title: Coagulation activation in children with sickle cell disease is associated with cerebral small vessel vasculopathy.
abstract: BACKGROUND
  Thrombotic complications in Sickle Cell Disease (SCD) arise since infancy, but the role of the coagulation system in children has been poorly explored. To determine its role in the development of clinical complications in childhood we measured coagulation and endothelial parameters in children with SCD at steady state.
  
  
  METHODS
  Markers of thrombin generation, fibrin dissolution and endothelial activation were evaluated in 38 children with SS-Sβ°, 6 with SC disease and 50 age and blood group matched controls. Coagulation variables were correlated with markers of hemolysis and inflammation, with the presence of cerebral and lung vasculopathy and with the frequency of clinical complications.
  
  
  RESULTS
  SS-Sβ° patients presented higher levels of factor VIII, von Willebrand factor antigen (VWF:Ag) and collagen binding activity, tissue plasminogen activator antigen (t-PA:Ag), D-dimer, p-selectin, prothrombin fragment1+2 (F1+2) and lower ADAMTS-13:activity/VWF:Ag (p<0.05) compared to controls and SC patients. In SS-Sβ° patients coagulation variables correlated positively with markers of inflammation, hemolysis, and negatively with HbF (p<0.05). Patients with cerebral silent infarcts showed significant decrease in t-PA:Ag and ADAMTS-13 Antigen and a tendency toward higher D-dimer, F1+2, TAT compared to patients without them. D-dimer was associated with a six fold increased risk of cerebral silent infarcts. No correlation was found between coagulation activation and large vessel vasculopathy or other clinical events except for decreased t-PA:Ag in patients with tricuspid Rigurgitant Velocity >2.5m/sec.
  
  
  CONCLUSIONS
  SS-Sβ° disease is associated with extensive activation of the coagulation system at steady state since young age. ADAMTS-13 and t-PA:Ag are involved in the development of cerebral silent infarcts.
authors.affiliation: Clinic of Pediatric Hematology-Oncology, Department of Pediatrics, Azienda Ospedaliera- Università di Padova, Padova, Italy.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Colombatti
authors.forename: Emiliano
authors.initials: E
authors.lastname: De Bon
authors.forename: Antonella
authors.initials: A
authors.lastname: Bertomoro
authors.forename: Alessandra
authors.initials: A
authors.lastname: Casonato
authors.forename: Elena
authors.initials: E
authors.lastname: Pontara
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Omenetto
authors.forename: Graziella
authors.initials: G
authors.lastname: Saggiorato
authors.forename: Agostino
authors.initials: A
authors.lastname: Steffan
authors.forename: Tamara
authors.initials: T
authors.lastname: Damian
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Cella
authors.forename: Simone
authors.initials: S
authors.lastname: Teso
authors.forename: Renzo
authors.initials: R
authors.lastname: Manara
authors.forename: Patrizia
authors.initials: P
authors.lastname: Rampazzo
authors.forename: Giorgio
authors.initials: G
authors.lastname: Meneghetti
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Basso
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Sartori
authors.forename: Laura
authors.initials: L
authors.lastname: Sainati
mesh_terms: D000293:Adolescent; D000755:Anemia, Sickle Cell / Q000097:blood* / Q000378:metabolism; D001777:Blood Coagulation; D001808:Blood Vessels / Q000503:physiopathology*; D001921:Brain / Q000098:blood supply*; D002648:Child; D002675:Child, Preschool; D005260:Female; D006801:Humans; D007223:Infant; D008168:Lung / Q000098:blood supply; D008297:Male; D013917:Thrombin / Q000096:biosynthesis
chemical_list: D013917:Thrombin