Perinatal/Pediatric Haemostasis

July 19, 2002
14:00 to 18:00
Plaza Room
Boston Park Plaza Hotel

Chairman:  U. Nowak-Göttl, Germany
Co-chairs:  E. F. Grabowski, USA; M. Hellgren, Sweden; A. S. Kemahli, Turkey;
G. Kenet, Israel; P. Massicotte, Canada; W. Muntean, Austria;
M. Peters, Netherlands

The chair and co-chairs and approximately 55 Subcommittee members were present. Issues discussed were as follows:

1. Platelets and Thrombin generation:
Thrombocytopenia: J. Bussel summarized again the available data on intracranial hemorrhage (ICH) occurring in acquired childhood ITP in the US and other countries. Causative factors, predictors and outcome were discussed as a basis for an understanding of the disease. No controlled data are available to date on whether treatment can prevent ICH from occurring during childhood ITP. Thus, multicenter controlled therapeutic trials are recommended (study end-point: ICH).

V. Bardet et al. reported on inherited thrombocytopenias with respect to new diagnostic techniques (flow cytometry, genetic analysis, ultrastructural studies) and therapeutic approaches. A consensus was discussed.

Thrombin generation in neonatal plasma: W. Muntean et al. reported on the thrombin generation capacity in neonatal plasma compared with adult plasma. The authors focused on the role of antithrombin and tissue factor pathway inhibitor (TFPI). They clearly demonstrated that, under physiological conditions (low plasma dilution and low amounts of TF), cord plasma clots earlier than adult plasma, and FXa- and FIIa-generation starts earlier, due mainly to low levels of TFPI and AT. The authors concluded that, despite low levels of procoagulatory factors, sufficient hemostasis is achieved in neonatal plasma.

2. Venous thrombosis in children:
Testing of prothrombotic risk factors and pediatric controlled studies: Based on the presentations given (P. Mathwey, M. Peters & F. Rosendaal, E. Grabowski & M. Manco-Johnson) and the literature available, important questions concerning pediatric population-based studies were discussed. One of the main questions was whether every child with symptomatic venous thrombosis should be tested for prothrombotic risk factors or whether a distinction should be made between low/intermediate- and high-risk patients. It was furthermore discussed whether meta-analysis of literature data on the incidence of genetic risk factors will help to classify children at risk, and whether meta-analyses have (dis)advantages compared with controlled multicenter studies in children and vice versa. Another question was whether pediatric studies should always be controlled by using age-matched healthy children. The last issue raised at this session was whether the testing of asymptomatic family members is indicated, and if so in what cases.

3. Coagulation factor concentrates:
Protein C-deficiency: C. Escuriola et al. reported on indications, dosages, and laboratory monitoring during the use of human protein C concentrate in children with congenital and acquired protein C deficiency. Data obtained from case series suggest that human protein C is effective in treating congenital protein C deficiency. Six out of eight children with acquired protein C deficiency and with severe disturbance of the microcirculation due to meningococcal septicemia survived after the administration of human protein C concentrate. The authors conclude that controlled studies should be carried out in children to obtain evidence-based data on the cost/benefit ratio of human protein C concentrate. Furthermore, comparative studies between human protein C concentrate and activated protein C concentrate are recommended with respect to clinical benefits as well as to potential side effects.

Recombinant factor VIIa (rFVIIa): E. Grabowski discussed the in vitro hypothesis of inactivated r-FVIIa being used in preclinical studies to interrupt the TF pathway of coagulation. This hypothesis is based on experimental data showing the expression of enzymatically active TF-Factor VIIa complex by HGECs exposed to various combinations of TNF-alpha and Shiga toxin-1.

Von Willebrand disease: B. Zieger reported on indications, dosages, and duration of application of von Willebrand factor concentrate or Desmopressin in children with different types of von Willebrand disease. Unclarified issues, e.g., for what ages Desmopressin is acceptable, adequate postoperative management in view of the possibility of volume overload and hyponatremia, and the possible intranasal application of Desmopressin should be clarified in controlled prospective studies in children.

4. Pediatric Stroke
Population-based data on ischemic stroke in pediatric patients were summarized by leading stroke experts from ten countries (M. Bonduel, Argentina; W. Muntean et al. Austria; G. deVeber et al., Canada; I. Husson et al., France; R. Straeter et al., Germany; G. Kenet et al., Israel; S. de Vries et al., The Netherlands; A. Kemahli, Turkey; V. Ganesan & F. Kirkham, United Kingdom; J.K. Lynch et al., US). Underlying diseases, imaging methods, presence of prothrombotic risk factors, and therapeutic options were discussed. A consensus paper on uniform stroke classifications, imaging methods, and laboratory screening as a basis for international multicenter therapeutic trials was proposed.