Coagulation and Fibrinolysis in Obstructive Sleep Apnoea

Abstract

Obstructive sleep apnoea (OSA) is a common disease which is characterised by repetitive collapse of the upper airways during sleep resulting in chronic intermittent hypoxaemia and frequent microarousals, consequently leading to sympathetic overflow, enhanced oxidative stress, systemic inflammation, and metabolic disturbances. OSA is associated with increased risk for cardiovascular morbidity and mortality, and accelerated coagulation, platelet activation, and impaired fibrinolysis serve the link between OSA and cardiovascular disease. In this article we briefly describe physiological coagulation and fibrinolysis focusing on processes which could be altered in OSA. Then, we discuss how OSA-associated disturbances, such as hypoxaemia, sympathetic system activation, and systemic inflammation, affect these processes. Finally, we critically review the literature on OSA-related changes in markers of coagulation and fibrinolysis, discuss potential reasons for discrepancies, and comment on the clinical implications and future research needs.

Keywords: OSA; coagulation; fibrinolysis; obstructive sleep apnoea; platelets.

Figure 1

The coagulation cascade and fibrinolysis and how obstructive sleep apnoea (OSA) interacts with them. APC—activated protein C; AT-III—antithrombin III; EPCR—endothelial protein C receptor; IX—factor IX; IXa—activated factor IX; PAI-1—plasminogen activator inhibitor-1; TAFI—thrombin activated fibrinolysis inhibitor; TAFIa—activated thrombin activated fibrinolysis inhibitor; TAT—thrombin-antithrombin complex; TF—tissue factor; TFPI—tissue factor pathway inhibitor; tPA—tissue plasminogen activator; uPA—urokinase plasminogen activator; uPAR—urokinase type plasminogen activator receptor; Va—activated factor V; VIIIa—activated factor VIII; X—factor X; Xa—activated factor X; XI—factor XI; Xia—activated factor XI; XII—Factor XII; XIIa—activated factor XII.

Figure 2

The mechanism of platelet adhesion and aggregation. 5-HT—serotonin; ADP—adenosine diphosphate; GP Ia-IIa—glycoprotein Ia-IIa; GP IIb-IX-V—glycoprotein IIb-IX-V; GP IV—glycoprotein IV; PSGL-1—P-selectin glycoprotein ligand 1; TXA₂—thromboxane-A2; vWF—von Willebrand factor.

Figure 3

The role of endothelium in regulation of haemostasis (A) and endothelial injury (B) in OSA. AT-III—antithrombin III; HYAL—hyaluronidase; LDL-C—low-density lipoprotein cholesterol; MMPs—matrix metalloproteinases; NO—nitric oxide; PAI-1—plasminogen activator inhibitor-1; PGI₂—prostacyclin; ROS—reactive oxygen species; TF—tissue factor; vWF—von Willebrand factor.