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Haemophilia Patients (haemophilia + patient)

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Medical Sciences	98%

Selected Abstracts

Acute intestinal obstruction due to intramural haemorrhage in small intestine in a patient with severe haemophilia A and inhibitor

EUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2005
Khaled M. A. Ramadan
Abstract:, Patients with severe haemophilia A usually present with joint, gastrointestinal and urinary tract haemorrhage. Bleeding elsewhere is often precipitated by pre-existing pathology or trauma. We report a patient with severe haemophilia A, who presented with symptoms of acute intestinal obstruction. He has a factor VIII inhibitor and receives recombinant factor VIIa on demand at home. The CT scan of abdomen showed dilated small intestine with fluid filled loops and a long segment in the jejunum with marked transmural thickening. There was no other pathology in the small intestine. These appearances were consistent with intramural haemorrhage in the small intestine as the cause of acute obstruction. He was managed conservatively with recombinant factor VIIa and this resulted in resolution of his symptoms. This case highlights an unusual presentation of bleeding in a haemophilia patient. Intestinal obstruction due to haemorrhage in the small intestinal wall is extremely rare and only previously reported in a few haemophilia patients. It also highlights the effectiveness of conservative management with recombinant factor VIIa as opposed to immediate exploratory surgery. [source]

Emerging clinical concerns in the ageing haemophilia patient

HAEMOPHILIA, Issue 6 2009
B. A. KONKLE
Summary., The availability of safe replacement clotting factor concentrates together with effective antiviral drugs to treat human immunodeficiency and hepatitis C viruses and the provision of care at designated haemophilia treatment centres have resulted in a new phenomenon in haemophilia management , the ageing patient. Today, increasing numbers of persons with haemophilia (PWH) are middle-aged and older, and they face the same age-related health issues as the general population. The impact of these risks on PWH is unclear, however, and there is a paucity of information about how to manage comorbidities in this patient population. This review focuses on five comorbidities that uniquely affect older PWH: cardiovascular disease, liver disease, cancer, renal disease and joint disease. Available research is summarized and potential management approaches are suggested. [source]

Successful liver surgery in a haemophilia patient with high titre factor VIII inhibitor

HAEMOPHILIA, Issue 6 2009
A. E. JONES
No abstract is available for this article. [source]

Co-morbidity in the ageing haemophilia patient: the down side of increased life expectancy

HAEMOPHILIA, Issue 4 2009
E. P. MAUSER-BUNSCHOTEN
Summary., Because of an increased life expectancy, (age-related) co-morbidity is becoming a common occurrence in haemophilia patients. In this review, haemophilia-related and non-haemophilia-related medical problems, treatment recommendations and psychosocial consequences in ageing haemophilia patients are discussed. Haemophilic arthropathy is an important cause of pain and disability, and a frequent indication for surgery in haemophilia patients. In addition, many adult patients are infected with hepatitis C or HIV, the consequences and treatment of which can add to physical and mental discomfort. Moreover, inhibitors against factor VIII can also develop in adulthood, especially in patients with mild haemophilia. Hypertension is reported to occur more often in haemophilia patients than in the general population. Other internal problems, like renal abnormalities, overweight, diabetes mellitus and hypercholesterolemia are discussed. Haemophilia seems to protect against cardiovascular disease, although the incidence is increasing. Recommendations are given on dealing with tooth extractions, surgical interventions and sexuality problems in patients with haemophilia. In addition to haemophilia in itself, co-morbidity has a major psychological impact, and an important effect on quality of life. It can also result in complex treatment regimens, in which coordination between health care workers is essential. [source]

Open heart surgery with mitral valve replacement , ordeal of an undiagnosed haemophilia patient.

INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY, Issue 2 2003
K. Ghosh
No abstract is available for this article. [source]

Acute intestinal obstruction due to intramural haemorrhage in small intestine in a patient with severe haemophilia A and inhibitor

Knowledge of disease and adherence in adult patients with haemophilia

HAEMOPHILIA, Issue 4 2010
K. LINDVALL
Summary., Patients with moderate and severe haemophilia are evaluated on a regular basis at their haemophilia centres but patients with mild haemophilia are seen less often because of fewer problems related to their disease. The needs of patients with milder forms of haemophilia, however, are often underestimated, both by the patient and staff at healthcare facilities. This study evaluated the knowledge of disease and adherence to treatment among patients with severe, moderate and mild haemophilia. This was a prospective multicentre study performed in Haemophilia Centres in Scandinavia. A total of 413 (67%) of 612 patients aged >25 years with mild, moderate and severe haemophilia completed a self-administered questionnaire. The mean age of the respondents was 49.7 years (range 25,87 years). Of the 413 respondents, 150 had a mild, 86 had a moderate and 177 had a severe form of haemophilia. A total of 22 (5%) patients did not know the severity of their disease, and 230 (56%) patients knew the effect of factor concentrate in the blood. Of the 413 respondents, 53 (13%) of the cohort never treated a haemorrhage. Patients with mild haemophilia, P , 0.001, were the least likely to treat a haemorrhage. The relative number of patients who were afraid of virus transmission by factor concentrate was about similar in the three groups, 27% of those with severe haemophilia, 26% with moderate and 24% with mild haemophilia. This study shows that the amount of knowledge among haemophilia patients about their disease and treatment is somewhat limited, and demonstrates the importance of continually providing information about haemophilia and treatment, especially to patients with a mild form of the disease. [source]

Thrombin generation in haemophilia A patients with mutations causing factor VIII assay discrepancy

HAEMOPHILIA, Issue 4 2010
R. GILMORE
Summary., Up to 40% of patients with mild haemophilia A have a discrepancy whereby factor VIII (FVIII) measurements by a two-stage chromogenic assay (FVIII:CCH) are disproportionately reduced compared with the FVIII one-stage clotting value (FVIII:C). Which assay best reflects the coagulation potential and clinical phenotype in this patient group is of clinical significance, yet remains unclear. We have assessed the global coagulant ability of haemophilia patients with FVIII assay discrepancy using calibrated automated thrombography (CAT). A total of 18 patients with mutations Arg531His/Cys or Arg698Trp causing FVIII discrepancy were investigated, together with 12 haemophilia patients with concordant FVIII values and 15 normal controls. Factor VIII levels in all patients and controls were measured using both one-stage clotting assay and two-stage chromogenic assay. Thrombin generation was assessed in platelet-poor plasma by CAT using a low tissue factor concentration (1 pm). FVIII:CCH values were below normal in all patients, and in the discrepant group were between 1.5- and 8-fold lower than FVIII:C values. CAT parameters were affected in all haemophilia patients. The endogenous thrombin potential (ETP) was reduced to 58,67% of the mean normal value (1301 nm min,1), whereas peak thrombin was further reduced to 27,30% of the mean normal value (178 nm) in both discrepant and concordant patient groups. Analysis of the discrepant patient group showed the most significant correlation between the one-stage FVIII:C assay and ETP (r2 = 0.44) and peak thrombin parameters (r2 = 0.27). [source]

Mild haemophilia: a disease with many faces and many unexpected pitfalls

HAEMOPHILIA, Issue 2010
K. PEERLINCK
Summary., Despite major advances in diagnosis and treatment, the management of patients with mild haemophilia (MH) remains a major challenge. Mild haemophilia is defined by factor levels between 0.05 and 0.40 IU mL,1. The bleeding associated with mild haemophilia is most frequently episodic, occurring during surgery or following trauma. Spontaneous bleeding is rare. Diagnosis is sometimes delayed because of insensitivity of screening clotting assays or discrepancies in factor VIII activity as measured by different assays. The treatment of choice in mild haemophilia A is desmopressin, which typically induces a 2,6-fold increase of factor VIII over baseline. However, desmopressin has its limitations in this setting such as the occurrence of tachyphylaxis and failure to respond in an undetermined proportion of patients. Factors underlying poor biological response or magnitude of response to desmopressin are incompletely understood. Inhibitor development in mild haemophilia is particularly distressing. This complication arises at an older age in this patient group because of infrequent need for factor VIII replacement. Inhibitors in mild haemophilia patients often cross-react with endogenous factor VIII resulting in severe spontaneous bleeding frequently in a postoperative setting. Intensive perioperative use of factor VIII and some specific mutations induce a particularly high risk for inhibitor development, but risk factors are incompletely understood. For reasons of the older age of the patients, treatment of bleeding with bypassing agents may cause major thrombotic complications. Data on therapeutic options for inhibitor eradication in patients with mild haemophilia are particularly scarce. With increased life-expectancy for all haemophilia patients, the group of elderly patients with mild haemophilia requiring major surgery will further increase. Prevention of inhibitors, particularly in this patient group, should be a major topic of interest in both clinic and research. [source]

Ethanol lock therapy for the treatment of catheter-related infections in haemophilia patients

HAEMOPHILIA, Issue 6 2009
M. RAJPURKAR
Summary., Central venous access devices (CVAD) are increasingly being used for optimal delivery of clotting factor concentrates in patients with haemophilia with poor peripheral venous access. The utility of CVAD is particularly well recognized in young patients starting factor prophylaxis and in patients with inhibitors undergoing immune tolerance induction (ITI). A catheter-related infection (CRI) remains the most common complication of CVAD in haemophilia patients and is the most frequent indication for its removal. Additionally, in some patients the infection results in significant morbidity and mortality and also contributes to failure of the ITI regimen. Ethanol-lock therapy (ELT) is a treatment modality that has been used to treat CRI in patients with indwelling catheters for home parenteral nutrition and chemotherapy. The aim of this study was to report the success in treating CRI in haemophilia patients using ELT. Three severe haemophilia A patients undergoing ITI regimen who developed CVAD infections resistant to conventional management with antibiotics were treated by ELT according to the institutional technique. All three patients responded well to ELT with clearance of the CVAD infection. There were no adverse side effects. To our knowledge, this is the first report of ELT in patients with haemophilia. The role of ELT needs to be investigated in larger studies for treatment of CRI in patients with bleeding disorders. [source]

Cost minimization analysis to compare activated prothrombin complex concentrate (APCC) and recombinant factor VIIa for haemophilia patients with inhibitors undergoing major orthopaedic surgeries

HAEMOPHILIA, Issue 5 2009
P. O. BONNET
Summary., Benefits of bypassing agents for maintaining haemostasis in major surgeries have been described in the literature; however, their use has a substantial economic impact. This study assessed the cost of FEIBA, an activated prothrombin complex concentrate and recombinant factor VIIa (rFVIIa) when used in inhibitor patients undergoing major surgeries. After reviewing published literature, a cost minimization model was developed describing dosing regimens recommended and used during major surgeries for FEIBA (pre-operative: 75,100 U kg,1; postoperative: 75,100 U kg,1 q 8,12 h days 1,5 and 75,100 U kg,1 q 12 h days 6,14) and rFVIIa (pre-operative: 90 ,g kg,1; intra-operative: 90 ,g kg,1 q 2 h; postoperative: 90 ,g kg,1 q 2,4 h days 1,5 and 90 ,g kg,1 q 6 h days 6,14). Using a 75 kg patient and US prices, total drug cost was calculated for three scenarios: use of FEIBA or rFVIIa alone and a third case combining rFVIIa pre- and intra-operative and FEIBA throughout a 14-day postoperative period. Dosage amounts of modelled bypassing agents were similar to cases in the literature. Using FEIBA instead of rFVIIa would decrease total drug cost by >50% and save over $400 000 per surgery. Sequential use of both bypassing agents would increase total drug cost by 9% when compared with FEIBA alone, but would remain >40% lower than rFVIIa alone. Univariate sensitivity analyses confirmed robustness of results. As large amounts of bypassing agents are necessary for patients with inhibitors to undergo major surgeries, cost is a major consideration. Use of FEIBA alone or in combination with rFVIIa has emerged as a cost-saving approach. [source]

Co-morbidity in the ageing haemophilia patient: the down side of increased life expectancy

The benefits of prophylactic treatment with APCC in patients with haemophilia and high-titre inhibitors: a retrospective case series

HAEMOPHILIA, Issue 3 2009
L. A. VALENTINO
Summary., Prophylactic infusion of factor concentrates is a safe, effective intervention for preventing arthropathy in patients with haemophilia; on-demand treatment is insufficient to prevent the orthopaedic complications and subsequent haemophilic arthropathy that stem from recurrent joint haemorrhages. The usefulness of prophylaxis in haemophilia patients without inhibitors suggests that patients with haemophilia and inhibitors could derive similar benefits. In patients with haemophilia and high-titre (>5 BU mL,1) inhibitors, bleeding episodes are treated with bypassing agents such as activated prothrombin complex concentrates (APCCs) and recombinant activated factor VII (rFVIIa, NovoSeven®; Novo Nordisk A/S, Bagsvaerd, Denmark). It is possible to administer bypassing therapy regularly to prevent haemorrhages, with the goal of limiting arthropathy and serious life- and limb-threatening bleeding. The data evaluating the efficacy and safety of this approach in patients with inhibitors are limited, consisting of results from one prospective trial and retrospective case reports. This report describes our experience with the prophylactic use of the APCC Factor Eight Inhibitor Bypassing Activity, Anti-Inhibitor Coagulant Complex, Vapor Heated (FEIBAÔ; Baxter AG, Vienna, Austria). Data from patients at one treatment centre were retrospectively evaluated. Case records of six patients with haemophilia A or B and high-titre inhibitors were identified. When APCC was administered regularly, most patients exhibited a reduction in the numbers of haemorrhages, an improvement in orthopaedic status, and an improvement in quality of life. Prophylaxis with APCC can reduce haemorrhages and halt further joint deterioration in patients with haemophilia and inhibitors. [source]

Efficacy of recombinant activated factor VII vs. activated prothrombin complex concentrate for patients suffering from haemophilia complicated with inhibitors: a Bayesian meta-regression

HAEMOPHILIA, Issue 2 2009
M. J. TREUR
Summary., The optimal on-demand treatment of joint bleeds in haemophilia patients with inhibitors is a source of debate, with studies reporting various efficacy levels for different drugs and dosage regimens. To analyse, in a unified Bayesian meta-regression model, the published efficacy of recombinant activated factor VII (rFVIIa) and/or activated prothrombin complex concentrate (aPCC) as on-demand treatments for joint bleeds in haemophilia patients with inhibitors. A systematic search was carried out to identify studies reporting on dosage and efficacy of rFVIIa and aPCC in the treatment of joint bleeds in the target patient population. Data were abstracted and included in the model and adjusted for potential sources of heterogeneity. Pooled efficacy levels for typical rFVIIa and aPCC regimens were estimated. Seventeen studies, collectively reporting on >2000 joint bleeds, were included. Medication type combined with dosage was the only significant explanatory parameter. The model predicts that a typical regimen of 90 ,g kg,1 rFVII repeated every 3 h if needed results in cumulative joint bleed resolution of 66%, 88% and 95% after 12, 24 and 36 h, respectively. In comparison, a typical regimen of 75 IU kg,1 aPCC repeated every 12 h if needed results in cumulative joint bleed resolution of 39%, 62% and 76%, respectively. These differences were statistically significant and were also robust in sensitivity analyses. This analysis suggests that a typical rFVIIa regimen will resolve joint bleeds more effectively than a typical aPCC regimen after 12, 24 and 36 h. [source]

Differential response to bypassing agents complicates treatment in patients with haemophilia and inhibitors

HAEMOPHILIA, Issue 1 2009
E. 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 outcome of moderate haemophilia compared with severe and mild haemophilia

HAEMOPHILIA, Issue 1 2009
I. E. M. DEN UIJL
Summary., Information on outcome and treatment of patients with moderate haemophilia is scarce. In this study, we compared self-reported burden of disease in moderate haemophilia to severe and mild haemophilia. A nationwide questionnaire on bleeding pattern, treatment, impairment and quality of life was sent to 1567 Dutch patients with haemophilia. Out of 1066 respondents (response rate: 68%), 16% had moderate, 44% severe and 39% mild haemophilia. Median age was 36 years. Although overall outcome in moderate haemophilia was in between severe and mild haemophilia, moderate haemophilia patients did report a substantial burden of disease. The majority of patients with moderate haemophilia (73%) reported bleeds in the previous year; and a considerable proportion of moderate patients reported joint impairment (43%), chronic pain (15%), needed orthopaedic aids (24%) or were unemployed because of disability (27%). Within the group of moderate haemophilia patients, a large variation in bleeding pattern and outcome was observed. A quarter of patients with moderate haemophilia reported a more severe phenotype and intermittent use of prophylaxis. These patients reported frequent bleeding, with a median of eight bleeds per year, including two joint bleeds, and 68% reported joint impairment. In conclusion: Although outcome in moderate haemophilia is generally in between severe and mild haemophilia, moderate haemophilia patients reported a substantial burden of disease, and for more than 25% of patients with moderate haemophilia long term prophylaxis was implemented because of frequent bleeds. [source]

Haemophilia care then, now and in the future

HAEMOPHILIA, Issue 2009
J. OLDENBURG
Summary., Epidemiological data show the benefits of dramatically improved haemophilia care in all life-stages. There are improved administration techniques and dosing regimens, a shift from on-demand treatment to prophylaxis, successful treatment protocols for immune tolerance induction in patients with inhibitors and enhanced approaches to overall patient management. Improvements also include the introduction of virus inactivation methods for plasma derived clotting factor concentrates and the development of recombinant factor VIII therapy, which practically eliminated the risk of infectious disease transmission. Recombinant factor concentrates are recommended as treatment of choice by several guidelines today. All these developments have resulted in increased health-related quality of life and life expectancy in haemophilia patients, who are transitioning from childhood to adulthood with healthy joints and an overall healthy status today. Because of increased life expectancy, these patients are expected to experience age-related clinical problems that were not previously observed in this population. With respect to this, the spectrum of haemophilia care will be extended to diseases of older ages with the need of including further disciplines in comprehensive haemophilia care programmes. Despite these advances, the short half-life of factor VIII, requiring re-administration every 2 or 3 days and the development of inhibitors remains a challenge. Bayer's research and development currently focuses on the optimization of recombinant coagulation factors to address these challenges. Haemophilia care has experienced significant improvements within the past decades. Novel technologies and continued clinical research have facilitated the development of treatment regimen that resulted in dramatic increases in the life expectancy and quality of life of haemophilia patients. To set the scene for the following papers dealing with haemophilia care from paediatrics to geriatrics, developments behind these improvements and some aspects of future research will be presented in this paper. [source]

Obesity: a new disaster for haemophilic patients?

HAEMOPHILIA, Issue 5 2008
A nationwide survey
Summary., The prevalence of obesity, an important risk factor for both cardiovascular disease and arthropathy, is strongly increasing in the general population, but data for the haemophilia population are scarce. Obesity may have a more profound effect on arthropathy and on cardiovascular disease in patients with haemophilia. To assess the prevalence of obesity in haemophilia patients and install adequate measures, if necessary. We performed a nationwide postal survey to measure the prevalence of overweight and obesity in Dutch haemophilia patients in 1992 (n = 980) and 2001 (n = 1066). A random sample of the Dutch male population served as the control group. In adult haemophiliacs, the prevalence of overweight (BMI 25,30 kg m,2) increased from 27% to 35% (95% CI 31.1,38.0) and the prevalence of obesity (BMI ,30 kg m,2) doubled from 4% to 8% (95% CI 6.0,10.1), which was comparable with the general population. The increased prevalence of obesity in boys with haemophiliacs, which tripled in 10 years, is alarming. The increased prevalence of overweight and obesity in patients with haemophilia may have a profound effect on morbidity and quality of life of haemophilia patients by aggravating pre-existing arthropathy and predisposing aged patients to cardiovascular disease. Measures to prevent overweight in haemophiliacs are therefore urgently needed. [source]

Recombinant activated factor VII for haemophilia patients with inhibitors undergoing orthopaedic surgery: a review of the literature

HAEMOPHILIA, Issue 2 2008
A. 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]

Low-dose immune tolerance induction for paediatric haemophilia patients with factor VIII inhibitors

HAEMOPHILIA, Issue 2 2008
A. UNUVAR
Summary., The development of an inhibitor against factor VIII (FVIII) is a serious complication in children with haemophilia A. Immune tolerance induction (ITI) therapy is generally considered to be the best approach to eradicate the inhibitor. In this paper, the low-dose (,50 IU kg,1 twice or three times weekly with plasma-derived factor concentrates) ITI regimen used in Turkey is discussed. This regimen was given to 21 haemophilia A patients with high titer inhibitors. The median age at the beginning of ITI was 9 years and exposure days were 25. The median pre-ITI historical peak inhibitor titer, and inhibitor titer when ITI started were 80 BU (range 6.0,517), 19.2 BU (range 3.6,515), respectively. Complete immune tolerance was defined as the time at which at least two negative inhibitor assays was obtained with no anamnestic response. Our two cases were not reached in follow-up period. Immune tolerance could be achieved in 5 of 19 (26.3%) patients within a median time of 6 months. Partial tolerance was obtained in 7 patients while treatment failed in spite of significant decreased inhibitor levels in the other patients. A relapse developed in one immune-tolerized patient, one year later. The level of inhibitor titer at the beginning of ITI (,10 BU), the pre-ITI historical peak inhibitor titer (<50 BU), and the time between the first diagnosis inhibitor to starting ITI (<12 months) were main factors in the success (complete or partial tolerance) of ITI. In conclusion, the outcome of low-dose ITI protocol was not satisfactory in this retrospective study. [source]

Effect of recombinant factor VIIa variant (NN1731) on platelet function, clot structure and force onset time in whole blood from healthy volunteers and haemophilia patients

HAEMOPHILIA, Issue 5 2007
D. F. BROPHY
Summary., NN1731 is a novel variant of recombinant factor VIIa (rFVIIa) that binds to activated platelets, but has greater enzymatic activity than rFVIIa in generating FXa and thrombin. The effect of NN1731 on clot structure and platelet function was characterized ex vivo in whole blood from healthy volunteers and haemophilic patients. Blood samples from six healthy volunteers, nine haemophilia A patients with and without inhibitors and one acquired haemophilia A patient, were spiked with increasing concentrations (0.32, 0.64 and 1.28 ,g mL,1) of rFVIIa and NN1731. Platelet contractile force (PCF) or platelet function, clot elastic modulus (CEM) or clot structure, and force onset time (FOT) or the thrombin generation time (TGT) were determined using the Hemodyne Hemostasis Analysis System (HASÔ). Baseline PCF, CEM and FOT values in patients were abnormal compared to healthy volunteers' baseline values. Overall, haemophilia blood samples with or without inhibitors spiked with NN1731 had significantly greater PCF, CEM and shorter FOT values relative to samples spiked with corresponding doses of rFVIIa. The variability in response to treatment between patients was greater with rFVIIa compared to NN1731. At 1.28 ,g mL,1 (90 ,g kg,1), NN1731 normalized PCF, CEM and FOT in nine of 10 patients, while rFVIIa normalized these parameters in four of 10 patients. Increasing in vitro concentrations of NN1731 normalized platelet function, clot structure and thrombin generation consistently in haemophilia blood with or without inhibitors. NN1731 may be a promising haemostatic agent for patients with bleeding disorders. These results should be confirmed in an in vivo study. [source]

European Study on Orthopaedic Status of haemophilia patients with inhibitors

HAEMOPHILIA, Issue 5 2007
M. MORFINI
Summary., ,Development of inhibitors against factor VIII (FVIII) or factor IX (FIX) in haemophilia patients is one of the most serious complications of repeated exposure to replacement therapy and has major clinical and economic consequences. To evaluate the relationship between inhibitor status of haemophilia patients and their quality of life (QoL) and degree of arthropathy and to compare the orthopaedic status of patients with/without inhibitors. An observational, cross-sectional, case control study enrolling: group A (n = 38), males aged 14,35 years, with severe congenital haemophilia A or B who had inhibitors against FVIII/FIX >5 years; group B (n = 41), as group A, but aged 36,65 years and group C (n = 49), as group A, but without inhibitors. Socio-demographics: medical history, clinical characteristics and QoL were assessed. In groups A and B, 16% and 27% were hospitalized for orthopaedic procedures vs. 4% in group C. Patient mobility was also severely reduced in groups A and B, with 24% and 22% using wheelchairs vs. 4% in group C, and 50% and 51% needing a walking aid vs. 29% in group C. Significantly more joint pain was reported by patients in group A vs. those in group C; clinical/radiological orthopaedic scores were also worse in group A vs. group C. Significantly more joint abnormality was reported by patients in group A vs. group C. The burden of orthopaedic complications and the impact on QoL are more severe in haemophilia patients who have developed inhibitors than in those without inhibitors. [source]

Safety and efficacy of a sucrose-formulated recombinant factor VIII product for the treatment of previously treated patients with haemophilia A in China

HAEMOPHILIA, Issue 4 2007
J. 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]

Force fluctuations during the Maximum Isometric Voluntary Contraction of the quadriceps femoris in haemophilic patients

HAEMOPHILIA, Issue 1 2007
L.-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]

Treatment of chronic hepatitis C in patients with haemophilia: a review of the literature

HAEMOPHILIA, Issue 5 2006
D. POSTHOUWER
Summary., Chronic hepatitis C is a major cause of morbidity and mortality in haemophilia patients. In contrast to studies in the general population, the studies of antiviral therapy in haemophilia patients are limited and often include small numbers of patients. A review of the literature was performed to assess the efficacy of interferon (IFN)-based therapy for patients with haemophilia chronically infected with hepatitis C virus (HCV). Studies were identified by electronic searches (Medline, Embase) and hand searches in references of key articles. Data of the included studies were pooled, and responses to therapy were stratified according to treatment regimen, HIV co-infection status, and treatment history. The main outcome was a sustained virological response (SVR) defined as absence of HCV RNA both at the end of treatment and 24-week post-treatment. Thirty-five studies were identified that included 1151 patients. After pooling the data of included patients, the SVR in HIV-negative treatment naïve patients was 22% for IFN monotherapy, 43% for IFN and ribavirin, and 57% for pegylated IFN and ribavirin, respectively. Re-treatment with IFN and ribavirin of those who failed to respond to previous IFN monotherapy was successful in 33%. In HCV/HIV-coinfected patients, response to IFN monotherapy was 8% and to IFN combined with ribavirin 39%. Responses to IFN-based therapy in patients with haemophilia have been improved over time and are nowadays approximately 50,60%. However, data on haemophilic HCV/HIV-coinfected patients and in patients who failed to respond to previous therapy are limited and future studies in these specific patient population are necessary. [source]

Considerations in the evaluation of haemophilia patients for short-term prophylactic therapy: a paediatric and adult case study

HAEMOPHILIA, Issue 1 2006
L. LUCHTMAN-JONES
Summary., The long-term prophylactic administration of clotting factor concentrate in patients with haemophilia reduces bleeding events, slows joint deterioration, and improves quality of life. Prophylaxis can also be effective when used short-term to prevent or reduce bleeding associated with trauma, surgery, and athletic activities. While clinical trials are needed to establish the optimal length of prophylaxis following injury, several weeks and possibly months of treatment may be needed. Discontinuing therapy prematurely can result in rebleeding in the injured area. [source]

Identifying and managing inhibitor patients requiring orthopaedic surgery , the multidisciplinary team approach

HAEMOPHILIA, Issue 2005
C. LUDLAM
Summary., Until recently, surgery in haemophilia patients with inhibitors was strongly contraindicated and was therefore often not even contemplated. Inhibitor patients entering the surgical arena face unique challenges; the most frequently encountered problem during surgical intervention is bleeding, and thrombosis is occasionally observed. The activated prothrombin complex concentrate, FEIBATM, and recombinant activated factor VII (rFVIIa) are available as haemostatic cover during surgery. The use of rFVIIa enables inhibitor patients to undergo orthopaedic surgery with an expectation of success, and results are generally good. An organized team approach is critical to this success. However, further information is required to enable different procedures to be optimized in terms of both outcome and safety. [source]

Variability in clinical phenotype of severe haemophilia: the role of the first joint bleed

HAEMOPHILIA, Issue 5 2005
K. van Dijk
Summary., To quantify variation in clinical phenotype of severe haemophilia we performed a single centre cohort study among 171 severe haemophilia patients. Age at first joint bleed, treatment requirement (i.e. annual clotting factor use), annual bleeding frequency and arthropathy were documented. Because treatment strategies intensified during follow-up, patients were stratified in two age groups: patients born 1968,1985 (n = 91), or 1985,2002 (n = 80). A total of 2166 patient-years of follow-up were available (median 12.0 years per patient). Age at first joint bleed ranged from 0.2 to 5.8 years. Patients who had their first joint bleed later needed less treatment and developed less arthropathy. In patients born 1968,1985 during both on-demand and prophylactic treatment, the 75th percentile of annual joint bleed frequency was consistently four times as high as the 25th percentile. In both age groups variation in annual clotting factor use between 25th and 75th percentiles was 1.4,1.5 times for prophylaxis and 3.8 times for on-demand treatment. To conclude, the onset of joint bleeding is inversely related with treatment requirement and arthropathy and may serve as an indicator of clinical phenotype. Thus, providing a starting point for aetiological research and individualization of treatment. [source]

Helicobacter pylori infection in patients with haemophilia in Poland: prevalence and risk of upper gastrointestinal bleeding

HAEMOPHILIA, Issue 4 2005
A. B. Szczepanik
Summary., Infection with Helicobacter pylori is the main aetiological factor for erosive gastritis and duodenal or gastric peptic ulcers often complicated with life-threatening bleeding in patients with coagulation disorders. The aim of this prospective study was to evaluate the prevalence of Helicobacter pylori infection in haemophilia patients, and to assess the risk of gastrointestinal bleeding associated with this infection. From 2000 to 2002, 146 patients with haemophilia (129, haemophilia A; 13, haemophilia B), mean age, 39.9 years (±7.3), were investigated for H. pylori infection using IgG and IgA latex serological test. The control group included 100 men with no coagulation disorders, mean age, 40.9 years (±9.2). For 72 (49.3%) patients with haemophilia and 39 controls (39.0%) serological tests were positive indicating the presence of H. pylori infection (P =0.1112). A history of gastrointestinal bleeding was reported in 46 patients (31.5%) with haemophilia and in two control group patients (2.0%) (P < 0.0001). Gastrointestinal bleeding was significantly more frequent in patients with haemophilia infected with H. pylori (33/46; 71.7%) than in patients with no H. pylori infection (13/46; 28.3%; P = 0.0002). In conclusion, the prevalence of H. pylori infection in haemophilic patients in Poland is comparable with that in patients with no coagulation disorders. Helicobacter pylori infection is a risk factor for duodenal and gastric ulcer bleeding in haemophilia patients. In view of the high frequency of upper gastrointestinal bleeding associated with H. pylori infection, we believe that screening and eradication therapy are appropriate in haemophilia patients. [source]

Bone properties and muscle strength of young haemophilia patients

HAEMOPHILIA, Issue 4 2005
B. Falk
Summary., Purpose:, To evaluate bone properties, muscle strength and the relationship between the two, in young (7.0,17.7 years) haemophilia patients (h) and healthy boys (c). Subjects:, Twenty-seven boys with severe haemophilia and 33 healthy boys, of similar age, body mass, height, (mean ± sd for h and c, respectively: 11.2 ± 3.2 vs. 11.4 ± 2.9 years, 42.6 ± 16.6 vs. 41.6 ± 17.3 kg, 145 ± 18 vs. 146 ± 17 cm) and pubertal stage according to secondary sex characteristics, volunteered for the study. all subjects were physically inactive (as determined by questionnaire). Methods:, Subjects performed isokinetic elbow and knee extension and flexion tests at two angular velocities (biodex system ii dynamometer). Bone properties were evaluated by qualitative ultrasound (sunlight omnisenseTM), at the distal radius and tibial mid-shaft. H subjects received prophylactic factor viii treatment within the 24 h preceding testing. No test was performed in the presence of haemorrhage. Results:, Muscle strength was consistently higher in c compared with h, especially in the lower limbs (e.g. knee extension: 1.80 ± 0.44 vs 1.48 ± 0.53 N·m·kg,1 body mass, respectively, p = 0.01). No differences were observed in tibial or radial speed of sound between groups. Correlations between muscle strength and bone properties were observed only in the lower limbs and only in c (r = 0.37,0.48). Conclusion:, Muscle strength, especially lower limbs' strength, was lower in haemophilia patients compared with a matched, similarly inactive population of healthy boys. Nevertheless, at this age range, this relative weakness is not associated with inferior bone properties. [source]