The Coagulation and Protein C Pathways in Patients with Sleep Apnea
Department of Pulmonary and Critical Care Medicine, Mie University Graduate School of Medicine, Tsu-city, Mie, Japan.Beiträge zur Klinik der Tuberkulose (Impact Factor: 2.27). 06/2009; 187(4):209-13. DOI: 10.1007/s00408-009-9152-8
Patients with obstructive sleep apnea (OSA) have a high frequency of cardiovascular diseases and hypercoagulability is believed to be involved in the mechanism of those vascular events. We evaluated whether there is a dysfunction in the protein C anticoagulant pathway in patients with obstructive sleep apnea. Two hundred ninety-three patients were enrolled. To confirm the diagnosis of OSA, all-night polysomnography, including determination of SpO(2), was carried out. The apnea-hypopnea index (AHI) was used for judging the presence of sleep-breathing disorder. The plasma levels of the thrombin-antithrombin complex were higher in patients with AHI > 5 than in those without OSA, defined as AHI < 5. However, there was no statistically significant difference in the plasma level of either activated protein C/alpha-antitrypsin complex or soluble thrombomodulin between patients with AHI > 5 and those with AHI < 5. The results of this study showed for the first time that markers of the protein C anticoagulant pathway are not affected in patients with OSA and that the protein C pathway is probably not involved in the mechanism of hypercoagulability in subjects with sleep-disordered breathing.
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ABSTRACT: Many of the components contributing to coagulability are enhanced by repeated episodes of hypoxia, as occurs in obstructive sleep apnea, but no one has yet measured the global hemostatic properties of blood in an animal model of this disease. Using thromboelastography, a hemostatic assay, we measured hemostasis in six pentobarbital-anesthetized rats before and after 3h of repeated inspiratory occlusions lasting 30s applied every 2 min and compared the results to those in six identically prepared rats before and after 3h of resting breathing. Rats subjected to occlusions displayed faster onset of clotting (p<0.031) and more rapid coagulation (p<0.031). Thus, repeated inspiratory occlusions acutely cause hypercoagulability in rats. Thromboelastography, a simple test of hemostasis, may help evaluate the factors responsible for this increase and, in patients with obstructive sleep apnea, the risk of future cardiovascular disease.
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ABSTRACT: Obstructive sleep apnea syndrome (OSAS) is a chronic disease characterized by recurrent episodes of partial or complete upper airway collapse and obstruction during sleep, associated with intermittent oxygen desaturation, sleep fragmentation, and symptoms of disruptive snoring and daytime sleepiness. Increasing focus is being placed on the relationship between OSAS and all-cause and cardiovascular disease-related mortality, but it still largely unclear whether this association is causative or simply speculative and epidemiological. Basically, reliable clinical evidence supports the hypothesis that OSAS might be associated with essential and resistant hypertension, as well as with an incremental risk of developing stroke, cardiac rhythm perturbations (e.g., atrial fibrillation, bradyarrhythmias, supraventricular and ventricular arrhythmias), coronary artery disease, acute myocardial infarction, and heart failure. Although it is still unclear whether OSAS might represent an independent risk factor for several acute or chronic conditions, or rather might trigger cardiovascular disease in the presence of traditional cardiovascular risk factors (e.g., obesity, diabetes, and dyslipidemia), there is a plausible biological background underlying this association, in that most of the mechanisms implicated in the pathogenesis of OSAS (i.e., hypoxia, hypercapnia, negative intrathoracic pressure, micro-arousal, sympathetic hyperactivity, metabolic and hormonal changes, oxidative stress, phlogosis, endothelial dysfunction, hypercoagulability, and genetic predisposition) might also be involved in the pathogenesis of cardiovascular disorders. In this article we discuss the different aspects of the relationship between OSAS and pathogenically different conditions such as systemic hypertension, coronary artery disease, stroke, metabolic abnormalities, arrhythmias, and heart failure, and we also discuss the kaleidoscope of phenomena implicated in the pathogenesis of this challenging disease.
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ABSTRACT: Obstructive sleep apnea (OSA) is associated with systemic inflammation and a hypercoagulable state. The current study aim was to investigate whether mandibular advancement splint (MAS) therapy affects inflammatory and hemostatic parameters in patients with mild-to-moderate OSA. Twenty-two patients with mild-to-moderate OSA and 16 control subjects were studied. OSA subjects were treated with a titratable MAS for 6 months. Baseline plasma C-reactive protein, interleukin-1β, interleukin-10, interleukin-6, P-selectin, fibrinogen, D-dimer, plasminogen activator inhibitor-1 (PAI-1), thrombin-antithrombin complex, activated thrombin-activatable fibrinolysis inhibitor (TAFIa), 6-keto-PGF1α, glucose, and fibrin clot lysis time (CLT) were measured in all subjects. After 3 months of MAS therapy, measurements were repeated for the 22 patients, and after 6 months all measurements were repeated for all study subjects. MAS treatment reduced significantly AHI at 3 months (24 vs 13.1/h) and further improved it at 6 months (13.1 vs 7.05/h). Compared with controls, OSA subjects had a significant higher baseline mean levels of fibrinogen, TAFIa, 6-keto-PGF1α, and glucose. MAS treatment significantly improved levels of IL-1β, D-dimer, TAFIa, and CLT. Despite residual apneas, MAS treatment group presented similar measured homeostatic and inflammatory levels to controls except for glucose. Treatment with MAS in mild-to-moderate OSA subjects improves the inflammatory profile and homeostatic markers. Niżankowska-Jędrzejczyk A; Almeida FR; Lowe AA; Kania A; Nastałek P; Mejza F; Foley JH; Niżankowska-Mogilnicka E; Undas A. Modulation of inflammatory and hemostatic markers in obstructive sleep apnea patients treated with mandibular advancement splints: a parallel, controlled trial. J Clin Sleep Med 2014;10(3):255-262.
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