flu - like symptoms ( including fever , severe headache , myalgia , chills , nausea and vomiting , conjunctival suffusion , abdominal pain , anorexia , coughing and sore throat ) occur for more than 5 - 7 days .
the second phase , immunologic , occurs immediately after the bacteriemic phase or 1 - 3 days after asymptomatic period .
ten percent of patients with leptospirosis are affected by a severe form of disease or weil 's syndrome ( with a mortality rate of 5 - 40% ) ( 2 ) .
common symptoms of this syndrome are due to liver , kidney and blood vessels involvement . symptoms of this severe disease occur after 3 to 7 days and include persistent jaundice , decreased urine output , anemia , rash , hypotension , shock , changes in consciousness , skin and mucosal hemorrhagic lesions and pulmonary hemorrhage ( 1 - 6 ) . on entering the body
, there is widespread hematogenous dissemination and penetration of tissue barriers , including invasion to the central nervous system and aqueous humor of the eye .
transendothelial migration of spirochetes is facilitated by a systemic vasculitis , accounting for a broad spectrum of clinical illness ( 2 , 7 ) .
severe vascular injury can be developed , leading to pulmonary hemorrhage , ischemia of the renal cortex and tubular - epithelial cell necrosis , and destruction of the hepatic architecture , resulting in jaundice and liver cell injury , with or without necrosis ( 2 , 8 - 11 ) .
immune - mediated mechanisms have been postulated to affect the severity of symptoms and immune mechanisms , including circulating immune complexes , anticardiolipin antibodies , and antiplatelet antibodies , but their significance has not been proven yet ( 2 ) .
old age , pneumonia , renal failure , and thrombocytopenia are associated with a bad prognosis ( 1 ) .
thrombocytopenia occurs in the absence of disseminated intravascular coagulation and may accompany progressive renal dysfunction ( 2 ) .
in this study , we investigated the role of corticosteroids to improve thrombocytopenia due to leptospirosis .
this study was approved by the ethics committee of mazandaran university of medical sciences ( code no : 9186 , date : december 19 , 2012 ) .
the sample size in each group was calculated based on previous studies including that performed by villanueva et al .
the sample size was calculated as 22 based on the following formula , but we enrolled 56 patients . 

n = ( 2  ( z1-/2 + z1- )  )/(1 - 2 ) = 22 
 
 1 = 8.3 , 
 2 = 7.6 , 
  = 0.05 , 
  = 0.2 , 
  = 0.0625 .
totally , 187 patients were admitted as leptospirosis based on clinical and epidemiologic criteria in razi hospital of ghaemshahr , north of iran from august 2011 to september 2013 ( two years ) ( serology tests had not positive results in all cases , those patients diagnosed clinically with false negative serology results were excluded ) .
thrombocytopenia was classified to mild ( plt < 150000 ) , moderate ( plt < 100000 ) and severe ( plt
platelet count had normal findings in 17 patients and 98 cases had mild thrombocytopenia and thus excluded .
the treatment group received corticosteroid ( prednisolone 1 mg / kg / day ) in addition to antibiotic therapy ( ceftriaxone 1 g / iv / daily ) until improvement of thrombocytopenia or for a maximum one - week and the control group received the same dosage of antibiotics , but received placebo instead of corticosteroid during this period .
exclusion criteria were patients with negative mat or those with any health - threatening complications caused by corticosteroid or patients who had previous intake of steroids or other antibiotics two weeks or less prior to the diagnosis of disease and patients whom their clinician did not administered steroids due to some compelling factors like hypersensitivity to steroids , and finally those who were not willing to participate .
sixteen patients due to absence of serologic evidence ( mat had negative results ) were excluded and the final analysis was performed on 56 patients in two divided groups .
statistical analysis was performed by independent t - test , chi - square , kaplan - meier , log rank and breslau using spss software ( version 13 ) . to confirm the diagnosis of leptospirosis by mat ,
serum was separated immediately and poured into a sterile polypropylene tube and sent to the reference laboratory of hisarak while maintaining the cold chain .
patients age in the two groups ( cases and controls ) was compared using independent t - test , which had no significant difference ( p = 0.254 ) .
the average age in case group was 49.75  8.45 and 46.68  11.26 years in the control group .
gender was assessed using chi - square test , which revealed no statistical difference between the two groups ( p = 0.789 ) .
treatment group included 14 females and 14 males and control group 13 females and 15 males .
time needed for the improvement of thrombocytopenia was evaluated in the two groups using kaplan - meier and log rank test .
the treatment group required a mean duration of 4.41  0.197 days and the control group 5.72  0.318 days .
the treatment group had a median of 4  0.215 days and the control group 5  0.255 days ( log rank was 8.625 ) , which was statistically significant ( p = 0.003 ) ( degree of freedom ( df ) = 1 ) ( figure 1 and table 3 ) .   duration of hospitalization in the two groups was compared using kaplan - meier , log rank and breslau test .
the treatment group had a mean of 5.24  0.244 days and the control group 6.23  0.329 days .
the treatment group had a median of 5  0.221 days and the control group 6  0.297 days ( log rank was 4.825 ) ; therefore , there was a significant difference between them ( p = 0.028 ) , df = 1 and breslau = 4.916 with df = 1 and p = 0.027 ( figure 2 and table 3 ) .  
there was no significant difference between the two groups regarding mortality rate , intubation , platelet count , duration of icu admission , and pulmonary , renal or hepatic involvement . in our study , five patients expired including two patients in the case group ( one in moderate thrombocytopenia subgroup and the other in the severe thrombocytopenia subgroup ) and three in the control group ( all in the severe thrombocytopenia subgroup ) .
the two groups were divided into two subgroups according to the severity of thrombocytopenia ( table 2 ) as moderate ( 50000 < plt < 100000 ) and severe ( plt < 50000 ) .
the two subgroups of moderate and severe thrombocytopenia were compared regarding required time for thrombocytopenia improvement ; p - values in moderate and severe subgroup were 0.016 and 0.001 , respectively , which was statistically significant . besides , duration of hospital
stay was compared between moderate and severe subgroups using brislow test ; p - values were 0.06 and 0.006 , respectively , there was no significant differences in moderate group , but the group there were severe a statistical difference was significant ( table 3 ) .
there was no significant difference between the two subgroups ( moderate and severe thrombocytopenia ) between the case and control groups regarding mortality , intubation , length of stay in icu , pulmonary , renal or hepatic involvement and platelets count .  
abbreviations : icu , intensive care unit ; cxr , chest x - ray ; n / v , nausea and vomiting ; loc , decreased level of consciousness ; lap , lymphadenopathy ; esr , erythrocyte sedimentation rate ; crp , c - reactive protein ; inr , international normalized ratio ; bill - t , bilirubin - total ; bill - d , bilirubin - direct ; ast , aspartate aminotransferase ; alt , alanine aminotransferase ; alk.p , alkaline phosphatase .   duration = duration in days required for the improvement of thrombocytopenia .   hospitalization = length of hospital stay ( in days ) .
there was no significant difference between the two groups regarding renal , pulmonary or hepatic involvement , intubation , mortality rate and hospitalization duration in icu .
the above situations were not improved with treatment of glucocorticoid . despite the fact , required duration for the improvement of thrombocytopenia and duration of hospitalization in two groups were different significantly . on the other hand , treatment with
corticosteroids have an essential role in the treatment of many immune - associated diseases , such as sle , rheumatoid arthritis ( ra ) and itp .
prednisolone ( 1 mg / kg / day ) is used for the treatment of mild itp ( immune or idiopathic thrombocytopenic purpura ) ; while , high - dose corticosteroid ( steroid pulse therapy ) is used for the severe forms ( 1 , 13 ) .
russell villanueva et al . in the philippines , performed an investigation on 36 patients with leptospirosis and found no significant reduction in mortality , duration of hospitalization and dialysis rates between the control and steroids groups ( 12 ) .
furthermore , a study by trivedi et al . in india performed on 602 patients showed that renal and liver involvements had no effect on mortality ( 14 ) . similarly , in this study , statistical analysis showed that renal , lung or liver involvements and the severity of thrombocytopenia had no effect on mortality .
contrary to our results , a clinical trial on 30 patients by vv shenoy et al . in india showed that corticosteroid therapy within 12 hours of pulmonary involvement due to leptospirosis decreased the mortality rate ( 15 ) .  
our study showed that corticosteroid therapy decreased hospital stay only in severe subgroup thrombocytopenia ( not in the moderate subgroup ) . to optimally determine whether adjunctive steroid use in leptospirosis is beneficial , an adequately powered randomized control trial with a larger sample size is recommended .
 background : thrombocytopenia is associated with a bad prognosis in leptospirosis.objectives:we investigated the effect of corticosteroids to improve thrombocytopenia due to leptospirosis.patients and methods : in a clinical trial , all patients admitted with leptospirosis in razi hospital of ghaemshahr , north of iran were enrolled in a 2-year study . 
 totally , 56 patients with moderate to severe thrombocytopenia were randomized to control and treatment groups . 
 the treatment group received corticosteroid ( prednisolone 1 mg / kg / day for maximum one week ) in addition to the standard antibiotic therapy.results:there was no significant difference regarding age and gender between the two groups ( p = 0.254 , p = 0.789 , respectively ) . 
 the mean duration to improve thrombocytopenia was 4.41  0.197 days in the treatment group and 5.72  0.318 days in the control group , which was significantly different ( p = 0.003 ) . 
 duration of hospitalization in the treatment group was 5.24  0.244 days and 6.23  0.329 days in the control group , which was significantly different ( p = 0.028 ) . 
 the two groups had no significant difference regarding mortality , intubation , level of platelet , duration of icu admission and pulmonary , renal or hepatic involvement.conclusions:corticosteroid therapy decreased the length of hospitalization only in severe subgroup thrombocytopenia , but not in the moderate subgroup . 
1. Background
2. Objectives
3. Patients and Methods
4. Results
5. Discussion