High-dose intravenous methylprednisolone therapy in patients with Graves’ orbitopathy is associated with the increased activity of factor VIII

Abstract

Purpose Venous thromboembolic events (VTE), with their life-threatening manifestation as pulmonary embolism, are potential adverse effects of intravenous methylprednisolone (IVMP) pulse therapy, partially due to a hypercoagulable state. The aim of the study was to analyze the influence of IVMP on selected hemostatic parameters in patients with moderateto-severe Graves' orbitopathy (GO). Methods 26 euthyroid patients with GO were treated with 12 pulses of IVMP (6 × 0.5, 6 × 0.25 g every week). Hemostatic variables [factor (F) II, FV, FVII, FVIII, fibrinogen, antithrombin, activated partial thromboplastin time (aPTT), prothrombin time, international normalized ratio of prothrombin time, platelets and D-dimer] were analysed before, 24 and 48 h after 1st, 6th and 12th pulse. Results A constant, transient trend in changes of some hemostatic variables was observed after all assessed pulses. We discovered an increase in median activity of FVIII 24 and 48 h after pulses, with a shortening of aPTT 24 h after each IVMP pulse (p < 0.00005). FVII decreased 24 h after each pulse (p < 0.0005 after 1st and 12th, p < 0.00005 after 6th). Fibrinogen level decreased 48 h after each pulse (P < 0.00005). We did not observe any statistically significant changes in hemostatic parameters in the long-term evaluation. Therapy was concluded in one patient after the 9th pulse due to pulmonary embolism. Conclusions The increase of FVIII activity is a consequence of treatment with IVMP and occurs after each pulse. In patients with additional risk factors of VTE, anticoagulation prophylaxis should be considered.

Glucocorticoid Directly Enhances mRNA Levels of Endogenous Coagulation Factor VIII in Human Liver Sinusoidal Endothelial Cells

“…GC-induced coagulation-related hematological changes were investigated earlier in studies on Cushing syndrome, which is a condition involving excessive endogenous GC secretion [3][4][5][6]16) ; studies on multiple sclerosis or Graves' disease when steroid-pulse therapy is used 17,18) ; and studies on healthy people when standard GC doses are administered 19,20) . Based on these studies, GCs are thought to increase coagulation factors such as FII:C, FVIII:C, FIX:C, FXI:C, FXII:C, and VWF, with the changes in FVIII:C and VWF being most marked.…”

Therapy of moderate-to-severe Graves’ orbitopathy with intravenous methylprednisolone pulses is not associated with loss of bone mineral density

“…This therapy is recommended by the European Group on Graves' Orbitopathy (EUGOGO) due to higher efficacy and fewer adverse effects compared to oral GCs [1][2][3][4]. There are studies, however, which report side effects associated with this therapy (e.g., pulmonary embolism, myocardial infarction, severe cerebrovascular events, acute liver damage and sudden death, as well as changes in coagulation status and blood pressure) [1,2,[4][5][6][7][8]. One of the most serious side effects of long-term treatment with GCs is osteoporosis [9][10][11].…”

Effect of Glucocorticoid Administration in Intravenous Pulses on Selected Parameters of the Coagulation System

“…Their study showed the direct effect of GCs on the coagulation parameters. In a recent study, Miskiewicz et al assessed the effect of intravenous pulse therapy with MTP on the coagulation system in patients with thyroid orbitopathy [ 9 ]. This study showed a reproducible and statistically significant increase in the activity of the plasma coagulation factor VIII 24 h and 48 h after the administration of 1, 6, and 12 pulses.…”