Part One Clinical Analysis Of Hospitalized Children With Primary Immune Thrombocytopenia Part Two Retrospective Analysis Of Hereditary Coagulation Factor X Deficiency Part Three Study On The Number And Function Of MDSC Of Peripheral Blood In Adult ITP Pat

Objective:To investigate the factors affecting the chronicity of childhood primary immune thrombocytopenia(ITP)and compare the efficacy of different first-line treatment regimens.Methods:301 children with ITP hospitalized in our hospital between September 2013 and October 2018 were retrospectively analyzed.Results:Three hundred and one children were included.In this cohort,ITP occurred in 150 boys and 151 girls,with a median age of 8(0.17-17)years.110(36.5%),92(30.6%)and 99(32.9%)children were classified as newly diagnosed,persistent and chronic ITP,respectively.The media duration of follow-up was 41.92(1.07-74.03)months.In the end of the follow-up(October 2019),among the 202 newly diagnosed/persistent ITP children,79(59 newly diagnosed and 20 persistent ITP)achieved remission within 1 year after initial diagnosis,remission rate 39.3%;122(50 newly diagnosed and 72 persistent ITP)developed chronic disease,chronicity rate 60.7%;one child underwent splenectomy.Of the 99 children with chronic ITP,5 patients underwent splenectomy.In multivariable regression analysis,insidious onset of symptoms[P=0.000,OR=3.754,95%CI(1.882-7.488)]increased the risk of chronicity,while positive titer of anti-platelet membrane glycoprotein[P=0.021,OR=0.446,95%CI(0.224-0.888)]may reduce the risk of chronicity.And no difference was found in the analysis of subtype of anti-platelet membrane glycoprotein(P=0.305).The efficacy of the first-line treatment of IVIG and steroid combined with IVIG was better than that of steroid(P=0.028,0.028),while there was no difference between IVIG and steroid combined with IVIG(P=0.086).Conclusion:Pediatric ITP patients with insidious onset of symptoms are at increased risk of chronic disease,while positive titer of anti-platelet membrane glycoprotein may reduce the risk.In the first-line treatment of children with newly diagnosed/persistent,the efficacy of IVIG and steroid combined with IVIG is better than that of steroid.Objective:To analyze the clinical characteristics,laboratory examination,diagnosis,treatment and outcome of hereditary factor X(FX)deficiency.Methods:Clinical data of 11 patients with hereditary FX deficiency from July 2009 to February 2021 were retrospectively analyzed.Results:There were 3 males and 8 females.Median age was 39(5?55)years.The media duration of follow-up was 81.67(1.87?142.73)months.There were 10(90.9%)cases with bleeding symptoms,7 cases(70%)had ecchymosis or hemorrhage after skin bump,7 cases(70%)had nosebleed,6 cases(60%)had gingival hemorrhage,and 1 case(10%)had muscle hematoma.Among the female patients,there were 6 cases of menorrhagia(75%)and 1 case of bleeding after vaginal delivery(12.5%).Family history was found in 1 case.Eight patients had a history of surgery,and four(50%)had postoperative bleeding.Laboratory findings were characterized by significantly prolonged activated partial thromboplastin time(APTT),prothrombin time(PT),and decreased FX activity(FX:C).Four cases received gene mutation analysis and 5 new mutations were found.Four cases(36.4%)were treated with prothrombin complex concentrates(PCC),7(63.6%)with fresh frozen plasma(FFP).One female patient(16.7%)had significantly reduced menstrual volume after PCC prophylactic therapy.One patient received FFP for prophylactic infusion with no bleeding occurred during and after operation.Conclusion:Most patients with hereditary FX deficiency have bleeding symptoms.There is no significant correlation between severity of bleeding symptoms and FX:C.Prophylaxis should be applied in patients with severe bleeding tendencies.Gene mutation test is significant for screening,diagnosis,and prognosis prediction of the disease.Objective:1.To detect the classification and number of MDSCs in the peripheral blood of adult ITP patients;2.To detect cytokines IFN-?,IL-1?,IL-6,IL-10,IL-17/IL-17A,TNF-?,TGF-?1,Arg1,iNOS in the peripheral blood of adult ITP patients;3.To explore the possible mechanism of MDSCs involved in the pathogenesis of ITP.Methods:A total of 32 outpatients and inpatients from our hospital from September 2020 to February 2021 were selected.Twenty-one patients with ITP were in active disease state(PLT<30�109/L)and were classified as non-response group(no response,NR);eleven patients with ITP achieved complete remission after treatment(PLT>100�109/L),and were classified into the complete response group(complete response,CR).Flow cytometry(FCM)was used to analyze the classification,proportion of MDSCs and proportion of regulatory T cells(Tregs)in the peripheral blood of the two groups.The levels of cytokin es such as IFN-y,IL-1?,IL-6,IL-10,IL-17/IL-17A,TNF-?,TGF-?1,Argl and iNOS in the peripheral blood serum of the two groups were analyzed by ELISA.Results:(1)MDSCs and its subgroups in two groups.The percentage of MDSCs in CR group was significantly higher than that in NR group,and the difference was statistically significant(8.42�4.79%vs.4.79�3.69%,P=0.023);the percentage of G-MDSC,M-MDSC and e-MDSC in CR group were higher than NR group,and the difference was not statistically significant(0.91�0.91%vs.0.47�0.41%,P=0.152;4.44�3.49%vs.2.76�3.26%,P=0.186;2.80�3.00%vs.1.92�1.84%,P=0.307).(2)Cytokines in patients of the two groups.IFN-y in CR group was lower than that in NR group,and the difference was not statistically significant(2.53�1.25 vs.3.13�1.59,P=0.277);IL-1? in CR group was higher than that in NR group,and the difference was not statistically significant(8.09�4.22 vs.7.83�2.33,P=0.822);IL-6 in CR group was lower than that in NR group,and the difference was not statistically significant(1.99�1.28 vs.3.01�2.84,P=0.175);There was no difference between IL-10 of the two groups of(0.39�0.29 vs.0.37�0.44,P=0.917);IL-17/17A in CR group was higher than that in NR group,and the difference was not statistically significant(45.10�46.04 vs.25.30�25.51,P=0.123),TNF-? in CR group was lower than that in NR group,and the difference was not statistically significant(0.96�0.67 vs.1.50�2.32,P=0.429);Argl in CR group was higher than that in NR group,but the difference was not statistically significant(7.88�10.79 vs.3.52�3.96,P=0.247);TGF-?1 in CR group was significantly higher than that in NR group,and the difference was statistically significant(18.02�23.44 vs.2.55�3.27,P=0.029);iNOS was significantly higher in CR group than that in NR group,the difference was statistically significant(9277.94�4118.14 vs,4382.71 �4383.12,P=0.003).(3)The correlation between MDSC and TGF-?1,iNOS in ITP patients.The percentage of MDSCs in patients with ITP is positively correlated with TGF-?1(r=0.495,P=0.005),and is positively correlated with iNOS(r=0.535,P=0.003).(4)The correlation between MDSCs and Tregs in ITP patients.The percentage of MDSCs in circulation of ITP patients has no correlation with the percentage of Tregs(r=-0.018,P=0.96).(5)The correlation between MDSCs and T cells,CD4+T cells,CD8+T cells,the tatio of CD4+/CD8+in patients with ITP.The percentage of MDSCs in circulation of ITP patients is negatively correlated with the percentage of T cells(r=-0.573,P=0.003),and is not correlated with CD4+T cells,CD8+T cells and the ratio of CD4+/CD8+T cells(r=-0.258,P=0.213;r=-0.213,P=0.267;r=0.05,P=0.812).(6)The correlation between MDSC and platelet count in ITP patients.There was no correlation between the percentage of MDSC in circulation and platelet count in ITP patients(r=0.343,P=0.054).Conclusion:(1)The percentage of MDSC in ITP patients in the CR group was significantly higher than that in NR group,and the reduction of MDSC was involved in the immunopathogenesis of ITP.(2)TGF-?1 and iNOS in circulation of the CR group were significantly higher than those of NR group.TGF-?1 and iNOS of adult patients with ITP decreased in the acute phase,and the percentage of MDSCs was positively correlated with the TGF-?1 and iNOS.(3)The percentage of MDSCs is negatively correlated with percentage of total T cells,and MDSCs exerts an immunomodulatory function by inhibiting T cells.(4)MDSCs can be seen as a new target for ITP immunotherapy.Platelets are specialized cells function to prevent bleeding and minimize blood vessel injury,and are also the predominating factor in the process of hemostasis and thrombosis while implicated in other processes including inflammation and metastasis.The current model of platelet formation states that platelets are produced by megakaryocytes,which are themselves generated by a process of controlled differentiation and maturation of bone-marrow stem and progenitor cells.Megakaryocytes release platelets by extending long,branching processes,designated proplatelets,into sinusoidal blood vessels.Bone marrow cavity and extracellular matrix composition together with cytokines(eg:thrombopoietin)are key regulators of megakaryopoiesis by supporting cell differentiation and platelet release.Recent studies have considerably advanced our understanding of the mechanisms of megakaryopoiesis and platelet formation.The review summarizes the current scientific progress in the mechanisms of megakaryopoiesis and thrombopoiesis.