SCIENTIFIC SUBCOMMITTEE SESSION
7 July 2007 Palexpo, Geneva, Switzerland
Perinatal/Pediatric Hemostasis
Chair: G. Kenet (Israel)
Co-Chairs: J. Journeycake (USA), P. Massicotte (Canada), P. Mathew(USA),
P. Monagle (Australia), W. Muntean (Austria), N. Schlegel (France)
A: Pediatric thrombosis- chairs: P Massicote, U Nowak-Gottl
Recurrence is a major end-point in VTE studies, yet there are few evidence based data about this issue in pediatric patients. Comparison between neonates and children was emphasized, focusing on outcome studies available for neonatal RVT. Neonates exhibit a very low risk of reported recurrence as compared to older children. Spontaneous VTE, prothrombotic risk factors and presence of co-morbid states have been shown to increase recurrence rate, whereas D-Dimer elevation and higher factor VIII have been associated with adverse outcome of pediatric VTE. The duration as well as intensity of anticoagulant treatment to prevent recurrence in children still need to be elucidated.
Recommendation: More data should be collected on recurrence rate among neonates and children, including impact of anticoagulation therapy and presence of risk factors.
Data on recurrent stroke and Cerebral Sinus vein thrombosis (CSVT) from pooled international databases held at the hospital for sick kids, Toronto, University of Munster, Tel Hashomer hospital- Israel, and Great Ormond Street hospital, UK were presented. The impact of thrombophilic risk factors upon risk of recurrent stroke was evaluated. Data were available from 678 stroke patients (age range: 1 month to 21 years) followed for a median of 36 months. Recurrence rates were significantly higher among patients with cardiovascular diseases and increased lipoprotein(a) levels. The presence of any prothrombotic risk factor doubled the risk for recurrence after adjustment for presence of cardiovascular disease, whereas the use of either antiplatelet or anticoagulant therapy significantly reduced it.
For CSVT recurrence, 396 children were prospectively followed. Age at onset (>2 years, non-administration of antipagulants, persistant venous occlusion and presence of FIIG20210A variant were independently associated with higher recurrence risk.
Recommendations: Due to the paucity of information regarding the risk of recurrent stroke in children, pooled international data collection and further collaborative studies are strongly encouraged
B: Therapy of pediatric Thrombosis. Chairs: W Mountean, M Bonduel
The differences between children and adults treated with unfractionated Heparin (UFH) regarding bleeding tendency, monitoring tests, the mechanism of action and half life of UFH were discussed.
Recommendations: Further specific and targeted studies of pharmacokinetics, dosing schedules and monitoring strategies in children should be done .A position paper, which recommends the desired strategies for assessing UFH therapy in neonates and children has been suggested.
TPA is being given for childhood stroke according the adult guidelines with small deviation, despite the differences in physiologic and fibrinolytic systems of children as compared to adults. Preliminary data of TPA therapy in pediatric patients with stroke were presented.
Due to minimal information concerning the safety and appropriate dosing of tPA in childhood stroke, a multi-centre cohort safety and dose-finding study has been designed to assess tPA in childhood stroke by the International Pediatric Stroke Study (IPSS).
Recommendation: International collaboration i s encouraged.
Newer anticoagulant agents are available and licensed, with potential advantages over heparin, low molecular weight heparin and warfarin. Summery of bivalirudin pilot study and preliminary data on argatroban study in children with thrombosis were presented. Laboratory studies utilizing thromboelastography with five different anticoagulants and their potential in-vitro reversibility by rFVIIa were discussed.
Recommendation : Randomized controlled clinical trials are recommended since the use of anticoagulation recently increased in children despite lack of information.
A proposal for a new international multicenter study has been made, based upon better outcome with lower rate of post-phlebitic sy in children reported treated with systemic thrombolysis as compared to standard anticoagulant therapy.
Recommendation : Studies are required to asses the role of thrombolytics (either systemic or regional vs heparin alone) in pediatric VTE.
C: Pediatric bleeding –chairs: N Schlegel, M Rand
Bleeding history evaluation in children is often diffuculat and has been challenged before. A specific adjusted bleeding questionnaires has been validated in Sick-kids hospital, Toronto. Pediatric-specific bleeding questionnaire based on the ISTH Bleeding questionnaire for the diagnosis of Type 1 von Willebrand Disease (VWD) was applied in collaboration with colleagues in: Kingston, Canada; Vicenza, Italy and Oakland, USA.
Recommendation: Use of standard bleeding questionnaires should be practiced, le ading to better diagnosis and treatment for children with bleeding disorders
The feasibility and efficacy of questionnaire and bleeding score in neonates, infants and children who were scheduled to undergo various surgeries, was presented.
A proposal for use of bleeding score composed of combined questionnaire results, lab tests and surgical bleeding risk assesment was made.
R ecommendation: Collaborative international data collection of bleeding score results and outcome is proposed
A study that evaluated peri-operative PTT screening was discussed. Retrospective chart analysis of 492 consecutive patients (age 1-17 yrs., Median 5), referred for hemostatic assessment, after evaluation of PTT screening and history, for standardized laboratory workup was presented. Only in 35% of patients prolonged PTT was confirmed, 2.4% suffered from significant bleeding disorder (BD). The positive predictive value (PPV) to detect BD for prolonged PTT in combination with positive bleeding history was higher.
Recommendation : Since PTT screening yields many false positive results, an effort of the ISTH Pediatric SSC to validate standard questionnaires and scores for evaluation of bleeding risk in children undergoing surgery is urgently required.
D. Perinatal Hemostasis – chair: J Journeycake
Neonatal IVH : past, present and future perspectives : P Mathew
Neonatal IVH is responsible for many adverse sequelae including post hemorrhagic hydrocephalus, cerebral palsy and death. Reducing the risk of progression to higher grades of IVH in VLBW infants and thereby reducing adverse long term outcome by proper intervention therapy should be attempted.
A study to investigate the natural history of early germinal matrix-(GM-IVH) in very low birth weight (VLBW) infants and to evaluate the safety of using rFVIIa in preterm infants was presented
Recommendation: A prospective study of the natural history of neonatal IVH has been proposed and submitted for funding.