Kate Khair

The impact of prophylactic treatment on children with severe haemophilia

Twenty‐seven children with severe haemophilia receiving regular prophylactic factor concentrate were evaluated to examine the overall effectiveness of prophylaxis in modern haemophilia care. The median age at the start of prophylaxis was 6.2 years (range 1.3–15.9 years) and the cumulative length of follow‐up was 808 months (mean 30, range 7–76 months).

Prophylactic and therapeutic recombinant factor VIIa administration to patients with Glanzmann's thrombasthenia: results of an international survey.

Summary.  Background: Antibodies to glycoprotein (GP) IIb‐IIIa and/or HLA may render platelet transfusions ineffective to stop bleeding or to cover surgery in patients with Glanzmanns thrombasthenia (GT). Anecdotal reports suggest recombinant factor (rF)VIIa might be a therapeutic alternative in these situations. Objectives: An international survey was conducted to evaluate further the efficacy and safety of rFVIIa in GT patients. Patients: We analyzed the use of rFVIIa during 34 surgical/invasive procedures and 108 bleeding episodes in 59 GT patients including 29 with current or previous antiplatelet antibodies, and 23 with a history of refractoriness to platelet transfusion. Results: rFVIIa was effective in 29 of the 31 evaluable procedures, and in 77 of the 103 evaluable bleeding episodes of which eight had a recurrence. A significantly higher success rate was observed in severe bleeding episodes when an arbitrarily defined ‘optimal regimen’ derived from the Canadian pilot study results (≥ 80 µg kg−1 rFVIIa/injection, dosing interval ≤ 2.5 h, three or more doses before failure declaration) was used compared with other regimens (77%; 24/31 vs. 48%, 19/40; χ2, P = 0.010). Patients given maintenance doses had significantly fewer recurrences within 48 h of bleed cessation compared with those not given any (Fishers exact test, P = 0.022). One thromboembolic event and one blood clot in the ureter occurring in surgical patients following prolonged continuous infusion of high‐dose rFVIIa and antifibrinolytic drug use have been previously reported. Conclusion: rFVIIa seems a potential alternative to platelet transfusion in GT patients, particularly in those with antiplatelet antibodies and/or platelet refractoriness.

The use of recombinant factor VIIa in children with inherited platelet function disorders

Summary. Inherited deficiencies of platelet surface glycoproteins such as Glanzmanns thrombasthenia (GT) or Bernard–Soulier syndrome (BSS) can lead to a severe bleeding diathesis. In the past, bleeding episodes in these patients have often required platelet transfusion to secure haemostasis but recently a number of patient reports have suggested that recombinant factor VIIa (rVIIa) may also be effective. We have used rVIIa on 33 occasions in seven children with inherited platelet function disorders over a 2‐year period: five had GT, one had BSS and one had storage pool disease with a severe phenotype. Bleeding ceased with rVIIa alone in 10 of 28 acute bleeding episodes, but recurred in two of these. The two features that predicted response to rVIIa were the severity of the bleeding and the delay from the onset of bleeding to treatment. Five episodes of planned surgical intervention were treated successfully with rVIIa. Eighteen out of the 28 acute episodes and none of the planned surgical episodes required blood product support. We have found variable efficacy of rVIIa for acute bleeding episodes in this small series of children with inherited platelet function defects but larger studies are warranted, particularly as rVIIa is a relatively low‐risk treatment approach for these disorders.

Pilot testing of the 'Haemo-QoL' quality of life questionnaire for haemophiliac children in six European countries.

Summary.  In a multinational working group, an instrument (Haemo‐QoL) to assess quality of life in children/adolescents with haemophilia and their parents has been developed. In co‐operation with haemophilia treatment centres in six European countries, approximately 10 children/adolescents with haemophilia per country and their parents were asked to participate in the pilot‐testing. Both self‐reported and parent‐reported questionnaires were provided for two age‐groups of children (4–16 years). Medical data was collected from physicians from patient files. Answers to open questions from participants (58 children and 57 parents) confirmed the content of 116 of the preliminary items. Cognitive debriefing revealed that the majority of the Haemo‐QoL was rated favourably, but 29 questions were recommended to be omitted and several items to be reformulated. Preliminary psychometric testing of the revised 77 item questionnaire in the same sample showed acceptable reliability and validity, which will be examined in a subsequent study with a larger patient sample.

Health status and health-related quality of life of children with haemophilia from six West European countries

Summary.  A multicentre, international, cross‐sectional study was carried out in the frame of field testing of the first haemophilia‐specific quality‐of‐life (QoL) questionnaire (Haemo‐QoL). The aim of this paper is to describe health status and health care and their impact on QoL in haemophilic children in Western Europe. Children aged 4–16 years with severe haemophilia without inhibitors were enrolled by 20 centres in France, Germany, Italy, the Netherlands, Spain and the United Kingdom. Clinical information was collected by the physicians with a medical documentation form. Health‐related QoL (HRQoL) of children was assessed with Haemo‐QoL, available for three age groups. Clinical data were available in 318 patients, 85.5% with haemophilia A. The mean age at first bleeding was 11 months, at first joint bleed 25 months. Functional joint impairments were found in 11.3%. Prophylaxis treatment was given to 66.7% of children in whom breakthrough bleeds occurred 0.4 times a month compared to 1.1 bleeds in children receiving on‐demand treatment. A significantly higher factor consumption was found only in the two younger age groups of prophylaxis patients compared to on‐demand patients. HRQoL was satisfactory in this cohort: young children were impaired mainly in the dimension ‘family’ and ‘treatment’, whereas older children had higher impairments in the so‐called ‘social’ dimensions, such as ‘perceived support’ and ‘friends’. Health care of children in Western Europe is progressively improving with a large diffusion of home treatment and prophylaxis. This provides a high level of health status and HRQoL, being better in haemophilic adolescents on prophylaxis.

Bruising and bleeding in infants and children : a practical approach

Bruising and bleeding are commonly seen in children and are usually associated with minor injury and trauma. However, in two groups of children the bruising may be more significant than expected: those with an underlying haemostatic abnormality, such as an inherited bleeding disorder, or those who have been subjected to non‐accidental injury (NAI). Diagnosing inherited bleeding disorders in children is fraught with difficulty, from venous access to interpretation of results; the possibility of NAI should be borne in mind, even in those children with proven significant bleeding disorders when the severity of the injury and the history are non‐compatible. We describe the investigation of the haemostatic system in children with bruising and/or bleeding with emphasis on the key haemostatic disorders that need to be excluded.

Central venous access devices in children with congenital coagulation disorders: complications and long-term outcome.

Reliable venous access is essential to facilitate the administration of prophylactic factor concentrate or blood products in children with congenital coagulation disorders and immune tolerance therapy (ITT) regimens in those who develop high responding inhibitors. Poor venous access is even more problematic in very young children, the vast majority of whom will require the insertion of central venous access devices (CVADs). Previous studies have suggested that infection rates are low and that there are few long‐term complications associated with CVAD usage. We have reviewed 86 CVADs that have been inserted, since 1988, in 58 children with congenital bleeding disorders, aged 6 d to 16·5 years, attending Great Ormond Street Hospital, London, and the National Childrens Hospital, Dublin. The devices have remained in situ for 2 weeks to 92 months (median 22·5 months). Early (0–2 weeks) complications of CVAD insertion included nine bleeding episodes, one extravasation of factor concentrate, three allergic reactions to factor concentrate and five catheter infections. Overall, CVAD infection was the commonest problem encountered, with 52 devices (60%) becoming infected. Twenty‐seven CVADs (31%) required removal. Infection rates in children without inhibitors (29/68) were 1/20 patient–months or 1·6 infections/1000 patient–days, but infection rates for those with inhibitors were 1/8·5 patient–months or 4·3/1000 patient–days. Staphylococcus epidermidis was the predominant organism (25/52) isolated. Blockage of CVAD (four) and catheter disconnection (four) were the most frequently occurring non‐infectious long‐term complications. Skin erosion of the port was also seen in three children, in one child at 20 months, in one at 29 months and in one at 34 months after insertion. This study demonstrates a high CVAD infection rate and highlights the long‐term complications of CVAD usage.

Recombinant factor VIIa in the management of surgery and acute bleeding episodes in children with haemophilia and high responding inhibitors.

Summary.  The management of acute and surgical bleeding episodes in children with severe factor VIII or IX deficiency who develop high responding inhibitors presents a major therapeutic challenge to clinicians. Recombinant factor VIIa (rVIIa) is an effective, reliable and safe treatment that can be used to treat acute bleeding episodes prior to commencing an immune tolerance programme and to cover surgical procedures until the immune tolerance programme is successful. In a significant minority of patients, immune tolerance therapy is ineffective and an alternative haemostatic agent such as rVIIa is required for life‐long treatment. The present study evaluated the use of rVIIa in a paediatric setting. Twelve children, aged 1–16 years, were treated successfully with rVIIa to prevent surgical bleeding in 20 surgical procedures (19 central venous access device insertion or removal, 1 dental extraction). Minor postoperative haematomata developed in 2 out of 20 cases after regular rVIIa therapy had been discontinued and resolved with a short course of rVIIa in both cases. Three children had six life‐ or limb‐threatening bleeding episodes. All bleeding episodes resolved with regular rVIIa treatment although topical fibrin glue was needed in one child with a frenulum tear. One patient required two red cell transfusions for symptomatic anaemia resulting from two separate bleeding episodes. The rVIIa therapy was well tolerated and there was no evidence of treatment‐related complications. We conclude that rVIIa is the treatment of choice for the management of surgery and acute life‐ or limb‐threatening bleeding in children with haemophilia and high responding inhibitors.

Can early subclinical gait changes in children with haemophilia be identified using the GAITRite walkway.

Summary.  Development of haemophilic arthropathy has long‐term implications for functional mobility in people with haemophilia, but early manifestations are often asymptomatic and difficult to identify. Earlier identification of joint damage may improve outcomes. The aim of this case note review was to determine whether the GAITRite® system (electronic pressure sensitive walkway) could identify early changes in gait patterns in boys with haemophilia compared with their peers.

Factors affecting the Haemophilia Joint Health Score in children with severe haemophilia

Joint damage from bleeding episodes leads to physical or functional limitations in people with haemophilia. Various factors may influence the frequency and severity of joint damage. This study examined whether age, prophylaxis, history of high‐titre inhibitors (HTI) and bleeding events influenced the Haemophilia Joint Health Score (HJHS) in children. Medical and physiotherapy notes of boys with severe haemophilia, aged 4–18 years, were reviewed to identify factors associated with increased HJHS. The HJHS of 83 boys (median age: 11) ranged from 0 to 25, with 44/83 (53%) having a score of zero. The median HJHS was 0 (mean 2.6). In the non‐HTI group, the HJHS for boys on late prophylaxis was 2.68 times higher than those who started early and the HJHS was on average 10% higher for every additional recent bleed. In this group the odds of having a zero score fell by 30% for every year increase in age. Boys with a history of HTI had higher HJHS scores than the non‐HTI group, and age, number of recent bleeds and tolerized status were positively associated with HJHS. The score rose on average by 28% for every year of age and by 76% for non‐tolerized boys. This study provides further evidence supporting early prophylaxis use and the importance of immune tolerance therapy. The HJHS is a useful tool for identifying and tracking changes in joint health with respect to therapy or disease progression. With improvements in haemophilia treatment, the disproportionate number of zero scores will continue to make interpretation of the HJHS challenging.