Study On The Clinical Correlation Between Platelet-specific Antibodies And Other Factors And Immune Thrombocytopenia In Childre

ObjectiveImmune thrombocytopenia(ITP)is a hemorrhagic autoimmune disease characterized by thrombocytopenia.The etiology and pathogenesis of ITP are not completely clear,which is mainly considered as excessive platelet destruction and thrombocytopenia due to abnormal cellular immunity and humoral immunity.Specific antibodies against platelet antigens are produced in patients.Platelet-specific antibodies can lead to platelet destruction and increase,and their clinical correlation with ITP needs to be further clarified.The purpose of this study was to investigate the effects of platelet-specific antibodies and other factors on the clinical characteristics,course of disease,and therapeutic efficacy of ITP in children and analyze the correlation,so as to provide an objective basis for the diagnosis and treatment of children with ITP.MethodsA total of 113 cases who visited the Children’s Blood Oncology Department of Affiliated Hospital of Qingdao University with ITP from April 2019 to April 2022 and had complete clinical data were retrospectively collected.According to the results of platelet-specific antibodies,they were divided into a positive group and a negative group,where the positive group was divided into GPIIb/IIIa group,GPIb/Ix group,and GPIIb/IIIa+GPIb/Ix group according to different antibody types.According to the course of the disease,they were divided into new-onset group,persistent group and chronic group.Clinical data of the children were collected,including gender,age,predisposing factors,routine blood test at the beginning of the disease,the degree of initial bleeding,platelet-specific antibodies,autoantibodies,regulatory lymphocyte subsets,bone marrow cell morphology,first-line treatment response(glucocorticoids and immunoglobulin),treatment duration,and dynamic detection of platelet levels(one week,one month,three months,six months and one year).Statistical analysis of the data showed that P<0.05 indicated statistically significant difference.Results1.Clinical characteristics:(1)General data:Among the 113 cases included,67 were male(59.29%)and 46 were female(40.71%),with more males than females(c~2=3.90,P<0.05);77 cases(68.14%)were aged from 0 to 6 years old,and 36 cases(31.86%)were aged from 7 to 14 years old.The cases aged from 0 to 6 years old were significantly more than those aged from 7 to 14years old(c~2=14.88,P<0.01).Among the children aged 0–6 years old,63 cases(81.82%)had new findings,6 cases(7.79%)had persistent symptoms,and 8 cases(10.39%)had chronic symptoms.The new findings were significantly more than those of persistent and chronic symptoms(c~2=81.53,P<0.01).Among the children aged 7–14 years old,there were 30 new cases(83.33%),2 persistent cases(5.56%)and 4 chronic cases(11.11%),and the number of new cases was significantly more than that of persistent and chronic cases(c~2=40.67,P<0.01).However,there was no statistical difference between persistent and chronic cases.(2)Inducing factors:57 cases had no inducing factor,while 56 cases had it.The inducing factors included vaccination in 5 cases(8.92%)and infection in 51 cases(91.07%).The ITP induced by infection was significantly higher than that by vaccination(c~2=37.79,P<0.01).In children with infection-induced ITP,there were 45 cases(88.24%)of respiratory tract infection,3 cases(5.88%)of digestive tract infection,and 3 cases(5.88%)of other system infection,among which respiratory tract infection was the most common(c~2=29.82,P<0.01).According to the etiology of the infection,there were 8 cases(15.69%)with EB virus infection,2 cases(3.92%)with cytomegalovirus infection,9 cases(17.65%)with mycoplasma infection,1 case(1.96%)with streptococcus pneumoniae infection,and31 cases(60.78%)with unknown etiology,which were obviously higher than those of others(c~2=10.00,P<0.01).(3)The bleeding severity at the onset of disease:grade 0 in 16 cases(14.16%),grade1 in 47 cases(41.59%),grade 2 in 32 cases(28.32%),grade 3 in 14 cases(12.39%)and grade 4 in 4 cases(3.54%).There was no significant difference between the grades 1 and2,but they were all higher than the bleeding severity of grades 0,3 and 4(c~2=50.76,P<0.01).(4)Course of disease:93 cases(82.3%)in the new onset group,8 cases(7.08%)in the persistent group and 12 cases(10.62%)in the chronic group.The incidence in the new onset group was significantly higher than those in the persistent and chronic groups(c~2=122.14,P<0.01).2.The correlation analysis of platelet specific antibody and ITP(1)Platelet-specific antibodies:There were 110 cases whose platelet-specific antibodies were detected,among which 78 cases(70.91%)were positive.There were 32negative cases(20.09%),and the number of positive cases was significantly higher than that of negative cases(c~2=19.24,P<0.01).In the positive group,there were 65 new cases(83.33%),5 persistent cases(6.41%)and 8 chronic cases(10.26%),and the new cases were significantly higher than those of persistent and chronic cases(c~2=87.92,P<0.01).In the positive group,there were 27 cases(34.62%)in the GPIIb/IIIa group,4 cases(5.13%)in the GPIb/Ix group,and 47 cases(60.25%)in the GPIIb/IIIa+GPIb/Ix group.The percentages of the cases in the GPIIb/IIIa+GPIb/Ix group were significantly higher than those in the former two groups(c~2=35.62,P<0.01).(2)Analysis of clinical data:There was no significant difference with gender,age,degree of initial bleeding or inducing factors(P>0.05);(3)Analysis with laboratory tests:(1)There was no significant difference from the initial routine blood test,lymphocyte subsets and bone marrow megakaryocyte count(P>0.05).(2)Autoantibody:Autoantibody testing was performed in 92 of 110 children who underwent platelet-specific antibody testing,of which 48 were positive(52.17%).Autoantibody test was performed in 64 of 78 children with positive platelet-specific antibodies,and 39 cases(60.94%)were positive.Autoantibody testing was performed in28 of 32 platelet-specific antibody negative children,and nine cases(32.14%)were positive.The numbers of children with positive platelet-specific antibody+autoantibody were significantly higher than those with negative platelet-specific antibody+autoantibody(c~2=6.47,P<0.05).In the children with positive platelet-specific antibody+autoantibody,32 cases(82.05%)were newly diagnosed,2 cases(5.13%)were persistent,5 cases(12.82%)were chronic,and the number of newly diagnosed cases was significantly more than that of persistent and chronic cases(c~2=42.00,P<0.01).In the 24 GPIIb/IIIa-positive groups,9cases(37.50%)were autoantibody positive,15 cases(62.50%)were negative,3 cases(100.00%)were autoantibody positive in the GPIb/Ix group,and 27 cases(72.97%)were autoantibody positive and 10 cases(27.03%)were negative in the 37 GPIIb/IIIa+GPIb/Ix-positive groups.The positive rate of autoantibody in the GPIIb/IIIa+GPIb/Ix positive group was higher than that in the GPIIb/IIIa positive group and the GPIb/Ix positive group(c~2=9.03,P<0.01).Among the children who were GPIIb/IIIa+GPIb/Ix positive combined with autoantibody positive,22 cases(81.48%)were in the new hair group,1 case(3.60%)in the persistent group,and 4 cases(18.18%)in the chronic group.The numbers in the new hair group were significantly more than those in the persistent group and the chronic group(c~2=28.67,P<0.01).(4)Treatment analysis:Ninety-five of one hundred and ten children tested for platelet-specific antibodies received first-line treatment;Among the 78 patients with positive platelet-specific antibodies,72 were treated,including 44 cases(61.11%)of complete reaction,16 cases(22.22%)of effective reaction,83.33%of total effective rate,and 12 cases(16.67%)of ineffective reaction.The total effective rate was obviously higher than that of non-effective rate(c~2=32.00,P<0.01).Among the 32 patients with platelet-specific antibody negativity,23 were treated,including 8 cases(34.78%)with complete reaction,1 case(4.35%)with effective reaction,14 cases(60.87%)with no effect,and 39.13%with total effective rate.The total effective rate of patients with platelet-specific antibody positivity after treatment was significantly higher than that in the negative group(c~2=15.98,P<0.01).Among the60 effectively treated children in the positive group,52(86.67%)were new-onset ITP children,3(5.00%)were persistent ITP children,and 5(8.33%)were chronic ITP children.The new-onset ITP group was significantly higher than the persistent and chronic groups(c~2=76.90,P<0.01).There was no statistical significance between the first-line treatment effect and platelet-specific antibody subtype(P>0.05).(5)Follow-up analysis:(1)The platelet counts in the antibody positive and antibody negative groups within one month of treatment were(143.92±109.89)×10~9/L and(119.00±82.99)×10~9/L,respectively,and the values in the positive group were significantly higher than those in the negative group(t=1.154,P<0.01).In the positive group,the platelet counts in the new onset,persistent and chronic groups were(236.36±94.92)×10~9/L,(37.69±19.23)×10~9/L,(136.68±52.63)×10~9/L,respectively.The platelet counts in the new onset group were significantly higher than those in the persistent and chronic groups(F=733.72,P<0.01).There was no significant difference in platelet count and platelet-specific antibody at 1week,3 months,6 months and 1 year after treatment(all P>0.05).The differences of platelet counts among different subtypes of platelet-specific antibodies at different follow-up times were not statistically significant(P>0.05).(2)Outcome:After one-year follow-up,12 of 93 cases(12.90%)in the new-onset group developed persistence,including 7 of 65 cases(10.77%)with positive platelet-specific antibodies;Twenty-seven cases(29.03%)developed chronic disease,including 18of 65 cases(27.69%)with positive platelet-specific antibodies.Seven of the eight cases(87.50%)in the persistence group developed chronic,including four of five cases(80.00%)with positive platelet-specific antibodies;All children in the chronic group did not recover;The development of persistent children into chronic disease was significantly higher than that of new-onset children(c~2=29.75,P<0.01).3.The influence of multiple factors on ITPEarly platelet count was a risk factor for the progression of ITP(P<0.05,OR=1.02).For every 1×10~9/L increase in early platelet count,the possible risk of progression increased1.02times.No predisposing factor was the risk factor for progression(P<0.05,OR=2.48),and the risk of progression predisposing factor was 2.48 times.Conclusions1.68.14%of children with ITP occurr in preschool age.Infection is the most common inducing factor,and respiratory tract infection is the most common.The initial bleeding severity of the disease is mainly grade 1 and 2,and there are more children with new-onset ITP.2.The positive rate of platelet-specific antibody in children with ITP is 70.91%,and the new ITP is the majority in positive children.At the same time,when combined with autoantibody positivity,the new ITP is significantly more than persistent ITP and chronic ITP,which suggests that regular follow-up should be conducted to guard against the occurrence of autoimmune diseases.3.Children with ITP with positive platelet-specific antibodies respond better to first-line treatment,and most of them are diagnosed with new ITP.The efficacy of platelet count in children with positive platelet-specific antibodies is more significant after one month of treatment.4.Multivariate analysis show that the absence of predisposing factors and platelet count at the beginning of the disease are the risk factors for the progression of ITP.