with bleeding. The risk of bleeding after H. pylori cure was not higher in hypersecretory duodenal ulcer patients (P > 0.3), nor among patients with previous bleeding episodes (P > 0.2). Conclusions: In H. pylori -positive duodenal ulcer patients, the coexistence of elevated basal acid output and pentagastrin acid output leads to a sixfold increase in the risk of bleeding. After H. pylori cure, gastric acid hypersecretion is not a risk factor for bleeding. However, duodenal ulcer recurrence with bleeding may occasionally occur in patients cured of H. pylori, even if acid output is normal. [source] Review article: primary prophylaxis for portal hypertensive bleeding in cirrhosisALIMENTARY PHARMACOLOGY & THERAPEUTICS, Issue 7 2000Vlachogiannakos Variceal bleeding is a consequence of portal hypertension, which in turn is the major complication of hepatic cirrhosis. Given the high rate of mortality of the first bleeding episode, primary prophylaxis to prevent bleeding from varices and portal hypertensive gastropathy is the current optimal therapeutic approach. The difficulty in identification of patients with varices who will bleed, before they do so, can justify a strategy of treating all patients with varices prophylactically. We evaluated the various therapies that have been assessed in randomized controlled trials for prevention of first bleeding, using meta-analysis where applicable. The current first choice treatment is non-selective ,-blockers; it is cheap, easy to administer, and is effective in preventing the first variceal haemorrhage and bleeding from gastric mucosa. Combination drug therapy of ,-blockers and nitrates looks promising, but needs further evaluation in randomized controlled trials. The conflicting results of the randomized studies of endoscopic banding ligation and the small number of patients and clinical events, as well as the cost, do not warrant any change in current practice. However, endoscopic banding ligation may be a reasonable alternative for patients who cannot tolerate, or have contraindications to ,-blockers or no haemodynamic response to the drug therapy, but this must be proved in randomized trials. [source] rFVIIa, for acute rebleeding of a cerebral cavernous malformationEUROPEAN JOURNAL OF NEUROLOGY, Issue 1 2007K. Engelhardt Recurrent bleeding episodes of cavernomas especially in the brainstem can cause progressive neurological deficits. Therefore brainstem cavernomas are still a therapeutic dilemma and a treatment challenge for the neuro critical care community. We report a 39-year-old woman with spontaneous ataxia diplopia and vomiting, who has been treated for multiple intracerebral cavernomas during the last 10 years. A cerebral computed tomography (cCT) revealed a re-bleeding cavernoma in the left cerebral peduncle with consecutive obstructive hydrocephalus. As a result of the difficult anatomical location, no surgical approach was possible. As an off-label treatment, recombinant activated factor VII (rFVIIa) was administered to prevent possible further bleeding and especially further sequelae. The patient recovered well and no adverse events and especially no further bleeding of the cavernoma were observed. To our knowledge, this is the first report of the safe and successful use of rFVIIa to treat re-bleeding episodes in cavernomas. Further clinical studies are needed to specify the future potential of rFVIIa. [source] Comprehensive elements of a physiotherapy exercise programme in haemophilia , a global perspectiveHAEMOPHILIA, Issue 2010G. BLAMEY Summary., Exercise programmes for people with haemophilia are usually designed and implemented to help manage the recovery after a haemarthrosis or a muscle bleed, or as a tool to help prevent bleeding episodes from occurring. In this article, we have identified individual components of exercise that are often applied as separate entities, but may also need to be implemented in concert for optimized impact. Although it may be necessary on occasion to bias an exercise programme towards one component over the others, it is important to recognize that the various elements of exercise are not mutually exclusive. Decreased flexibility, strength and proprioception, will result in an impairment of balance and a loss of function. Programme design should whenever possible be guided by proven methodology in terms of how each component is incorporated, and more specifically how long to perform the exercise for and how many repetitions should be performed. We recognize, however, that this is not always possible and that there is significant value in drawing from the experience of clinicians with specialized training in the management of haemophilia. In this study, both perspectives are presented, providing reference-based reviews of the mechanics of the various elements of exercise as well as the expert opinions of the authors. Research that has been completed using patients with conditions other than haemophilia may or may not have a direct application with the bleeding disorders population, but the programme design based on principles of tissue healing in addition to disease specific knowledge should be encouraged. [source] The value of early treatment in patients with haemophilia and inhibitorsHAEMOPHILIA, Issue 3 2010K. KAVAKLI Summary., Development of inhibitors to infused factor concentrates represents a major clinical and economic challenge in the treatment of haemophilic patients. It has been shown that a delay in initiation of treatment leads to requirement of a larger number of injections to stop the bleeding but this has never been formally linked to costs associated with the bleeding. The objectives of this study were to assess the relationship between time to initiation of NovoSeven® and total costs, number of doses administered and time to bleeding resolution in mild to moderate bleeding episodes. Data on time to treatment initiation, time to bleeding resolution and on all resource use related to the bleeding were extracted from medical records in Turkey for 129 bleeding episodes. Regression analysis was used to assess the impact of time to treatment on outcomes. Longer time to treatment initiation increased both total costs associated with the bleeding, the number of doses needed and the time to bleeding resolution. Treatment in hospital was associated with significantly longer time to treatment, higher costs and longer time to bleeding resolution as compared with home treatment or outpatient treatment. When controlling for other bleeding characteristics, the cost of bleedings treated in hospital was more than 150% higher. This study shows that treatment with NovoSeven® should be initiated as soon as possible after the onset of bleeding in order to minimize costs and optimize outcomes. Home treatment reduces time to treatment initiation and also reduces costs related to the bleeding. [source] FEIBA® in treatment of acute bleeding episodes in patients with haemophilia A and factor VIII inhibitors: a retrospective survey in regional haemophilia centreHAEMOPHILIA, Issue 3 2009P. SMEJKAL Summary., FEIBA® (factor eight inhibitor by-passing activity) is used to achieve haemostasis in haemophiliacs with inhibitor. The aim of this study was to evaluate efficacy and consumption of the product in treatment of haemorrhages in haemophiliacs with factor VIII inhibitor, and determine factors that can influence the results of treatment. We used data from our haemophilia centre from years 2000,2008. Six haemophiliacs with factor VIII inhibitor were treated on demand with FEIBA® for 61 bleeding episodes (45 haemarthroses, six muscle bleeds, six other sites bleeds and four multiple sites bleeds). The median cumulative dose of FEIBA® per bleeding episode was 205 U kg,1. Bleeding was stopped in 96.7% (59 of 61) of events but re-bleeding occurred in 3 events (4.9%) within 48 h after cessation of bleeding. In home treatment (20 of 61) bleeding stopped in 90% (18 of 20) without recurrence and the median consumption per event was reduced to 153 U kg,1. Without the use of home treatment the median consumption was 250 U kg,1 per event and bleeding ceased definitely in 92.7% (38 of 41) of cases. The cumulative dose of FEIBA® was lower for three episodes with re-bleeding: median 96 U kg,1 but not in the two cases of ineffective treatment: 361 U kg,1. FEIBA® in management of bleeding episodes completely resolved the haemorrhage in 91.8% of events and in a further 4.9% if treatment was restarted. Using home treatment saved expenditure due to the lower cumulative dose needed for treatment of haemorrhage. [source] Differential response to bypassing agents complicates treatment in patients with haemophilia and inhibitorsHAEMOPHILIA, Issue 1 2009E. BERNTORP Summary., The bypassing agents factor eight inhibitor bypassing activity (FEIBA) anti-inhibitor coagulant complex and recombinant activated factor VII (rFVIIa) have been established as safe and effective therapies for treating bleeding episodes in haemophilia patients with inhibitors. However, the efficacy of each bypassing agent can vary, and neither agent is universally effective. The reasons for such variability have yet to be confirmed, but may involve patient-specific factors and the mechanisms of action (MOAs) and pharmacokinetic profiles of these two agents. This issue underscores the necessity of both products in the comprehensive care of patients with haemophilia and inhibitors. The objective of this review is to discuss the evidence of a differential haemostatic response to bypassing agents and the potential roles of MOA and patient-specific factors in contributing to the differences in response. [source] Clinical safety surveillance study of the safety and efficacy of long-term home treatment with ReFacto® utilizing a computer-aided diary: a Nordic multicentre studyHAEMOPHILIA, Issue 1 2009P. PETRINI Summary., A Nordic multicentre, open-label, non-interventional postmarketing surveillance study was carried out during a period of 24 months evaluating safety and efficacy of ReFacto as prophylactic or on-demand replacement therapy in patients with haemophilia A treated by self-medication. Fifty-seven patients were enrolled and studied for safety; efficacy was evaluated in 39 patients who received ReFacto for 24 months and recorded sufficient diary data on a hand-held computer. The compliance of using the device was good in small children, variable in adults and poor in teenagers. The fact that the overall compliance was low constituted a limitation of the number of patients with reliable diary data. Overall safety was rated as excellent or good by the clinicians for all patients at all visits and overall efficacy at 24 months evaluated to be excellent (74%) or good (26%). It was noticed that ,50% of patients/parents reported no absences from school or work owing to bleeding episodes during the study period. Among patients on regular prophylaxis, 6 of the 30 patients (20%) receiving ReFacto experienced no bleeding episodes. A median of four bleeding episodes occurred during the 24-month study period, and 93% of the episodes were resolved with ,2 ReFacto infusions. In the 7 on-demand patients, there was a median of 18 bleeding episodes, 87% of which resolved with ,2 ReFacto infusions. Interestingly, 42% of the ReFacto infusions taken by the patients classified to the on-demand group were registered as prophylactic treatment. In conclusion, ReFacto demonstrated good safety and efficacy in prophylaxis as well as treatment of bleeding episodes. [source] Hypothyroidism and acquired von Willebrand's syndrome: a systematic reviewHAEMOPHILIA, Issue 3 2008E. MANFREDI Summary., Acquired von Willebrand's syndrome type I is the supposed main underlying cause of bleeding tendency in hypothyroid patients. The purpose of this systematic review was to summarize the published evidence on the association between hypothyroidism and acquired von Willebrand's syndrome. All published clinical epidemiological and interventional studies, case reports and in vitro studies that investigated the association between hypothyroidism and acquired von Willebrand's syndrome were identified by a computer-assisted search of the MEDLINE and EMBASE electronic databases. A quality assessment was performed for clinical epidemiological studies. A total of 41 papers were included. A total of 22 epidemiological in vivo studies, two in vitro studies and 47 case reports were finally analyzed. No high quality in vivo study was identified. Almost all bleeding episodes described in the case reports were mucocutaneous. von Willebrand factor (VWF) antigen value was available for 23 patients: median value 28 U/dL (range: 4,45); VWF activity was available for 24 patients: median value 28.5 U/dL (range: <3,55); factor VIII activity was available for 16 patients: median value 47 U/dL (range: 9,74). Acquired von Willebrand's syndrome may be the main factor responsible for bleeding diathesis in overt hypothyroid patients. Even if bleeding episodes are mainly mild and mucocutaneous, blood transfusion, drug administration or surgical procedure may be required. [source] The co effect of prophylaxis and radiosynovectomy on bleeding episodes in haemophilic synovitisHAEMOPHILIA, Issue 3 2008J. BRECELJ Summary., Prophylactic substitution treatment and radiosynoviorthosis have a leading role in preventing irreversible haemophilic arthropathy. The aim of the study was to evaluate the effects of prophylaxis treatment and radiosynovectomy on the length of intervals between subsequent haemorrhages in haemophilic patients. Thirty-three joints were treated with radiosynovectomy in 28 patients with bleeding disorders. 90Y colloid was used in knees and 186Re colloid for elbows, shoulders and ankles. Twenty patients were on prophylaxis. Joint X-rays were evaluated on the Pettersson scale between 0 (normal) and 13 (severe joint destruction). During an observation period (range 6,44 months) bleeding episodes were recorded and data statistically analysed. Before radiosynovectomy, increasing intensity of the prophylaxis 10% lengthens intervals between two haemorrhages by 1% (P < 0.05). In patients with a Pettersson score higher than nine, intervals between bleedings are shorter by 73% (P < 0.05), in comparison with patients with lower Pettersson scores of 0,5. After radiosynovectomy, the length of the first non-bleeding interval increased by 120% (to 60 days) in comparison with the intervals before the procedure (P < 0.001). But, in the following year and half, every subsequent non-bleeding interval was 8% shorter (P < 0.1). In that period, prophylaxis shortened the non-bleeding interval by 1.7% (P < 0.05) per 10% increase of its intensity. Radiosynovectomy is more efficient in patients with less affected joints and is less efficient in younger patients. Prophylaxis reduced time between the bleedings episodes after isotope application. Before radiosynovectomy, prophylaxis reduces the number of haemorrhages. Our findings support data previously published by Rodriguez-Merchan et al. [J Thromb Haemost, 5 (2007) P-W-126]. [source] Recombinant activated factor VII for haemophilia patients with inhibitors undergoing orthopaedic surgery: a review of the literatureHAEMOPHILIA, Issue 2 2008A. OBERGFELL Summary., Arthropathy is prevalent in patients with haemophilia and inhibitors and is a major source of pain and disability, significantly reducing quality of life. Recombinant activated factor VII (rFVIIa; NovoSeven®) is one of the treatments available for acute life-threatening bleeding episodes in haemophilia patients with inhibitors. It has also been used successfully in a range of orthopaedic surgical procedures in these patients. This is a review of published data on elective orthopaedic procedures in haemophilia patients with inhibitors under cover of rFVIIa from January 2002 to November 2006. Articles were retrieved from MEDLINE using specified search parameters. Twelve articles covering a total of 80 orthopaedic procedures were identified. In the vast majority of cases, rFVIIa provided safe and effective haemostatic cover during orthopaedic surgery with no bleeding complications. There was variation in the administered dose, although the majority of patients were treated with 90 ,g kg,1 bolus followed by either continuous infusion or bolus infusion. Of those cases reporting bleeding complications, most were considered to be related to an inadequate amount of rFVIIa. The cumulative experience presented here suggests that rFVIIa is safe and effective for providing adequate haemostatic cover for haemophilia patients with inhibitors undergoing orthopaedic surgery. The optimal dosing regimen and mode of administration has yet to be identified. Further controlled trials are needed to confirm these experiences. [source] A cost evaluation of treatment alternatives for mild-to-moderate bleeding episodes in patients with haemophilia and inhibitors in BrazilHAEMOPHILIA, Issue 5 2007M. C OZELO Summary., The first-line treatment for mild-to-moderate bleeding episodes in patients with haemophilia and inhibitors in Brazil is currently activated prothrombin complex concentrate (aPCC), with recombinant activated factor VII (rFVIIa) used as second-line therapy or as a last resort. The aim of this study was to determine the cost and effectiveness of these treatments from the perspective of the Brazilian National Health Service. A decision analysis model was constructed to assess total direct medical costs (including drug costs, costs of outpatient or inpatient care, ambulance transportation and cost of concomitant medications) of first-line treatment with aPCC or rFVIIa. Clinical outcome and resource utilization data were obtained both retrospectively and prospectively and validated by the consensus of an expert panel of Brazilian haematologists. A total of 103 bleeds in 25 patients were included in the analysis. rFVIIa resolved bleeds more quickly (4.4 h) than aPCC (62.6 h) and was more effective (100% vs. 56.7% respectively). Mean total direct medical costs (from initiation to cessation of bleed) were estimated to be US$13 500 (aPCC) and US$7590 (rFVIIa). Extensive sensitivity analyses confirmed the cost-effectiveness of rFVIIa. Compared with aPCC, rFVIIa was more effective and less expensive when used as first-line treatment for mild-to-moderate bleeding episodes in patients with haemophilia and inhibitors in Brazil. rFVIIa should be considered a first-line treatment for the management of these patients. [source] Safety and efficacy of a sucrose-formulated recombinant factor VIII product for the treatment of previously treated patients with haemophilia A in ChinaHAEMOPHILIA, Issue 4 2007J. SHI Summary., The use of plasma-derived products has contributed to a high rate of blood-borne infections among haemophilia patients in China. Recombinant factor VIII (rFVIII) products that are manufactured without human or bovine albumin and include dedicated viral inactivation steps, hold a significant safety advantage over plasma products. However, there is little information published on the use of rFVIII products in non-caucasian populations. This is the first reported evaluation of the efficacy and safety of a rFVIII product in Chinese haemophiliacs. An open-label, non-randomized, prospective, multicentre trial enroled previously treated Chinese patients with haemophilia A. All treatments were administered using a sucrose-formulated rFVIII-FS (Kogenate®). Forty-nine patients received totals of 291 infusions (mean, 5.94/patient) and 742 140 IU rFVIII-FS (mean, 2550.3 IU/infusion). Of the 60 acute bleeding episodes that were treated, 90% were successfully managed with only one (81.7%) infusion or two (8.3%) infusions. Physicians reported haemostasis control for acute bleeds to be ,Excellent' or ,Improved' with rFVIII-FS therapy. No FVIII inhibitors were detected in any patient. Only one treatment-related adverse event was reported, which was mild dizziness that resolved spontaneously. rFVIII-FS was efficacious, safe and well tolerated in the treatment of previously treated patients with haemophilia A in China. [source] Evaluation of pharmacokinetics, efficacy and safety of Immunate® solvent detergent in previously treated patients with severe haemophilia AHAEMOPHILIA, Issue 1 2007L. NEMES Summary., Immunate® Solvent Detergent (S/D) is a plasma derived, purified, human factor VIII (FVIII) , von Willebrand factor (VWF) complex subjected to two virus inactivation/removal processes: S/D and vapor heat treatment. This prospective, multicentre, three-part clinical study evaluated the pharmacokinetics (in comparison to the predecessor product Immunate®), efficacy and safety of Immunate® S/D in 56 previously treated patients with severe haemophilia A. Subjects received Immunate® S/D on-demand, as a prophylactic regimen or both. The results of the pharmacokinetic population demonstrate that Immunate® and Immunate® S/D were equivalent with respect to the FVIII , and to the retrospectively VWF , parameters assessed. A total of 623 bleeding episodes were reported in 47/56 subjects. The duration of prophylaxis ranged from 0.1--5.2 months with a total of 175.6 months. The median number of bleeds per month in subjects on prophylaxis was 0 (range 0--10). Ninety-six percent of bleeding episodes were rated as having an excellent or good response. For most bleeding episodes (89%), subjects required only one infusion with a mean dose of 29.6 IU kg,1. No FVIII inhibitory antibodies were observed in any subject. No related serious adverse events were reported. Thus, the introduction of S/D treatment did not alter the PK characteristics and function of VWF and FVIII molecules of Immunate® S/D which is effective and safe for treatment of bleeding episodes, management of surgical procedures, and prophylaxis. [source] Force fluctuations during the Maximum Isometric Voluntary Contraction of the quadriceps femoris in haemophilic patientsHAEMOPHILIA, Issue 1 2007L.-M. GONZÁLEZ Summary., In the general population, the degenerative processes in joints are directly related to adult age, and osteoarthrosis represents the most frequent musculoskeletal alteration. In the haemophilic patient, the degenerative processes in the joint begin at very early ages, and are directly related to musculoskeletal bleeding episodes, which are occasionally subclinical and constitute haemophilic arthropathy. In the haemophilic patient, arthropathy constitutes the most frequent, severe and disabling pathology, and its assessment includes muscular force-related parameters. We have studied the value of Maximum Isometric Voluntary Contraction in the quadriceps femoris of 46 subjects, 28 haemophiliacs (16 severe, eight moderate and four mild) and 18 healthy individuals with a view to establishing appropriate values of force and to restoring physical therapy recommendations. The maximum force values were significantly greater (P < 0.001) in the healthy individuals group. The mild haemophiliacs group also presented significant differences of force (P < 0.05) in relation to the severe and moderate haemophilic patient groups. The mild and severe haemophilia patients presented greater fluctuations of force (P < 0.001) than the control group, the haemophilia group have a minor skill to produce constant force. The seriousness of the arthropathy in the knee is directly related to diminished values of maximum force. Our work evidences that patients with severe haemophilia present a greater degree of arthropathy in relation to moderate and mild haemophilia patients. Haemophilic arthropathy is associated with muscular atrophy and strength deficit. In haemophilic patients, the deficit of maximum force and the presence of fluctuations may suggest an increased risk of bleeding during physical activities and the need to programme specific physical therapy guidelines which increase muscular power through resistance training. [source] Cyclosporin A can achieve immune tolerance in a patient with severe haemophilia B and refractory inhibitorsHAEMOPHILIA, Issue 1 2007D. C. A. CROSS Summary., Immune tolerance induction (ITI) is described in a patient with severe haemophilia B complicated by the presence of an inhibitor. A number of ITI regimes were attempted without success and the patient suffered from frequent relapses and bleeding episodes. Successful ITI was achieved with the additional use of cyclosporin A. The patient developed nephrotic syndrome although had a negative Bethesda titre at this time. When cyclosporin A therapy was ceased, the inhibitor titre rose and the patient suffered again from bleeding episodes. Cyclosporin A was reintroduced at a lower dose. The patient has now received cyclosporin A for 10 years, during which time he has relapsed three times for short periods (2 weeks). He is also on prophylaxis with factor IX three times a week with preinfusion levels >1% and without bleeding. [source] Periodontal status and IOTN interventions among young hemophiliacsHAEMOPHILIA, Issue 4 2006S. AZHAR Summary., ,Fifty-two young individuals suffering from severe haemophilia A and B volunteered to be compared with school- and college-going students for oral health status description and subsequent management. A total of 244 students (84.42% boys and 15.58% girls) with the age group of 13,23 years were divided into two groups, A and B (controls). The purpose of this study was to increase awareness about evidence-based dental practices by oral examinations followed by comparisons of periodontal health and prevalence of malocclusions among medically compromised students and healthy controls. Results described the oral health in severe haemophilic population to be compromised with combined simplified health index score of 0.50 and Decayed/Modified/Filled Teeth (DMFT) index score of 2.07 when compared with 0.42 and 0.95, respectively, among group B. Although prevalence of malocclusion and orthodontic treatment needs among group A were higher, yet it was not confirmed as a reason for degraded dental and periodontal status. However, spontaneous and/or toothbrush (trauma)-induced gingival bleeding episodes among group A could be explained as factors discouraging oral hygiene maintenance, particularly self-administered measures. Four haemophiliacs presented with symptoms of Temporomandibular Joint Dysfunction Syndrome (TMPDS). Evidence-based oral medicine and clinical practices need to be encouraged and applied to enhance the quality of life among haemophiliacs, particularly in developing world. Dental treatment needs of haemophilic population appear to be greater and maybe incorporated in routine dental practices, at institutional and individual levels. [source] Evaluation of the impact of information about treatment-related risks in patients receiving blood-derived or recombinant medicationsHAEMOPHILIA, Issue 5 2004D. Magli-Barioz Summary., The aims of the study were to evaluate the impact of a written information about treatment related risks in patient receiving blood derived or recombinant medications. Haemophiliac patients and patients with constitutional or acquired immune deficiencies are concerned by this treatment and these information. Our objectives are to evaluate the efficacy of the written information, the knowledge of the patients about these medications and the psychological, emotional impact if these information. The study is based on questionnaires which specified how the patient treat bleeding episodes, their knowledge about viral safety of blood products, the patient's perception of his or her health status and relationship with the physician. Psychological and emotional status are evaluated with the Hospital Anxiety and Depression Scale. The results show the difficulty to inform patients: if the information generate only limited anxiety in patients with haemophilia or immune deficiencies, we observe that the delivery of a written information got a mediocre effect on overall knowledge. We think that this information must be appropriate for patients and be communicated orally within the patient,physician relationship. [source] The management of inhibitors in haemophilia A: introduction and systematic review of current practiceHAEMOPHILIA, Issue 4 2003S. Paisley Summary., Haemophilia is the commonest bleeding disorder in the UK, affecting approximately 5400 people, almost all of them male. In haemophiliacs, reduced levels, or absence, of factor VIII (FVIII) cause bleeding episodes, typically into joint spaces or muscles. Haemophilia is generally treated with exogenous FVIII. However, in some haemophiliacs, therapeutically administered FVIII comes to be recognized as a foreign protein, stimulating the production of antibodies (inhibitors), which react with FVIII to render it ineffective. Alternative treatment strategies then have to be used to manage bleeding episodes. In addition, strategies have been developed to attempt to abolish inhibitor production through the induction of immune tolerance. A systematic review was undertaken of current international practice for the clinical management of haemophilia A patients with inhibitors to FVIII, concentrating on literature published from 1995 onwards. Although it can be difficult to determine what constitutes current practice, current guidelines indicate that immune tolerance induction is seen as desirable, with the choice of regimen dependent on patient characteristics, familiarity with regimens and cost. Various approaches, based on similar factors, are used to control bleeding episodes. [source] The epidemiology of inhibitors in haemophilia A: a systematic reviewHAEMOPHILIA, Issue 4 2003J. Wight Summary., This paper emphasizes the importance of distinguishing between the prevalence, incidence and cumulative incidence of inhibitors in haemophilia A. Incidence and cumulative incidence data will include patients with transient inhibitors or whose inhibitors have been eliminated by treatment. As these will not be included in prevalence data, prevalence studies will tend to give rise to lower figures than incidence studies. As a result, the most accurate estimates of the true risk of inhibitor development comes from prospective studies of newly diagnosed haemophiliacs who are tested regularly for the presence of inhibitors. This paper reports a systematic review of the best available evidence relating to the epidemiology of inhibitors in haemophilia A. Cohort studies, registry data reporting incidence or prevalence of inhibitors in patients with haemophilia A, and prospective studies of factor VIII (FVIII) in the treatment of previously untreated patients which reported the development of inhibitors as an outcome, were included in the review. The overall prevalence of inhibitors in unselected haemophiliac populations was found to be 5,7%. The cumulative risk of inhibitor development varied (0,39%). Incidence and prevalence were substantially higher in patients with severe haemophilia. Studies of patients using a single plasma-derived FVIII (pdFVIII) preparation reported lower inhibitor incidence than those using multiple pdFVIII preparations or single recombinant FVIII preparations. Incidence data should be used to estimate the likely demand for treatments aimed at eliminating inhibitors, whereas the best estimates of the overall burden to the National Health Service (NHS) of treating bleeding episodes in patients with continuing inhibitors will come from prevalence studies. [source] A global view on prophylaxis: possibilities and consequencesHAEMOPHILIA, Issue 2003A. D. Shapiro Summary., Prophylactic infusion therapy, both primary and secondary, has proven of great benefit to patients with haemophilia, specifically those with severe disease or bleeding episodes and patterns that have lead to development of arthropathy. At this time, optimal outcome in patients with severe haemophilia has been proven achievable with primary prophylaxis initiated at an early age in a regimen of three times weekly or every other day for patients with factor VIII deficiency, and twice weekly for those with factor IX deficiency. Despite the demonstrated benefit of primary prophylaxis, this treatment regimen has not been uniformly adopted into clinical practice even in developed countries. In developing countries, where issues of allocation of precious health care resources are of paramount importance, access to adequate treatment for persons with haemophilia on a programme of on-demand therapy is not commonly available; the cost of primary prophylaxis, even with intermediate purity plasma-derived factor concentrates or plasma fractions such as cryoprecipitate, renders this treatment the exception rather than the rule. [source] European data of a clinical trial with a sucrose formulated recombinant factor VIII in previously treated haemophilia A patientsHAEMOPHILIA, Issue 2002C. Rothschild Summary., To increase the safety of antihaemophilic treatment, the production process of full-length recombinant factor VIII (FVIII) KOGENATE® Bayer (Kogenate®FS)has been modified. Human albumin is no longer added as stabilizer during purification and in final formulation. Instead, the new KOGENATE® Bayer production process uses sucrose as a stabilizer in the formulation and adds solvent/detergent virus inactivation step. An European clinical trial was carried out in Germany and France in previously treated patients with severe haemophilia A who had more than 100 exposure days to exogenous FVIII. Pharmacokinetic data was analysed according to one-stage and chromogenic assays. Efficacy and safety during home therapy and in surgical procedures were evaluated; inhibitor formation was carefully monitored. Safety and efficacy were evaluated in 33 European patients for 24 months. Patients received more than 13 million IU KOGENATE® Bayer. Over 75% of patients accrued more than 100 exposure days with the new product. Of 875 bleeding episodes, 90.7% were treated with 1 or 2 infusions and 75.8% of responses to treatment were rated as ,excellent' or ,good'. Prophylactic treatment was the most common mode of therapy (60.7% of infusions). The product was well-tolerated and FVIII recovery studies were consistent throughout the study period. Only 0.26% of adverse events were reported to be drug related. No evidence of de novo inhibitor formation was observed. Overall, KOGENATE® Bayer was efficacious, safe and well-tolerated for the treatment of haemophilia A in multitransfused patients. [source] Safety and efficacy of a new recombinant FVIII formulated with sucrose (rFVIII,FS) in patients with haemophilia A: a long-term, multicentre clinical study in JapanHAEMOPHILIA, Issue 3 2001A. Yoshioka The recombinant full-length FVIII product Kogenate® has been reformulated using sucrose (rFVIII,FS) instead of human serum albumin as a stabiliser in purification and formulation. The in vivo recovery, haemostatic efficacy, and safety of rFVIII,FS were investigated in 20 previously treated patients with severe or moderate haemophilia A for , 24 weeks. In vivo recoveries of 73.5 ± 16.3%, 78.4 ± 16.1%, and 82.8 ± 23.9% after the initial infusion of 50 IU kg,1 rFVIII,FS and at weeks 12 and 24, respectively, showed no significant changes over time. A total of 1115 infusions (mean dose 24.1 ± 8.4 IU kg,1) were included in the analysis of haemostatic efficacy. One (80.5%) or two (8.2%) infusions achieved adequate haemostasis in 88.7% of all bleeding episodes, and haemostatic efficacy was judged ,excellent' or ,good' in 749 of 764 episodes (98.0%). The haemostatic efficacy was judged as ,excellent' or ,good' in 924 of 1115 (82.9%) infusions. Twenty-one adverse events were observed in 12 patients in the total 1541 infusions included in the safety analysis. Causality with respect to rFVIII,FS could not be ruled out in three events in one HIV-negative patient: elevated CD4(%), decreased CD8(%), and elevated CD4/CD8 ratio. No FVIII inhibitor development was observed in any patient. ELISA assay testing for antibodies to rFVIII, baby hamster kidney cell (BHK) protein, and murine IgG were all negative. These results show that rFVIII,FS is a safe and effective for long-term treatment of patients with haemophilia A. [source] Recombinant factor IX (BeneFix®) by adjusted continuous infusion: a study of stability, sterility and clinical experienceHAEMOPHILIA, Issue 2 2001P. Chowdary The safety and efficacy of adjusted continuous infusion (CI) of recombinant factor IX (FIX; BeneFix®) was assessed in vitro and in a clinical study. BeneFix® was reconstituted at 100 IU mL,1 with or without unfractionated heparin (4 U mL,1) and stored at either 4 °C or room temperature. Reconstituted BeneFix® retained at least 90% activity over 14 days if stored at 4 °C but stability was reduced at room temperature. BeneFix® reconstituted in a sterile pharmacy was free of bacterial contamination. Six patients with haemophilia B received seven CIs of BeneFix® to cover routine surgery and severe bleeding episodes. The CIs lasted between 3 and 10 days. In all cases, haemostasis was excellent and the desired therapeutic FIX level was easily maintained. No thrombotic episodes or inhibitor development occurred but two patients developed thrombophlebitis at the infusion site when heparin was not added to the infusion. BeneFix® is not currently licensed for CI and we suggest that studies to enable licensing should be established as soon as possible. [source] Safety and efficacy of solvent/detergent-treated antihaemophilic factor with an added 80 °C terminal dry heat treatment in patients with haemophilia AHAEMOPHILIA, Issue 3 2000J. S. Powell Plasma-derived factor VIII concentrates remain an important resource for haemophilia A patients. To improve the safety of these preparations, various methods of viral removal and inactivation have been used that are designed to eliminate both enveloped and non-enveloped viruses. There have been rare reports that some viral inactivation processes altered the immunogenicity of some concentrates, leading to the development of factor VIII inhibitors in previously treated haemophilia A patients. This study evaluated the safety, efficacy and lack of neo-antigenicity of a highly purified factor VIII preparation which undergoes both solvent/detergent treatment and final dry heat treatment at 80 °C for 72 h. The study included: (i) a single blind, single-dose crossover pharmacokinetic study in 18 previously treated patients, comparing sibling lots of the unheated preparation (Koate® -HP) and the heat-treated preparation (Koate® -DVI), and (ii) an extended home treatment programme for 36 patients at two haemophilia treatment centres primarily to assess immunogenicity. Clinical parameters were assessed at regular intervals. The results confirm that Koate® -HP and Koate® -DVI are bioequivalent, and that Koate® -DVI is safe and efficacious for treatment of acute bleeding episodes and for surgery. Furthermore, the heat-treated preparation is not associated with the development of inhibitors in previously treated patients. [source] Current management of adult idiopathic thrombocytopenic purpura in practice: a cohort study of 201 patients from a single center,INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2004J. Zimmer Summary To define usefulness and response to therapy and outcome in adults with idiopathic thrombocytopenic purpura (ITP) in clinical practice. We retrospectively reviewed a cohort of 201 consecutive patients with ITP, diagnosed between 1985 and 1994. In particular, we analyzed the therapies used, their response rates, prognostic indicators of response and outcome. In 62 patients, with minor bleeding episodes and a mean (±SD) platelet count of 88 ± 23 × 109/l, no treatment was used and chronic ITP was diagnosed in 59%. A total of 139 patients, with bleeding episodes in 71.2% cases and a mean platelet count of 20 ± 13 × 109/l, received at least one treatment. Three patients died (1.5% of the series). Corticosteroids were used in 118 patients, with an initial response rate of 82.2% and a long-term complete response (CR) of only 22.9%. Intravenous immunoglobulin was used in 26 patients, with an initial transient response in more than 60%. A splenectomy was performed in 55 patients, with an initial response rate of 92.5% and a long-term CR in 60%. Young age and prior response to corticosteroids were significant predictors of a durable response to splenectomy. Danazol was given in 37 patients, with a favorable response in 73% of cases. Our results illustrate the guidelines of the American Society of Hematology. Patients with moderate thrombocytopenia do not require treatment. In severe cases, splenectomy is the only treatment giving durable cures in a significant proportion of patients. Despite frequent chronicity, ITP is life-threatening only in a minor subset of patients. [source] | ||||||||||