brucellosis is a frequently encountered zoonotic disease in the developing countries , and considered as an important public health problem .
people can be contracted especially through contaminated meat , milk , and dairy products as well as direct contact with the excrements or body secretions of the infected animals .
are small , gram  negative , facultative , intracellular , and pathogenic bacteria ; they invade mononuclear phagocytic system cells and proliferate there .
brucellosis is an inflammatory disease that can infect any organs or systems in the body .
it is diagnosed through the clinical , serological , and microbiological test results of the patients ( 1 ) .
the acute phase reactants increase as a result of the inflammatory process in brucellosis ( 1 , 2 ) . in endemic regions ; however , the laboratory conditions may not always be suitable or sufficient for diagnosis .
since the second antibody titer , assessed in the follow - up after treatment , may remain at a high level , it is difficult to decide whether to stop or continue the medical treatment ( 1 ) .
therefore , authors believe that additional diagnosis methods may be useful in the follow - up process . leukocyte count and high sensitive c - reactive protein ( hs - crp ) are frequently used as inflammatory markers in patients diagnosed with brucellosis . besides these markers , the current study investigated whether the values of mean platelet volume ( mpv ) and red blood cell distribution ( rdw ) could be considered as surrogate markers during the illness phase .
mean platelet volume ( mpv ) is a measure of platelet size . as part of the routine complete blood count test cycle ,
mpv is generated by full blood count analyzers but mostly overlooked by clinicians ( 3 ) .
mpv is one of the most commonly used surrogate markers of platelet function . comparing with small platelets ,
large ones contain more granules , aggregate with collagen more quickly , have higher thromboxane a2 levels , and express more glycoprotein ib and iib / iiia receptors ( 4 - 6 ) .
it reveals the presence of inflammatory burden and disease activity in many diseases including preeclampsia , acute pancreatitis , unstable angina , myocardial infarction , and cases of systemic inflammation such as ulcerative colitis and crohn s disease ( 7 ) . as for rdw , it is a measure of heterogeneity in the size of circulating red blood cells .
it is one of the standard complete blood count components , and is calculated as a percentage by dividing the standard deviation of the red cell volume by the mean corpuscular volume .
various studies revealed the clinical implications of rdw about the presence of various pathologies such as inflammatory bowel disease , celiac disease , pulmonary embolism , and coronary artery disease .
moreover , inflammatory and infectious pathological diseases such as acute pancreatitis , bacteremia , sepsis , and septic shock are proven as predictive values ( 8) . in a study by lippi et al .
( 9 ) , a graded association of rdw with hs - crp and erythrocyte sedimentation rate were reported , independent of various confounding factors . besides inflammation , oxidative stress
although erythrocytes possess a great antioxidant capacity and regularly serve as the chief oxidative sink , they are liable to oxidative damage which reduces cell survival ( 10 ) .
according to a population - based study ( 11 ) , higher rdw were independently associated with poorer pulmonary function .
nevertheless , it still unknown whether rdw is a simple marker and not a mediator of carotid artery atherosclerosis .
indeed the discovery of a putative causative mechanism is prevented by the lack of epidemiological studies which would reveal the presence of an association between atherosclerosis and anisocytosis .
among the studies published to date , we encountered a single prospective study that examined the mpv , rdw and hs - crp values of patients with acute brucellosis and those convalescing from brucellosis .
the current study aimed to investigate the mpv , rdw , and crp values as inflammatory markers of the disease ( 8) .
the data of 250 patients diagnosed with in the university hospital , together with the data of 101 healthy controls were assessed .
the study was approved by the local ethics committee of baskent university , and in conformity with the helsinki declaration , all patients signed the informed consents ( ka08/198 ) .
the study evaluated 88 patients with the history of acute brucellosis who were in their first first - year follow - up .
the study included patients over the age of 18 diagnosed with brucellosis and followed - up from 2008 to 2014 . in the clinic ,
the patients diagnosed with brucellosis had high fever , chills , shivering , fatigue , sweating , and muscle and joint aches .
the microbiological and serological tests were performed on subjects blood samples . those with an agglutination titer  1/160 and/or brucella spp .
the patients participating in the study were treated with doxycycline ( six weeks ) , rifampicin ( six weeks ) , or streptomycin ( 21 days ) .
the crp level of the subjects was normal , and they did not have any complaints .
the leukocyte counts and the mpv , rdw and high sensitive c - reactive protein ( hs - crp ) values of the patients were compared with those of the controls .
the study excluded patients with abnormal renal and liver function test results or with other infectious diseases and inflammatory conditions .
blood samples were analyzed in the hematological laboratory of the hospital , using standard tubes containing 2 ml blood and 0.04 ml of 7.5% k3 salt of ethylene di amine tetra acetic acid ( edta ) .
since the mpv values could have increased under the influence of edta , the measurements were performed within two hours ( 12 ) .
afterwards , the serum samples were separated from the cells by placing them in the centrifuge for ten minutes at 3000 rpm . the patients were diagnosed with brucellosis through the standard tube agglutination test ( standart tube agglutination , spinreact , spain ) , the coombs test (  1/160 ) and/or brucella spp .
an electronic cell counter ( cell - dyne 3700 , abbott , abbott park , il , usa ) was used to determine the wbc counts .
were used to analyze the hematological parameters , which included hemoglobin ( hb , range 14 - 18 g / dl for male , 12 - 16
g / l for female ) , white blood cell count ( wbc , range 4.5 - 11  109/l ) , platelet count ( plt , range 150 - 400  109/l ) , mpv ( range 7 - 12 fl ) and rdw ( range 11.6 - 15.5% ) .
spectrophotometric methods ( abbott aeroset , tokyo , japan ) were used tomeasure serum crp levels .
the spss software was employed to carry out the statistical analyses . comparing the groups ,
the t -test and chi - square tests were used for continuous categorical variables , respectively .
mann - whitney u test was used to compare nonhomogeneous groups in pairs . in order to observe the correlation between mpv and the other variables , a simple correlation test (
the numeric values were expressed as mean  sd , and the level of significance as p < 0.05 .
blood samples were analyzed in the hematological laboratory of the hospital , using standard tubes containing 2 ml blood and 0.04 ml of 7.5% k3 salt of ethylene di amine tetra acetic acid ( edta ) .
since the mpv values could have increased under the influence of edta , the measurements were performed within two hours ( 12 ) .
afterwards , the serum samples were separated from the cells by placing them in the centrifuge for ten minutes at 3000 rpm .
the patients were diagnosed with brucellosis through the standard tube agglutination test ( standart tube agglutination , spinreact , spain ) , the coombs test (  1/160 ) and/or brucella spp . culture growth .
an electronic cell counter ( cell - dyne 3700 , abbott , abbott park , il , usa ) was used to determine the wbc counts .
were used to analyze the hematological parameters , which included hemoglobin ( hb , range 14 - 18 g / dl for male , 12 - 16 g / l for female ) , white blood cell count ( wbc , range 4.5 - 11  109/l ) , platelet count ( plt , range 150 - 400  109/l ) , mpv ( range 7 - 12 fl ) and rdw ( range 11.6 - 15.5% ) .
spectrophotometric methods ( abbott aeroset , tokyo , japan ) were used tomeasure serum crp levels .
the spss software was employed to carry out the statistical analyses . comparing the groups ,
the t -test and chi - square tests were used for continuous categorical variables , respectively .
mann - whitney u test was used to compare nonhomogeneous groups in pairs . in order to observe the correlation between mpv and the other variables , a simple correlation test (
the numeric values were expressed as mean  sd , and the level of significance as p < 0.05 .
the study included 351 subjects , which 250 of them were categorized in the acute brucellosis group , and 101 in the control group .
among the 250 patients with brucellosis , 115 were male and 135 were female , while 50 of the 101 controls were male and 51 were female .
the blood values of the 88 patients were recorded for further follow - ups a year after treatment .
there was no significant difference between the acute brucellosis and control groups regarding age or gender ( p > 0.05 ) ( table 1 ) .
the mean leukocyte count was 7.3  2.9 and 7.4  2.0 (  10/mm ) in the ab and the control groups , respectively .
the leukocyte count was insignificantly higher than that of in the control group ( p > 0.05 ) .
the mean leukocyte count found in the first year follow - up of the patients with brucellosis was 7.1  2.0 (  10/mm ) .
when the leukocyte counts in the acute phase and in the first - year follow - up were compared , no difference was observed and the counts were similar to those of the control group ( p > 0.05 ) .
the mean crp levels were 32.57  53.20 mg / dl , and 4.81  4.89 mg / dl in the ab and control groups , respectively .
the crp level in the ab group was significantly higher compared with that of the control group ( p < 0.05 ) . in the follow - up year , the crp values remained in the normal range : 5.44  8.91 mg / dl ( p > 0.05 ) .
the mean mpv levels were 7.64  1.30 fl , and 7.67  1.29 fl in the ab and control groups , respectively .
similar to the control group , the mpv level remained within the normal range in the ab group ; this result was statistically significant ( p > 0.05 ) . in the follow - up year the mpv value was 7.65  1.54 fl , same as those of the acute phase and the control group ( p > 0.05 ) .
the mean rdw levels were 16.24  2.14% and 15.90 1.45% in the ab and control groups , respectively .
the rdw level was not significantly higher in the ab group compared to that of the controls . in the follow - up year , there was insignificant difference between the rdw value in the ab and control groups ( 16.10  1.79% ) ( p > 0.05 ) ( tables 1 and 2 ) . while the crp values of the patients in the acute phase were higher compared to those of the controls , their mpv and rdw values had no differences .
similarly , the leukocyte counts of the brucellosis patients in the acute phase and during the follow - up did not differ , and were not different from those of the control group .
when the blood parameters were compared after a year of follow - up , it was observed that the mpv , rdw and leukocyte values had not changed , while the crp values had improved as expected in the period of convalescence .
it was found that the leukocyte count in acute brucellosis patients correlated with mpv and rdw ( r = -0.149 , p = 0.009 ; r = + 0.177 , p = 0.002 ; r = + 0.128 , p = 0.015 , respectively ) .
it was also observed that the age parameter correlated with crp ( r = + 0.272 , p <
0.001 , respectively ) , and the leukocyte count correlated with crp and rdw ( r = + 0.438 , p < 0.001 ; r = -0.124 , p = 0.029 , respectively ) ( table 3 ) .
although the differences in some of these parameters appeared to be statistically significant in the former studies because of negative factors like insufficient size of the patient group , examining 250 patients with brucellosis in the recent decade during the acute phase and in the first - year follow - up showed that the mpv and rdw values of the patients failed to yield significant results in diagnosis and treatment .  
abbreviations : crp : c - reactive protein , mpv : mean platelet volume , rdw : red blood cell distribution .  
data are presented as mean  sd .   abbreviations : crp : c - reactive protein , mpv : mean platelet volume , rdw : red blood cell distribution .  
data are presented as mean  sd .   abbreviations : crp : c - reactive protein , mpv : mean platelet volume , rdw : red blood cell distribution .
the mean leukocyte count was 7.3  2.9 and 7.4  2.0 (  10/mm ) in the ab and the control groups , respectively .
the leukocyte count was insignificantly higher than that of in the control group ( p > 0.05 ) .
the mean leukocyte count found in the first year follow - up of the patients with brucellosis was 7.1  2.0 (  10/mm ) .
when the leukocyte counts in the acute phase and in the first - year follow - up were compared , no difference was observed and the counts were similar to those of the control group ( p > 0.05 ) .
the mean crp levels were 32.57  53.20 mg / dl , and 4.81  4.89 mg / dl in the ab and control groups , respectively .
the crp level in the ab group was significantly higher compared with that of the control group ( p < 0.05 ) . in the follow - up year , the crp values remained in the normal range : 5.44  8.91 mg / dl ( p > 0.05 ) .
the mean mpv levels were 7.64  1.30 fl , and 7.67  1.29 fl in the ab and control groups , respectively .
similar to the control group , the mpv level remained within the normal range in the ab group ; this result was statistically significant ( p > 0.05 ) . in the follow - up year the mpv value was 7.65  1.54 fl , same as those of the acute phase and the control group ( p > 0.05 ) .
the mean rdw levels were 16.24  2.14% and 15.90 1.45% in the ab and control groups , respectively .
the rdw level was not significantly higher in the ab group compared to that of the controls . in the follow - up year , there was insignificant difference between the rdw value in the ab and control groups ( 16.10  1.79% ) ( p > 0.05 ) ( tables 1 and 2 ) . while the crp values of the patients in the acute phase were higher compared to those of the controls , their mpv and rdw values had no differences .
similarly , the leukocyte counts of the brucellosis patients in the acute phase and during the follow - up did not differ , and were not different from those of the control group .
when the blood parameters were compared after a year of follow - up , it was observed that the mpv , rdw and leukocyte values had not changed , while the crp values had improved as expected in the period of convalescence .
it was found that the leukocyte count in acute brucellosis patients correlated with mpv and rdw ( r = -0.149 , p = 0.009 ; r = + 0.177 , p = 0.002 ; r = + 0.128 , p = 0.015 , respectively ) .
it was also observed that the age parameter correlated with crp ( r = + 0.272 , p <
0.001 , respectively ) , and the leukocyte count correlated with crp and rdw ( r = + 0.438 , p < 0.001 ; r = -0.124 , p = 0.029 , respectively ) ( table 3 ) .
although the differences in some of these parameters appeared to be statistically significant in the former studies because of negative factors like insufficient size of the patient group , examining 250 patients with brucellosis in the recent decade during the acute phase and in the first - year follow - up showed that the mpv and rdw values of the patients failed to yield significant results in diagnosis and treatment .  
abbreviations : crp : c - reactive protein , mpv : mean platelet volume , rdw : red blood cell distribution .  
data are presented as mean  sd .   abbreviations : crp : c - reactive protein , mpv : mean platelet volume , rdw : red blood cell distribution .  
abbreviations : crp : c - reactive protein , mpv : mean platelet volume , rdw : red blood cell distribution .
brucellosis is a zoonotic systemic inflammatory disease , which is particularly encountered around the mediterranean ( 13 ) .
the role of platelets in the pathophysiology of brucellosis is not demonstrated yet . in this context , the current study mainly aimed to compare the mpv levels in the acute and post - treatment phases of brucellosis with those of the control group .
the present study showed that the mpv and leukocyte values of patients with acute brucellosis were not different from those of the controls .
infections , and particularly respiratory , urinary , gastrointestinal , bone and meningeal infections , affect the thrombocyte count and functions in various ways .
while mild anemia and leukopenia are frequently observed in brucellosis , isolated thrombocytopenia and pancytopenia are found less often .
there is usually an association between these complications and acute infections ( 8 , 14 ) .
several reports indicate that elevated wbc count is generally the earliest laboratory result to reveal the presence of inflammation and leukocytosis ( 15 , 16 ) .  
the current study indicated that the leukocyte count of patients with acute brucellosis remained within the normal range without early inflammatory marker .
crp is a sensitive acute - phase protein ; and increased in all acute inflammatory processes , however it lacks specificity .
it was observed that the leukocyte count in patients with acute brucellosis did not differ from those of the control group , while the crp level was higher ( table 1 ) .
thus , it proved to be a good marker to diagnose and monitor the efficiency of the treatment ( 17 - 19 ) .
the fact that the crp values of the patients with acute brucellosis in the current study were high showed that it was still a very valuable inflammatory marker .
the role of platelets in brucellosis pathophysiology is not demonstrated yet . in this context , the current study mainly aimed to compare the mpv and rdw levels in the acute and post - treatment phases of brucellosis with their levels in the control group .
moreover , there was a correlation between mpv and the degree of platelet activation and inflammatory responses .
platelet distribution width ( pdw ) is a direct measurement of the platelet size variability .
the most frequently used measure of platelet size , mpv , is a simple marker of platelet function and activation ( 20 ) .
mpv is accepted as a suitable indicator of platelet activation ( 21 , 22 ) .
although activated platelets normally release antibacterial peptides ( 23 ) , there is evidence suggesting the presence of certain pathogens that can exploit activated platelets by binding to their surfaces to start or spread an infection ( 24 ) .
moreover , previous studies reported that mpv changes were associated with various non - infectious inflammatory processes , a condition implying that such changes may indicate disease activity in the inflammation ( 25 - 27 ) .
however , the current study found no difference between the patients with acute brucellosis and the controls regarding the leukocyte , mpv , and rdw values ; a result implying that these parameters are not significant markers to diagnose and treat this disease ( table 1 ) . compared with other inflammation markers , the overall accuracy of mpv to predict diseases
was generally found superior in the literature . there was a correlation between mpv and crp .
high mpv levels also occur in infectious diseases like pulmonary tuberculosis , cchf , and hydatid cyst disease ( 30 - 32 ) . on the other hand ,
lower mpv levels were detected by some researchers in active inflammatory bowel disease , rheumatic arthritis , ankylosing spondylitis , acute pancreatitis , and appendicitis ( 7 , 8 , 25 , 33 ) .
what all these conflicting results indicate is that both higher and lower mpv levels may be of diagnostic and prognostic value for various inflammatory diseases . to the authors ' best knowledge ,
the current study was the first to report decreased mpv level in patients with acute brucellosis comparing the control group . as indicated above ,
examined the mpv values of 39 patients and found the values of 7.84  1.15 fl in the acute phase and 7.83  0.9 fl in the post - treatment phase ( 1 ) . while these values were within the normal range of mpv
, the researchers detected a significant difference comparing them with the mpv values of the controls .
however , when the current study examined the mpv values found in the prospective study on the 250 patients with brucellosis followed up in the last decade , no significant differences were observed among the controls , and the values were within the normal range .   in another study by kucukbayrak et al
, the main mpv value of 40 patients with brucellosis was 7.58  1.96 fl in the beginning of the treatment and 7.90  1.96 fl at the end .
they showed that all the values remained within the normal range , but the difference between the pre- and post - treatment values was statistically significant ( 14 ) .
the current study results on mpv were in disagreement with the results of these two studies .
although most studies in the literature reported mpv as an inflammatory marker in many infectious and rheumatological diseases as well as a guiding parameter in diagnosis and treatment ( 7 , 8 , 19 , 25 - 27 , 30 , 32 , 33 ) , the present study determined that it is not a significant inflammatory marker for brucellosis patients .   a study by lippi et al .
( 9 ) reported a graded association between rdw and high - sensitivity c - reactive protein and erythrocyte sedimentation rate , independent of various confounding factors . besides inflammation , oxidative stress
erythrocytes have immense antioxidant capacity and serve as the chief oxidative sink , but they are vulnerable against oxidative damage which decreases cell survival ( 34 ) .
although kucukbayrak et al . reported high rdw levels in patients with brucellosis before treatment and following it ( 8) , the current study with 250 patients found that the rdw values remained within the normal range before and after treatment , without any statistically significant difference in comparison to those of the control group .
thus , the current study showed that rdw is not a reliable marker in the diagnosis and treatment of patients with brucellosis .
the current study results suggested that these values do not play an important role in the diagnosis and treatment of brucellosis . among the studies in the literature on the inflammatory markers of mpv , rdw , leukocyte count and crp for brucellosis , the present study has the greatest number of patients , and stands as the only prospective study made so far .
it was found that mpv and rdw values are not surrogate markers in the diagnosis and treatment of brucellosis . among other inflammatory markers ,
high crp is still the most valuable marker for the treatment and follow - up of brucellosis .
in contrast , leukocyte count was not found a significant inflammatory marker during the acute phase .
the data in the literature regarding this subject generally remain controversial , since they were obtained from patient groups of limited size .
the current study was distinguished by the fact that it was performed on the largest patient group so far .
it may still be possible for mpv and rdw to act as guiding parameters to diagnose brucellosis .
there is still a need for further prospective , multicenter studies with a large sample size to fully clarify the issue .
 background : brucellosis is an inflammatory disease which may infect any organs or systems in the body . 
 mean platelet volume ( mpv ) is one of the most frequently used surrogate markers of platelet function . 
 it reveals the presence of disease activity in many inflammatory diseases . 
 red blood cell distribution width ( rdw ) is a parameter that measures variation in red blood cell size or red blood cell volume . 
 its predictive value approves inflammatory and infectious diseases.objectives:the current study aimed to determine the assessment levels of red blood cell distribution in cases with acute brucellosis.patients and methods : the current study investigated whether mpv and rdw played any roles in acute brucellosis diagnosis . 
 the study was conducted from 2008 to 2014 through prospective examination of the inflammatory markers found in adult patients with acute brucellosis.results:the follow - up within the year after treatment was examined . 
 the values of age , gender , leukocyte count , c - reactive protein , rdw and mpv were recorded . 
 the study included 351 subjects , 250 of them in the acute brucellosis group and 101 in the control group . 
 the mean mpv levels were 7.64  1.30 fl , and 7.67  1.29 fl in the acute brucellosis and control groups , respectively ( p > 0.05 ) . 
 the mean crp levels were 32.57  53.20 mg / dl , and 4.81  4.89 mg / dl in the acute brucellosis and control groups , respectively ( p < 0.05 ) . 
 there was no statistically significant difference between the two groups regarding the rdw level and the mean leukocyte count ( p > 0.05).conclusions : while the crp value was in patients with acute brucellosis in the current study , the mpv , rdw and leukocyte counts were within the normal range . 
 crp value remains the most valuable inflammatory marker in cases of acute brucellosis . 