title: Tissue factor-positive monocytes in children with sickle cell disease: correlation with biomarkers of haemolysis.
abstract: Tissue Factor (TF) initiates thrombin generation, and whole blood TF (WBTF) is elevated in sickle cell disease (SCD). We sought to identify the presence of TF-positive monocytes in SCD and their relationship with the other coagulation markers including WBTF, microparticle-associated TF, thrombin-antithrombin (TAT) complexes and D-dimer. Whether major SCD-related pathobiological processes, including haemolysis, inflammation and endothelial activation, contribute to the coagulation abnormalities was also studied. The cohort comprised children with SCD (18 HbSS, 12 HbSC, mean age 3·6 years). We demonstrated elevated levels of TF-positive monocytes in HbSS, which correlated with WBTF, TAT and D-dimer (P = 0·02 to P = 0·0003). While TF-positive monocytes, WBTF, TAT and D-dimer correlated with several biomarkers of haemolysis, inflammation and endothelial activation in univariate analyses, in multiple regression models the haemolytic markers (reticulocytes and lactate dehydrogenase) contributed exclusively to the association with all four coagulant markers evaluated. The demonstration that haemolysis is the predominant operative pathology in the associated perturbations of coagulation in HbSS at a young age provides additional evidence for the early use of therapeutic agents, such as hydroxycarbamide to reduce the haemolytic component of this disease.
authors.affiliation: Division of Research Haematology, Department of Pediatrics, Marian Anderson Comprehensive Sickle Cell Anaemia Care and Research Centre, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107, USA. yamaja.setty@jefferson.edu
authors.forename: B N Yamaja
authors.initials: BN
authors.lastname: Setty
authors.forename: Nigel S
authors.initials: NS
authors.lastname: Key
authors.forename: A Koneti
authors.initials: AK
authors.lastname: Rao
authors.forename: Suhita
authors.initials: S
authors.lastname: Gayen-Betal
authors.forename: Suba
authors.initials: S
authors.lastname: Krishnan
authors.forename: Carlton D
authors.initials: CD
authors.lastname: Dampier
authors.forename: Marie J
authors.initials: MJ
authors.lastname: Stuart
mesh_terms: D000755:Anemia, Sickle Cell / Q000097:blood*; D000990:Antithrombin III; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D004730:Endothelium, Vascular / Q000378:metabolism; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005434:Flow Cytometry / Q000379:methods; D006461:Hemolysis / Q000502:physiology*; D006801:Humans; D018836:Inflammation Mediators / Q000032:analysis; D009000:Monocytes / Q000737:chemistry*; D010447:Peptide Hydrolases / Q000097:blood; D013925:Thromboplastin / Q000032:analysis*
chemical_list: D015415:Biomarkers; D005338:Fibrin Fibrinogen Degradation Products; D018836:Inflammation Mediators; C046193:antithrombin III-protease complex; C036309:fibrin fragment D; D000990:Antithrombin III; D013925:Thromboplastin; D010447:Peptide Hydrolases