title: Non-activated plasma-derived PC improves amputation rate of children undergoing sepsis.
abstract: Low circulating protein C (PC) levels have been observed in sepsis, especially in patients with Neisseriae Meningitides infections. Poor clinical outcome and high limb amputation rates have been associated in infected patients with low circulating PC levels. Published studies using activated PC replacement therapy patients with sepsis have shown reduced mortality rates, however, its use has been associated with severe bleeding events. Paediatric sepsis studies using non-activated plasma-derived PC (Ceprotin®) are lacking. We present a retrospective study in children with sepsis who were treated with Ceprotin® focusing on amputation rate post treatment. Thirty subjects were identified. Median age at diagnosis was 2 years. Twenty-one (70%) were treated for Nesseria Meningitides and one (3%) for Streptococcus-A β-haemolyticus, another 8 (26%) patients with malignancies were treated for neutropenic sepsis. Following Ceprotin® administration, a significant increase in leukocyte count (p=0.004), neutrophil count (p=0.001) and PC (pretreatment=13%, posttreatment=88.5%; p=0.0001) was seen. Prothrombin time (pretreatment =30.3 seconds, posttreatment =16.5; p=0.000) and activated partial thromboplastin time (pretreatment =61.8 sec, postreatment =42.6 sec; p=0.000) were significantly reduced, while fibrinogen levels were significantly elevated (pretreatment =1.9 g/dL, posttreatment =4.4 g/dL; p=0.000). The median time between admission to intensive care and Ceprotin® administration was 10 hrs. Limb amputation rate was reduced (16-23% versus 30-50% from previous studies) and there were no haemorrhagic events observed. This study demonstrates the safe administration of non-activated plasma-derived PC concentrate in patients with sepsis who are coagulopathic and it associated with a reduction in amputation rates.
authors.affiliation: Hematology Dept, Our Lady's Children's Hospital, Dublin, Ireland; Hematology Dept, San Maurizio Regional Hospital, Bolzano, Italy; Trinity College University, Dublin, Ireland. Electronic address: apiccin@gmail.com.
authors.forename: Andrea
authors.initials: A
authors.lastname: Piccin
authors.affiliation: Hematology Dept, Our Lady's Children's Hospital, Dublin, Ireland.
authors.forename: Aengus
authors.initials: A
authors.lastname: O' Marcaigh
authors.affiliation: Hematology Dept, Our Lady's Children's Hospital, Dublin, Ireland.
authors.forename: Corrina
authors.initials: C
authors.lastname: Mc Mahon
authors.affiliation: Trinity College University, Dublin, Ireland.
authors.forename: Ciaran
authors.initials: C
authors.lastname: Murphy
authors.affiliation: Hematology Dept, Our Lady's Children's Hospital, Dublin, Ireland.
authors.forename: Ikechukwu
authors.initials: I
authors.lastname: Okafor
authors.affiliation: Department of Diagnostic and Clinical Medicine and Public Health University of Modena and Reggio Emilia, Modena Italy.
authors.forename: Luigi
authors.initials: L
authors.lastname: Marcheselli
authors.affiliation: Anesthesiology Dept, Our Lady's Children's Hospital, Dublin, Ireland.
authors.forename: William
authors.initials: W
authors.lastname: Casey
authors.affiliation: Anesthesiology Dept, Temple Street Hospital, Dublin, Ireland.
authors.forename: Liam
authors.initials: L
authors.lastname: Claffey
authors.affiliation: Hematology Dept, Our Lady's Children's Hospital, Dublin, Ireland; Trinity College University, Dublin, Ireland.
authors.forename: Owen Patrick
authors.initials: OP
authors.lastname: Smith
mesh_terms: D000293:Adolescent; D000671:Amputation, Surgical / Q000379:methods*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D007958:Leukocyte Count; D008297:Male; D008585:Meningitis, Meningococcal / Q000097:blood / Q000188:drug therapy; D009345:Neisseria meningitidis / Q000302:isolation & purification; D011486:Protein C / Q000378:metabolism*; D012189:Retrospective Studies; D018805:Sepsis / Q000097:blood* / Q000188:drug therapy / Q000382:microbiology / Q000601:surgery*
chemical_list: D011486:Protein C
keywords: Neisseria Meningitides; amputation; neutropenia; protein C; sepsis