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Paper text:
familial mediterranean fever ( fmf ) is an inherited disease characterized by recurrent attacks of serositis , fever , and erysipelas - like skin rash .
the disease is common in mediterranean countries , and the incidence of the disease has been reported as 1/200 in ashkenazi jews and 1/1000 in turks .
colchicine treatment has been shown to be effective in preventing the development of amyloidosis and in reducing proteinuria .
it has been suggested that thrombocyte activation has an important role in the pathogenesis of atherosclerosis in various inflammatory diseases .
platelet activation has been thought to play a triggering role in arterial disorders , and mean platelet volume ( mpv ) is considered a good indicator of platelet activation [ 610 ] .
thus , mpv and pdw measurements may help predict the risk of atherosclerosis . as mpv and pdw measurements are readily available diagnostic parameters ,
their use in evaluation of diseases that may predispose patients to atherosclerosis has become popular .
a few studies have assessed the role of mpv in prediction of atherosclerosis risk in fmf patients [ 1117 ] , but they have reported contradictory results .
therefore , it was necessary to investigate the usefulness of mpv in the prediction of such a risk among a relatively large study population .
neutrophil - to - lymphocyte ratio ( nlr ) may serve as a marker of subclinical inflammation in patients with fmf . in this study
, we aimed to investigate whether mpv and pdw could be used as parameters for prediction of atherosclerosis risk in fmf patients , and if nlr might be helpful in the diagnosis of subclinical inflammation of fmf .
patients diagnosed with fmf according to tel - hashomer criteria   and who had started colchicine therapy were included in the study .
the study population consisted of 75 fmf cases ( 42 f , 33 m ) with an inflammatory attack encountered within the study period , 157 attack - free patients ( 84 f , 73 m ) , and 77 ( 39 f , 38 m ) healthy controls . the diagnosis of fmf attack was based on clinical ( fever , abdominal pain , skin rash , arthritis , pleuritis ) and laboratory ( erythrocyte sedimentation rate ( esr ) > 20 mm / h and c - reactive protein ( crp ) > 5 mg / l ) findings .
consecutive episodes with an interval of at least 10 days were accepted as separate attacks .
white blood cell ( wbc ) count , platelet count , neutrophil count , lymphocyte count , nlr ( absolute neutrophil - to - absolute lymphocyte ratio ) , mpv , pdw , crp , esr values , mefv mutations , and demographic features of the patients were recorded .
wbc and platelet counts , mpv and pdw values , and the demographic data of the control group were also noted .
all blood samples were studied in the same regularly checked analyzer ( abbott cell - dyn 3700 , united states ) .
the data were evaluated using spss ( statistical package for social sciences ) 18.0 program for windows .
kolmogorov - smirnov and shapiro - wilk tests were used to assess whether the data were distributed normally .
numerical variables with normal distribution are shown as mean  standard deviation and these values were compared using either the t test or 1-way anova test .
the comparison of the groups with abnormally distributed numerical data was performed with mann - whitney u test or kruskal - wallis test .
correlations between parameters with normal and abnormal distribution were computed through pearson s and spearman s correlation analysis , respectively .
the data were evaluated using spss ( statistical package for social sciences ) 18.0 program for windows .
kolmogorov - smirnov and shapiro - wilk tests were used to assess whether the data were distributed normally .
numerical variables with normal distribution are shown as mean  standard deviation and these values were compared using either the t test or 1-way anova test .
the comparison of the groups with abnormally distributed numerical data was performed with mann - whitney u test or kruskal - wallis test .
correlations between parameters with normal and abnormal distribution were computed through pearson s and spearman s correlation analysis , respectively .
a total of 75 ( 42 f , 33 m ) fmf patients with attack , 157 ( 84 f , 73 m ) fmf patients without attack , and 77 ( 39 f , 38 m ) healthy controls were included in the study .
mean ages were 8.43.5 in the attack group , 9.13.6 in the attack - free group , and 8.33.5 in the healthy control group .
leucocyte count was higher than normal 27 ( 36% ) in the attack groups and 6 ( 3.8% ) in attack - free groups .
thrombocyte count was higher than normal value in 61 ( 81.3% ) attack group subjects and 10 ( 6.4% ) attack - free subjects .
crp value was higher than normal in 20 ( 26.7% ) attack group patients and 5 ( 3.2% ) in the attack - free groups .
esr value higher than normal value in 58 ( 77.3% ) and not detected in any of the patients in the attack - free group .
when attack and attack - free groups were compared in terms of number of patients who were homozygous , compound heterozygous or heterozygous , there were not any statistically significant differences between groups ( p=0.10 ) .
there were no significant differences between patients in the attack and attack - free groups in terms of 1-allele or 2-allele mutations ( p=0.09 ) .
mean esr , crp value , and platelet count were higher in the attack group than in the attack - free group ( p<0.001 , p<0.001 , p=0.002 , respectively ) ( table 1 ) .
however , there were no statistically significant differences among the attack , attack - free , and control groups in terms of mean mpv and pdw value ( p=0.25 , p=0.96 ) ( table 1 ) .
mean nlr value was higher in the attack group than in the attack - free group and control group ( p<0.001 , p<0.001 , respectively ) ( table 1 ) .
no significant difference was found between the attack - free group and control group ( p=0.76 ) ( table 1 ) .
a positive correlation was found between the mpv and pdw in the attack group and the attack - free group ( r=0.61 , p<0.001 and r=0.66 , p<0.001 , respectively ) .
a negative correlation was found between platelet counts and mpv in the attack group and the attack - free group ( r=0.36 , p=0.001and r=0.32 , p<0.001 , respectively ) .
a negative correlation also was found between platelet count and pdw in the attack group and the attack - free group ( r=0.33 , p=0.003 , r=0.22 , p=0.007 , respectively ) .
. outcomes of clinical and subclinical inflammation are unclear during fmf attack and in the attack - free period . as in other clinical entities accompanied by inflammation ,
previous studies have investigated associations between mpv and atherosclerosis , myocardial infarction ( mi ) , post - mi prognosis , post - percutaneous coronary intervention outcome , stent thrombosis , in - stent restenosis , stroke , venous thromboembolism , behet s diseases with venous thrombosis , gestational diabetes , preeclampsia , rheumatoid arthritis , ankylosing spondylitis , psoriasis , disease activity in ulcerative colitis , subclinical hypothyroidism , celiac disease , and von willebrand factor in impaired glucose intolerance and in hepatitis b infection .
hormonal and immune system agents , including thrombopoietin , granulocyte - macrophage colony - stimulating factor , interleukin-1 , tumor necrosis factor - alpha ( tnf- ) , and interleukin-6 ( il-6 ) , affect maturation of thrombopoietic cells and the release of platelets into circulation . increased il-6 and tnf- were shown in fmf patients during attack and in the attack - free period .
mpv is an easily available parameter related with thrombocyte activation , which does not require additional cost .
there is limited data concerning the relationship between mpv and atherosclerosis risk in fmf patients [ 1117 ] .
while higher mpv values have been reported in some of these studies , others have found lower mpv values in attack and attack - free periods of fmf patients compared with the control groups .
furthermore , higher mpv values have been found in the controls and the attack - free period compared with the attack period of patients ( table 2 ) [ 1113,15 ] . also , mpv was higher in the attack - free group than the control group in a study consisting of pediatric and adult patients . in the same study population ,
mpv was significantly lower in fmf patients with amyloidosis than in patients without amyloidosis and in control subjects .
in addition , fmf patients without amyloidosis had higher mpv values than healthy controls in the same study . however , the results of these studies are controversial in terms of relation of mpv and fmf . in our study , mpv was comparable between fmf patients with attack , patients in attack - free period , and healthy controls .
our results do not support any of the previous studies reporting mpv as being higher or lower in fmf patients compared to healthy subjects .
on the other hand , pdw is another marker thought to be related with inflammation and atherothrombotic events .
we suggest that mpv and pdw values are not affected by inflammation in childhood fmf .
all of our study population was under colchicine treatment , which might reduce inflammation and result in lack of significant difference in mpv and pdw values between fmf patients and healthy controls .
fmf patients have higher nlr values , an inflammatory marker , than healthy controls . in the present study
, we found higher nlr in the fmf attack group than in the attack - free fmf patients and healthy controls , and the latter 2 groups had similar nlr values .
it was higher in the attack group compared to the attack free and control groups but lymphocyte count was similar among all 3 groups .
thus , the difference in nlr was due to the difference in neutrophil count between groups .
these results suggest that nlr may indicate fmf attack , but nlr can not be used as a subclinical inflammation marker .
platelet count , esr , crp , and wbc were higher in the attack group than in the attack - free patients and healthy controls , as expected .
mpv was positively correlated with pdw , and it was negatively correlated with platelet count in fmf patients of our study population .
our results are consistent with a study by sahin et al . , performed with fmf patients with attack , and another study by makay et al . with attack - free fmf patients .
mpv was reported as negatively correlated with platelet count in patients with coronary artery disease and in healthy persons .
our results suggest that inflammatory process in fmf does not affect platelet volume . on the other hand
, it has been reported that large platelets are consumed during the serosal inflammation in patients with fmf .
also , our study group consisted of a turkish population and was performed only in 1 center .
in conclusion , we found no difference in mpv and pdw values between fmf patients and healthy controls , while nlr was higher in fmf patients in the attack period than in fmf patients in attack - free period and healthy controls .
our results suggest that mpv and pdw values do not predict atherosclerosis risk in fmf children , and nlr may be an indicator for attack period but not attack - free period .
backgroundfamilial mediterranean fever ( fmf ) is an autoinflammatory disease characterized by recurrent attacks of serositis , fever , and rash . 
 clinical and subclinical inflammatory processes may contribute to atherosclerosis in fmf patients , with mean platelet volume ( mpv ) as a potential indicator for atherosclerosis risk and neutrophil - to - lymphocyte ratio ( nlr ) as a marker for subclinical inflammation in these patients . in this study 
 , we investigated whether mpv can be used as an indicator for atherosclerosis risk and if nlr is a marker for subclinical inflammation in fmf patients.material/methodsthe study consisted of 75 fmf patients in attack , 157 attack - free patients , and 77 healthy controls . 
 white blood cell count neutrophil - to - lymphocyte ratio , platelet count , mpv , pdw c - reactive protein levels , and erythrocyte sedimentation rate were recorded.resultsthere were no significant differences between attack , attack - free , and control groups in terms of mean mpv and pdw value . 
 nlr value was higher in the attack group . 
 nlr value was similar in attack - free and control groups.conclusionswe found that mpv and pdw values are similar in fmf patients and healthy controls . 
 nlr was higher in fmf patients in the attack period . 
 therefore , our results suggest that mpv and pdw values do not predict atherosclerosis risk in pediatric fmf patients , and nlr may be an indicator for attack period but not attack - free period .