Tissue factor‐positive monocytes in children with sickle cell disease: correlation with biomarkers of haemolysis

• Type of Material: Article
• Authors: B. N. Tamaja Setty, Thomas Jefferson University; Nigel S. Key, University of North Carolina; A. Koneti Rao, Temple University; Suhita Gayen-Betal, Thomas Jefferson University; Suba Krishnan, Thomas Jefferson University; Carlton D Dampier, Emory University; Marie J. Stuart, Thomas Jefferson University
• Language: English
• Date: 2012-05-01
• Publisher: Wiley: 12 months
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2012 Blackwell Publishing Ltd.
• Final Published Version (URL): http://dx.doi.org/10.1111/j.1365-2141.2012.09065.x
• Title of Journal or Parent Work: British Journal of Haematology
• ISSN: 0007-1048
• Volume: 157
• Issue: 3
• Start Page: 370
• End Page: 380
• Grant/Funding Information: This work was supported by grants P60HL62148 (MJS, BNYS, CDD, and AKR), and U54 HL70585 (MJS, BNYS, CCD and SK) from the National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD.
• Keywords: ANEMIA; RED-BLOOD-CELLS; ACUTE CHEST SYNDROME; ENDOTHELIAL-CELLS; PLASMA; Sickle cell disease; Life Sciences & Biomedicine; Hematology; MICROPARTICLES; FACTOR EXPRESSION; tissue factor-positive monocytes; biomarkers of haemolysis; biomarkers of inflammation; WHOLE-BLOOD; POTENTIAL ROLE; coagulation abnormalities; PATHOPHYSIOLOGY; Science & Technology
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Pathology

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.