药物引起的中性粒细胞减少症..pptVIP

Clinical presentation Immune-mediated destruction Present： days to weeks after beginning the drug often with acute and explosive symptoms Rechallenge：prompt recurrence even with low doses. Clinical presentation Direct or indirect toxicity Present：may be delayed for months asymptomatic or presents with an insidious onset Rechallenge: requires both a latent period and high drug doses before recurrence is observed Thank you for your attention! * Pharmacotherapy: A Pathophysiologic Approach eChapter 24. Drug-Induced Hematologic Disorders Kamakshi V. Rao * 阿什肯纳兹犹太人（英语：Ashkenazi Jews）北欧犹太教 * * 免疫介导的损伤 —药物或更普遍的是有活性代谢物的药物，不可逆地与嗜中性粒细胞细胞膜结合 —此作用结果会产生抗体或T细胞，会直接改变嗜中性粒细胞细胞膜的结构 —例如丙硫氧嘧啶与嗜中性粒细胞细胞膜结构，作用类似半抗原引发抗体产生 它有以下三种方式（三个图的说明） * 半抗原机制—药物与血细胞细胞膜结合后形成一个类似半抗原的物质，会吸引抗体过来破坏它这个半抗原，造成这个血细胞死亡 * 免疫复合物机制—药物会引起抗体产生，这个产生的抗体和药物在血清中形成一个复合物，然后与细胞膜非特异性结合（或吸附在细胞膜上），补体细胞就会以为它是外来物质就会破坏使其溶解 * 自身免疫机制—药物会与血浆蛋白质结合，它会与细胞膜接触后刺激抗体的产生 抗体会与这个复合物（药物与血浆蛋白质结合形成的东西）一起活化补体的产生，补体细胞会将这个细胞当做外来物质，将其溶解 * 直接或间接的毒害 —直接对骨髓细胞的前驱细胞造成损害 —此作用机制的药物包括吩噻嗪类尤其是氯丙嗪，普鲁卡因胺，氯氮平和氨苯砜 * The ANC is numerically equal to the product of the white blood cell count (WBC) and the fraction of polymorphonuclear cells多形核细胞 (PMNs) and band forms noted on the differential analysis差示分析 * Leukopenia refers specifically to a low WBC due to any cause, while granulocytopenia refers to a reduced number of granulocytes. * * 红框中药物表示发生概率较高 * * Drug-induced neutropenia and agranulocytosis Outline Introduction Epidemiology Definitions Pathogenesis Clinical presentation Drug induced neutropenia/agranulocytosis Prevention and screening Treatment Summary and recommendation * Introduction Most cases of neutropenia in adults are acquired and are due to decreased granulocyte production or increased destruction. Predictable and dose related Mechanisms are varied The propensity to infection depends upon the adequacy of bone marrow reserve * Definitions Neutropenia中性粒细胞减少症 : ANC1500/microL Agranulocytosis中性粒细胞缺乏症: ANC 500/microL ANC = WBC (cells/mi