Korean Journal of Psychosomatic Medicine (정신신체의학)

Korean Psychosomatic Society (한국정신신체의학회)
권호 표지
DOI QR코드

DOI QR Code

Clozapine Administration Potentiate Platelet Activation in Patients with Schizophrenia : Retrospective Study

클로자핀을 투여한 조현병 환자에서 혈소판 활성 증가에 관한 후향적 연구

  • Kim, Hyun-Ah (Department of Psychiatry, College of Medicine, Konyang University) ;
  • Lee, Jong Wook (Konyang University Myunggok Medical Research Institute) ;
  • Kim, Seung-Jun (Department of Psychiatry, College of Medicine, Konyang University) ;
  • Oh, Hong-Seok (Department of Psychiatry, College of Medicine, Konyang University) ;
  • Im, Woo Young (Department of Psychiatry, College of Medicine, Konyang University) ;
  • Kim, Ji-Woong (Department of Psychiatry, College of Medicine, Konyang University)
  • 김현아 (건양대학교 의과대학 정신건강의학교실) ;
  • 이종욱 (건양대학교 명곡의과학연구소) ;
  • 김승준 (건양대학교 의과대학 정신건강의학교실) ;
  • 오홍석 (건양대학교 의과대학 정신건강의학교실) ;
  • 임우영 (건양대학교 의과대학 정신건강의학교실) ;
  • 김지웅 (건양대학교 의과대학 정신건강의학교실)
  • Received : 2018.09.29
  • Accepted : 2018.12.15
  • Published : 2018.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

Objectives : Clozapine is a widely prescribed antipsychotic drug for schizophrenia and is known to increase the risk of cardiovascular disease due to its metabolic side effects. However, little is known about the effect of clozapine on the platelet activation, another important factor in the development of cardiovascular disease. In this study, we tried to investigate the effect of clozapine on platelet activity in patients with schizophrenia by comparing the mean platelet component (MPC) values before and after the clozapine administration. Methods : A retrospective review of medical records of patients with schizophrenia, who newly started clozapine treatment from September 1st, 2003 to April 30th, 2007 at the Department of Psychiatry, Konyang University Hospital in Republic of Korea was performed. The final statistical analysis included 14 participants. Bayer ADVIA $120^{(R)}$ system was used to measure MPC. Results : Among the 14 participants, five subjects were males (28.60%), and ten subjects were females (71.40%). The mean age of participants was $37.50{\pm}11.64years$. Average of duration of illness was $91.00{\pm}93.96months$, with the mean dosage of clozapine taken by participants at the time of the last blood test was $337.50{\pm}109.52mg$. The mean MPC measurement before and after receiving clozapine was $26.12{\pm}2.22g/dL$ and $25.14{\pm}2.08g/dL$ respectively. Wilcoxon signed rank test showed that there was a statistically significant decrease in MPC levels after clozapine administration (V=16, p=0.024). Conclusions : Decreased MPC levels after clozapine administration implies that clozapine may increase platelet activation which could have an adverse effect on the occurrence of thromboembolic disease. Our findings also suggest that careful monitoring of the risk factors of cardiovascular diseases, such as platelets activity, is necessary when administering clozapine.

연구목적 클로자핀은 조현병 치료에 널리 처방되는 항정신병약물로, 대사성 부작용 등으로 인한 심뇌혈관질환의 위험을 증가시키는 것으로 알려져 있다. 하지만, 클로자핀이 심뇌혈관질환의 발생에 중요한 영향을 미치는 또 다른 요소인 혈소판 활성 정도에 어떤 영향을 미치는지에 대해서는 알려진 바가 거의 없다. 본 연구에서는 클로자핀 투여 전후 평균혈소판요소 (mean platelet component, MPC) 값 비교를 통하여 조현병 환자에서 클로자핀이 혈소판 활성에 미치는 영향을 알아보고자 하였다. 방 법 2003년 9월 1일부터 2007년 4월 30일까지의 기간 동안 건양대학교 병원 정신건강의학과에서 클로자핀을 새롭게 투여 받기 시작한 환자들을 대상으로 의무기록을 후향적으로 검토 하였다. 최종 통계 분석에는 14명이 포함되었다. 평균혈소판요소는 Bayer ADVIA $120^{(R)}$ system를 이용하여 측정하였다. 결 과 14명의 연구 대상자 중, 남성은 4명(28.60%), 여성은 10명(71.40%)이었으며, 평균 나이는 $37.50{\pm}11.64$세였다. 유병 기간은 평균 $91.00{\pm}93.96$개월 이었으며 피험자들이 마지막 혈액 검사를 한 시점에 복용하였던 클로자핀 용량의 평균은 $337.50{\pm}109.52mg$이었다. 클로자핀 투여 전과 투여 후의 평균혈소판요소 값은 각각 $26.12{\pm}2.22g/dL$과 $25.14{\pm}2.08g/dL$ 이었다. 윌콕슨 부호-순위 검정에서 클로자핀 투여 후 MPC 값이 유의미하게 감소하였다(V=16, p=0.024). 결 론 본 연구의 결과는 클로자핀 투여가 혈소판을 활성화하며, 이로 인해 혈전색전성 질환 등의 발생에 부정적인 영향을 미칠 수 있음을 시사한다. 또한 클로자핀 투여 시 혈소판 활성에 대한 평가를 포함하여 뇌혈관질환의 위험성에 대한 주의 깊은 모니터링이 필요함을 시사한다.

Keywords

JSSCBG_2018_v26n2_188_f0001.png 이미지

Fig. 1. Comparison of MPC measurement before and after clozapine administration.

Table 1. Clinical characteristics of participants

JSSCBG_2018_v26n2_188_t0001.png 이미지

Table 2. Comparison of MPC measurement before and after clozapine administration

JSSCBG_2018_v26n2_188_t0002.png 이미지

References

  1. Hert MD, Detraux J, Winkel RV, Yu W, Correll CU. Metabolic and cardiovascular adverse effects associated with antipsychotic drugs. Nat Rev Endocrinol 2011;8:114-126.
  2. Masopust J, Maly R, Valis M. Risk of venous thromboembolism during treatment with antipsychotic agents. Psychiatry and Clinical Neurosciences 2012;66:541-552. https://doi.org/10.1111/pcn.12001
  3. Parker C, Coupland C, Cox JH. Antipsychotic drugs and risk of venous thromboembolism: nested case-control study. BMJ 2010;341:c4245. https://doi.org/10.1136/bmj.c4245
  4. Lund BC, Perry PJ, Brooks JM. Clozapine use in patients with schizophrenia and the risk of diabetes, hyperlipidemia, and hypertension: a claims-based approach. Arch Gen Psychiatry 2001;58:1172-1176. https://doi.org/10.1001/archpsyc.58.12.1172
  5. Muszalska AD, Jabonska JR, Nowak P, Kontek B. The first- and second-generation antipsychotic drugs affect ADPinduced platelet aggregation. The World Journal of Biological Psychiatry 2010;11:268-275. https://doi.org/10.3109/15622970802505792
  6. Hagg S, Spigset O. Antipsychotic-Induced Venous Thromboembolism: A Review of the Evidence. CNS Drugs 2002;16: 765-776. https://doi.org/10.2165/00023210-200216110-00005
  7. Semiz M, Yucel H, Kavakci O, Yildirim O, Zorlu A, Yilmaz MB, Kucukdurmaz Z, Canan F. Atypical antipsychotic use is an independent predictor for the increased mean platelet volume in patients with schizophrenia: A preliminary study. J Res Med Sci 2013;18:561-566.
  8. Lee J, Powell V, Remington G. Mean platelet volume in schizophrenia unaltered after 1year of clozapine exposure. Schizophr Res 2014;157:134-136. https://doi.org/10.1016/j.schres.2014.04.038
  9. Gasparyan AU, Ayvazyan L, Mikhailidis DP, Kitas G. Mean Platelet Volume: A Link Between Thrombosis and Inflammation?. Current Pharmaceutical Design 2011;17:47-58. https://doi.org/10.2174/138161211795049804
  10. Kim DS, Ryu SH, Lee JW, Kim YD, Choi YC. Mean Platelet Component to Measure Platelet Activation in Ischemic Stroke-Preliminary Study. J Korean Neurol Assoc 2002;20:223-226.
  11. Muszalska AD, Wachowicz B. Platelet haemostatic function in psychiatric disorders: Effects of antidepressants and antipsychotic drugs. The World Journal of Biological Psychiatry 2017;18:564-574. https://doi.org/10.3109/15622975.2016.1155748
  12. Roberts CK, Sindhu KK. Oxidative stress and metabolic syndrome. Life Sciences 2009;84:705-712. https://doi.org/10.1016/j.lfs.2009.02.026
  13. van Rooy MJ, Duim W, Ehlers R, Buys AV, Pretorius E. Platelet hyperactivity and fibrin clot structure in transient ischemic attack individuals in the presence of metabolic syndrome: a microscopy and thromboelastography(R) study. Cardiovasc Diabetol 2015;14:86. https://doi.org/10.1186/s12933-015-0249-5
  14. Axelsson S, Hagg S, Eriksson AC, Lindahl TL, Whiss PA. In vitro effects of antipsychotics on human platelet adhesion and aggregation and plasma coagulation. Clinical and Experimental Pharmacology and Physiology 2007;34:775-780. https://doi.org/10.1111/j.1440-1681.2007.04650.x
  15. Chu SG, Becker RC, Berger PB, Bhatt DL, Eikelboom JW, Konkle B, Mohler EK, Reilly MP, Berger JS. Mean platelet volume as a predictor of cardiovascular risk: a systematic review and meta-analysis; Journal of Thrombosis and Haemostasis 2010;8:148-156. https://doi.org/10.1111/j.1538-7836.2009.03584.x
  16. Macey MG, Carty E, Webb L, Chapman ES, Zelmanovic D, Okrongly D, Rampton DS, Newland AC. Use of Mean Platelet Component to Measure Platelet Activation on the ADVIA 120 Haematology System. Cytometry 1999;38:250-255. https://doi.org/10.1002/(SICI)1097-0320(19991015)38:5<250::AID-CYTO8>3.0.CO;2-K
  17. Wallaschofski H, Eigenthaler M, Kiefer M, Donne M, Hentschel B, Gertz HJ, Lohmann T. Hyperprolactinemia in Patients on Antipsychotic Drugs Causes ADP-Stimulated Platelet Activation That Might Explain the Increased Risk for Venous Thromboembolism: Pilot Study. Journal of Clinical Psychopharmacology 2003;23:479-483. https://doi.org/10.1097/01.jcp.0000088914.24613.51
  18. Paciullo CA. Evaluating the association between clozapine and venous thromboembolism. Am J Health-Syst Pharm 2008; 65:1825-1829. https://doi.org/10.2146/ajhp070638