Journal
BRITISH JOURNAL OF HAEMATOLOGY
Volume 157, Issue 3, Pages 370-380Publisher
WILEY
DOI: 10.1111/j.1365-2141.2012.09065.x
Keywords
Sickle cell disease; tissue factor-positive monocytes; coagulation abnormalities; biomarkers of haemolysis; biomarkers of inflammation
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Funding
- National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD [P60HL62148, U54HL70585]
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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 388100%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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