Anabolic–Androgenic Steroid Abuse Impairs Fibrin Clot Lysis

Abstract

Abuse of anabolic–androgenic steroids (AASs) is suspected to increase the risk of cardiovascular disease (CVD) and cardiovascular mortality in otherwise healthy individuals. AAS abuse may increase the incidence of CVD by altering the hemostatic balance toward a procoagulant state. Studies on the effect of AAS abuse on the fibrinolytic system, however, have either demonstrated a profibrinolytic effect or no effect of AAS abuse, but the overall effect of AAS on fibrinolysis has not been addressed so far. This cross-sectional study investigated the effect of AAS on fibrin clot lysis, fibrin structure, and the hemostatic proteins, potentially affecting these measures in current and former AAS abusers and healthy age-matched controls. The study population consisted of 37 current and 33 former AAS abusers, along with 30 healthy age-matched controls. Fibrin clot lysis, fibrin structure properties, fibrinogen, coagulation factor XIII (FXIII) plasminogen, plasmin inhibitor, plasminogen activator inhibitor-1 (PAI-1), and thrombin activatable fibrinolysis inhibitor (TAFI) were determined. Fibrin clot lysis was significantly reduced in participants abusing AAS compared with former abusers and controls (p < 0.001). Plasma fibrinogen, plasminogen, and plasmin inhibitor were significantly increased in current abusers (p < 0.05). No significant differences were observed with respect to measures of fibrin structure properties, PAI-1, and TAFI (p > 0.05). In conclusion, AAS abuse depresses fibrin clot lysis. This effect is not associated with alterations in fibrin structure but is rather caused by increased plasma concentrations of fibrinogen, FXIII, and plasmin inhibitor. These findings suggest that AAS abuse may be associated with increased thrombotic disease.

Effect of Anabolic–Androgenic Steroid Abuse on the Contact Activation System

“…compared with controls (4,5). In line with these findings, we presently observe elevated concentrations of HK in both current and former AAS abusers.…”

“…to enhance muscle strength and size. AAS abuse, however, may cause many adverse reactions and is associated with cardiovascular, neuroendocrine, psychiatric, and hepatic side effects (3)(4)(5)(6)(7)(8)(9)(10).…”

“…Synthetic AAS were previously considered as drugs with potential use in treatment of patients with coagulation factor deficiencies or deficiencies in the regulatory mechanisms of coagulation or fibrinolysis (3), as synthetic AAS increase the plasma concentration of many proteins including proteins of the haemostatic system (3)(4)(5).…”

“…2 Synthetic AASs were previously considered as drugs with potential use in treatment of patients with coagulation factor deficiencies or deficiencies in the regulatory mechanisms of coagulation or fibrinolysis, 3 as synthetic AASs increase the plasma concentration of many proteins including proteins of the hemostatic system. [3][4][5] Illicit use of synthetic AAS in combination with numerous other drugs has been reported in professional athletes and is in particular prevailing among recreational strength athletes 3 to enhance muscle strength and size. AAS abuse, however, may cause many adverse reactions and is associated with cardiovascular, neuroendocrine, psychiatric, and hepatic side effects.…”

“…AAS abuse, however, may cause many adverse reactions and is associated with cardiovascular, neuroendocrine, psychiatric, and hepatic side effects. [3][4][5][6][7][8][9][10] Of notice is the effect of synthetic AAS on the contact activation system (CAS) consisting of coagulation factor XII (FXII), prekallikrein (PK), and high-molecular-weight kininogen (HK). Activation and propagation of this system lead to cleavage of HK and formation of bradykinin (BK) which mediates vasodilation through binding to the BK B2 receptor on vascular endothelial cells 11 and stimulates inflammatory reactions by this action.…”