TITLE The Study Of Morbidity Mechanism And Early Stage Diagnosis Of Thrombotic Thrombocytopenic Purpura

Objective This study includes theoretical study and clinical cases analysisl.To investigate the pathology、pathophysiology (vWF polymer and ADAMTS-13enzyme activity dynamic balance and influencing factors)、clinical data、various influncing factor of the incidence (animal experimetal data) of TTP in the literature review,and to explore the pathogenesis of TTP.2.Through dinical analysis of five TTP cases and literature review of108TTP cases,to explore the early diagnositic cirteria of the TTP.Methods:1.Through the comparison between TTP and DIC in pathological and clinical features,to explore the pathogenesis and early diagnosis of TTP points.2.Using the basic theory of molecular biology,blood circulation mechanic,to investigate the role of the micro vascular blood flow shear stress in TTP.3.To explore the relationship of ADAMTS-13and TSP-1from the evolution theory of biological macromolecules.4.Through the analysis of initial symptoms,characteristics of the TTP patients and the emergence of abnormal laboratory parameters,to explore the early diagnostic criteria of TTP.Conclusion(including inferences):1.A11aspects of the TTP pathogenesis,such as vascular endothelial injury,activation of vWF polymer and the enzymatic effect of ADAMTS-13,all correlates to high-shear in circulating arteriole blood flow.But it’s difficult to form such high-shear stress in pulmonary circulation,that may be the reason why the lung is seldom involved in TTP patients(but frequently in DIC patients).2.Both ADAMTS-13and TSP-1can modulate the activity and structure of VWF polymer.The former is to inactivite the vWF polymer through enzymatic hydrolysis.The later is to decrease the activity of the polymer through degration.And ADAMTS-13molecular contains eight repeated domain of TSP-1,which indicates that two molecules are homologous.In this paper we firstly proposed that according to the molecular evolution tree,ADAMTS-13is evolved from TSP-1,which is functionally strengthened and specialized.3.In view of the TTP pathogenesis,microvascular blood flow’s high shear stress plays an important role.TTP patients are the non-shock state, which helps early diagnosis and be consistent with huge clinical data.4.As two convenient parameters,the microvascular hemolytic anemia and thrombocytopenia are good candidates for the early diagnosis of TTP(in the first24-48hours,after ruling out other disease).