TREATMENT OF SICKLE CELL VASO-OCCLUSIVE CRISIS WITH HIGH DOSE IVIG

这个子项目是许多研究子项目中利用 资源由NIH/NCRR资助的中心拨款提供。子项目和 调查员(PI)可能从NIH的另一个来源获得了主要资金， 并因此可以在其他清晰的条目中表示。列出的机构是 该中心不一定是调查人员的机构。 镰状细胞性贫血是世界上最常见的血液病之一。这种疾病最常见的临床表现是血管闭塞发作(“危象”)的复发，目前除了支持性护理和止痛药外，没有其他治疗方法。 我们最近使用小鼠镰状细胞病模型的研究表明，附着在毛细血管后血管壁和收集小静脉的白细胞(WBC)通过与镰状红细胞(RBCs)1，2相互作用在血管闭塞中发挥关键作用。在寻找导致这些相互作用的分子机制时，我们发现IVIG对RBCs、WBC和内皮之间的相互作用产生了深远的影响，改善了提睾肌小静脉的血流，最重要的是，影响了镰状细胞小鼠的总体生存。 因此，我们希望在一项试点阶段的I/II临床研究中评估大剂量静脉免疫球蛋白(IVIG)在因血管闭塞危象而住进西奈山医学中心的镰状细胞病患者中的作用。 假设： 1)因血管闭塞危象入院的镰状细胞病患者可耐受IVIG。 2)IVIG能有效改善镰状细胞病患者的血管闭塞危象。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Sickle cell anemia is one of the most common hematologic disease in the world. The most common clinical manifestation of this disease is the recurrence of vascular occlusive episodes ("crises") for which there is currently no therapy other than supportive care and analgesics. Our recent studies using a mouse model of sickle cell disease suggest that leukocytes (WBCs) that are adherent to the vessel wall of post-capillary and collecting venules play a key role in vascular occlusion by interacting with sickle eythrocytes (RBCs)1,2. In search for the molecular mechanisms responsible for these interactions, we found that IVIG had a profound effect on the interactions among RBCs, WBCs, and the endothelium, improved blood flow in venules of the cremaster muscle and, most importantly, impacted on the overall survival of sickle cell mice. We therefore want to evaluate high-dose intravenous immune globulin (IVIG) in a pilot phase I/II clinical study in sickle cell disease patients that are admitted to Mount Sinai Medical Center for vaso-occlusive crisis. Hypothesis: 1) IVIG is tolerated by patients with sickle cell disease admitted with vaso-occlusive crisis. 2) IVIG can be effective in ameliorating vaso-occlusive crisis in patients with sickle cell disease.