Muhammad Shoaib, Muhammad Usman, Rabia Fatima, Sajid Aziz, Muhammad Wasif Malik, Muhammad Javaid Asad and Sikandar Khan Sherwani

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1 Americn-Eursin Journl of Toxicologicl Sciences 7 (4): , 2015 ISSN IDOSI Publictions, 2015 DOI: /idosi.ejts Reltionship Among Alnine Amino-Trnsferse (ALT), Prtil Thromboplstin (APTT) nd Electrolyte Levels in Dengue Fever Positive Ptients of Rwlpindi District Muhmmd Shoib, Muhmmd Usmn, Rbi Ftim, Sjid Aziz, Muhmmd Wsif Mlik, Muhmmd Jvid Asd nd Sikndr Khn Sherwni 1 Institute of Medicl Technology, ShifTmeer-e-Millt University, Islmbd, Pkistn 2 Deprtment of Microbiology, Fculty of Biologicl Sciences, Quid-i-Azm University Islmbd, 44000, Pkistn 3 Deprtment of Microbiology, Absyn University, Peshwr, 25, 000, Pkistn 4 Biologicl Production Division, Ntionl institute of Helth Islmbd, Pkistn 5 Deprtment of Biochemistry, PMAS-Arid Agriculture University Rwlpindi 46000, Pkistn 6 Deprtment of Microbiology, Federl Urdu University of Arts, Science nd Technology, Pkistn Abstrct: Dengue fever (DF) hs become mjor public problem in recent yers nd it is more frequent in tropicl nd subtropicl regions nd most commonly in urbn nd peri-urbn res, cused by Dengue virus which belongs to the fmily Flviviride. The present study ws designed to find out reltionship mong blood biochemicl prmeters i.e. ALT, APTT nd electrolytes nd to study their ssocition with ge. Blood of serology positive Dengue fever ptients ws collected for mesurement of vlues of ALT, APTT nd electrolytes. The dt ws nlyzed by using SPSS 16 nd cross tbultion nd Person Chi-Squre test ws employed to find out significnt reltionship mong vribles. Lbortory hemtologicl findings in dengue fever were thrombocytopeni,leucopeni, neutropein, APTT nd rised hemtocrit vlues. There ws significnt rise in blood biochemicl prmeter like ALT which is suggestive liver dmge in disese. It ws observed tht ALT levels were significntly relted (P=0.01) with ge while there ws no significnt reltionship between ge nd APTT vlues. Similrly ALT nd APTT levels were significntly correlted (P=0.001) with ech other. A significnt reltionship (P=0.03) ws observed between Sodium ions nd ALT/APTT levels nd between Potssium ions nd APTT levels (P=0.04) while no significnt reltionship ws observed between Potssium nd ALT levels nd similrly Chloride with ALT/APTT levels. It is concluded tht ptients of middle nd higher ge nd hving previous history of liver disese should be especilly monitored for liver functioning when dmitted with confirmed Dengue fever. Key words: Dengue ALT APTT Hemtocrit Thrombocytopeni INTRODUCTION Ministry of helth Pkistn reported 1500 lbortory confirmed cses of dengue fever including the 15 deths Pkistn is one of the WHO Est Mediterrnen to WHO on 25October 2010 [8]. Region country in which dengue fever is mjor public Dengue fever is cused by Dengue virus which helth issue nd hs fced first confirmed outbrek of belongs to the fmily Flviviride nd genus Flvivirus. dengue hemorrhgic in 1994, lter on DEN-3 nd DHF It hs four different serotypes DEN-1, DEN-2, DEN-3, ws first reported in Dengue outbrek hs been DEN-4 which re ntigeniclly similr to ech other with reported with expnsion of infection with incresed some exception [4]. A person recovers from the infection frequency nd severity from the lrge cities of Pkistn in of ny one serotype of dengue virus become immune Corrisponding Author: Muhmmd Shoib, Institute of Medicl Technology, ShifTmeer-e-Millt University, Islmbd, Pkistn. 214

2 Am-Eurs. J. Toxicol. Sci., 7 (4): , 2015 permnently for tht serotype nd my become prtilly sequentil infections of dengue virus (IgG positive) nd immune, temporrily immune or both for the other in cses of hemorrhgic dengue [9]. The min objective of serotypes [5]. the current study is to study reltionship mong Alnine Hemtologicl bnormlities mong the dengue Amino-trnsferse (ALT), APTT nd electrolyte levels in ptient re vrying from mild to severe. Lbortory Dengue Fever serology positive ptients nd it correltion hemtologicl findings ssocited with dengue fever re with ge. This reltionship will help to understnd the thrombocytopeni (Pltelet count below 50,000/ul) progression of disese in ge groups. leucopeni (Leukocyte count 4000/ul or below) nd neutropein, prolonged ctivted prtil thromboplstin MATERIAL AND METHODS time nd rised hemtocrit vlues. Men hemoglobin nd hemtocrit vlues re usully norml. In dengue fever Plce of Reserch: The study ws crried out in Tertiry ptients there is significnt rise in biochemicl prmeters Cre hospitls of Rwlpindi. of the blood like ALT, APTT nd electrolytes. Alnine Amino-trnsferse is relted with liver prenchyml Popultion Concerned: Study ws focused on ptients destruction nd results in Acute Liver filure. with febrile condition dmitted s suspected Dengue Dysfunctioning of liver results in decresed production of Fever ptients. protein nd clotting fctor due to which APTT my be observed [6]. Smple Size: Dt of 115 ptients dmitted s serology Acute liver filure in ssocition with Dengue tests confirmed dengue fever cses in Tertiry Cre hemorrhgic fever ws initilly reported during the hospitls of Rwlpindi ws tken. epidemics in Indonesi in the 1970s. Lter, it ws reported during the 1987 epidemic in Thilnd nd the 1990 Inclusion Criteri: Ptients with Dengue Fever confirmed epidemic in Mlysi. Dengue virus serotypes DEN-1, 2 by ELISA test were included in this study. & 3 hve been isolted from the ptients dying from liver filure with both primry nd secondry dengue Exclusion Criteri: Ptient with symptoms like dengue infections. Dengue ntigens hve been detected in fever nd not confirmed by ELISA test were excluded from heptocytes, in Kupffer cells nd occsionlly in cute the study. inflmmtory cells in these ptients [7]. A reserch reported tht in DHF the verge levels of Smple Collection: Blood smples were collected by AST nd ALT re greter thn in clssic dengue fever. venipuncture technique nd blood collected in APTT nd There is greter heptic injury mong ptients with gel tubes. 215

3 Smple Processing: Blood serum of suspected dengue fever ptients ws collected for confirmtion of Dengue Fever employing immunosorbnt ssy (ELISA) [10]. Furthermore, blood serum ws nlyzed for Alnine Amino-trnsferse (ALT) Spectrophotometery (kinetic method) to investigte effect of dengue virus on liver functioning [11] nd serum Electrolyte by using (Equipment: BACKMAN COULTER CX-9). Citrted plsm ws used for the nlysis of prtil thromboplstin time nlyze on Semi-utomted instrumentkc 4 Amelung Am-Eurs. J. Toxicol. Sci., 7 (4): , 2015 (Biotech) [6]. Fever Sttisticl Anlysis: SPSS 16 sttisticl tool ws used for nlysis of dt, nd cross tbultion nd chi-squre test were employed to find out ssocition between the study vribles hving significnce level t =0.05 nd 95% confidence intervl. RESULTS AND DISCUSSION Totl 115 No. (N=115) serology test positive ptients were included in this study nd out of these 92 ptients (80%) were mlesnd 23 ptients (20%) were femles. Proportion of ptients in different ge groups is shown in (Tble 1). Fever ws most common symptom of presenttion found in 115 ptients (100%), body pin ws present in 73 ptients (63.56%) nd vomiting ws found in 67 ptients (58.3%) (Tble 2). Person Chi-squre test ws used to find out ssocition mong ge nd ALT levels of the ptients with 95% confidence intervl nd =0.05. Anlysis of the study dt showed highly significnt ssocition mong the ge nd ALT levels (Tble 3-). Ptients hving yers of ge hd higher level of ALT s compred with other ge groups. (Figure 1 indictes different ge groups nd corresponding level of ALT). While no significnt reltionship between ge nd APTT ws observed (Tble 3-b). Sttisticl nlysis of study dt of ALT nd APTT levels with help of Person Chi-Squre test showed highly significnt ssocition (P=0.01) between ALT nd APTT levels (Tble 4). Figure 2 illustrtes significnt ssocition between ALT nd APTT Levels. It ws observed tht with the increse of ALT levels APTT levels lso increse. According to the WHO, Acute Liver filure ws reported initilly in Indonesi in 1970s. Lter, it ws reported in Thilnd in 1987 dengue epidemic nd in 1990 epidemic in Mlysi. WHO 1997 reported tht Dengue ntigens hd detected in heptocytes nd in Kupffer cells, Tble 1: Distribution of gender in ge groups Age nd Sex Crosstbultion F M Age 1-20 yers yers yers Above yers Totl Tble 2: Clinicl symptom Symptom Count Percentge % Body Pin Vomiting Bleeding Hedche Chi-Squre Tests Tble 3: Assocition between the ge nd ALT levels of ptients Vlue Df Asymp. Sig. (2-sided) Person Chi-Squre Likelihood Rtio Tble 4: ALT nd APTT ssocition Chi-Squre Tests Vlue df Asymp. Sig. (2-sided) Person Chi-Squre Likelihood Rtio Tble 5: Sodium nd ALT levels ssocition Chi-Squre Tests Vlue Df Asymp. Sig. (2-sided) Person Chi-Squre Likelihood Rtio Tble 6: Sodium nd APTT ssocition Chi-Squre Tests Vlue df Asymp. Sig. (2-sided) Person Chi-Squre Likelihood Rtio Tble 7: Potssium nd ALT ssocition Chi-Squre Tests Vlue Df Asymp. Sig. (2-sided) Person Chi-Squre Likelihood Rtio Tble 8: Potssium nd APTT ssocition Chi-Squre Tests Vlue df Asymp. Sig. (2-sided) Person Chi-Squre Likelihood Rtio

4 Am-Eurs. J. Toxicol. Sci., 7 (4): , 2015 Fig. 1: ALT ssocition with ge Fig. 2: Cross tbultion between ALT nd APTT Levels2 Fig. 3: Sodium Correltion with APTT nd ALT 217

5 Am-Eurs. J. Toxicol. Sci., 7 (4): , 2015 Fig. 4: Assocition between APTT nd Potssium similr studies were crried out by Vinodh et l., why APTT ws observed high in hypoklemi ptients. Pichrdo et l. nd Senevirtne et l. [12-14]. The The Figure 4 shows significnt ssocition of Potssium finding of our study sure tht levels of ALT re higher ions nd APTT levels. Out of totl 30 ptients with very which mens tht Liver is lso ffected with Dengue virus high vlues of APTT 08 ptients showed hypoklim nd infection tht result in incresed level of APTT, These out of 46 ptients with moderte levels of APTT 10 results re in line with other resercher crried out in ptients (21.7%) were presented with hypoklemi, different prts of world. - Chloride ions (Cl ) hs no significnt ssocition with Among blood electrolytes Sodium ions (N+) ALT nd APTT nd other vribles. Norml chloride level showed significnt reltionship with ALT nd APTT found in 91 ptients (79.1%) of totl popultion (N=115), levels (Tble 5 & 6) nd Figure 3 shows significnt 19 ptients (16.5%) were hyperchloremic nd 5 ptients ssocition (P=0.03) of ALT nd APTT levels in the (4.3%) were hving hypochloremi (<96 mmol/l) ptients with hypontremi. In 38 ptients ALT levels (Figs. 2, 3). were very high nd out of these 18 ptients (47.4%) showed hypontremi. While in 40 cses ALT levels were REFERENCES modertely high nd out of these 11ptients (27.5%) were present Hypontremi. APTT levels were very high in 1. Hlsted, S.B., Dengue. Lncet, 370: totl 30 ptients out of which in 13 ptients (43.3%) were 2. Gubler, D.J., Dengue nd Dengue hypontremic nd totl 46 cses showed moderte levels hemorrhgic fever. Clin. Microbiology Rev., of APTT out of which 16 ptients (34.8%) were present 11: with Hypontremi. 3. Mrtin, B.E., P. Kork nd A. Osterhus, There ws no significnt ssocition between Dengue virus pthogenesis, n integrted view. Potssium ions (K+) nd ALT levels (Tble 7) but there Clin. Microbiology. Rev., 22: ws significnt ssocition (P=0.04) between K+ nd 4. Guh-Spir, D. nd B. Schimmer, Dengue fever: APTT levels (Tble 8). The level of confidence intervl new prdigms for chnging epidemiology. Emerg. ws 96%. Themes Epidemiol., 2: It is hypothesize the low levels of N nd K due to 5. WHO Dengue guidelines for dignosis, tretment, infusion which were given immeditely fter the dmission prevention nd control (Edition 2009). of the ptients. So due to hemodilution Sodium levels 6. Arshd, I., A. Hussin, F.A. Mlik nd S.A.R. Shh, were decresed tht hve ssocition with ALT nd Dengue Fever; Clinico-pthologic correltion APTT (Fig. 2). Hypoklemi hve significnt ssocition nd their ssocition with poor outcome. with APTT becuse it is one of the clotting fctors tht Professionl Med J. Mr., 18(1):

6 Am-Eurs. J. Toxicol. Sci., 7 (4): , WHO., Dengue hemorrhgic fever: 11. Hung, X.J., Y.K. Choi, S.H. Im, O. Yrimg, E. Yoon nd dignosis, tretment, prevention nd control, 2 edn. nd H.S. Kim, AST nd ALT detection Genev: World Helth Orgniztion. techniques. J. Sensors, 6(7): World helth orgniztion, Dengue fever 12. Vinodh, B.N., C. Bmmigtti, A. Kumr nd V. Mittl, outbrek in Pkistn. Avilble t Dengue fever with cute liver filure. int/csr/don/rchive/disese/dengue_fever/en/. J. Postgrd Med., 51: De Souz, L.J.d., J.G. Alves, R.M.R. Nogueir, 13. Pichrdo, M.V., C.R. Jimenez, O.R. Espinos, C.G. Neto, D.A. Bstos, E.W.S. Siqueir, I.L. Mrtinez nd M.M.B.M. Altmirno, J.T.D.S. Filho, T.A. Cezrio, C.E. Sores nd Dengue Bullentin, 30: th R.d C. Crneiro, (8 April 2004), Aminotrnsferse 14. Senevirtne, S.L., G.N. Mlvige nd H.J.D. Silv, Chnges nd Acute Heptitis in Ptients With Liver involvement in dengue infections. Dengue Fever. The Brzilin Journl of Infectious Trnsctions of the Royl Society of Tropicl Diseses, 8(2): Medicine nd Hygiene, 100: Nrynn, M., M.A. Arvind, P. Ambikpthy, R. Prem nd M.P. Jeypul, Dengue Fever-Clinicl nd Lbortory Prmeters Associted with Complictions; Dengue Bulletin, 27:

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