The Egyptian Journal of Hospital Medicine (April 2018) Vol. 71(1), Page

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1 The Egypian Journal of Hospial Medicine (April 2018) Vol. 71(1), Page Mean Plaele Volume versus Toal Leukocye Coun and C-reacive Proein as an Indicaor for Moraliy in Sepsis Hazem M. Abd El Rahman, Sanaa F. Mahmoud, Ahmed W. Ezza, Alaa E. Roshdy Deparmen of Aneshesia, Inensive Care and Pain Managemen Faculy of Medicine, Ain Shams Universiy Corresponding auhor: Alaa E Roshdy; Mobile: ; alaaroshdy86@gmail.com ABSTRACT Background: sepsis is a major cause of morbidiy and moraliy, and he incidence is rising, probably due o he growing elderly populaion, anibioic resisance, immunosuppressive medicaion and, invasive surgery. Pneumonia is he mos common infecion leading o sepsis, followed by urinary rac infecions and abdominal infecions. These infecions are usually localized and conrolled by he immune sysem, bu hey can someimes spread and cause sepsis. Mean plaele volume (MPV) is a measuremen ha describes he average size of plaeles in blood. MPV is ordered rouinely as par of he complee blood coun panel by an auomaed flow cyomery machine. In sepic shock, mos of he coagulaion facors are depleed and plaele coun is decreased, a close relaionship beween sepsis severiy and hrombocyopenia has already been documened. Aim of he Work: his work aimed o find a relaion beween he mean plaele volume and moraliy in paiens wih sepsis in correlaion wih C-reacive proein and oal leukocye coun. Mehods: 80 adul criically ill paiens of boh sexes wih sepsis and sever sepsis who admied o he unis of Criical Care Medicine Ain Shams Universiy Hospials. The mean plaele volume (MPV) evaluaed and correlaed o boh oal leukocye coun (TLC) and C-reacive proein (CRP) on a daily basis saring from he day of admission and over 14 days. In addiion, paiens observed regarding oucomes including moraliy and discharge from ICU. Resuls: MPV was able o deec sepsis prognosis wih high saisical significance from admission, CRP also was a good predicor and on he conrary TLC had poor prognosic value on admission and afer 24 hours, bu for he whole hospial say a significan associaion was found. Conclusion: elevaed MPV on admission is an imporan marker for sepsis diagnosis and prognosis. Progressively elevaed MPV during hospial say correlaes well wih moraliy. Decreased plaele coun afer admission is significanly associaed wih moraliy in sepic paiens. MPV and plaele coun can be used as prognosic markers for sepsis and indicaors of moraliy on daily basis. Keywords: sepsis, sepsis markers, mean plaele volume (MPV). INTRODUCTION Infecious diseases are a global healh problem, causing many deahs per year. Respiraory infecions as well as diarrhea, malaria, measles and HIV/AIDS are major causes of morbidiy and moraliy worldwide (1). Many of he signs and sympoms ha are associaed wih infecious diseases are a direc manifesaion of he hos immune response. For many years, physicians have recognized he hallmarks of a localized bacerial infecion: dolor, rubor, calor and umor. These signs resul from differen leukocyes and heir meabolies in he immune sysem, which aemp o kill he invading pahogen. For he hos, he challenge wih infecions is o recognize he foreign invaders and o direc he appropriae immune response effecively wihou inflicing self-damage. The body uses differen mechanisms o avoid such inappropriae responses, bu occasionally his mechanism fails causing severe issue damage and deah (2). Sepsis was firs menioned in Homer s poems around 2,700 years ago. The word sepsis comes from he word σñψις, (sipsi), which in original Greek means decomposiion of organic maer. During he lae 19 h and he 20 h cenuries, sepsis was described as a sysemic infecion supposedly caused by he invasion of he blood sream by pahogenic microorganisms. However, paiens sill died of sepsis even when he microorganisms had been eradicaed wih anibioics (3). Sepsis and sepic shock are major healhcare problems, affecing millions of people around he world each year and killing as many as one in four and ofen more (4). Similar o polyrauma, acue myocardial infarcion, or sroke, early idenificaion and appropriae managemen in he iniial hours afer sepsis develops improved oucomes (5). Mean plaele volume (MPV) describes he average size of plaeles in a blood sample and rouinely measured by auomaed hemaology analyzers using eiher elecrical impedance or opical fluorescence mehod (6). A rise in MPV during sepsis caused by increased plaele desrucion and increased producion of larger 2373 Received: 20/1/2018 DOI: / Acceped: 30/1/2018

2 Mean Plaele Volume and younger plaeles (7).There is a srong relaion beween MPV and prognosis described by medical researchers, so an increase in plaele size in a paien wih bacerial infecion could sugges ha he infecion has become invasive (8). PATIENTS AND METHODS This sudy carried ou on 80 adul criically ill paiens of boh sexes wih sepsis and sever sepsis who admied o he unis of Criical Care Medicine Ain Shams Universiy Hospials. Inclusion Crieria Age more han 18 years. Paiens presened wih sepsis defined as a suspeced source of infecion plus 2 of he following: Fever of >38º or hypohermia <36º Hear rae of >90 beas/min Respiraory rae of >20 breahs per minue or PaCO 2 <32 mmhg Whie blood cells >12 x 10 9 /cmm or <4 x 10 9 /cmm, or >10% immaure forms. Paiens presened wih severe sepsis defined as sepsis associaed wih secondary organ dysfuncion. Exclusion Crieria Age less han 18 years. Pregnan females. Paiens wih acue cerebro-vascular even. Paiens wih acue coronary syndrome. Paiens on chemoherapy. Paiens wih malignan hemaological disease. Paiens wih immunosuppression. Paiens wih acive hemorrhage. Paiens who had used ani-plt drugs such as clopidogrel prior o admission. All paiens included in his sudy were subjeced on admission o he followings: A. Hisory: Personal daa: name, age and gender. Presen hisory of medical condiion. Pas medical hisory including: - Hear disease. - Liver disease - Renal disease - Hyperension. - Diabees mellius. - Hemaological disorder. - Oncological disorder. B. Clinical examinaion: Complee physical examinaion was done wih emphasis on: - Vial signs :( hear rae, mean pressure, respiraory rae, emperaure). - Menal saus according o Glasgow Coma Score (GCS) - Ches examinaion. - Cardiac examinaion. - Abdominal examinaion. C. Laboraory invesigaions Done on admission and daily during he period of he sudy and included: - Serum Na, K. - Urea, creainine. - Random blood sugar. - C-reacive proein. - Complee blood picure (Hemoglobin, Whie blood coun (TLC), Plaele coun, and mean plaele volume (MPV)). D. Radiological examinaion ha helps o deec source of sepsis included: - Ches X-ray. - Ulrasound of he abdomen. - CT abdomen wih conras. - Echo. E. Sepsis workup Blood culures from one cenral and wo peripheral lines. Spuum culure or mini bronchioalveolar lavage. Urine culure. Culure from a known source like abscess or issue Cerebrospinal fluids analysis (in suspeced cases of meningiis) Period of he sudy The mean plaele volume (MPV) was evaluaed and correlaed o boh oal leukocye coun (TLC) and C-reacive proein (CRP) on a daily basis saring from he day of admission and over 14 days. In addiion, paiens observed regarding oucomes included moraliy and discharge from ICU. The sudy was approved by he Ehics Board of Ain Shams Universiy. Resuls Our sudy was carried on 80 adul paiens of boh sexes admied o ICU wih sepsis, paiens (45%) survived and paiens (55%) were non-survivors. Demographic Daa: 61% were male and 39% were females. Age ranged from 46 o 91 years wih a mean 68 ± 9.34 years. Sex did no affec moraliy, no saisical significance found. Age found o affec moraliy, he mean age of non-survivors was higher han of survivors (73.5 ± 6.68 years and 61 ± 7.19 years respecively). 2374

3 Hazem Abd El Rahman e al. Table 1: relaion beween demographic daa and moraliy (N = 36) (N = 44) Tes of sign P No. % No. % Sex Male female χ 2 = Age ± ± 6.68 = * < * χ 2 chi square es : Suden -es *: P< 0.05: Significan, P < 0.01: Highly significan Pas Medical Hisory: associaed co-morbidiies significanly affeced he moraliy. Table 2: relaion beween co-morbidiies hisory and moraliy (N=44) P No. % No. % HTN * * DM Cardiac disease Kidney disease * <0.001 * Liver disease * <0.001 * COPD χ 2 chi square es : Suden -es *: P< 0.05: Significan, P < 0.01: Highly significan Vial signs: vial signs of paiens significanly affeced he moraliy. Table 3: relaion beween vial signs and moraliy: Mean blood pressure ± 4.93 Temperaure ± 0.27 Respiraory rae ± 1.78 Hear rae ± (N=44) ± ± ± ± : Suden -es *: P< 0.05: Significan, P < 0.01: Highly significan Complee Blood Picure: difference was found beween survivors and non-survivors concerning hemoglobin concenraion, hemaocri value and plaele coun. Table 4: relaion beween complee blood picure and moraliy Hb % (g/dl) HCT (%) Plaele Coun ( 10 3 /µl) Complee blood picure ± ± ± Non survivors (N=44) ± ± ± P * <0.001 * * <0.001 * * <0.001 * * <0.001 * p = * <0.001 * = * <0.001 * = * <0.001 * : suden -es *: P< 0.05: significan, P < 0.01: highly significan Source of sepsis: he mos common was ches infecion in 32 of paiens, bu saisical significance was no found beween source of sepsis and moraliy

4 Mean Plaele Volume Table 5: relaion beween source of sepsis and moraliy Source of sepsis (N=44) P No. % No. % Ches infecion Urinary rac infecion Blood sream infecion Skin and sof issue infecion Abdominal infecion MPV: significanly affeced he oucome, as saisical significance was found beween moraliy and elevaed MPV on admission, afer 24 hours and elevaed MPV average during he whole hospial say. had a higher MPV comparing o survivors. Table 6: relaion beween MPV and moraliy On admission Afer 24 hours Average MPV (fl) Min- Max Min- Max Mean Min- Max Mean N= ± ± ± Non survivors N= ± ± ± P * * * <0.001 * * <0.001 * : suden -es *: P< 0.05: significan, P < 0.01: highly significan CRP level: affeced he oucome, saisical significance was found beween moraliy and elevaed CRP on admission, afer 24 hours and elevaed CRP average. Table 7: relaion beween CRP level and moraliy CRP (mg/dl) N=36 On admission Afer 24 hours Average ± ± ± Non survivors N= ± ± ± P * <0.001 * * <0.001 * * <0.001 * : suden -es *: P< 0.05: significan, P < 0.01: highly significan TLC: no saisical significan difference was found beween moraliy and TLC on admission and afer 24 hours, bu during he whole hospial say significanly affeced he oucome. 2376

5 Sensiiviy Sensiiviy Hazem Abd El Rahman e al. Table 8: relaion beween TLC and moraliy On admission Afer 24 hours TLC ( 10 3 /µl) N= ± ± Non survivors N= ± ± P Average : Suden -es *: P< 0.05: significan, P < 0.01: highly significan ± ± * <0.001 * Specificiy CRP ON ADMISSION MPV ON ADMISSION TLC ON ADMISSION Figure 1: ROC curve showing relaion beween CRP, MPV, TLC and moraliy on admission CRP 24 Hr MPV 24 Hr TLC 24 Hr Specificiy Figure 2: ROC curve showing Relaion beween CRP, MPV, TLC afer 24 hours and moraliy 2377

6 Sensiiviy Mean Plaele Volume Specificiy CRP Average MPV Average TLC Average Figure 3: ROC curve showing relaion beween he average of CRP, MPV, TLC and moraliy DISCUSSION Currenly, sepsis is a major concern; wihin he las decade, several rials and proocols have focused on his condiion, aiming o esablish beer measures for is managemen and prevenion of poenial complicaions. Therapeuic measures wih considerable posiive impacs have been largely emphasized; however, assessing he prognosis of sepsis remains difficul (9). Several physiological and blood chemisry parameers are used in daily pracice in inensive care unis for boh diagnosis and prognosis in sepic paiens (e.g. CRP and TLC). Mean plaele volume (MPV), which is generally overlooked by clinicians and is parameer changes have been already observed and some sudies suggesed ha MPV increases during sepsis as in acue appendiciis, pancreaiis, infecive endocardiis, and malaria, his es is rouinely provided by a full blood coun analyzer, no requiring any complex or expensive echnologies (10). In his sudy, a comparison beween mean plaele volume (MPV), oal leukocye coun (TLC) and C-reacive proein (CRP) levels were done o assess he possible role of mean plaele volume in predicion of moraliy and prognosis of paiens wih sepsis. Regarding he oucome, he moraliy rae in his sudy was 55%, men were more o develop sepsis as 61% of paiens were males and 39% were females, he mean age in our sudy was 68 ± 9.34 years. Gender did no affec moraliy as no significan difference was found beween males and females 57% and 51.61% respecively. In conrary o sex, age was found o affec moraliy significanly, as he mean age in he non-survivors group was higher han in he survivors group 73.5 ± 6.68 years and 61 ± 7.19 years respecively wih p value < A significan associaion was found beween associaed co-morbidiies and moraliy, especially hepaic and renal disease as all paiens presened wih hepaic or chronic kidney disease were non-survivors.we found a significan relaion beween vial signs and moraliy. Nonsurvivors compared o survivors end o have lower mean blood pressures, higher body emperaures, higher respiraory raes, and higher hear raes.the mean of plaele coun for paiens on admission was ± /µl. For he whole hospial say; mean of plaele coun was significanly lower in non survivors compared o survivors 122 ± /µl and 187 ± /µl respecively wih p value (< 0.001).Ches infecion was he mos common primary source of infecion wih 40% of paiens, bu no significan difference beween he source of sepsis and moraliy.in his sudy, MPV on admission ranged beween fl/l wih a mean of 9.71 ± 0.77 fl/l which was consisen wih Guclu e al. (11) sudy, who repored ha MPV levels higher han 8 fl/l had a good role for sepsis diagnosis. The cu off value for MPV was 9.6 fl which was found o be significan and of a magniude considered o be clinically useful, wih sensiiviy 61.5%, specificiy 69.4%, p value (0.003) and accuracy 65.7% in predicing moraliy. The cu off value for MPV was 9.7 fl which was found o be significan and of a magniude considered o be clinically useful, wih sensiiviy 75%, specificiy 69.4% (p value <0.001) and accuracy 72.3% in predicing moraliy. The cu off value for MPV during 2378

7 Hazem Abd El Rahman e al. whole hospial say was 10.2 fl which was found o be significan and of a magniude considered o be clinically useful, wih sensiiviy 77.3%, specificiy 83.3%(p value <0.001) and accuracy was 80% in predicing moraliy. Concerning he relaion beween he CRP level on admission and moraliy, he cu off value for CRP level was 101 mg/l which was found o be significan and of a magniude considered o be clinically useful, wih sensiiviy 63.6%, specificiy 75%(p<0.001) and accuracy was 68.75% in predicing moraliy. Concerning he relaion beween he CRP level afer 24 hours and moraliy, he cu off value for CRP level was 94 mg/l which was found o be significan and of a magniude considered o be clinically useful, wih sensiiviy 72.7%, specificiy was 77.8% (p <0.001) and accuracy was 75% in predicing moraliy. The cu off value for CRP level during whole hospial say was 90 mg/l which was found o be significan and of a magniude considered o be clinically useful and sensiiviy was 81.8%, specificiy was 80.5% and % (p <0.001) and accuracy was 81.25% in predicing moraliy. Concerning he relaion beween TLC on admission and moraliy, he cu off value for TLC was /µl which was no significan wih sensiiviy 54.5%, specificiy was 66.7% (p 0.579) and accuracy was 60% in predicing moraliy. Concerning he relaion beween TLC afer 24 hours and moraliy, he cu off value for TLC was /µl which was no significan wih sensiiviy 63.64%, specificiy was 66.7%) (p 0.077) and accuracy was 65% in predicing moraliy. Concerning he relaion beween he average of TLC during he whole hospial say and moraliy, he cu off value for TLC was /µl which was found o be significan and of a magniude considered o be clinically useful, wih sensiiviy 70.45%, specificiy was 66.66%(p <0.001 and accuracy was 68.75% in predicing moraliy. CONCLUSION We concluded ha elevaed mean plaele volume on admission is an imporan marker in sepsis wih increased moraliy in paiens wih elevaed mean plaele volume on admission and from his sudy we can recommend: Rouine measuremen of he MPV in sepsis paiens as is increase can predic moraliy. Conduc furher sudies on larger samples of paiens. REFERENCES 1. Adhikari NK, Fowler RA, Bhagwanjee S e al. (2010): Criical care and he global burden of criical illness in aduls. Lance, 376(9749): Angus DC and van der Poll T (2013): Severe sepsis and sepic shock. N. Engl. J. Med., 369(9): Majno G (1991): The ancien riddle of sigma ea psi ioa sigma (sepsis). J. Infec. Dis., 163(5): Angus DC, Linde-Zwirble WT, Lidicker J e al. (2001): Epidemiology of severe sepsis in he Unied Saes: analysis of incidence, oucome, and associaed coss of care. Cri. Care Med., 29(7): Dellinger RP, Levy MM, Rhodes A, Annane D, Gerlach H, Opal SM, Sevransky JE, Sprung CL, Douglas IS, Jaeschke R and Osborn TM (2013): Surviving sepsis campaign: inernaional guidelines for managemen of severe sepsis and sepic shock. Inensive Care Medicine, 39(2): Jackson SR and Carer JM (1993): Plaele volume: laboraory measuremen and clinical applicaion. Blood Rev., 7: Warkenin TE, Aird WC and Rand JH (2003): Plaele-endohelial ineracions: sepsis, HIT, and aniphospholipid syndrome.hemaology Am. Soc. Hemaol. Educ. Program, (1): Jones AE, Trzeciak S and Kline JA (2009): The sequenial organ failure assessmen score for predicing oucome in paiens wih severe sepsis and evidence of hypoperfusion a he ime of emergency deparmen presenaion. Cri. Care Med., 37(5): Rocco JR, Rocco PRM, Noé RM e al. (2003): Escore prognósico para unidade semi-inensiva pós-operaória. Rev. Bras. Ter. Inensiva, 15(4): Yilmaz Z, Eralp O and Ilcol YO (2008): Evaluaion of plaele coun and is associaion wih plaelecri, mean plaele volume, and plaele size disribuion widh in a canine model of endooxemia. Ve. Clin. Pahol., 37: ) Guclu E, Durmaz Yand Karabay O. (2013): Effec of severe sepsis on plaele coun and heir indices. Afr. Healh Sci., 13: