CLINICAL TRIAL: TREATMENT OF SICKLE CELL VASO-OCCLUSIVE CRISIS WITH HIGH DOSE IV

这个子项目是许多研究子项目中的一个 由NIH/NCRR资助的中心赠款提供的资源。子项目及 研究者（PI）可能从另一个NIH来源获得了主要资金， 因此可以在其他CRISP条目中表示。所列机构为 研究中心，而研究中心不一定是研究者所在的机构。 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。 我们最近使用镰状细胞病小鼠模型的研究表明，粘附于毛细血管后和集合小静脉血管壁的白细胞（WBC）通过与镰状红细胞（RBC）相互作用在血管闭塞中发挥关键作用1，2。在寻找负责这些相互作用的分子机制时，我们发现IVIG对RBC、WBC和内皮细胞之间的相互作用具有深远的影响，改善了提睾肌小静脉中的血流，最重要的是，影响了镰状细胞小鼠的总体生存率。 因此，我们希望在西奈山医疗中心因血管闭塞危象而入院的镰状细胞病患者中进行一项I/II期临床试验，以评估大剂量静脉注射免疫球蛋白（IVIG）。 假设： 第一章 因血管闭塞危象入院的镰状细胞病患者可耐受IVIG。 （二） IVIG可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.