Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
Not provided
The alterations of coagulation and fibrinolysis parameters have been described in patients with endogenous Cushing's syndrome (CS) and those treated with glucocorticosteroids (GCs). The change in hemostatic process is associated with an increased risk of venous thromboembolic events (VTE) and pulmonary embolism (PE). Anticoagulation prophylaxis reduces thromboembolic complications in endogenous and exogenous hypercortisolism. The impact of the intravenous GCs therapy on hypercoagulability, however, remains unclear and perplexing. According to the European Group On Graves' Orbitopathy (EUGOGO), patients with active, severely symptomatic and sight-threatening Graves' orbitopathy (GO) should be treated with high dose intravenous methylprednisolone (IVMP) pulses. There are, however, 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). 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. Nevertheless, even smaller cumulative therapy may be associated with fatal cardiovascular complications. Hence the aim of our study was to evaluate the effects of IVMP therapy on hemostatic process in patients with GO. All of patients were treated according to EUGOGO recommendations with standard doses of methylprednisolone with standard recommended schedule. Inclusion criterion for the therapy was according to EUGOGO guidelines moderate-to-severe and active GO (12 pulses of IVMP 6x0.5g followed by 6x0.25g every week).
The end point of the study was a change in hemostatic variables' levels in laboratory tests. There were short- and long-term hemostatic changes analysed during IVMP therapy: comparisons of laboratory tests before, 24h and 48h after selected pulses, and between the beginning of 1st, 6th and 12th IVMP pulses, respectively. Hemostatic variables that were evaluated: factor [F] II, FV, FVII, FVIII, fibrinogen, antithrombin, activated partial thromboplastin time, prothrombin time, platelets and D - dimer. Moreover, analyses were performed concerning clinical data (such as age, sex, body mass index, smoking, duration time of GO, presence of hypertension, basal markers of thyroid function) between independent groups (patients with initially increased/reduced selected markers versus without increased/reduced selected markers).
Not provided
Not provided
Not provided
Not provided
Not provided
| Label | Type | Description | Intervention Names |
|---|---|---|---|
| active, moderate-to-severe GO | Each participant received IVMP according to EUGOGO recommendations (cumulative dose of methylprednisolone 4.5 g, treatment duration 12 weeks in single weekly intravenous pulses, first 6 weeks 0.5g of IVMP, next 6 weeks 0.25g of IVMP). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Methylprednisolone | Drug |
|
| Measure | Description | Time Frame |
|---|---|---|
| Change in activity of coagulation factor VIII from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse | 24 hours | |
| Change in activity of coagulation factor VIII from baseline (before therapy) to the end of the course of therapy with methylprednisolone | 12 weeks | |
| Change in of activated partial thromboplastin time (seconds) from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse | 24 hours | |
| Change in activated partial thromboplastin time (seconds) from baseline (before therapy) to the end of the course of therapy with methylprednisolone | 12 weeks |
| Measure | Description | Time Frame |
|---|---|---|
| Change in activity of coagulation factor II from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse | 24 hours | |
| Change in activity of coagulation factor V from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse |
| Measure | Description | Time Frame |
|---|---|---|
| Change in activity of coagulation factor VIII from baseline (before administration of methylprednisolone) to 48 hours after the first intravenous pulse | 48 hours | |
| Change of activated partial thromboplastin time (seconds) from baseline (before administration of methylprednisolone) to 48 hours after the first intravenous pulse |
Inclusion Criteria:
Exclusion Criteria:
Not provided
Not provided
Not provided
Not provided
Patients admitted to the Endocrine Department
The collected data will be shared in a publication. It includes all laboratory results from all points of evaluation: hemostatic variables- factor [F] II, FV, FVII, FVIII, fibrinogen, activated partial thromboplastin time, prothrombin time, international normalized ratio of prothrombin time, platelet count and D - dimer.
The results of the study will be published in 2018
Not provided
Not provided
Not provided
| ID | Term |
|---|---|
| D006111 | Graves Disease |
| D049970 | Graves Ophthalmopathy |
| D013927 | Thrombosis |
| D054556 | Venous Thromboembolism |
| ID | Term |
|---|---|
| D005094 | Exophthalmos |
| D009916 | Orbital Diseases |
| D005128 | Eye Diseases |
| D006042 | Goiter |
Not provided
Not provided
| ID | Term |
|---|---|
| D008775 | Methylprednisolone |
| ID | Term |
|---|---|
| D011239 | Prednisolone |
| D011246 | Pregnadienetriols |
| D011245 | Pregnadienes |
| D011278 | Pregnanes |
Not provided
Not provided
Not provided
Not provided
Not provided
Venous blood was collected in the morning following a 12 hour fast. This was utilized for preparation of serum, 3.2% sodium citrate plasma, and citrate platelet - poor plasma after double centrifugation. Hemostatic parameters were analyzed within 1 - 1.5 hour after blood sampling, except for FVIII activity measured in platelet - poor plasma stored frozen at -70°C until assay.
| 24 hours |
| Change in activity of coagulation factor VII from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse | 24 hours |
| Change in prothrombin time (seconds) from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse | 24 hours |
| Change in fibrinogen (mg/dl) from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse | 24 hours |
| Change in D-Dimer (ng/dl) from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse | 24 hours |
| Change in PLT count from baseline (before administration of methylprednisolone) to 24 hours after first intravenous pulse | 24 hours |
| Change in activity of coagulation factor II from baseline (before therapy) to the end of the course of therapy with methylprednisolone | 12 weeks |
| Change in activity of coagulation factor V from baseline (before therapy) to the end of the course of therapy with methylprednisolone | 12 weeks |
| Change in activity of coagulation factor VII from baseline (before therapy) to the end of the course of therapy with methylprednisolone | 12 weeks |
| Change in prothrombin time (seconds) from baseline (before therapy) to the end of the course of therapy with methylprednisolone | 12 weeks |
| Change in fibrinogen (mg/dl) from baseline (before therapy) to the end of the course of therapy with methylprednisolone | 12 weeks |
| Change in D-Dimer (ng/dl) from baseline (before therapy) to the end of the course of therapy with methylprednisolone | 12 weeks |
| Change in PLT count from baseline (before therapy) to the end of the course of therapy with methylprednisolone | 12 weeks |
| 48 hours |
| Change in activity of coagulation factor VIII from baseline (before therapy) to the sixth pulse of the methylprednisolone | 6 weeks |
| Change activated partial thromboplastin time (seconds) from baseline (before therapy) to the sixth pulse of the methylprednisolone | 6 weeks |
| D013959 |
| Thyroid Diseases |
| D004700 | Endocrine System Diseases |
| D006980 | Hyperthyroidism |
| D001327 | Autoimmune Diseases |
| D007154 | Immune System Diseases |
| D015785 | Eye Diseases, Hereditary |
| D030342 | Genetic Diseases, Inborn |
| D009358 | Congenital, Hereditary, and Neonatal Diseases and Abnormalities |
| D016769 | Embolism and Thrombosis |
| D014652 | Vascular Diseases |
| D002318 | Cardiovascular Diseases |
| D013923 | Thromboembolism |
| D013256 |
| Steroids |
| D000072473 | Fused-Ring Compounds |
| D011083 | Polycyclic Compounds |