The effects of postponing prophylactic treatment on long-term outcome in patients with severe hemophilia.
TL;DR: The effect of postponing prophylaxis on long-term arthropathy was studied in a cohort of 76 patients with severe hemophilia born between 1965 and 1985, finding that most patients have their first joint bleed after the age of 2 years.
About: This article is published in Blood.The article was published on 2002-04-01. It has received 250 citations till now. The article focuses on the topics: Arthropathy & Hemarthrosis.
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TL;DR: These evidence‐based guidelines offer practical recommendations on the diagnosis and general management of hemophilia, as well as the management of complications including musculoskeletal issues, inhibitors, and transfusion‐transmitted infections.
Abstract: Hemophilia is a rare disorder that is complex to diagnose and to manage. These evidence-based guidelines offer practical recommendations on the diagnosis and general management of hemophilia, as well as the management of complications including musculoskeletal issues, inhibitors, and transfusion-transmitted infections. By compiling these guidelines, the World Federation of Hemophilia aims to assist healthcare providers seeking to initiate and/or maintain hemophilia care programs, encourage practice harmonization around the world and, where recommendations lack adequate evidence, stimulate appropriate studies.
1,733 citations
Cites background from "The effects of postponing prophylac..."
...An increased number of arthropathic joints, loss of joint movement, and muscle atrophy leading to inactivity are associated with a lower BMD [27]....
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...Bone mineral density (BMD) is decreased in people with hemophilia [26,27]....
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TL;DR: The WFH Guidelines for the Management of Hemophilia panelists and co-authors thank the panelists for their time and share their views on how to better understand and treat hemophilia.
Abstract: Alok Srivastava 1 | Elena Santagostino 2 | Alison Dougall 3 | Steve Kitchen 4 | Megan Sutherland 5 | Steven W. Pipe 6 | Manuel Carcao 7 | Johnny Mahlangu 8 | Margaret V. Ragni 9 | Jerzy Windyga 10 | Adolfo Llinás 11 | Nicholas J. Goddard 12 | Richa Mohan 13 | Pradeep M. Poonnoose 14 | Brian M. Feldman 15 | Sandra Zelman Lewis 16 | H. Marijke van den Berg 17 | Glenn F. Pierce 18 | on behalf of the WFH Guidelines for the Management of Hemophilia panelists and co-authors*
751 citations
TL;DR: The once-in-a-lifetime opportunity to assess the importance of knowing the carrier and removal status of canine coronavirus in the context of thrombosis and haemostasis is presented.
504 citations
TL;DR: Prophylaxis was more effective when started early (≤36 months), with patients having fewer joint bleeds and arthropathy in children with hemophilia, particularly when it is initiated early in life.
397 citations
Patent•
06 May 2004TL;DR: In this article, the first and second polypeptide chains were used to construct a chimeric monomer-dimer hybrid protein with a biologically active molecule in the first chain.
Abstract: The invention relates to a chimeric monomer-dimer hybrid protein wherein said protein comprises a first and a second polypeptide chain, said first polypeptide chain comprising at least a portion of an immunoglobulin constant region and a biologically active molecule, and said second polypeptide chain comprising at least a portion of an immunoglobulin constant region without the biologically active molecule of the first chain. The invention also relates to methods of using and methods of making the chimeric monomer-dimer hybrid protein of the invention.
310 citations
References
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TL;DR: In this article, an extension of generalized linear models to the analysis of longitudinal data is proposed, which gives consistent estimates of the regression parameters and of their variance under mild assumptions about the time dependence.
Abstract: SUMMARY This paper proposes an extension of generalized linear models to the analysis of longitudinal data. We introduce a class of estimating equations that give consistent estimates of the regression parameters and of their variance under mild assumptions about the time dependence. The estimating equations are derived without specifying the joint distribution of a subject's observations yet they reduce to the score equations for multivariate Gaussian outcomes. Asymptotic theory is presented for the general class of estimators. Specific cases in which we assume independence, m-dependence and exchangeable correlation structures from each subject are discussed. Efficiency of the proposed estimators in two simple situations is considered. The approach is closely related to quasi-likelih ood. Some key ironh: Estimating equation; Generalized linear model; Longitudinal data; Quasi-likelihood; Repeated measures.
17,111 citations
TL;DR: It appears to be possible to prevent haemophilic arthropathy by giving effective continuous prophylaxis from an early age, and preventing the VIII:C or IX:C concentration from falling below 1% of normal.
Abstract: In Sweden, prophylactic treatment of boys with severe haemophilia has been practised since 1958 in an attempt to convert the disease from a severe to a milder form. The present study population consisted of 60 severe haemophiliacs (52 A, 8 B), aged 3-32 years. Treatment is started when the boys are 1-2 years of age, the regimens used being 24-40 IU F VIII kg-1 three times weekly in haemophilia-A cases (i.e. greater than 2000 IU kg-1 annually) and 25-40 IU F IX kg-1 twice weekly in haemophilia-B cases. The orthopaedic and radiological joint scores (maximum scores of 90 and 78, respectively) are evaluated as recommended by the World Federation of Haemophilia. Of those subjects aged 3-17 years, 29 out of 35 individuals had joint scores of zero. The oldest group had only minor joint defects. The VIII:C and IX:C concentrations had usually not fallen below 1% of normal. All 60 patients are able to lead normal lives. In conclusion, it appears to be possible to prevent haemophilic arthropathy by giving effective continuous prophylaxis from an early age, and preventing the VIII:C or IX:C concentration from falling below 1% of normal.
928 citations
"The effects of postponing prophylac..." refers background in this paper
...Last Pettersson score (maximum 78) 0 (0-2) 5 (3-13) 7 (0-17) 8 (4-14)...
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...5 (0-1) 11 (7-13) 32 (24-42) 100 (81-132)...
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...Clinical score (maximum 90)* 1 (0-2) 3 (1-5) 5 (2-8)...
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...of joint bleeds before start of prophylaxis 16 (5-44)...
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TL;DR: It is hypothesized that no direct relationship exists between increasing factor dosage and orthopaedic outcomes over time and optimal therapeutic regimens for persons with haemophilia are established.
Abstract: . Objective. Arthropathy is the major cause of morbidity in haemophilia. In an attempt to establish optimal therapeutic regimens for persons with haemophilia, we hypothesized that no direct relationship exists between increasing factor dosage and orthopaedic outcomes over time.
Design. A longitudinal uncontrolled 6 year study was carried out. Ankles, knees and elbows of patients were studied using physical and X-ray examination scores. Bleeding episodes and treatment regimens were determined. The amount of time lost from work and school, as well as days in hospital, was also monitored.
Setting. Twenty-one international haemophilia centres were used to accrue and follow patients over the 6 year period.
Subject. Severe (< 1 %) factor VIII deficient patients under the age of 25 without inhibitors were recruited into the study.
Intervention. The status of the six major joints of these patients were measured annually for mobility. X-ray evaluation of these joints was carried out at the beginning and end of the study. Using a World Federation of Haemophilia joint and X-ray score, stability, progression or regression of arthropathy was evaluated.
Results. Physical and X-ray examination scores increased significantly with age, and the number of joint bleeds were significant in determining the Δ score. Approximately 10% of patients entered with all six joints normal. Of these, 50% remained so. Year-long prophylaxis significantly reduced the rate at which joints deteriorate both on physical (P = 0.02) and X-ray examination (P = < 0.001). Patients on prophylaxis had significantly fewer days lost from work or school, as well as fewer days spent in hospital (P = < 0.01).
Conclusions. Higher doses of factor per se do not necessarily produce improved orthopaedic outcomes. However, full time prophylaxis is likely to produce the best orthopaedic outcome. The most critical factor for a good orthopaedic outcome is the reduction of joint bleeds.
608 citations
Additional excerpts
...Last Pettersson score (maximum 78) 0 (0-2) 5 (3-13) 7 (0-17) 8 (4-14)...
[...]
...Clinical score (maximum 90)* 1 (0-2) 3 (1-5) 5 (2-8)...
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...Clinical score (maximum 90)* 0 (0-1) 2 (0-5) 4 (1-6) 4 (0-5)...
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TL;DR: To review long‐term prophylactic factor treatment in young patients with severe haemophilia A and B, focusing on the orthopaedic and radiological outcome.
Abstract: Objectives. To review long-term prophylactic factor treatment in young patients with severe haemophilia A and B, focusing on the orthopaedic and radiological outcome.
Design. We received 34 patients with severe haemophilia A (n=29) and B (n=5), aged 7–22 years. Age at start of treatment was 1–4.5 years. Dosages of factor concentrate (F VIII and F IX, respectively) were 25–40 IU/kg body weight, three times a week for haemophilia A and twice a week for haemophilia B. The patients had been checked annually over a 5-year period (1990–95). Orthopaedic and radiological joint scores were evaluated according to recommendations by the World Federation of Haemophilia.
Setting. All results were obtained at the Department for Coagulation Disorders, University of Lund, Malmo University Hospital, Malmo, Sweden.
Results. Orthopaedic and radiological joint scores were found to have remained unchanged during follow-up in almost all patients and to be still zero (i.e. no unaffected joints) in 79% (n=27) of the patients.
Conclusion. There is a growing international consensus haemophilic arthropathy can be prevented by administering early high-dose prophylaxis. The results of the present investigation strongly support this opinion.
327 citations
"The effects of postponing prophylac..." refers methods in this paper
...Clinical score (maximum 90)* 1 (0-2) 3 (1-5) 5 (2-8)...
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...Clinical score (maximum 90)* 0 (0-1) 2 (0-5) 4 (1-6) 4 (0-5)...
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...Therefore, we used (1) the age at start of prophylaxis and (2) the time between the first joint bleed and the start of prophylaxis as additional indicators of treatment delay....
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TL;DR: The frequency of joint bleeds and orthopaedic joint scores were evaluated in 121 patients with severe haemophilia who had started prophylactic treatment with clotting factor concentrates at least once weekly before the age of 10.
Abstract: The frequency of joint bleeds and orthopaedic joint scores were evaluated in 121 patients with severe haemophilia who had started prophylactic treatment with clotting factor concentrates at least once weekly before the age of 10. 75 of the patients started before the age of 3, 31 at the age of 3-5 and 15 at the age of 6-9. Each subgroup was evaluated separately. In addition, a regimen of one infusion weekly was compared with that of two (haemophilia B) or three (haemophilia A) infusions weekly in each patient. A significant decrease in the overall number of joint bleeds per year was found after shortening the infusion interval (P<0.005), but the individual bleeding pattern varied. In survival analysis of the first pathologic joint score event, those who started prophylaxis before the age of 3 had a better outcome overall than those starting at later ages (P=0.001). However, in subgroup analysis, no significant difference was seen in the annual number of joint bleeds and the development of arthropathy between those starting with, or shifting to, the more intensive regimen before the age of 3 and those that were put on this regimen at the age of 3-5. Age at start of prophylaxis was found to be an independent predictor for the development of arthropathy (P=0.0002), whereas dose and infusion interval at start were not. Our data emphasize the importance of starting replacement therapy during the first years of life. However, it seems that when beginning the regimen it can be individualized and adjusted according to the bleeding pattern. In this way, the need for a venous access system may be assessed on an individual basis.
267 citations
"The effects of postponing prophylac..." refers background in this paper
...Last Pettersson score (maximum 78) 0 (0-2) 5 (3-13) 7 (0-17) 8 (4-14)...
[...]
...Clinical score (maximum 90)* 1 (0-2) 3 (1-5) 5 (2-8)...
[...]
...of joint bleeds before start of prophylaxis 16 (5-44)...
[...]
...Clinical score (maximum 90)* 0 (0-1) 2 (0-5) 4 (1-6) 4 (0-5)...
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