Persistent Endothelial Damage after Intravenous Immunoglobulin Therapy in Kawasaki Disease

Abstract

Background: Kawasaki disease (KD) is an acute systemic vasculitis of unknown etiology. Although endothelial cell damage associated with vasculitis might lead to the hypercoagulability that is involved in coronary artery disease, the changes in coagulation after intravenous immunoglobulin therapy (IVIG) have not been well investigated in KD. The aims of this study were to address the changes in coagulation before and after IVIG in KD, and to further elucidate the coagulation-inflammation axis, with special attention to endothelial damage. Methods: We retrospectively collected the laboratory data before and after IVIG in 26 pediatric KD patients treated at the Nara Prefecture Western Medical Center between May 2010 and April 2012. Prothrombin time (PT), activated partial thromboplastin time (APTT) and levels of fibrin/fibrinogen degradation products (FDP) and D-dimer were assessed as coagulation markers. Fibrinogen, ferritin, serum amyloid A, procalcitonin and urine F2 microglobulin were assessed as inflammation markers. Thrombomodulin, antithrombin, factor VIII activity (FVIII:C), and von Willebrand factor antigen (VWF:Ag) were used to assess endothelial damage. Results: Prolonged PT and APTT before IVIG were significantly shortened after IVIG, and elevated levels of FDP and D-dimer were significantly decreased. Elevated levels of inflammation markers had decreased significantly after IVIG, but levels of FVIII:C and VWF:Ag remained high, even after IVIG. Conclusions: Ameliorated inflammation by IVIG might improve the hypercoagulable state. Nevertheless, our results suggest that endothelial damage might be prolonged in IVIG-treated patients. Control of endothelial damage in KD is critical. i 2014 S. Karger AG, Basel

Serum Levels of Syndecan-1 in Patients With Kawasaki Disease

“…KD is a type of acute vasculitis that leads to endothelial cell damage individuated by SDC-1 shedding 5–7 and consequently, serum levels of SDC-1 are increased. In our study, the results of serum SDC-1 levels indicate more remarkable SDC-1 shedding and endothelial cell damage in KD patients when compared with HC and FC.…”

“…In earlier studies circulating endothelial cells, endothelial microparticles, thrombomodulin, antithrombin, von Willebrand factor antigen and coagulation factor VIII activity were used as indicators of endothelial cell damage in KD. 6,7,31 Although SDC-1 was a biomarker for glycocalyx damage indicating endothelial injury, there were no reports about the implication of SDC-1 in KD. We exhibited an increase of serum SDC-1 as a potential novel biomarker of activation and damage of endothelial cells in KD.…”

“…Previous studies have shown that inflammation was ameliorated after IVIG treatment while endothelial damage may be prolonged. 7…”

“…This damage has been shown to persist even years after treatment with intravenous immunoglobulin (IVIG) therapy. 5–7 The endothelial glycocalyx covers the luminal surface of the vascular endothelium which serves as a protective barrier. 8 Syndecan-1 (SDC-1) is expressed on the glycocalyx of epithelial cells, endothelial cells and plasma cells and is the most prominent of 4 subtypes of syndecan.…”

Thrombosis in Autoimmune Diseases: A Role for Immunosuppressive Treatments?

“…Actually, IVIg increases blood viscosity, 84,85 and seems to be able to induce arterial vasospasm 86 and endothelial damage. 87 Another question is about the manufacturing processes of IVIg preparations, which may contain substances with a high prothrombotic potential. High levels of anticardiolipin/antiphospholipid antibodies were found in some preparations, which could promote a thrombotic event via the development of APS.…”