cd157在pnh诊断中的应用.pptVIP

CD157鉴定粒/单核细胞PNH克隆 唐古生 副主任医师、副教授 上海长海医院血液内科、全军血液病研究所 概 要 PNH概念、发病机制和临床表现 PNH流式诊断指标变迁及现状 流式PNH诊断的临床应用建议 CD157对PNH临床诊断应用的评价 What is PNH An acquired clonal disorder resulting from a somatic mutation of the X-linked phosphatidylinositol glycan complementation Class A (PIGA) in a hematopoietic stem cell This gene encodes an enzyme that catalyzes the first step in the biosynthetic pathway of the glycosylphosphatidylinositol (GPI) anchor Expansion of this clone is responsible for the clinical manifestations of the disease European Journal of Haematology, 2015 Eculizumab Consequences of Hemolysis in PNH Defective Red Cells Lack Complement Defense Proteins Attack by Complement Anemia Intravascular Hemolysis and Release of Cell Contents Hemoglobinemia Iron Loss Hemoglobinuria Nephrotoxicity Nitric oxide sequestration Increased Lactate Dehydrogenase Muscle spasm and abdominal pain Vascular smooth muscle effect Pulmonary hypertension Platelet activation and thrombosis Pathogenesis of PNH Deficiency of complement regulatory proteins, is responsible for nearly all the important pathologic findings in PNH patients – Hemolytic anemia – Thrombosis – Pain – Renal failure Bone marrow failure appears to occur by a different mechanism Classification scheme for PNH Classical PNH, which includes hemolytic and thrombotic patients; PNH in the context of other primary disorders, such as aplastica nemia or myelodysplastic syndrome; Subclinical PNH, in which patients have small PNH clones but no clinical or laboratory evidence of hemolysis or thrombosis. Blood 2005;106:3699–3709 International PNH Interest Group (I-PIG) Diagnosis of PNH Ham test, sucrose hemolysis test and the complement lysis sensitivity test Antibodies against CD55 and CD59 on RBCs were the most common flow method used to diagnose PNH until recently Flow cytometry now universally accepted as the best method of choice of diagnosing PNH The Problem With CD55/CD59 Sent out 18 specimens to 92 laboratories using stabilized