Persistent endothelial damage after intravenous immunoglobulin therapy in Kawasaki disease

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.

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 β2 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.

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.

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.