Systematic review on the effect of glucocorticoid use on procoagulant, anti‐coagulant and fibrinolytic factors

Abstract

To cite this article: van Zaane B, Nur E, Squizzato A, Gerdes VEA, Bü ller HR, Dekkers OM, Brandjes DPM. Systematic review on the effect of glucocorticoid use on procoagulant, anti-coagulant and fibrinolytic factors. J Thromb Haemost 2010; 8: 2483-93.Summary. Background: Whether glucocorticoid use contributes to a hypercoagulable state, and thereby enhances the thrombotic risk, is controversial. Objective: We aimed to examine the effects of glucocorticoid use on coagulation and fibrinolysis. Methods: MEDLINE and EMBASE databases were searched to identify published studies comparing glucocorticoid treatment with a glucocorticoid-free control situation. Subjects could be either patients or healthy volunteers. Two investigators independently performed study selection and data extraction. Results were expressed as standardized mean difference, if possible; data were pooled with a random-effects model. Results: Of the 1967 identified publications, 36 papers were included. In healthy volunteers, a clear rise in factor (F)VII, VIII and XI activity was observed after glucocorticoid treatment, but these data alone provided insufficient evidence to support hypercoagulability. However, during active inflammation, glucocorticoids significantly increased levels of plasminogen activator inhibitor-1 (PAI-1), whereas levels of von Willebrand factor (VWF) and fibrinogen decreased. Perioperative use of glucocorticoids inhibited the increase in tissue-type plasminogen activator induced by surgery. Conclusions: The present study showed differential effects of glucocorticoids depending on the clinical situation in which it is given, most likely as a result of their disease modifying properties. Clinical outcome studies are needed to adequately assess the risk-benefit of glucocorticoid use per population when thrombotic complication is the focus.

MANAGEMENT OF ENDOCRINE DISEASE: The burden of Cushing's disease: clinical and health-related quality of life aspects

“…Glucocorticoids also upregulate the synthesis of plasminogen activator inhibitor type 1, the main inhibitor of the fibrinolytic system (49). This hypercoagulability state is a crucial factor predisposing CD patients to thromboembolic events, mostly after surgery and during inferior (62). Before introduction of anticoagulant prophylaxis, 10% of CD patients died due to thromboembolism and 10% had vascular morbidity.…”

The coagulopathy and thrombotic risk associated with L-Asparaginase treatment in adults with acute lymphoblastic leukaemia

“…25 Results from several in vitro studies have suggested that corticosteroids may directly activate coagulation and inhibit fibrinolysis by increasing the synthesis and secretion of vWF and plasminogen activator inhibitor-1 (PAI-1). 26 Prednisolone has been associated with an increase in FVIII, vWF and PAI-1. 27,28 Dexamethasone has been shown to cause a modest but clear rise in the activity of FVII, FVIII, FIX and fibrinogen in healthy volunteers, but to have no significant effect on PAI-1.…”

“…29 The use of corticosteroids during inflammatory states has been consistently associated with reduced levels of vWF and fibrinogen but increased PAI-1. 26 Systemic inflammation is known to be a potent prothrombotic stimulus and the inflammatory and coagulation systems are closely linked, therefore some of the prothrombotic changes induced by corticosteroid therapy may be balanced by the anti-inflammatory actions. 26,30,31 There are no randomised trials comparing the thrombosis risk associated with different corticosteroids in L-Asp-exposed patients.…”

“…26 Systemic inflammation is known to be a potent prothrombotic stimulus and the inflammatory and coagulation systems are closely linked, therefore some of the prothrombotic changes induced by corticosteroid therapy may be balanced by the anti-inflammatory actions. 26,30,31 There are no randomised trials comparing the thrombosis risk associated with different corticosteroids in L-Asp-exposed patients. However, a comparison of paediatric patients treated according to different Berlin-Frankfurt-Munster protocols indicated a much lower risk during induction with dexamethasone (1.8%) than with prednisolone (10.4%).…”

Oral Direct Anticoagulants in Thrombosis Management in Anti-Phospholipid Syndrome: Unanswered Questions

“…aPLs might increase the risk of VTE through various mechanisms, including affecting reactants involved in coagulation [4]. In addition glucocorticoid therapy might be associated with an increased risk of VTE [5].…”