Akademik Veri Yönetim Sistemi
Diğer Ülkelerden Üniversiteler Tarafından Desteklenmiş Proje, 2025 - 2027
Neonatal purpura fulminans (NPF) is a rare, life threatening condition, caused by congenital or acquired deficiencies of protein C or S. The diagnosis of homozygous protein C or S deficiency is often challenging and is based on the clinical findings of purpura fulminans, undetectable levels of protein C or protein S, a heterozygous state in the parents and if possible, identification of the molecular defect. Protein C and S activity levels are undetectable in homozygotes. It is essential that the laboratory use age-specific reference ranges for interpretation. Levels of protein C and S in healthy neonates are significantly below adult reference ranges, as low as 0.12 U/ml and 0.14 U/ml respectively. These physiologically low levels combined with acquired causes can lead to abnormal results. The usual recommendation of repeat testing in three to six months for confirmation is clearly impractical in this setting; testing of parents is therefore essential. If the causative mutation of protein C or S deficiency within a family is known, prenatal diagnosis is available for women at risk of having a child with homozygous deficiency. The management includes an acute phase of replacement therapy with fresh frozen plasma or protein C concentrate and a maintenance therapy that includes anticoagulation with warfarin or low molecular weight heparin (LMWH). Reliable venous access is imperative in order to facilitate treatment, however this may present another challenge in the management of such infants. Protein C concentrate has been administered successfully subcutaneously. Anticoagulation therapy should be initiated with administration of protein C replacement therapy (protein C concentrate or FFP/FP) and is an effective long term secondary prophylaxis. Initial anticoagulation consists of either unfractionated heparin (UFH) or LMWH, although the role of LMWH is not clearly defined in NPF. Maintenance therapy has historically been with warfarin therapy.8, 14 The use of new anticoagulants has not been described.
Objectives: To collect data on the diagnosis, management and outcome of NPF, which remains a rare but life-threatening disorder. Without international collaboration, the rarity of the disorder precludes the ability to investigate these variables.
Methods: Study Population and Sample Size
The study is being conducted under the auspices of the International Society of Thrombosis and Hemostasis (ISTH). Therefore, any ISTH member participant of the pediatric and neonatal subcommittee community will be entitled to partake in the study. Realistically, it is likely that only tertiary referral centres will be able to enter patients, given the rarity of the disease. We expect to altogether enroll approximately 6 to 8 patients per year.