Dewi Clark

Quantitation of bleeding symptoms in children with von Willebrand disease: use of a standardized pediatric bleeding questionnaire.

Summary.  Background: Excessive bruising and mucocutaneous bleeding are frequent presenting symptoms in childhood. A detailed bleeding history can distinguish children who may have an inherited bleeding disorder from those who are normal. There is a lack of standardization of such history taking in pediatric practise. Objectives: To assess the performance of a Pediatric Bleeding Questionnaire (PBQ), an adaptation of a standardized adult bleeding questionnaire and score that includes pediatric‐specific bleeding symptoms, in a cohort of children with von Willebrand disease (VWD). Patients/Methods: Bleeding scores were determined by interview, for children with a previous diagnosis of VWD and a control group of unaffected siblings. Results: Bleeding scores were obtained for 100 children with VWD, median age 10.9 years (range, 0.8–17.8 years), and 21 unaffected siblings. Median bleeding score in children with VWD was 7.0 (range, 0–29) and in the control group was 0 (range, −1–2). Bleeding score varied within and between each VWD type: definite type 1, n = 40, median, 9.0 (range, 2–18); possible type 1, n = 38, median, 2.0 (0–15); type 2, n = 6, median, 14.0 (3–17); and type 3, n = 16, median, 12.0 (4–29). Bleeding scores in affected children correlated with age (Spearman’s correlation coefficient, 0.35; P = 0.0004). The most frequent clinically significant bleeding symptoms were surgical bleeding, bleeding after tooth extraction and menorrhagia. Post‐circumcision bleeding, cephalohematoma, macroscopic hematuria and umbilical stump bleeding were clinically significant in 32% (of circumcised males), 4%, 4% and 3% of children, respectively. Conclusions: The PBQ provides a standardized quantitation of bleeding severity in children with VWD.

Use of a quantitative pediatric bleeding questionnaire to assess mucocutaneous bleeding symptoms in children with a platelet function disorder

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Normal range of bleeding scores for the ISTH-BAT: adult and pediatric data from the merging project.

Bleeding Assessment Tools (BATs) have been developed to aid in the standardized evaluation of bleeding symptoms. The Vicenza Bleeding Questionnaire (BQ), published in 2005, established a common framework and scoring key that has undergone subsequent modification over the years, culminating in the publication of the ISTH‐BAT in 2010. Understanding the normal range of bleeding scores is critical when assessing the utility of a BAT. Within the context of The Merging Project, a bioinformatics system was created to facilitate the merging of legacy data derived from four different (but all Vicenza‐based) BATs; the MCMDM1‐VWD BQ, the Condensed MCMDM‐1VWD BQ, the Pediatric Bleeding Questionnaire and the ISTH‐BAT. Data from 1040 normal adults and 328 children were included in the final analysis, which showed that the normal range is 0–3 for adult males, 0–5 for adult females and 0–2 in children for both males and females. Therefore, the cut‐off for a positive or abnormal BS is ≥4 in adult males, ≥6 in adult females and ≥3 in children. This information can now be used to objectively assess bleeding symptoms as normal or abnormal in future studies.

In vitro and in vivo stability of diluted recombinant factor VIII for continuous infusion use in haemophilia A

Summary.  Factor VIII (FVIII) replacement by continuous infusion (CI) is used postoperatively or after significant bleeding. For young paediatric patients, CI may require FVIII dilution. Variable stabilities of diluted full‐length recombinant FVIII Kogenate® FS (KG‐FS) have been reported under different storage conditions. We investigated the recovery and stability of diluted KG‐FS in vitro and in vivo. Kogenate® FS was diluted to 50–120 U mL−1 and its recovery and stability in glass vials or polypropylene syringes was determined. Furthermore, stability of KG‐FS diluted to 80 U mL−1‘administered’ via single‐ and double‐pump mock CI systems was tested. Finally, the in vivo stability of KG‐FS diluted to ∼60 U mL−1 and administered postsurgically by CI with the double‐pump to a paediatric patient with severe haemophilia A undergoing implantable venous access device placement was investigated. Initial KG‐FS dilution resulted in a 10–20% FVIII loss; a further 25–30% loss occurred over 72 h in vials or syringes. With the double‐pump, 1 h recovery was 35%, increasing to 80% by 24 h; the initial losses were because of the Y‐infusion of a 10‐fold larger volume of saline concomitantly with the FVIII. In vivo, CI resulted in stable FVIII activity levels within the target range. These in vitro results are important for the generation of CI guidelines for diluted KG‐FS in the paediatric haemophilic population. That FVIII losses occur upon dilution and with the double‐pump does not preclude use of diluted KG‐FS. Indeed, stable FVIII levels were maintained when diluted KG‐FS was administered by CI with the double‐pump to a paediatric patient postsurgically.

Impact of aerobic exercise on haemostatic indices in paediatric patients with haemophilia

UNLABELLED This study investigated the impact of aerobic exercise on laboratory assessments of haemostatic activity in boys (5-18 years of age) with haemophilia A (HA) or B (HB), examining the hypothesis that laboratory coagulation parameters temporarily improve with exercise. Thirty subjects meeting eligibility criteria (19 HA; 11 HB; mean age: 12.8 years) were invited to participate. They underwent a replacement factor washout period and were advised against strenuous activity for three days prior to the planned intervention. At study visit, baseline blood samples were drawn prior to exercise on a stationary cycle ergometer, aiming to attain 3 minutes (min) of cycling at 85 % of predicted maximum heart rate. Blood work was repeated 5 min (t5) and 60 min (t60) post exercise completion. Samples were assessed for platelet count (PC), factor VIII activity ( FVIII C), von Willebrand antigen (VWF:Ag), ristocetin cofactor activity (VWF:RCo) and platelet function analysis (PFA-100); maximum rate of thrombus generation (MRTG) in blood was measured via thromboelastography and plasma peak thrombin generation (PTG) via calibrated automated thrombography. Mean duration of exercise was 13.9 (± 2.6) min. On average, t5 samples showed significant elevation, relative to baseline in PC, FVIII:C, VWF:Ag, VWF:RCo and PTG, while FVIII C, VWF:Ag, VWF:RCo and MRTG were significantly elevated in t60 samples. Within the cohort, participants with severe HA showed no change in FVIII C levels with exercise. The greatest improvement in haemostatic indices was observed in post-adolescent males with mild-moderate HA, who thus represent the group most likely to benefit from a reduction of bleeding risk in the setting of exercise.