An association between oxygen desaturation and D-dimer in patients with obstructive sleep apnea syndrome

Summary

D-dimer, a degradation product of fibrin, is being increasingly used as a marker and prognostic factor in various thrombotic diseases. Previous reports have shown that obstructive sleep apnea is associated with platelet activation and hypercoagulability. The aim of the study was to assess the potential role of the plasma D-dimer test in patients with obstructive sleep apnea. We designed a prospective group comparison study in a tertiary- care, university-affiliated medical center. One hundred and three patients of mean age 57 years (range 50–76 years) with symptoms suggestive of obstructive sleep apnea were included. Polysomnography was performed in all cases, and blood was collected for plasma D-dimer measurement by MiniQuant turbidmetric assay. The demographic and polysomnograph data were compared between patients with normal and high (>250 ng/ml) D-dimer levels. The group with higher D-dimer values had lower mean minimal oxygen saturation (72.1±16.4 vs. 81.7±11.6%, p=0.008) and a longer mean period of oxygen saturation below 90% (84.1±86.2 vs. 38.5±70.8 minutes, p=0.032). There was no correlation of respiratory disturbance index and sleep architecture with D-dimer values. We concluded that sleep apnea syndrome is associated with fibrinolytic activity. Oxygen desaturation seems to be one of the mediatory factors in the putative connection between obstructive sleep apnea and hypercoagulability state.

Keywords

Obstructive sleep apnea - D-dimer - fibrinolysis - nocturnal hypoxia

• References

• 1 Young T, Palta M, Dempsey J. et al. The occurrence of sleep disordered breathing among middle-aged adults.. N Engl J Med 1993; 328: 1230-5.
• 2 Jenkison C. et al. Comparison of therapeutic and subtherapeutic nasal continuous positive airway pressure for obstructive sleep apnoea: a randomized prospective parallel trial.. Lancet 1999; 353: 2100-5.
• 3 Weiss JW, Launois SH, Anand A. et al. Cardiovascular morbidity in obstructive sleep apnea.. Prog Cardiovasc Dis 1999; 41: 367-76.
• 4 Young T, Peppard P, Palta M. et al. Population-based study of sleep disordered breathing as a risk factor for hypertension.. Arch Intern Med 1997; 157: 1746-52.
• 5 Ziegler MG, Nelesoen R, Mills P. et al. Sleep apnea, noradrenaline-release rate, and daytime hypertension.. Sleep 1997; 20: 224-31.
• 6 Laks L. Pulmonary arterial pressure in sleep apnea.. Sleep 1993; 16: S41-S43.
• 7 Peker Y, Kraczi H, Hedner J. et al. An independent association between obstructive sleep apnea and coronary artery disease.. Eur Respir J 1999; 14: 179-84.
• 8 Nahmias J, Lao R, Karetzky M. Right ventricular dysfunction in obstructive sleep apnea: reversal with nasal continuous positive airway pressure.. Eur Respir J 1996; 9: 945-51.
• 9 Hung J, Whitford EG, Parsons RW. et al. Association of sleep apnea with myocardial infarction in men.. Lancet 1990; 18: 261-4.
• 10 Partinen M, Palmaki H. Snoring and cerebral infarction.. Lancet 1985; 14: 1325-6.
• 11 He J, Kryger MH. et al. Mortality and apnea index in obstructive sleep apnea.. Chest 1988; 94: 9-14.
• 12 Lindberg E, Janson C, Svardsudd K. et al. Increased mortality among sleepy snorers: a prospective population based study.. Thorax 1998; 53: 631-7.
• 13 Davis MJ. The contribution of thrombosis to the clinical expression of coronary atherosclerosis.. Thromb Res 1996; 82: 1-32.
• 14 Virmani R, Kolodgie FD. et al. Lessons from sudden coronary death: a comprehensive morphological classification scheme for atherosclerotic lesions.. Arterioscler Thromb Vasc Biol 2000; 20: 1262-75.
• 15 Rosito GBA, Tofler GH. Hemostatic factors as triggers of cardiovascular events.. Cardiol Clin 1996; 14: 239-50.
• 16 Koenig W. Hemostatic risk factors for cardiovascular diseases.. Eur Heart J 1998; 19: C39-C43.
• 17 Shitrit D, Bendayan D A. et al. Significance of a plasma D-dimer test in patients with primary pulmonary hypertension.. Chest 2002; 122: 1674-8.
• 18 Rowbotham BJ, Marder VJ, Barlow GH. Measurement of crosslinked fibrin in diagnosis of venous thrombosis.. Thromb Haemost 1987; 57: 59-61.
• 19 American Thoracic Society- Medical Section of the American Lung Association.. Indications and standards for cardiopulmonary sleep studies.. Am Rev Respir Dis 1989; 139: 559-68.
• 20 American Academy of Sleep Medicine Task Force.. Sleep-related breathing disorders in adults: Recommendations for syndrome definition and measurement techniques in clinical research.. Sleep 1999; 22: 667-89.
• 21 Rechtschaffen A, Kales A. A manual of standardized terminology, techniques and scoring system for sleep stages of human subjects.. NIH Publication No. 204. Washington, DC: U.S. Government Printing Office; 1968
• 22 Shamsuzzaman ASM, Somers VK. Fibrinogen, stroke and obstructive sleep apnea.. Am J Respir Crit Care Med 2000; 162: 2018-20.
• 23 Wessendorf TE, Thilmann AF, Wang YM. et al. Fibrinogen levels and obstructive sleep apnea in ischemic stroke.. Am J Respir Crit Care Med 2000; 162: 2039-42.
• 24 Chin K, Ohi M, Kita H. et al. Effects of NCPAP therapy on fibrinogen levels in obstructive sleep apnea syndrome.. Am J Respir Crit Care Med 1996; 153: 1972-6.
• 25 Bokinsky G, Miller M, Ault K. et al. Spontaneous platelet activation and aggregation during obstructive sleep apnea and its response to therapy with nasal continuous positive airway pressure.. Chest 1995; 108: 625-30.
• 26 Eisensenhr I, Ehrenberg BL. et al. Platelet activation, epinephrine, and blood pressure in obstructive sleep apnea syndrome.. Neurology 1998; 51: 188-95.
• 27 Reinhart WH, Oswald J, Kuhn M. Blood viscosity and platelet function in patients with obstructive sleep apnea syndrome treated with nasal continuous positive airway pressure.. Clin Hemorsh Microcirc 2002; 27: 201-7.
• 28 Rangemark C, Hedner JA. et al. Platelet function and fibrinolytic activity in hypertensive and normotensive sleep apnea patients.. Sleep 1995; 18: 188-94.
• 29 Von Kanel R, Le DT, Nelesen RA. et al. The hypercoagulable state in sleep apnea is related to comorbid hypertension.. J Hypertension 2001; 19: 1445-51.
• 30 Dimsdale JE, Coy T, Ziegler MG. et al. The effect of sleep apnea on plasma and urinary catecholamines.. Sleep 1995; 18: 377-81.
• 31 Jern C, Eriksson E, Tengborn L. et al. Changes of plasma coagulation and fibrinolysis in response to mental stress.. Thromb Haemost 1989; 62: 767-71.
• 32 Wallen NH, Goodall AH, Li N. et al. Activation of hemostasis by exercise, mental stress and adrenaline: effects on platelet sensitivity to thrombin and thrombin generation.. Clin Sci 1999; 97: 27-35.
• 33 Kario K, Matsuo T, Kobayashi H. et al. Earthquake induced potentiation of acute risk factors in hypertensive elderly patients: possible triggering of cardiovascular events after a major earthquake.. J Am Coll Cardiol 1997; 29: 926-33.
• 34 Carey MJ, Rodgers GM. Disseminated intravascular coagulation: clinical and laboratory aspects.. Am J Hematol 1998; 50: 65-73.
• 35 Shilon Y, Shitrit AB, Rudensky B. et al. A rapid quantitative D-dimer assay at admission correlates with the severity of community acquired pneumonia.. Blood Coagul Fibrinolysis 2003; 14: 745-8.
• 36 Shitrit D, Izbicki G. et al. Prognostic value of D-dimer test in critically ill patients 24 and 48 hrs after admission.. Blood Coagul Fibrinolysis 2004; 15: 15-9.
• 37 Shitrit D, Bendayan D, Rudensky B. et al. Elevation of ELISA D-dimer levels in patients with primary pulmonary hypertension.. Respiration 2002; 69: 327-32.