الفهرس 
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Abstract
As regard to Platelets count, all studied participants have low baseline Platelets count and over time it was significantly increased in response to all treatment modalities (P=0.032) with the highest Platelets count reported in the 7th day of treatment initiation. And by comparing the mean of Platelets count at different time points among different treatment modalities the maximum increase was observed in children received IVIG with P<0.001. This making that treatment of ITP patients with IVIG more superior than other treatment regimens.
As regard to the Platelets indices (MPV and PDW), both were significantly increased in patients in response to all treatment modalities (p<0.001). For MPV no significant difference was observed among different treatment modality compared to each other (p=0.099), meanwhile PDW show significant difference among different treatment modality compared to each other (p=0.016), the highest PDW reported in the 7th day of treatment initiation and the maximum increase was observed in children received oral prednisolone. MPV and PDW are potentially useful markers for the early diagnosis of thromboembolic diseases. An increase in both occurs due to platelets activation (Vagdatli, Gounari et al. 2010), this is what happen in our study, both Platelets indices (MPV and PDW) show statistically significant increase over time regardless the type of treatment received (p<0.001).
Our results for CBC parameters are in agreement with previous studies carried on ITP pediatric patients for example, Shad et al 2005 reported that, the CBC should be within normal limits for age except for the low platelet count and mildly elevated platelet size. A peripheral smear should demonstrate normal morphology of all cell lines with a few large platelets (Shad, Gonzalez et al. 2005), Warrier et al 2012 reported that the abnormalities in RBC or WBC series are unusual in standard ITP in children (Warrier and Chauhan 2012), the two studies by Noris et al 2009 and Kistangari and McCrae 2013 reported that, ITP is characterized by isolated thrombocytopenia without abnormalities in erythrocyte or leukocyte number or morphology. Platelet size may be normal or increased (Noris, Klersy et al. 2009, Kistangari and McCrae 2013), McCRAE 2011 reported that, In ITP, the peripheral blood smear should appear normal except for the presence of thrombocytopenia, although platelets may be mildly enlarged in some individuals. Red cell and leukocyte morphology is normal (McCRAE 2011) and Rodeghiero et al 2009, Provan et al 2010, Neunert et al 2011 and Kühne et al 2013 all reported that, Primary ITP is characterized by the presence or absence of bleeding in an otherwise healthy child with isolated thrombocytopenia, defined as blood platelets of <100×109/l (normal range 150–400×109/l), and an otherwise normal complete blood count and peripheral blood smear (Rodeghiero, Stasi et al. 2009, Provan, Stasi et al. 2010, Neunert, Lim et al. 2011, Kühne and Imbach 2013).
There are no controlled data to support comparing the three treatment regimens in controlling pediatric children with acute ITP. We conducted a prospective cross sectional study to evaluate the effect of different treatment modalities: A (IVIG), B (IV methylprednisolone) and C (Oral prednisolone) on CBC parameters in patients with acute ITP to find out the most effective therapy as regard the rapidity of the PC increment between the three mentioned regimens.
Our findings show a more rapid response to IVIG than either IV or oral steroids and provide evidence to support its use emergency cases. Our results are in agreement with the previous study by Blanchette et al 1993 who shows that, IVIG increases the platelet count more rapidly than both no specific treatment and oral glucocorticoid therapy (Blanchette, Luke et al. 1993), another study by Rosthøj et al 1996 in Denmark on 43 children with newly diagnosed ITP, shows that IVIG were preferable to MPPT (Methylprednisolone pulse therapy) as the initial treatment for ITP (Rosthøj, Nielsen et al. 1996). Another prospective randomized trial by Fujisawa et al 2000 which aimed to determine the minimal essential treatment for childhood acute ITP, shows that, IVIg offered faster platelet enhancement compared with oral prednisolone (o-PSL) and methylprednisolone (mPSL), although neither mPSL no pulsed parenteral methylprednisolone (PmPSL) showed any advantage, even over o-PSL (Fujisawa, Iyori et al. 2000). Ancona et al. 2002 in his randomized study which aimed to comparing intravenous immunoglobulin (IVIG) with high-dose intravenous methylprednisolone in the treatment of children with acute ITP on 77 children show that IVIG (1 g/ kg/dose x 1-2 days) was effective in 80% of cases while methylprednisolone (MP) (30 mg/kg/dose for 2-3 days) was effective in 60% of cases in increasing platelet count above 50,000/ul within 48 hours, but without any difference at one week or later; no serious bleeding was noted in either of the treatment groups (Ancona, Parker et al. 2002). Also our results were agreed with a meta-analysis by Beck et al 2005 showing that children treated with IVIG more frequently had a platelet count above 20×109/L than those treated with steroids. This result was consistent regardless of the dose and duration of treatment (Beck, Nathan et al. 2005). Another study by Ou et al 2006 who performed a comparative study aimed to compare initial platelet count elevation and to determine the chance of developing persistent profound thrombocytopenia by intravenous immunoglobulin (IVIG) or prednisolone in the treatment of children with ITP, on 87 children concluded that, patients treated with IVIG demonstrated a higher percentage of patients with platelet count increasing above 20x10(3)/mm3 on the second day compared with patients treated with prednisolone initially (p<0.01). However, there was no difference in developing persistent platelet counts lower than 20 x 10(3)/mm3 at 6 months of follow-up between the IVIG and prednisolone groups (p=0.480) (Ou, Hsieh et al. 2006). At the Hematology Division of Children’s Hospital ‘‘Bambino Gesu’’, Vatican City, Rome, Baronci et al 2006 performed a retrospective study aimed to evaluate when to treat and what was the best treatment for children with ITP on 265 children shows that, IVIG and HDMP (7.5 mg/kg for 4 days) are the best treatments to reach quickly safe platelet levels≥30x10(9) /L (3-6 days) (Baronci, Pansini et al. 2006). Also our results were supported by the American Society of Hematology 2011 Guidelines for Immune Thrombocytopenic Purpura which reported that, Corticosteroids or IVIG are the preferred first-line treatment; IVIG is used for fast platelet response if required (Neunert, Lim et al. 2011). In a 4 year retrospective study in USA on 148 pediatric patients hospitalized with acute ITP aimed to compare the effectiveness of intravenous immunoglobulin (IVIG) alone, high dose methylprednisolone (HDMP) alone and the combination of IVIG and HDMP in the treatment of childhood ITP concluded that, IVIG followed by the combination of HDMP and IVIG is the most effective therapeutic modality in rapidly increasing the platelet count to safe levels in children with acute ITP when compared to HDMP alone within the first 24 hours (Gereige and Barrios 2014). In Iran, Eshagh-Hoseini et al 2016 performed a retrospective case-control study on 88 ITP patients, aimed to evaluate the effectiveness of Intravenous immunoglobulin (IVIg) and combination of IVIg and Methylprednisolone for childhood ITP treatment, and concluded that both IVIg alone and combination of IVIg and Methylprednisolone are equally effective in providing a platelet level > 50,000/μl early (Eshagh-Hoseini, Arsang-Jang et al. 2016). Heitink-Pollé et al 2018 performed a multicenter randomized trial in Netherlands aimed to evaluate the efficacy of a single dose of IVIg in reducing the rate of chronic ITP in children with newly diagnosed ITP on 206 children, 102 receive IVIg and 104 careful observation only. chronic ITP occurred in18.6% of the patients in the IVIg group and 28.9% in the observation group (relative risk, 0.64; 95% confidence interval [CI], 0.38-1.08) and complete response rates in the first 3 months were significantly higher in the IVIg group and concluded that, upfront treatment with IVIg led to faster recovery and less severe bleeding events (Heitink-Pollé, Uiterwaal et al. 2018). Also our results were in agreement with the more recent study done by Carcao et al 2020 who performed a randomized, double-blinded, placebo-controlled, multicenter prospective study which performed in 6 Canadian pediatric centers in the period from 2005 up to 2016, and aimed to compare IVMP+IVIG versus IVIG alone to raises platelet counts faster and concluded that there was a rapid response to IVIG with/without steroids and provide evidence to support the use of IVMP+IVIG in life-threatening situations (Carcao, Silva et al. 2020). On the other hand results of the present study were different from what was found in the previous Egyptian study at the Hematology/Oncology Clinic, Children Hospital, Ain Shams Univerisity on 350 patients with ITP, who were randomized to receive either high dose methyl prednisolone (HDMP) 10 mg/kg/day for 5 days (n=10) or IVIG 0.4 g/kg/day for 5 days (n=10) or conventional dose prednisone (CDP) 2 mg/kg/day for 4 weeks (n=10) and shows a dramatic response in the first two groups with complete response by the 5th day (p<0.001) (Khalifa, Tolba et al. 1993). Albayrak et al. 1994 in his randomized study shows that, IVIG (0.5 g/kg per day for 5 consecutive days), mega-dose MP (orally administered MP 30 mg/kg per day for 7 days or orally administered MP 50 mg/kg per day for 7 days) were equally effective (Albayrak, Islek et al. 1994) Duru et al 2002 perform a study aimed to compare the prognosis of children with acute ITP who received intravenous immunoglobulin G (IVIG), mega-dose MP, or no therapy on 50 children and showed that platelet counts at three days after starting therapy were significantly higher in both IVIG and mega-dose MP groups than in the no therapy group (p<.01), but there was no difference between the three groups at 10 and 30 days after initiation of therapy (Duru, Fisgin et al. 2002). In a randomized study in Turkey aimed to compare intravenous immunoglobulin versus mega dose methylprednisolone treatments in children with acute ITP on 42 children were randomly divided into two groups. 20 patients received mega-dose methylprednisolone (MDMP) in a dosage of 30 mg/kg/d for three days and 20 mg/kg/d for four days. 22 patients received intravenous immunoglobulin (IVIG) in a dosage of 1 g/kg/d two days. The mean platelet counts of both groups gradually increased and peaked on the 7th day (p>0.05), and conclude that Intravenous immunoglobulin (IVIG) (1 g/kg/d for 2 days) and MDMP treatments (30 mg/kg/d for 3 days, 20 mg/kg/d for 4 days, per orally) are equally effective in the treatment of acute ITP. Because of its non-biologic source, lower cost, fewer side effects and oral use, the author prefer oral preparations of MDMP in the treatment of childhood ITP (Erduran, Aslan et al. 2003). Another a retrospective study done in Turkey by Koçak et al 2007 on 162 children with ITP aimed to evaluate the clinical characteristics, response to treatment and outcome. The author found that, the rate of platelet recovery with mega-dose methylprednisolone (30 mg/kg/d for 3 and 20 mg/kg/d for 4 days) was similar to that obtained with intravenous immunoglobulin or oral prednisolone and concluded that the mode of treatment has no effect on the clinical course and prognosis of childhood ITP (Koçak, Aral et al. 2007). As regard to the response to different treatments modalities, our results shows that, patients who recived IVIG have higher CR than patients who recived Methylprednisolone or oral prednisolone but this difference not reach statistical significance (P=0.165) may be due to small sample size of the studied participants Our results were supported by the retrospective study by Baronci et al 2006 who found no statistically significant differences in CR related to different treatments used in his study (HDMP and IVIG) (Baronci, Pansini et al. 2006). On the other hand, our results were different from what was found in the previous Egyptian study by Khalifa et al 1993 who shows that, CR was achieved by the 5th day in patients received HDMP or IVIG (p<0.001) (Khalifa, Tolba et al. 1993) and the study of Heitink-Pollé et al 2018 who found that, the complete response rates in the first 3 months were significantly higher in the IVIg group (Heitink-Pollé, Uiterwaal et al. 2018). Study Strengths and Limitations StrengthsThe results of our study can be used to offer support for communities and countries that cannot afford expensive treatments such as IVIg. Our study evaluates the effect of different treatment modalities on all CBC parameters in patients with acute ITP not only the platelets count as most published papers do. The time required to reach the targeted platelets level was compared among the three treatment regimens. Up-to-our knowledge, limited number of studies comparing the three treatment modalities in children with ITP. The study was a prospective cohort study design which is a good analytical study design in evaluating different treatment regimen. This study contains useful new information for decision making in ITP management. The safety of different treatment modalities used was not assessed in our study. Small sample size. The developments of fetal complications along the course of treatment are not evaluated in the present study. Although IVIg treatment may increase platelet counts in the majority of children with newly diagnosed ITP, costs, and benefits of treatment should be carefully weighed. All used treatment regimens produce a significant rise in platelet count. IVIG regimen show earlier and higher rise in platelet count as compared to glucocorticoids. All treatment regimens are associated with the same outcomes. Based on the finding of the current study we recommended that: Use of either IVIG regimen or glucocorticoids is effective and can achieve good platelet count. The time required to reach the targeted platelets level must be measured. Individualization of care based on the medical, social, and other supporting evidence is the difficult but ideal choice to develop better targeted therapies in the future. Randomized controlled trials comparing existing treatments not only in terms of treatment response or efficacy but also in terms of their impact on the health-related quality of life of patients with ITP are needed. The present study is a prospective cross sectional study comparing the effect of different treatment modalities on CBC parameters in pediatric patients with acute ITP to find out the most effective therapy. The study included 45 pediatric patients (15 participants in each group). The mean age of the studied participants was 8.22±3.94 years and ranged from 1.2 to 16.0 years. At the time of admission, all CBC parameters (WBCs, Neutrophils, Lymphocytes, RBCs, Hemoglobin, Reticulocytes, Platelets count, MPV,PDW) were similar among the three study groups (P=0.708, 0.162, 0.292, 0.358, 0.727, 0.058, 0.378, 0.160, 0.143) respectively. Methylprednisolone and oral prednisolone significantly increased the total WBCs and Neutrophils percentage compared to IVIG and the maximum rise recorded after one week of treatment (P<0.001). Meanwhile, the Lymphocytes percentage found to be declined significantly in response to Methylprednisolone and oral prednisolone compared to the IVIG and the lowest percentage reported in the 7th day of treatment initiation (P<0.001). As regard RBCs count and Hemoglobin level, the three treatment modalities showed no significant difference (P=0.851, and 0.553). All treatment modalities significantly increased the Platelets count but the maximum increase was observed in children received IVIG with (P<0.001). Regarding the main platelet volume (MPV) and Platelets distribution width (PDW), both were significantly increased in response to all treatment modalities (P<0.001), MPV show no significant difference between the three studied groups (P=0.099). Meanwhile platelets distribution width (PDW) show significant difference between the three studied groups with the maximum increase in children received oral prednisolone with (P =0.016). The complete response rates by the 7th day of treatment were higher in the IVIg group (P=0.165). The present results and other existing data show conflict results about the most effective therapy for children with acute ITP. Larger, prospective, randomized trials are needed to confirm the data for better treatment for children with acute ITP, better outcomes and for better quality of life. There is a vital need for the development of individualized interventions programs tailored to the physical and psychological well-being of pediatrics with acute ITP in Assuit University.