I. Standardization of laboratory testing for coagulation abnormalities in children who present with thrombosis.

In the first part of the program, the types and prevalence of coagulation abnormalities detected in children presenting with thrombosis in various settings were reviewed and recommendations made, as follows.

Catheters, Dr. Tom Abshire, USA: Because of recent reports supporting the presence of genetic and acquired prothrombotic traits in the majority of children at the time of presentation with thrombosis, this group of infants and children would warrant a complete study.

Cancer, Leukemia, Dr. Ulrike Nowak-Göttl, Germany: An excess risk of thrombosis has been reported in the treatment of several pediatric malignancies. All episodes of thrombosis occurred in children with indwelling central venous catheters. The cost/effectiveness of screening children at the outset of therapy, and the need for prospective intervention trials in children identified with thrombophilia and cancer were stressed. In addition, the additive effect of chemotherapy was discussed. The association of an increased risk of venous thromboembolic events with the specific L-asparaginase obtained from Kyowa, Japan explained discrepant results of studies examining the relationship of thrombosis to L-asparaginase.

Stroke, Drs. Vinod Balasa, Ralph Gruppo, USA: The conclusion of Drs. Balasa and Gruppo was that a complete laboratory evaluation should be performed in children with stroke.

Hormones, Dr. Marjolein Peters, The Netherlands: Dr. Peters recommended that girls treated with high dose estrogens be evaluated, especially for free protein S level, prior to commencing therapy.

Bone Marrow Transplantation (BMT)/Venous Occlusive Disease (VOD): Dr. Donna DiMichele, USA: National collaborative groups should be utilized to collect data needed to develop recommendations regarding coagulation screening in children undergoing BMT and/or diagnosed with VOD.

Neonatal, Dr. Wolfgang Muntean, Austria: The consensus of the subcommittee participants was that the in the premature infant thrombosis is almost always related to blood flow, vascular obstruction by catheters and consumptive coagulopathies whereas the well term infant with thrombosis is more likely to manifest a genetic thrombophilia. Routine coagulation testing was recommended for term infants with thrombosis.

Antiphospholipid antibodies, Manco-Johnson, USA: Although more data is needed, children presenting with venous thromboembolism should be evaluated for the lupus anticoagulant and children with stroke should be studied for anticardiolipin antibodies. In children with thrombosis associated with SLE or varicella, the prevalence of antiphospholipid antibodies is quite high (70-80%). The overall prevalence of APA in neonates with stroke is probably low.

The Subcommittee resolved to draft a position paper making recommendations regarding laboratory coagulation testing of children with thrombosis in the absence of adequate data, and proposing future studies to obtain information necessary for a definitive recommendation. This will be accomplished in the next nine months and submitted prior to next year’s meeting.

2. Monitoring of long-term anticoagulation was reviewed by Drs. Patti Massacote (Canada) and Paul Monagle (Australia).
3. Intracranial hemorrhage in ITP, Dr. James Bussel, USA:

Dr. Bussel and Dr. Sutor reviewed consensus papers from North America, Germany and the UK. A decision was made to develop a consensus paper from this committee specifically regarding current areas of consensus and lack of consensus around "need to treat, " not addressing the treatment per se, for infants and children with ITP relative to platelet count. This paper will also be submitted prior to next year’s meeting. The second activity proposed in this section is continuation of an international registry of cases of intracranial hemorrhage in children with ITP. Because all treatment is designed to prevent this dreaded complication, factors associated with ICH determined by the registry will be useful to design prospective studies, intervention trials and future recommendations around treatment of ITP in children.

IV. Papers: Dr. J. Conard presented on behalf of Dr. Hellgren who was unable to attend. A summary of the recommendations for diagnosis and treatment of thromboembolism during pregnancy and the puerperium were presented. Input was received from participating committee members. The paper has undergone numerous drafts and will be submitted to the SSC Publications Review Committee within two to three months.

Rheology, Eric Grabowski, USA: Dr. Grabowski presented an elegant paper demonstrating that neonatal endothelial cells support increased activation of Factor Xa and an increased ability to express tissue factor in response to increased shear stress in vitro. In his model the neonatal phenotype is controlled by shear stress. Transcription of tissue factor as well as levels of TFPI and TPA was comparable in the neonatal and adult models. There was consensus that this type of model is needed to address many remaining unknowns in neonatal hemostasis and the subcommittee should expand its interest in the neonatal endothelial cell. Future meetings will devote more time to neonatal rheology and the subcommittee requests that members involved in this area of research submit suggestions for next year’s program.