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The Diagnostic Value of Soluble Urokinase Plasminogen Activator Receptor in Crimean-Congo Hemorrhagic Fever Disease in Emergency Department

Year 2021, Volume: 23 Issue: 1, 15 - 19, 30.04.2021
https://doi.org/10.18678/dtfd.820602

Abstract

Aim: The urokinase-type plasminogen activator (uPA) system consists of a protease, a receptor (urokinase-type plasminogen activator receptor, uPAR), and inhibitors that can be expressed on various cell types. Previous literature shows that the amount of soluble urokinase-type plasminogen activator receptor (suPAR) secreted from affected cells is higher in Crimean-Congo hemorrhagic fever (CCHF) patients than in healthy controls. Thus, we aimed to investigate the diagnostic value of suPAR in the differential diagnosis of CCHF in emergency services.
Material and Methods: Individuals over 16 years old with a preliminary diagnosis of CCHF disease were divided into two groups as real time-polymerase chain reaction (RT-PCR) and/or IgM positive (CCHF group) and RT-PCR and/or IgM negative (control group).
Results: Eighty patients were included in this study. Forty patients with CCHF virus PCR and/or CCHF virus IgM were identified as CCHF group and 40 patients included as negative control group. The median age of the patients was 45 (range, 16-91) years, and 49 patients (61.3%) were male. Leukocyte, platelet, and fibrinogen levels were significantly lower, while creatinine kinase, aPTT, and D-dimer levels were significantly higher in CCHF group. There was no statistically significant difference between the control group and CCHF group for SuPAR (p=0.386). In addition, control group patients not diagnosed with CCHF were examined, brucellosis, influenza, and pneumonia were found to be the most common.
Conclusion: The use of suPAR as a biomarker in the differentiation of patients with similar findings in emergency services was investigated and found to have no diagnostic value.

References

  • Ergonul O. Crimean-Congo hemorrhagic fever virus: new outbreaks, new discoveries. Curr Opin Virol. 2012;2(2):215-20.
  • Al-Abri SS, Abaidani IA, Fazlalipour M, Mostafavi E, Leblebicioglu H, Pshenichnaya N, et al. Current status of Crimean-Congo haemorrhagic fever in the World Health Organization Eastern Mediterranean Region: issues, challenges, and future directions. Int J Infect Dis. 2017;58:82-9.
  • Leblebicioglu H, Ozaras R, Fletcher TE, Beeching NJ, ESCMID Study Group for Infections in Travellers and Migrants (ESGITM). Crimean-Congo haemorrhagic fever in travellers: A systematic review. Travel Med Infect Dis. 2016;14(2):73-80.
  • Yilmaz G, Koksal I, Topbas M, Yilmaz H, Aksoy F. The effectiveness of routine laboratory findings in determining disease severity in patients with Crimean-Congo hemorrhagic fever: severity prediction criteria. J Clin Virol. 2010;47(4):361-5.
  • Kilinc C, Gückan R, Capraz M, Varol K, Zengin E, Mengeloglu Z, et al. Examination of the specific clinical symptoms and laboratory findings of Crimean-Congo hemorrhagic fever. J Vector Borne Dis. 2016;53(2):162-7.
  • Dreshaj S, Ahmeti S, Ramadani N, Dreshaj G, Humolli I, Dedushaj I. Current situation of Crimean-Congo hemorrhagic fever in Southeastern Europe and neighboring countries: a public health risk for the European Union? Travel Med Infect Dis. 2016;14(2):81-91.
  • Ergonul O, Celikbas A, Baykam N, Eren S, Dokuzoguz B. Analysis of risk-factors among patients with Crimean-Congo haemorrhagic fever virus infection: severity criteria revisited. Clin Microbiol Infect. 2006;12(6):551-4.
  • Yilmaz GR, Buzgan T, Irmak H, Safran A, Uzun R, Cevik MA, et al. The epidemiology of Crimean-Congo hemorrhagic fever in Turkey, 2002-2007. Int J Infect Dis. 2009;13(3):380-6.
  • Mostafavi E, Pourhossein B, Chinikar S. Clinical symptoms and laboratory findings supporting early diagnosis of Crimean-Congo hemorrhagic fever in Iran. J Med Virol. 2014 Jul;86(7):1188-92.
  • Owaysee Osquee H, Pourjafar H, Taghizadeh S, Haghdoost M, Ansari F. Laboratory features of 160 CCHF confirmed cases in Zabol of Iran: A 10-year study. J Infect. 2017;74(4):418-20.
  • Ploug M, Rønne E, Behrendt N, Jensen AL, Blasi F, Danø K. Cellular receptor for urokinase plasminogen activator. Carboxyl-terminal processing and membrane anchoring by glycosyl-phosphatidylinositol. J Biol Chem. 1991;266(3):1926-33.
  • Eugen-Olsen J. suPAR - a future risk marker in bacteremia. J Intern Med. 2011;270(1):29-31.
  • Yilmaz G, Mentese A, Kaya S, Uzun A, Karahan SC, Koksal I. The diagnostic and prognostic significance of soluble urokinase plasminogen activator receptor in Crimean-Congo hemorrhagic fever. J Clin Virol. 2011;50(3):209-11.
  • Tanyel E, Sunbul M, Fletcher TE, Leblebicioglu H. Aetiology of PCR negative suspected Crimean-Congo hemorrhagic fever cases in an endemic area. Pathog Glob Health. 2016;110(4-5):173-7.
  • Büyüktuna SA, Doğan HO, Unlusavuran M, Bakir M. An evaluation of the different biomarkers to discriminate bleeding in Crimean-Congo hemorrhagic fever. Ticks Tick Borne Dis. 2019;10(5):997-1002.
  • Akinci E, Bodur H, Sunbul M, Leblebicioglu H. Prognostic factors, pathophysiology and novel biomarkers in Crimean-Congo hemorrhagic fever. Antiviral Res. 2016;132:233-43.
  • Donadello K, Scolletta S, Covajes C, Vincent JL. suPAR as a prognostic biomarker in sepsis. BMC Med. 2012;10:2.
  • Bustamante A, García-Berrocoso T, Penalba A, Giralt D, Simats A, Muchada M, et al. Sepsis biomarkers reprofiling to predict stroke-associated infections. J Neuroimmunol. 2017;312:19-23.
  • Ostrowski SR, Plomgaard P, Fischer CP, Steensberg A, Møller K, Høyer‐Hansen G, et al. Interleukin-6 infusion during human endotoxaemia inhibits in vitro release of the urokinase receptor from peripheral blood mononuclear cells. Scand J Immunol. 2005;61(2):197-206.
  • Kofoed K, Andersen O, Kronborg G, Tvede M, Petersen J, Eugen-Olsen J, et al. Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study. Crit Care. 2007;11(2):R38.
  • Ostergaard C, Benfield T, Lundgren JD, Eugen-Olsen J. Soluble urokinase receptor is elevated in cerebrospinal fluid from patients with purulent meningitis and is associated with fatal outcome. Scand J Infect Dis. 2004;36(1):14-9.
  • Ostrowski SR, Ullum H, Goka BQ, Høyer-Hansen G, Obeng-Adjei G, Pedersen BK, et al. Plasma concentrations of soluble urokinase-type plasminogen activator receptor are increased in patients with malaria and are associated with a poor clinical or a fatal outcome. J Infect Dis. 2005;191(8):1331-41.
  • Eugen-Olsen J, Gustafson P, Sidenius N, Fischer TK, Parner J, Aaby P, et al. The serum level of soluble urokinase receptor is elevated in tuberculosis patients and predicts mortality during treatment: a community study from Guinea-Bissau. Int J Tuberc Lung Dis. 2002;6(8):686-92.
  • Ostrowski SR, Piironen T, Høyer-Hansen G, Gerstoft J, Pedersen BK, Ullum H. High plasma levels of intact and cleaved soluble urokinase receptor reflect immune activation and are independent predictors of mortality in HIV-1-infected patients. J Acquir Immune Defic Syndr. 2005;39(1):23-31.
  • Erkut N, Mentese A, Ozbas HM, Ermantaş N, Sümer A, Örem A, et al. The prognostic significance of soluble urokinase plasminogen activator receptor in acute myeloid leukemia. Turk J Haematol. 2016;33(2):135-40.
  • Karsen H, Cesur S, Karaağaç L, Binici I, Fidan Y, Oğüş E, et al. Can mannose-binding lectin and plasma level of soluble urokinase receptor be used in diagnosis and treatment monitorization of brucellosis patients? Mikrobiyol Bul. 2012;46(3):519-21.
  • Tsai PK, Tsao SM, Yang WE, Yeh CB, Wang HL, Yang SF. Plasma soluble urokinase-type plasminogen activator receptor level as a predictor of the severity of community-acquired pneumonia. Int J Environ Res Public Health. 2019;16(6):1035.
  • Nikkola A, Aittoniemi J, Huttunen R, Rajala L, Nordback I, Sand J, et al. Plasma level of soluble urokinase-type plasminogen activator receptor predicts the severity of acute alcohol pancreatitis. Pancreas 2017;46(1):77-82.
  • Huang Q, Xiong H, Yan P, Shuai T, Liu J, Zhu L, et al. The diagnostic and prognostic value of suPAR in patients with sepsis: A systematic review and meta-analysis. Shock. 2020;53(4):416-25.
  • Schulman H, Niward K, Abate E, Idh J, Axenram P, Bornefall A, et al. Sedimentation rate and suPAR in relation to disease activity and mortality in patients with tuberculosis. Int J Tuberc Lung Dis. 2019;23(11):1155-61.

Acil Serviste Kırım Kongo Kanamalı Ateş Hastalığında Soluble Ürokinaz Plazminojen Aktivatör Reseptörünün Tanısal Değeri

Year 2021, Volume: 23 Issue: 1, 15 - 19, 30.04.2021
https://doi.org/10.18678/dtfd.820602

Abstract

Amaç: Ürokinaz tipi plazminojen aktivatör (uPA) sistemi, çeşitli hücrelerden salınan proteaz, reseptör (ürokinaz tipi plazminojen aktivatör reseptör, uPAR) ve inhibitörlerden oluşur. Literatürde, enfekte olan hücrelerden salgılanan solüble ürokinaz plazminojen aktivatör reseptörü (suPAR) düzeyinin Kırım-Kongo kanamalı ateşi (KKKA) hastalarında sağlıklı kontrollere göre daha yüksek olduğu gösterilmiştir. Bu çalışmada acil serviste KKKA'nın ayırıcı tanısında suPAR'ın tanısal değerinin araştırılması amaçlanmıştır.
Gereç ve Yöntemler: KKKA hastalığı ön tanısı alan 16 yaşın üstündeki bireyler gerçek zamanlı polimeraz zincir reaksiyonu (real time-polymerase chain reaction, RT-PCR) ve/veya IgM pozitif (KKKA grubu) ve RT-PCR ve/veya IgM negatif (kontrol grubu) olarak iki gruba ayrıldı.
Bulgular: Bu çalışmaya 80 hasta dahil edildi. KKKA virus PCR ve/veya KKKA virus IGM’li 40 hasta KKKA grubu olarak ve 40 hasta negatif kontrol grup olarak belirlendi. Hastaların ortanca yaşı 45 (aralık, 16-91) yıldı ve 49 (%61,3) hasta erkekti. KKKA grubunda lökosit, trombosit ve fibrinojen seviyeleri istatistiksel anlamlı olarak düşüktü, kreatinin kinaz, aPTT ve D-dimer seviyeleri ise istatistiksel anlamlı olarak yüksekti. SuPAR için kontrol grubu ile KKKA grubu arasında istatistiksel olarak anlamlı bir farklılık yoktu (p=0.386). Ayrıca KKKA tanısı almayan kontrol grubu hastaları incelendiğinde, en sık bruselloz, influenza ve pnömoni olduğu bulundu.
Sonuç: Acil serviste benzer bulgulara sahip hastaların ayırt edilmesinde bir biyobelirteç olarak suPAR'ın kullanımı araştırıldı ve tanısal değeri olmadığı bulundu.

References

  • Ergonul O. Crimean-Congo hemorrhagic fever virus: new outbreaks, new discoveries. Curr Opin Virol. 2012;2(2):215-20.
  • Al-Abri SS, Abaidani IA, Fazlalipour M, Mostafavi E, Leblebicioglu H, Pshenichnaya N, et al. Current status of Crimean-Congo haemorrhagic fever in the World Health Organization Eastern Mediterranean Region: issues, challenges, and future directions. Int J Infect Dis. 2017;58:82-9.
  • Leblebicioglu H, Ozaras R, Fletcher TE, Beeching NJ, ESCMID Study Group for Infections in Travellers and Migrants (ESGITM). Crimean-Congo haemorrhagic fever in travellers: A systematic review. Travel Med Infect Dis. 2016;14(2):73-80.
  • Yilmaz G, Koksal I, Topbas M, Yilmaz H, Aksoy F. The effectiveness of routine laboratory findings in determining disease severity in patients with Crimean-Congo hemorrhagic fever: severity prediction criteria. J Clin Virol. 2010;47(4):361-5.
  • Kilinc C, Gückan R, Capraz M, Varol K, Zengin E, Mengeloglu Z, et al. Examination of the specific clinical symptoms and laboratory findings of Crimean-Congo hemorrhagic fever. J Vector Borne Dis. 2016;53(2):162-7.
  • Dreshaj S, Ahmeti S, Ramadani N, Dreshaj G, Humolli I, Dedushaj I. Current situation of Crimean-Congo hemorrhagic fever in Southeastern Europe and neighboring countries: a public health risk for the European Union? Travel Med Infect Dis. 2016;14(2):81-91.
  • Ergonul O, Celikbas A, Baykam N, Eren S, Dokuzoguz B. Analysis of risk-factors among patients with Crimean-Congo haemorrhagic fever virus infection: severity criteria revisited. Clin Microbiol Infect. 2006;12(6):551-4.
  • Yilmaz GR, Buzgan T, Irmak H, Safran A, Uzun R, Cevik MA, et al. The epidemiology of Crimean-Congo hemorrhagic fever in Turkey, 2002-2007. Int J Infect Dis. 2009;13(3):380-6.
  • Mostafavi E, Pourhossein B, Chinikar S. Clinical symptoms and laboratory findings supporting early diagnosis of Crimean-Congo hemorrhagic fever in Iran. J Med Virol. 2014 Jul;86(7):1188-92.
  • Owaysee Osquee H, Pourjafar H, Taghizadeh S, Haghdoost M, Ansari F. Laboratory features of 160 CCHF confirmed cases in Zabol of Iran: A 10-year study. J Infect. 2017;74(4):418-20.
  • Ploug M, Rønne E, Behrendt N, Jensen AL, Blasi F, Danø K. Cellular receptor for urokinase plasminogen activator. Carboxyl-terminal processing and membrane anchoring by glycosyl-phosphatidylinositol. J Biol Chem. 1991;266(3):1926-33.
  • Eugen-Olsen J. suPAR - a future risk marker in bacteremia. J Intern Med. 2011;270(1):29-31.
  • Yilmaz G, Mentese A, Kaya S, Uzun A, Karahan SC, Koksal I. The diagnostic and prognostic significance of soluble urokinase plasminogen activator receptor in Crimean-Congo hemorrhagic fever. J Clin Virol. 2011;50(3):209-11.
  • Tanyel E, Sunbul M, Fletcher TE, Leblebicioglu H. Aetiology of PCR negative suspected Crimean-Congo hemorrhagic fever cases in an endemic area. Pathog Glob Health. 2016;110(4-5):173-7.
  • Büyüktuna SA, Doğan HO, Unlusavuran M, Bakir M. An evaluation of the different biomarkers to discriminate bleeding in Crimean-Congo hemorrhagic fever. Ticks Tick Borne Dis. 2019;10(5):997-1002.
  • Akinci E, Bodur H, Sunbul M, Leblebicioglu H. Prognostic factors, pathophysiology and novel biomarkers in Crimean-Congo hemorrhagic fever. Antiviral Res. 2016;132:233-43.
  • Donadello K, Scolletta S, Covajes C, Vincent JL. suPAR as a prognostic biomarker in sepsis. BMC Med. 2012;10:2.
  • Bustamante A, García-Berrocoso T, Penalba A, Giralt D, Simats A, Muchada M, et al. Sepsis biomarkers reprofiling to predict stroke-associated infections. J Neuroimmunol. 2017;312:19-23.
  • Ostrowski SR, Plomgaard P, Fischer CP, Steensberg A, Møller K, Høyer‐Hansen G, et al. Interleukin-6 infusion during human endotoxaemia inhibits in vitro release of the urokinase receptor from peripheral blood mononuclear cells. Scand J Immunol. 2005;61(2):197-206.
  • Kofoed K, Andersen O, Kronborg G, Tvede M, Petersen J, Eugen-Olsen J, et al. Use of plasma C-reactive protein, procalcitonin, neutrophils, macrophage migration inhibitory factor, soluble urokinase-type plasminogen activator receptor, and soluble triggering receptor expressed on myeloid cells-1 in combination to diagnose infections: a prospective study. Crit Care. 2007;11(2):R38.
  • Ostergaard C, Benfield T, Lundgren JD, Eugen-Olsen J. Soluble urokinase receptor is elevated in cerebrospinal fluid from patients with purulent meningitis and is associated with fatal outcome. Scand J Infect Dis. 2004;36(1):14-9.
  • Ostrowski SR, Ullum H, Goka BQ, Høyer-Hansen G, Obeng-Adjei G, Pedersen BK, et al. Plasma concentrations of soluble urokinase-type plasminogen activator receptor are increased in patients with malaria and are associated with a poor clinical or a fatal outcome. J Infect Dis. 2005;191(8):1331-41.
  • Eugen-Olsen J, Gustafson P, Sidenius N, Fischer TK, Parner J, Aaby P, et al. The serum level of soluble urokinase receptor is elevated in tuberculosis patients and predicts mortality during treatment: a community study from Guinea-Bissau. Int J Tuberc Lung Dis. 2002;6(8):686-92.
  • Ostrowski SR, Piironen T, Høyer-Hansen G, Gerstoft J, Pedersen BK, Ullum H. High plasma levels of intact and cleaved soluble urokinase receptor reflect immune activation and are independent predictors of mortality in HIV-1-infected patients. J Acquir Immune Defic Syndr. 2005;39(1):23-31.
  • Erkut N, Mentese A, Ozbas HM, Ermantaş N, Sümer A, Örem A, et al. The prognostic significance of soluble urokinase plasminogen activator receptor in acute myeloid leukemia. Turk J Haematol. 2016;33(2):135-40.
  • Karsen H, Cesur S, Karaağaç L, Binici I, Fidan Y, Oğüş E, et al. Can mannose-binding lectin and plasma level of soluble urokinase receptor be used in diagnosis and treatment monitorization of brucellosis patients? Mikrobiyol Bul. 2012;46(3):519-21.
  • Tsai PK, Tsao SM, Yang WE, Yeh CB, Wang HL, Yang SF. Plasma soluble urokinase-type plasminogen activator receptor level as a predictor of the severity of community-acquired pneumonia. Int J Environ Res Public Health. 2019;16(6):1035.
  • Nikkola A, Aittoniemi J, Huttunen R, Rajala L, Nordback I, Sand J, et al. Plasma level of soluble urokinase-type plasminogen activator receptor predicts the severity of acute alcohol pancreatitis. Pancreas 2017;46(1):77-82.
  • Huang Q, Xiong H, Yan P, Shuai T, Liu J, Zhu L, et al. The diagnostic and prognostic value of suPAR in patients with sepsis: A systematic review and meta-analysis. Shock. 2020;53(4):416-25.
  • Schulman H, Niward K, Abate E, Idh J, Axenram P, Bornefall A, et al. Sedimentation rate and suPAR in relation to disease activity and mortality in patients with tuberculosis. Int J Tuberc Lung Dis. 2019;23(11):1155-61.
There are 30 citations in total.

Details

Primary Language English
Subjects Clinical Sciences
Journal Section Research Article
Authors

Kadir Küçükceran 0000-0001-9758-0803

Omer Karasahin 0000-0002-4245-1534

Orhan Delice 0000-0003-1629-4245

Ali Batur 0000-0002-2057-3215

Sibel İba Yılmaz 0000-0002-4123-0828

Engin Şebin 0000-0001-9150-8069

Mahmut Şenyurt This is me 0000-0002-7041-540X

Publication Date April 30, 2021
Submission Date November 3, 2020
Published in Issue Year 2021 Volume: 23 Issue: 1

Cite

APA Küçükceran, K., Karasahin, O., Delice, O., Batur, A., et al. (2021). The Diagnostic Value of Soluble Urokinase Plasminogen Activator Receptor in Crimean-Congo Hemorrhagic Fever Disease in Emergency Department. Duzce Medical Journal, 23(1), 15-19. https://doi.org/10.18678/dtfd.820602
AMA Küçükceran K, Karasahin O, Delice O, Batur A, İba Yılmaz S, Şebin E, Şenyurt M. The Diagnostic Value of Soluble Urokinase Plasminogen Activator Receptor in Crimean-Congo Hemorrhagic Fever Disease in Emergency Department. Duzce Med J. April 2021;23(1):15-19. doi:10.18678/dtfd.820602
Chicago Küçükceran, Kadir, Omer Karasahin, Orhan Delice, Ali Batur, Sibel İba Yılmaz, Engin Şebin, and Mahmut Şenyurt. “The Diagnostic Value of Soluble Urokinase Plasminogen Activator Receptor in Crimean-Congo Hemorrhagic Fever Disease in Emergency Department”. Duzce Medical Journal 23, no. 1 (April 2021): 15-19. https://doi.org/10.18678/dtfd.820602.
EndNote Küçükceran K, Karasahin O, Delice O, Batur A, İba Yılmaz S, Şebin E, Şenyurt M (April 1, 2021) The Diagnostic Value of Soluble Urokinase Plasminogen Activator Receptor in Crimean-Congo Hemorrhagic Fever Disease in Emergency Department. Duzce Medical Journal 23 1 15–19.
IEEE K. Küçükceran, O. Karasahin, O. Delice, A. Batur, S. İba Yılmaz, E. Şebin, and M. Şenyurt, “The Diagnostic Value of Soluble Urokinase Plasminogen Activator Receptor in Crimean-Congo Hemorrhagic Fever Disease in Emergency Department”, Duzce Med J, vol. 23, no. 1, pp. 15–19, 2021, doi: 10.18678/dtfd.820602.
ISNAD Küçükceran, Kadir et al. “The Diagnostic Value of Soluble Urokinase Plasminogen Activator Receptor in Crimean-Congo Hemorrhagic Fever Disease in Emergency Department”. Duzce Medical Journal 23/1 (April 2021), 15-19. https://doi.org/10.18678/dtfd.820602.
JAMA Küçükceran K, Karasahin O, Delice O, Batur A, İba Yılmaz S, Şebin E, Şenyurt M. The Diagnostic Value of Soluble Urokinase Plasminogen Activator Receptor in Crimean-Congo Hemorrhagic Fever Disease in Emergency Department. Duzce Med J. 2021;23:15–19.
MLA Küçükceran, Kadir et al. “The Diagnostic Value of Soluble Urokinase Plasminogen Activator Receptor in Crimean-Congo Hemorrhagic Fever Disease in Emergency Department”. Duzce Medical Journal, vol. 23, no. 1, 2021, pp. 15-19, doi:10.18678/dtfd.820602.
Vancouver Küçükceran K, Karasahin O, Delice O, Batur A, İba Yılmaz S, Şebin E, Şenyurt M. The Diagnostic Value of Soluble Urokinase Plasminogen Activator Receptor in Crimean-Congo Hemorrhagic Fever Disease in Emergency Department. Duzce Med J. 2021;23(1):15-9.