International Journal of Medical Laboratory Research (IJMLR)

 HEPARIN COFACTOR II AND HAEMATOLOGICAL PARAMETERS AMONG PATIENTS WITH OBSTRUCTIVE SLEEP APNOEA: A SINGLE CENTRE STUDY IN NORTH EAST MALAYSIA

MA Norasyikin, AA Suhair, Ramli Marini, Abdullah Baharudin, WA Zaidah

 

ABSTRACT:Background: Obstructive sleep apnoea (OSA) is seen among patients with various health co-morbidities. The reason of this study was to compare the haemostatic and haematological parameters between OSA patients and control group. Methods: A cross sectional comparative study was performed at a tertiary centre in Kelantan state of Malaysia. The diagnosis of OSA in all patients was confirmed by polysomnography. Laboratory parameters investigated were prothrombin time (PT), activated partial thromboplastin time (APTT), heparin cofactor (HC) II, activated protein C resistance (APC-R), von Willebrand factor (vWF) antigen, factor VIII assays, haemoglobin (Hb), haematocrit (Hct) and platelet count.. Result: A total of 14 male OSA patients and one female (n=15) with nearly age-matched 19 healthy individuals (female n=4) were recruited during seven months study period. All of them except one were overweight or obese and a few of them had other medical co-morbidities. Majority of them were already on definitive treatment for OSA. There were statistically significant mean differences in the levels of Hb, Hct, platelet count and HCII in the study group as compared with the control subjects.A low natural HCII among OSA group was recorded. These changes might render them at potential risk of chronic hypercoagulable state. Conclusions: Definitive risk of haemostatic abnormalities and outcomes of OSA patients with various medical co-morbidities should be further investigated. As OSA is an emerging disease in various developing countries, the long term related complications should be explored especially on transient or persistent haemostatic changes following treatment.
KEYWORDS: coagulation tests, medical co-morbidities, Heparin Cofactor II, hypercoagulable state, sleep apnoea.

 

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REFERENCES:

1. Kamil MA, Teng CL,Hassan SA. Snoring and breathing pauses during sleep in the Malaysian population. Respirology2007;12(3):375-80.

2. Park JG, Ramar K, Olson EJ. Updates on definition, consequences, and management of obstructive sleep apnea. Mayo Clin Proc2011;86(6):549-54; quiz 554-5.

3. Zamarron-Sanz C,  Ricoy-Galdbaldon J,  Gude-Sampedro F, Riveiro-Riveiro A.  Plasma levels of vascular endothelial markers in obstructive sleep apnoea .  Arch Med Res2006;37:552-5

4. Liak C,Fitzpatrick M. Coagulability in obstructive sleep apnea.Can Respir J2011; 18(6):338-48.

5. Cooper ST, Neese LL, DiCuccio MN, Liles DK, Hoffman M,Church FC. Vascular localization of the heparin-binding serpins

6. antithrombin, heparin cofactor II, and protein C inhibitor. Clin Appl Thromb Hemost1996; 2:185-91.

7. Dahlbäck B, Carlsson M, Svensson  PJ. Familial thrombophilia due to a previously unrecognized mechanism characterized by poor anticoagulant response to activated protein C: prediction of a cofactor to activated protein C. Proc Natl Acad Sci USA1993;90(3):1004–8.

8. Abdullah WZ, Moufak SK, Yusof  Z, Mohamad MS,Kamarul IM . Shortened activated partial thromboplastin time, a hemostatic marker for hypercoagulable state during acute coronary event. Transl Res2010;155(6):315-9.

9. Niżankowska-Jędrzejczyk A, Almeida FR, Lowe AA, Kania A, Nastałek P, Mejza F, et al. Modulation of inflammatory and hemostatic markers in obstructive sleep apnea patients treated with mandibular advancement splints: a parallel, controlled trial. Journal of clinical sleep medicine: JCSM: official publication of the American Academy of Sleep Medicine 2014;10(3):255-262.

10. Lin YS, Liu PH, Lin SW, Chuang LP, Ho WJ, Chou YT, et al. Simple obstructive sleep apnea patients without hypertension or diabetes accelerate kidney dysfunction: a population follow-up cohort study from Taiwan. Sleep and Breathing2017;21(1):85-91.

11. Young T,  Palta M,  Dempsey J,  Skatrud J,  Weber S,Badr S. The occurrence of sleep-disordered breathing among middle-aged adults. N Engl J Med1993;328(17):1230-5.

12. Deitcher SR, Caiola E, Jaffer A. Demystifying two common genetic predispositions to venous thrombosis. Cleve Clin J Med 2000;67(11):825-6.

13. Mirrakhimov  AE, Sooronbaev T, Mirrakhimov EM. Prevalence of obstructive sleep apnea in Asian adults: a systematic review of the literature. BMC Pulm Med2013;13(1):1-10.

14. Malhotra A, White DP. Obstructive sleep apnoea. Lancet2002;360(9238):237-45.

15. Choi JB, Loredo JS, Norman D, Mills PJ, Ancoli-Israel S, Ziegler MG, et al. Does obstructive sleep apnea increase hematocrit? Sleep Breath 2006;10(3):155-60.

16. Cirillo M, Laurenzi M, Trevisan M,Stamler J. Hematocrit, blood pressure, and hypertension. The Gubbio Population Study. Hypertension 1992;20:319-26.

17. Maio R, Sciacqua A, Bruni R, Pascale A, Carullo G, Scarpino PE,et al. Association between hemoglobin level and endothelial function in uncomplicated, untreated hypertensive patients. Clin J Am Soc Nephrol 2010;6(3):648-55.

18. Lehmann T, Mairbaurl H, Pleisch B, Maggiorini M, Bartsch P,Reinhart WH. Platelet count and function at high altitude and in high-altitude pulmonary edema. J Appl Physiol2006;100(2):690-4.

19. Oga T, Chin K, Tabuchi A, Kawato M, Morimoto T, Takahashi K,et al.Effects of obstructive sleep apnea with intermittent hypoxia on platelet aggregability. J.Atheroscler. Thromb2009;16(6):862-9.

20. Takamori N,  Azuma H , Kato M, Hashizume S, Aihara K, Akaike M, et al.High plasma heparin cofactor II activity is associated with reduced incidence of in-stent restenosis after percutaneous coronary intervention. Circulation2004;109(4):481-6.

21. Huang SS, Huang PH, Chen YH, Sung SH, Chiang KH, Chen JW,et al. Plasma heparin cofactor II activity is an independent predictor of future cardiovascular events in patients after acute myocardial infarction. Coron Artery Dis2008;19(8):597-02.

22. Nicolaes GA, Dahlbäck B. Congenital and acquired activated protein C resistance. Semin Vasc Med 2003;3(1): 33–46.

23. O'Donnell J, Laffan M. Elevated plasma factor VIII levels--a novel risk factor for venous thromboembolism. Clin Lab2001;47(1-2):1-6.

24. Kamphuisen PW, Eikenboom JCJ,Bertina RM. Elevated Factor VIII Levels and the Risk of Thrombosis. Arterioscler Thromb Vasc Biol 2001;21(5):731-8.

25. El Solh AA,  Akinnusi ME, Berim IG,  Peter AM, Paasch LL, Szarpa KZ. Hemostatic implications of endothelial cell apoptosis in obstructive sleep apnea. Sleep Breath2008;12(4):331-7.

26. McEvoy RD, Antic NA, Heeley E, Luo Y, Ou Q, Zhang X, et al. CPAP for prevention of cardiovascular events in obstructive sleep apnea. New Eng J Med 2016;375(10):919-31

27. Sutherland K, Almeida FR, de Chazal P, Cistulli PA. Prediction in obstructive sleep apnoea: diagnosis, comorbidity risk, and treatment outcomes. Expert Rev Respir Med 2018;12(4):293-307.