K Fischer

University Medical Center Utrecht, Utrecht, Utrecht, Netherlands

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Publications (172)655.85 Total impact

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    ABSTRACT: Objectives: The radiological Pettersson score (PS) is widely applied for classification of arthropathy to evaluate costly haemophilia treatment. This study aims to assess and improve inter- and intra-observer reliability and agreement of the PS. Methods: Two series of X-rays (bilateral elbows, knees, and ankles) of 10 haemophilia patients (120 joints) with haemophilic arthropathy were scored by three observers according to the PS (maximum score 13/joint). Subsequently, (dis-)agreement in scoring was discussed until consensus. Example images were collected in an atlas. Thereafter, second series of 120 joints were scored using the atlas. One observer rescored the second series after three months. Reliability was assessed by intraclass correlation coefficients (ICC), agreement by limits of agreement (LoA). Results: Median Pettersson score at joint level (PSjoint) of affected joints was 6 (interquartile range 3-9). Using the consensus atlas, inter-observer reliability of the PSjoint improved significantly from 0.94 (95 % confidence interval (CI) 0.91-0.96) to 0.97 (CI 0.96-0.98). LoA improved from ±1.7 to ±1.1 for the PSjoint. Therefore, true differences in arthropathy were differences in the PSjoint of >2 points. Intra-observer reliability of the PSjoint was 0.98 (CI 0.97-0.98), intra-observer LoA were ±0.9 points. Conclusions: Reliability and agreement of the PS improved by using a consensus atlas. Key points: • Reliability of the Pettersson score significantly improved using the consensus atlas. • The presented consensus atlas improved the agreement among observers. • The consensus atlas could be recommended to obtain a reproducible Pettersson score.
    European Radiology 09/2015; DOI:10.1007/s00330-015-4013-8 · 4.01 Impact Factor
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    ABSTRACT: Evidence about inhibitor formation in non-severe haemophilia and the potential role for clotting factor concentrate type is scant. It was the aim of this study to report inhibitor development in non-severe haemophilia patients enrolled in the European Haemophilia Safety Surveillance (EUHASS) study. Inhibitors are reported quarterly and total treated patients annually. Incidence rates and 95 % confidence intervals (95 % CI) were calculated according to diagnosis and concentrate used. Between 1–10–2008 and 31–12–2012, 68 centres reported on 7,969 patients with non-severe haemophilia A and 1,863 patients with non-severe haemophilia B. For haemophilia A, 37 inhibitors occurred in 8,622 treatment years, resulting in an inhibitor rate of 0.43/100 treatment years (95 % CI 0.30–0.59). Inhibitors occurred at a median age of 35 years, after a median of 38 exposure days (EDs; P25-P75: 20–80); with 72 % occurring within the first 50 EDs. In haemophilia B, one inhibitor was detected in 2,149 treatment years, resulting in an inhibitor rate of 0.05/100 years (95% CI 0.001–0.26). This inhibitor developed at the age of six years, after six EDs. The rate of inhibitors appeared similar across recombinant and plasma derived factor VIII (FVIII) concentrates. Rates for individual concentrates could not be calculated at this stage due to low number of events. In conclusion, inhibitors in non-severe haemophilia occur three times more frequently than in previously treated patients with severe haemophilia at a rate of 0.43/100 patient years (haemophilia A) and 0.05/100 years (haemophilia B). Although the majority of inhibitors developed in the first 50 EDs, inhibitor development continued with increasing exposure to FVIII.
    Thrombosis and Haemostasis 08/2015; 114(4). DOI:10.1160/TH14-12-1044 · 4.98 Impact Factor
  • W Foppen · I C van der Schaaf · K Fischer
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    ABSTRACT: Patients with haemophilia tend to bleed in large joints even during prophylactic replacement therapy. Detection of early blood-induced joint changes may improve monitoring of treatment. The aim of this study was to explore the value of routine ultrasound in detecting early joint abnormalities in children with haemophilia on prophylaxis. Sixty-four joints in 32 children with haemophilia were examined by one operator using the Haemophilia Early Arthropathy Detection with UltraSound protocol during annual multidisciplinary follow-up. Based on reported bleeding, the joint with the highest risk of blood-induced joint damage and the contralateral joint were examined. At the same day, clinical function was assessed according to the Haemophilia Joint Health Score (HJHS). Median age was 11.5 years (range = 5.5-16.4). Out of the 64 examined joints, one ankle was excluded because of previous surgery. Median lifetime joint bleeds/joint was three (interquartile ranges = 1-5). Clinical function of most joints was perfect: only 7/49 joints with reported bleeds scored positive due to swelling, muscle atrophy and/or range of motion loss (HJHS range = 1-2 points). Ultrasound showed abnormalities in 5/49 joints with reported bleeding, and 4/5 showed positive HJHS scores. Ultrasound abnormalities were present in 1/56 joints (1.8%, CI: 0.1-9.6%) without loss of clinical function. Ultrasound abnormalities were found during routine evaluation of joints in children with haemophilia on prophylaxis. Most joints with ultrasound abnormalities showed low HJHS scores too. Ultrasound could be used to evaluate whether minimal losses of clinical function might be caused by anatomical changes. © 2015 John Wiley & Sons Ltd.
    Haemophilia 07/2015; DOI:10.1111/hae.12769 · 2.60 Impact Factor
  • K Fischer · A Iorio · M Makris · A Gatt
    Haemophilia 07/2015; DOI:10.1111/hae.12764 · 2.60 Impact Factor
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    ABSTRACT: Haemophilia Joint Health Score (HJHS) is the most sensitive validated score for physical examination of joint health in haemophilia. HJHS performed at regular intervals can be used for clinical monitoring as well as for comparative outcomes research. To determine whether routinely collected HJHS could be used to compare outcome of three different prophylactic regimens in children with severe haemophilia A (primary) and which parameters caused variability in HJHS (secondary). International retrospective observational multi-centre study comparing routine HJHS in 127 children with severe haemophilia A born from 1995 to 2009, from London, Stockholm and Utrecht centres. Patient and treatment data were collected from the European Paediatric Network for Haemophilia Management registry and patient files. The independent effects of regimens, physiotherapists, age and inhibitor status on HJHS were explored, using multivariable regression analysis. Prophylaxis varied across participating centres, with differences in initial frequency of infusions (1× per week vs. 3× per week), age at reaching infusions ≥3× per week, and dose kg(-1) week(-1) at HJHS assessment. Evaluation at median age of 11 years showed an illogical association of HJHS with treatment regimen: the least intensive regimen had the lowest HJHS. The HJHS increased with age and history of inhibitor, as expected (internal validity). But the comparison of prophylactic regimens was obscured by systematic differences in assessment between physiotherapists, both within and between centres. Inter-physiotherapist discrepancies in routine HJHS hamper comparison of scores between treatment regimens. For multi-centre research, additional inter-observer standardization for HJHS scoring is needed. © 2015 John Wiley & Sons Ltd.
    Haemophilia 07/2015; DOI:10.1111/hae.12755 · 2.60 Impact Factor
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    ABSTRACT: Access to treatment and especially to long-term regular replacement treatment with clotting factor concentrates (prophylaxis) have caused dramatic contrasts in the clinical picture between haemophilia populations. An individual patient with severe haemophilia age 20 years can have normal joints or can be severely crippled and unable to work. Assessment of outcome in a standardized way has therefore become essential. Discuss the relevance and utility of the different outcome assessment tools in patient groups with different access to treatment. In the last decade new outcome assessment tools specific for haemophilia have been developed that measure all aspects of health according to the International Classification of Functioning, Disability and Health (ICF) model. These tools are directed at assessing the clinical and radiological status of joints as well as overall functioning, such as participation and psychosocial aspects, evaluating overall health-related quality of life (HRQOL). For deciding which tools to use in clinical practice or research, one needs to consider the specific context with regard to disease burden, healthcare environment and socioeconomic background of the patients being evaluated. Prospective systematic assessment of outcome in haemophilia and related bleeding disorders is important. Based upon recent literature a critical appraisal of outcome tools is described. © 2015 John Wiley & Sons Ltd.
    Haemophilia 06/2015; 21(4). DOI:10.1111/hae.12731 · 2.60 Impact Factor
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    ABSTRACT: Elderly patients with haemophilia (PWH) suffer from both haemarthrosis and haemophilic arthropathy (HA). Diagnosis of haemarthrosis in PWH is currently based on clinical presentation. No diagnostic protocols or validated criteria are available to identify haemarthrosis or to differentiate haemarthrosis from HA. The aim of this study is to identify symptoms and signs that can be used to differentiate haemarthrosis from HA. A narrative literature review was performed on symptoms associated with haemarthrosis and symptoms associated with HA. Additionally, literature on the diagnosis of haemarthrosis in patients without haemophilia, imaging techniques and biomarkers was searched. This review shows that there is no consensus about the symptoms associated with haemarthrosis and that there is limited literature about the symptoms associated with HA. Additionally, symptoms associated with haemarthrosis partly overlap with symptoms of HA, particularly those symptoms associated with flare-ups of HA. Due to the overlap in symptoms differentiating between these conditions is complex. Furthermore, differentiating based on imaging techniques or biomarkers causes practical difficulties. Despite the overlap in symptoms, differentiating between joint bleeds and flare-ups of HA based on clinical presentation still seems the most convenient and practical solution. Further research is necessary to identify specific symptoms that can be used to differentiate between the two conditions. © 2015 John Wiley & Sons Ltd.
    Haemophilia 04/2015; 21(3). DOI:10.1111/hae.12667 · 2.60 Impact Factor
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    ABSTRACT: Given the lifelong therapy in haemophilia patients, insight in non-adherence behaviour from a patient perspective is important to understand patients' difficulties with the following treatment recommendations. The aim of this study was to clarify the process underlying adherence (behaviour) to prophylactic treatment, from a patients' perspective. To develop a grounded theory, a qualitative study using individual in-depth interviews was performed to understand experiences, perceptions and beliefs concerning adherence to prophylaxis. From two Dutch treatment centres, 21 adults with haemophilia using prophylaxis were interviewed. Patients were asked how they experience their task to administer prophylaxis and how they adhere to this. The interviews were transcribed, coded and analysed in an iterative process, leading to the development of the grounded theory. Adherence was determined by the position of prophylaxis in life. The position of prophylaxis was determined by the perception of prophylaxis and the ability to exert prophylaxis. Patients' perception was influenced by two main factors: acceptance of haemophilia and feeling/fearing symptoms. The ability to exert prophylaxis was influenced by understanding haemophilia and prophylaxis and planning/infusion skills. The combination of different perceptions and skills led to four main positions of prophylaxis in life: (i) prophylaxis integrated in life, (ii) prophylaxis according to doctors' advice, struggling with irregular situations, (iii) prophylaxis is too much to handle, (iv) prophylaxis is a confrontation with illness. The adherence level gradually decreased from position 1 to 4. This information can be used to design tailored interventions to promote adherence. © 2015 John Wiley & Sons Ltd.
    Haemophilia 04/2015; DOI:10.1111/hae.12660 · 2.60 Impact Factor
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    ABSTRACT: Inhibitor development represents the most serious side effect of haemophilia treatment. Any difference in risk of inhibitor formation depending on the product used might be of clinical relevance. It was this study's objective to assess inhibitor development according to clotting factor concentrate in severe haemophilia A and B. The European Haemophilia Safety Surveillance (EUHASS) was set up as a study monitoring adverse events overall and according to concentrate. Since October 2008, inhibitors were reported at least quarterly. Number of treated patients was reported annually, specifying the number of patients completing 50 exposure days (Previously Untreated Patients, PUPs) without inhibitor development. Cumulative incidence, incidence rates and 95 % confidence intervals (CI) were calculated. Data from October 1, 2008 to December 31, 2012 were analysed for 68 centres that validated their data. Inhibitors developed in 108/417 (26 %; CI 22-30 %) PUPs with severe haemophilia A and 5/72 (7 %; CI 2-16) PUPs with severe haemophilia B. For Previously Treated Patients (PTPs), 26 inhibitors developed in 17,667 treatment years [0.15/100 treatment years (CI 0.10-0.22)] for severe haemophilia A and 1/2836 (0.04/100;(CI 0.00-0.20) for severe haemophilia B. Differences between plasma-derived and recombinant concentrates, or among the different recombinant FVIII concentrates were investigated. In conclusion, while confirming the expected rates of inhibitors in PUPs and PTPs, no class or brand related differences were observed.
    Thrombosis and Haemostasis 01/2015; 113(4). DOI:10.1160/TH14-10-0826 · 4.98 Impact Factor
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    ABSTRACT: - Copyright © 2014, Ferrata Storti Foundation.
    Haematologica 12/2014; 100(3). DOI:10.3324/haematol.2014.115709 · 5.81 Impact Factor
  • K Fischer
    Haemophilia 12/2014; 21(1). DOI:10.1111/hae.12586 · 2.60 Impact Factor
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    ABSTRACT: Health-related quality of life (HRQoL) assessment is recognized as an important outcome in the evaluation of different therapeutic regimens for persons with haemophilia. The Canadian Haemophilia Outcomes-Kids' Life Assessment Tool (CHO-KLAT) is a disease-specific measure of HRQoL for 4 to 18-year-old boys with haemophilia. The purpose of this study was to extend this disease-specific, child-centric, outcome measure for use in international clinical trials. We adapted the North American English CHO-KLAT version for use in five countries: France, Germany, the Netherlands, Spain and the United Kingdom (UK). The process included four stages: (i) translation; (ii) cognitive debriefing; (iii) validity assessment relative to the PedsQL (generic) and the Haemo-QoL (disease-specific) and (iv) assessment of inter and intra-rater reliability. Cognitive debriefing was performed in 57 boys (mean age 11.4 years), validation was performed in 144 boys (mean age 11.0 years) and reliability was assessed for a subgroup of 64 boys (mean age 12.0 years). Parents also participated. The mean scores reported by the boys were high: CHO-KLAT 77.0 (SD = 11.2); PedsQL 83.8 (SD = 11.9) and Haemo-QoL 79.6 (SD = 11.5). Correlations between the CHO-KLAT and PedsQL ranged from 0.63 in Germany to 0.39 in the Netherlands and Spain. Test-retest reliability (concordance) for child self-report was 0.67. Child-parent concordance was slightly lower at 0.57. The CHO-KLAT has been fully culturally adapted and validated for use in five different languages and cultures (in England, the Netherlands, France, Germany and Spain) where treatment is readily available either on demand or as prophylaxis. © 2014 John Wiley & Sons Ltd.
    Haemophilia 12/2014; 21(3). DOI:10.1111/hae.12597 · 2.60 Impact Factor
  • A. Nijdam · K. Kurnik · R. Liesner · R. Ljung · B. Nolan · P. Petrini · K. Fischer
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    ABSTRACT: To facilitate early prophylaxis, step-up regimens starting prophylaxis with infusions 1× week−1 were introduced. Choice of initial regimen may affect outcome. This study aims to classify initial prophylactic regimens and compare them on short-term outcome. From the ‘European Paediatric Network for Haemophilia Management' (PedNet) registry, patients with severe haemophilia A without inhibitors, born 2000–2012, receiving prophylaxis were included. Treatment centres were classified according to the initial frequency of prophylactic infusions and the age at reaching infusions ≥3× week−1. Bleeding, and central venous access device (CVAD) use were compared at age 4 years. In 21 centres with 363 patients, three regimens were identified: (i) start prophylaxis with ≥3× week−1 infusions before age three (full: 19% of centres, 18% of patients); (ii) start 1–2× week−1, increasing frequency as soon as possible (asap), reaching ≥3× week−1 before age three (43% of centres, 36% of patients); (iii) start 1–2× week−1, increasing frequency according to bleeding (phenotype), reaching ≥3× week−1 after age three (38% of centres, 46% of patients). Prophylaxis was started at median 1.2 years on the full and asap regimen vs 1.8 years on the phenotype regimen. Complete prevention of joint bleeds was most effective on the full regimen (32% full vs. 27% asap and 8% phenotype), though at the cost of using most CVADs (88% full vs. 34% asap and 22% phenotype). The three prophylaxis regimens identified had different effects on early bleeding and CVAD use. This classification provides the first step towards establishing the optimum prophylactic regimen.
    Haemophilia 12/2014; 21(4). DOI:10.1111/hae.12613 · 2.60 Impact Factor
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    ABSTRACT: Treatment of previously untreated patients (PUPs) with severe haemophilia A is complicated by the formation of inhibitors. Prediction of PUPs with high risk is important to allow altering treatment with the intention to reduce the occurrence of inhibitors. An unselected multicentre cohort of 825 PUPs with severe haemophilia A (FVIII<0.01 IU mL−1) was used. Patients were followed until 50 exposure days (EDs) or inhibitor development. All predictors of the existing prediction model including three new potential predictors were studied using multivariable logistic regression. Model performance was quantified [area under the curve (AUC), calibration plot] and internal validation (bootstrapping) was performed. A nomogram for clinical application was developed. Of the 825 patients, 225 (28%) developed inhibitors. The predictors family history of inhibitors, F8 gene mutation and an interaction variable of dose and number of EDs of intensive treatment were independently associated with inhibitor development. Age and reason for first treatment were not associated with inhibitor development. The AUC was 0.69 (95% CI 0.65–0.72) and calibration was good. An improved prediction model for inhibitor development and a nomogram for clinical use were developed in a cohort of 825 PUPs with severe haemophilia A. Clinical applicability was improved by combining dose and duration of intensive treatment, allowing the assessment of the effects of treatment decisions on inhibitor risk and potentially modify treatment.
    Haemophilia 12/2014; 21(2). DOI:10.1111/hae.12566 · 2.60 Impact Factor
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    ABSTRACT: Introduction and hypothesis: To predict who will undergo midurethral sling surgery (surgery) after initial pelvic floor muscle training (physiotherapy) for stress urinary incontinence in women. Methods: This was a cohort study including women with moderate to severe stress incontinence who were allocated to the physiotherapy arm from a previously reported multicentre trial comparing initial surgery or initial physiotherapy in treating stress urinary incontinence. Crossover to surgery was allowed. Results: Data from 198/230 women who were randomized to physiotherapy was available for analysis, of whom 97/198 (49 %) crossed over to surgery. Prognostic factors for undergoing surgery after physiotherapy were age <55 years at baseline (OR 2.87; 95 % CI 1.30-6.32), higher educational level (OR 3.28; 95 % CI 0.80-13.47), severe incontinence at baseline according to the Sandvik index (OR 1.77; 95 % CI 0.95-3.29) and Urogenital Distress Inventory; incontinence domain score (OR 1.03; per point; 95 % CI 1.01-1.65). Furthermore, there was interaction between age <55 years and higher educational level (OR 0.09; 95 % CI 0.02-0.46). Using these variables we constructed a prediction rule to estimate the risk of surgery after initial physiotherapy. Conclusion: In women with moderate to severe stress incontinence, individual prediction for surgery after initial physiotherapy is possible, thus enabling shared decision making for the choice between initial conservative or invasive management of stress urinary incontinence.
    International Urogynecology Journal 07/2014; 26(3). DOI:10.1007/s00192-014-2473-z · 1.96 Impact Factor
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    Blood transfusion = Trasfusione del sangue 05/2014; 12(Suppl 3):s515-s518. DOI:10.2450/2014.0008-14s · 2.37 Impact Factor
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    ABSTRACT: Haemophilia is a rare disease. To improve knowledge, prospective studies of large numbers of subjects are needed. To establish a large well-documented birth cohort of patients with haemophilia enabling studies on early presentation, side effects and outcome of treatment. Twenty-one haemophilia treatment centres have been collecting data on all children with haemophilia with FVIII/IX levels up to 25% born from 2000 onwards. Another eight centres collected data on severe haemophilia A only. At baseline, details on delivery and diagnosis, gene mutation, family history of haemophilia and inhibitors are collected. For the first 75 exposure days, date, reason, dose and product are recorded for each infusion. Clinically relevant inhibitors are defined as follows: at least two positive inhibitor titres and a FVIII/IX recovery <66% of expected. For inhibitor patients, results of all inhibitor- and recovery tests are collected. For continued treatment, data on bleeding, surgery, prophylaxis and clotting factor consumption are collected annually. Data are downloaded for analysis annually. In May 2013, a total of 1094 patients were included: 701 with severe, 146 with moderate and 247 with mild haemophilia. Gene defect data were available for 87.6% of patients with severe haemophilia A. The first analysis, performed in May 2011, lead to two landmark publications. The outcome of this large collaborative research confirms its value for the improvement of haemophilia care. High-quality prospective observational cohorts form an ideal source to study natural history and treatment in rare diseases such as haemophilia.
    Haemophilia 05/2014; 20(4). DOI:10.1111/hae.12448 · 2.60 Impact Factor
  • Frank W G Leebeek · Kathelijn Fischer
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    ABSTRACT: Background: In the Netherlands, the first formal haemophilia comprehensive care centre was established in 1964, and Dutch haemophilia doctors have been organised since 1972. Although several steps were taken to centralise haemophilia care and maintain quality of care, treatment was still delivered in many hospitals, and formal criteria for haemophilia treatment centres as well as a national haemophilia registry were lacking. Material and methods: In collaboration with patients and other stakeholders, Dutch haemophilia doctors have undertaken a formal process to draft new quality standards for the haemophilia treatment centres. First a project group including doctors, nurses, patients and the institute for harmonisation of quality standards undertook a literature study on quality standards and performed explorative visits to several haemophilia treatment centres in the Netherlands. Afterwards concept standards were defined and validated in two treatment centres. Next, the concept standards were evaluated by haemophilia doctors, patients, health insurance representatives and regulators. Finally, the final version of the standards of care was approved by Central body of Experts on quality standards in clinical care and the Dutch Ministry of Health. Results: A team of expert auditors have been trained and, together with an independent auditor, will perform audits in haemophilia centres applying for formal certification. Concomitantly, a national registry for haemophilia and allied disorders is being set up. Discussion: It is expected that these processes will lead to further concentration and improved quality of haemophilia care in the Netherlands.
    Blood transfusion = Trasfusione del sangue 04/2014; 12(Suppl 3):s501-s504. DOI:10.2450/2014.0041-14s · 2.37 Impact Factor
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    ABSTRACT: In elderly people with haemophilia (PWH), surgery of more than one joint of the lower extremities might be needed. Multiple joint procedures (MJP) were introduced in 1995, defined as any combination of Total Knee or Total Hip Arthroplasty or Ankle Arthrodesis during one in-hospital stay. The expectation is that by means of such procedures this specific population is able to physically function better for an extended period of time. Thus, they will participate in their society in an optimal way. In this study, we tried to describe an outcome after MJP, including pre- and post-operative pain and range of motion (ROM), and recommend measurement tools. 22 of 37 PWH who underwent MJP between 1995 and 2012 were available for assessment. Pain (WFH score) and range of motion were compared pre and postoperatively. Current outcome was described by VAS per joint, nocturnal and overall pain, MACTAR, Hemophilia Activity List, SF36, and EQ-5D. Mean age at surgery was 50, 3 years (SD 8, 3); mean follow-up 12 years (1-18 years). Pain (VAS) decreased post-surgery (Median 1 - 1, 5), but moderate pain remained. Extension of knees slightly increased, but both knee flexion and ankle plantar and dorsal flexion decreased. PWH reported the ability to stand longer but also pointed at specific problems, e.g. riding a bike (MACTAR). The HAL showed limited activities (functional domains), especially in the 'complex lower extremity' (22, 8/100). The SF36 and EQ-5D showed a mix of physical problems of our population, while experiencing moderate pain and reasonable physical functioning. This led us to the conclusion that adequate follow-up is needed: ROM of all joints, VAS of all joints as well as nocturnal and overall pain, HAL, SF36 and EQ5D. Performance based activities and participation need further attention.
    Haemophilia 03/2014; 20(2):276-81. DOI:10.1111/hae.12285 · 2.60 Impact Factor
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    ABSTRACT: Recently we reported data suggesting that platelets could compensate for the bleeding phenotype in severe haemophilia A (HA). The aim of this study was to confirm these results in a larger population with a detailed characterisation of clinical phenotype. Patients with diagnostic severe HA (FVIII:C <1%) were scored for clinical phenotype by integrating data on age at first joint bleed, joint damage, bleeding frequency and FVIII consumption. Phenotype was defined as onset of joint bleeding-score + arthropathy-score + joint bleeding-score + (2* treatment intensity-score). After a washout period of three days, blood was collected for measurement of basal level of platelet activation, platelet reactivity, endothelial cell activation and presence of procoagulant phospholipids in plasma. Thirty-three patients with severe HA were included, 13 patients with a mild, 12 patients with an average and eight patients with a severe clinical phenotype. No relevant differences in basal level of platelet activation, platelet reactivity, endothelial cell activation and procoagulant phospholipids between all three groups were observed. The mean annual FVIII consumption per kg did not correlate with the platelet P-selectin expression and glycoprotein (GP)IIbIIIa activation on platelets. In conclusion, variability in clinical phenotype in patients with diagnostic severe HA is not related to platelet activation or reactivity, measured as platelet degranulation and platelet GPIIbIIIa opening.
    Thrombosis and Haemostasis 01/2014; 111(6). DOI:10.1160/TH13-07-0546 · 4.98 Impact Factor

Publication Stats

3k Citations
655.85 Total Impact Points


  • 2001–2015
    • University Medical Center Utrecht
      • • Julius Center for Health Sciences and Primary Care
      • • Department of Hematology
      • • Department of Neurology
      Utrecht, Utrecht, Netherlands
  • 2007
    • University of Texas MD Anderson Cancer Center
      Houston, Texas, United States
  • 2003
    • Utrecht University
      • Division of Pediatrics
      Utrecht, Utrecht, Netherlands