High-dose intravenous methylprednisolone therapy in patients with Graves\u2019 orbitopathy is associated with the increased activity of factor VIII

P Miśkiewicz,B Rutkowska-Hinc,A Kondracka,J Milczarek-Banach,T Bednarczuk

doi:10.1007/s40618-018-0907-z

Abstract

PurposeVenous 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 moderate-to-severe Graves’ orbitopathy (GO).Methods26 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.ResultsA 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.ConclusionsThe 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.

Highlights

The alterations of coagulation and fibrinolysis parameters have been described in patients with endogenous Cushing’s syndrome (CS) [1,2,3,4,5] and those treated with1 3 Vol.:(0123456789)Journal of Endocrinological Investigation (2019) 42:217–225 glucocorticosteroids (GCs) [6,7,8].This change in hemostatic process is associated with an increased risk of venous thromboembolic events (VTE) and pulmonary embolism (PE) [5, 9]
There are some reports of fatal adverse effects associated with this treatment even after smaller cumulative intravenous methylprednisolone (IVMP) doses
In the Bartalena et al study, there was a case of death due to myocardial infarction 1 week after the

Summary

Introduction

The alterations of coagulation and fibrinolysis parameters have been described in patients with endogenous Cushing’s syndrome (CS) [1,2,3,4,5] and those treated with1 3 Vol.:(0123456789)Journal of Endocrinological Investigation (2019) 42:217–225 glucocorticosteroids (GCs) [6,7,8].This change in hemostatic process is associated with an increased risk of venous thromboembolic events (VTE) and pulmonary embolism (PE) [5, 9]. There are, reports of fatal side effects that may be associated with this therapy (e.g., PE, myocardial infarction, severe cerebrovascular events, acute liver damage and sudden death) [14,15,16,17]. For this reason, the cumulative dose of IVMP should not exceed 8 g within each treatment course, and pulses should not be given on consecutive or alternate days, except for the case of dysthyroid optic neuropathy [13, 15, 18].

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