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. 2012 May;157(3):370-80.
doi: 10.1111/j.1365-2141.2012.09065.x. Epub 2012 Feb 24.

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

B N Yamaja Setty  1 , Nigel S Key, A Koneti Rao, Suhita Gayen-Betal, Suba Krishnan, Carlton D Dampier, Marie J Stuart
Affiliations

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

B N Yamaja Setty et al. Br J Haematol. 2012 May.

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.

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Conflict of interest statement

DISCLOSURE OF CONFLICT OF INTEREST

We declare that we have no conflict of interest.

Figures

Figure 1
Figure 1. Flow Cytometric Analysis of tissue factor (TF)-positive Monocytes from a representative Control, and Patients with HbSC and HbSS Disease
Following incubation of whole blood with desired antibodies, monocytes were analysed by flow cytometry as described. 5000 CD14-positive events were collected and analysed for percent TF-positive events. Representative dot plots from a control (Panel B), and patients with HbSC (Panel C) and HbSS disease (Panel D) are depicted. TF-negative (Quadrant Q1) and TF-positive (Quadrant Q2) regions were set up using a blood sample stained with anti-CD14-PE and FITC-labeled isotype-matched negative control antibody (Panel A).
Figure 2
Figure 2. Correlation between percent tissue factor (TF)-positive monocytes and percent reticulocyte count (panel A), whole blood TF procoagulant activity and plasma lactate dehydrogenase (LDH) levels (panel B), plasma levels of thrombin-antithrombin (TAT) complexes and percent reticulocyte count (panel C), and plasma levels of D-dimer and percent reticulocyte count (panel D)
The solid and dotted lines represent the regression fit to the data from all patients with SCD, and the 95% confidence interval curves, respectively. The r-, p-, and n-values for the correlation are shown in the respective panels.
Figure 3
Figure 3. Correlation between percent tissue factor (TF)-positive Monocytes and either Whole Blood TF Procoagulant Activity (panel A), Microparticle-associated TF (panel B), Plasma Levels of thrombin-antithrombin (TAT) Complexes (panel C), or Plasma Levels of D-Dimer (panel D)
The solid and dotted lines represent the regression fit to the data from all patients with SCD, and the 95% confidence interval curves, respectively. The r-, p-, and n-values for the correlation are shown in the respective panels.
See this image and copyright information in PMC

References

    1. Adedeji MO, Cespedes J, Allen K, Subramony C, Hughson MD. Pulmonary thrombotic arteriopathy in patients with sickle cell disease. Archives of Pathology and Laboratory Medicine. 2001;125:1436–1441. - PubMed
    1. Ataga KI, Cappellini MD, Rachmilewitz EA. β-Thalassaemia and sickle cell anaemia as paradigms of hypercoagulabilty. British Journal of Haematology. 2007;139:3–13. - PubMed
    1. Ataga KI, Brittain JE, Desai P, May R, Jones S, Delaney J, Strayhorn D, Hinderliter A, Key NS. Association of coagulation activation with clinical complications in sickle cell disease. PLoS One. 2012;7:e2978. - PMC - PubMed
    1. Belcher JD, Marker PH, Weber JP, Hebbel RP, Vercellotti GM. Activated monocyes in sickle cell disease: potential role in the activation of vascular endothelium and vaso-occlution. Blood. 2000;96:2451–2459. - PubMed
    1. Blann AD, Mohan JS, Bareford D, Lip GY. Soluble P-selectin and vascular endothelial growth factor in steady state sickle cell disease: relationship to genotype. Journal of Thrombosis and Thrombolysis. 2008;25:185–189. - PubMed

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