Pathogenesis And Intervention Study Of Thrombocytopenia Following Hematopoietic Stem Cell Transplantation

Background and Objective:Hematopoietic stem cell transplantation is the only effective method for the treatment of hematologic malignancies,Often associated with a variety of complications after transplantation,including graft-versus-host disease(GVHD),infection,transplantation associated thrombotic microangiopathy(TA-TMA),bleeding and so on.After allogeneic transplantation,platelet graft was mostly 9-20 days.The incidence of thrombocytopenia after allogeneic transplantation 5-37%,TP can increase the risk of bleeding after transplantation,patients with opportunistic infections,transplantation related mortality and severity are closely correlated with aGVHD,seriously affect the transplantation survival rate and quality of life.At present,the specific pathogenesis of TP is still unknown.Therefore,we study the possible mechanisms of thrombocytopenia after HSCT in order to improve the prognosis.The number of megakaryocytes in bone marrow of TP is decreased,this is different from Immune thrombocytopenic purpura(ITP).ITP is an autoimmune disease,anti platelet autoantibodies can be detected in vivo.The study confirmed that the plasma or purified platelet membrane glycoprotein antibody in ITP patients can inhibit the generation of megakaryocytes in vitro,leading to a decrease in the number of megakaryocytess,while maturation of megakaryocytes disorder.Allogeneic hematopoietic stem cell transplantation also has an important effect on the immune system,especially in patients with GVHD after allo-HSCT.Some studies have found that GVHD is closely related to thrombocytopenia after transplantation,and the severity of GVHD is inversely proportional to the number of platelets.Studies have shown that the distribution of the ploidy of the patients with TP after transplantation presents a left shift phenomenon,that is,there are more immature megakaryocytess.Therefore,perhaps after allogeneic transplantation immune regulation disorder caused by autoantibodies may be a cause of megakaryocyte in damage increased,as a result of megakaryocyte formation decreased with maturation disorder,common to the occurrence of thrombocytopenia after transplantation.Due to pre treatment before transplantation,Severe bone marrow suppression may occur,the number of platelets is seriously low,which may endanger the life of patients with major organ hemorrhage.The combination of TPO and c-Mpl receptors has a specific effect on megakaryocytes,and can stimulate the proliferation and differentiation of the progenitor cells in vitro and in vivo.Previous studies have indicated that TPO can promote the reconstruction of platelets and reduce the platelet transfusion.We analyzed the relationship between +4 days after allogeneic transplantation and the use of TPO for 2 weeks and the reconstruction of megakaryocytes after HSCT,and further to study the relationship between TPO and prognosis.Methods:1.To study the mechanism of TP,Study included criteria for:after +90 days after HSCT,the platelet count was<50×109/L for more than 7 days,and the granulocyte and red lines were well reconstructed.According to different types of platelet recovery,patients were divided into 3 groups:delay platelet recovery(DPR),secondary failure of platelet recovery(SFPR)and good graft function(GGF).Bone marrow were collected in 45 cases with TP,24 patients with GGF and 24 healthy volunteers were selected as control.We analyzed ploidy of megakarycytes.We examined megakaryocytes associated antibodies and platelet associated antibodies(PAIgG),the levels of TPO,megakaryocytes number in bone marrow.2.We analyzed the relationship between +4 days after allo-HSCT and the use of TPO for 2 weeks and the reconstruction of megakarycytes after allo-HSCT,and further to study the relationship between TPO and prognosis.293 patients with allo-HSCT were collected from January 2013 to December 2014.Among them,the use of TP0135 cases,do not use TPO140 cases.Analysis and comparison of the two groups of patients with the ratio of megakarycytes reconstruction and prognosis of the two groups.Results:1.(1)The antibody bingding to megakarycytes of TP group was significantly higher than that of the other two groups.TP combination with GVHD group was higher than that without GVHD group.There was no significant difference between the TP group and other groups in the platelet associated PAIgG(2)The allo-HSCT patients who had thrombocytopenia exhibited significant shifts toward low ploidy cells(left shift),which were accompanied by a marked increase in 2N cells and significant decreases in 8N and 16N cells.(3)TPO levels in TP were significantly higher than Other two groups,there is no difference between the DPR group and the SFPR group.The number of GGF group was higher than that of TP group.2.Of the 270 patients,there were 58 patients with DPR,78 patients with SFPR,134 patients with GGF,135 cases of patients with TPO,19 patients with DPR,34 patients with SFPR,135 patients in the control group,39 patients with DPR,44 patients occurred SFPR.In the control group,DPR and SFPR were higher than those in the TPO group.No significant survival advantage was seen using TPO,but it can improve the prognosis of patients with DPR,and also prolong the survival of patients with AA and MDS.Conclusions:1.The pathogenesis of TP is different from ITP,generation of bone marrow megakaryocyte associated antibody may make abnormol megakaryocyte proliferation and maturation,also may make the megakaryocyte damage increased,megakaryocytes in bone marrow decreased,lead to the occurrence of thrombocytopenia after transplantation,GVHD induced immune disorders may have effect on them.2.TPO can effectively promote the reconstruction of platelets after transplantation.The application of TPO can prolong the survival of patients with DPR and improve the prognosis of patients with MDS and AA.