The Experts below are selected from a list of 225 Experts worldwide ranked by ideXlab platform
Joseph Mattana - One of the best experts on this subject based on the ideXlab platform.
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acute pancreatitis during sickle cell vaso occlusive painful crisis
American Journal of Hematology, 2003Co-Authors: Shahid Ahmed, Anita K Siddiqui, Rina Siddiqui, Miriam Kimpo, Linda Russo, Joseph MattanaAbstract:Sickle cell disease is characterized by chronic hemolytic anemia and vaso-occlusive painful crisis. The vascular Occlusion in sickle cell disease is a complex process and accounts for the majority of the clinical manifestations of the disease. Abdominal pain is an important component of vaso-occlusive painful crisis and may mimic diseases such as acute appendicitis and cholecystitis. Acute pancreatitis is rarely included as a cause of abdominal pain in patients with sickle cell disease. When it occurs it may result form biliary obstruction, but in other instances it might be a consequence of microvessel Occlusion causing ischemia. In this series we describe four cases of acute pancreatitis in patients with sickle cell disease apparently due to Microvascular Occlusion and ischemic injury to the pancreas. All patients responded to conservative management. Acute pancreatitis should be considered in the differential diagnosis of abdominal pain in patients with sickle cell disease.
Hau C Kwaan - One of the best experts on this subject based on the ideXlab platform.
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catastrophic multiple organ ischemia due to an anti pr cold agglutinin developing in a patient with mixed cryoglobulinemia after treatment with rituximab
American Journal of Hematology, 2009Co-Authors: Joshua Ruch, Brandon Mcmahon, Glenn Ramsey, Hau C KwaanAbstract:Cold agglutinin disease occurring with cryoglobulinemia is a rare occurrence. Here, we report a patient with mixed cryoglobulinemia that was treated with rituximab and, after response, developed an anti-Pr cold agglutinin that manifested with hemolysis and Microvascular Occlusion causing mesenteric ischemia and cerebral infarction. Unlike previous reports of patients with cryoglobulinemia and cold agglutinin disease, our patient did not have a detectable cryoprecipitate when his cold agglutinin manifested.
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an igm lambda monoclonal antibody in a patient with anti pr cold agglutinin causing erythrocyte agglutination and catastrophic thrombosis
Blood, 2008Co-Authors: Hau C Kwaan, Joshua Ruch, Brandon Mcmahon, Ivy WeissAbstract:Erythrocyte agglutination causing Microvascular Occlusion is a rare albeit clinically significant event. This is seen in cold agglutinin disease and in cerebral malaria caused by Plasmodium falciparum. We studied a patient with autoimmune hemolytic anemia, characterized by massive hemolysis and the presence of both an anti-Pr antibody and a cold hemagglutinin. In addition, he suffered from catastrophic mesenteric ischemia necessitating surgical resection and extensive and multiple ischemia strokes. His surgical specimens, including colon, ileum and gall bladder, were studied with informed consent. Eluate from his agglutinated erythrocytes showed that he had an IgM lambda monoclonal antibody against the Pr antigen. The patient’s peripheral blood showed extensive erythrocyte agglutination that was worse at cold temperatures. H&E staining of the colon and ileum showed ischemia and necrosis with widespread Microvascular Occlusion caused by agglutinated erythrocytes. To characterize the intravascular agglutinated erythrocytes, immunoperoxidase staining was done and positive for IgM and lambda light chain and negative for IgG and kappa light chain. We thus concluded that the cold agglutinin on the intravascular agglutinated erythrocytes was an IgM lambda. To investigate why the circulating agglutinated erythrocytes resulted in widespread Microvascular Occlusion, we studied adhesive molecules including CD 62E (E-selectin), CD62P (P-selectin), CD54 (ICAM-1) and CD 106 (VCAM-1) and found all of them expressed on the agglutinated erythrocytes within the occluded vessels and on the endothelial cells of the involved vessels. The data suggests that the endothelial cells were activated at the site of vascular Occlusion, thereby promoting adhesion of the agglutinated erythrocytes to the vascular endothelium.
Umut A Gurkan - One of the best experts on this subject based on the ideXlab platform.
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microfluidic electrical impedance assessment of red blood cell mediated Microvascular Occlusion
Lab on a Chip, 2021Co-Authors: Yuncheng Man, Debnath Maji, Sanjay P Ahuja, Jane A Little, Michael A Suster, Pedram Mohseni, Umut A GurkanAbstract:Alterations in the deformability of red blood cells (RBCs), occurring in hemolytic blood disorders such as sickle cell disease (SCD), contribute to vaso-Occlusion and disease pathophysiology. There are few functional in vitro assays for standardized assessment of RBC-mediated Microvascular Occlusion. Here, we present the design, fabrication, and clinical testing of the Microfluidic Impedance Red Cell Assay (MIRCA) with embedded capillary network-based micropillar arrays and integrated electrical impedance measurement electrodes to address this need. The micropillar arrays consist of microcapillaries ranging from 12 μm to 3 μm, with each array paired with two sputtered gold electrodes to measure the impedance change of the array before and after sample perfusion through the microfluidic device. We define RBC Occlusion index (ROI) and RBC electrical impedance index (REI), which represent the cumulative percentage Occlusion and cumulative percentage impedance change, respectively. We demonstrate the promise of MIRCA in two common red cell disorders, SCD and hereditary spherocytosis. We show that the electrical impedance measurement reflects the Microvascular Occlusion, where REI significantly correlates with ROI that is obtained via high-resolution microscopy imaging of the microcapillary arrays. Further, we show that RBC-mediated Microvascular Occlusion, represented by ROI and REI, associates with clinical treatment outcomes and correlates with in vivo hemolytic biomarkers, lactate dehydrogenase (LDH) level and absolute reticulocyte count (ARC) in SCD. Impedance measurement obviates the need for high-resolution imaging, enabling future translation of this technology for widespread access, portable and point-of-care use. Our findings suggest that the presented microfluidic design and the integrated electrical impedance measurement provide a reproducible functional test for standardized assessment of RBC-mediated Microvascular Occlusion. MIRCA and the newly defined REI may serve as an in vitro therapeutic efficacy benchmark for assessing the clinical outcome of emerging RBC-modifying targeted and curative therapies.
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microfluidic assessment of red blood cell mediated Microvascular Occlusion
Lab on a Chip, 2020Co-Authors: Yuncheng Man, Jane A Little, Erdem Kucukal, Quentin D Watson, Jurgen Bosch, Peter A Zimmerman, Umut A GurkanAbstract:Abnormal red blood cell (RBC) deformability contributes to hemolysis, thrombophilia, inflammation, and Microvascular Occlusion in various circulatory diseases. A quantitative and objective assessment of Microvascular Occlusion mediated by RBCs with abnormal deformability would provide valuable insights into disease pathogenesis and therapeutic strategies. To that end, we present a new functional microfluidic assay, OcclusionChip, which mimics two key architectural features of the capillary bed in the circulatory system. First, the embedded micropillar arrays within the microchannel form gradient microcapillaries, from 20 μm down to 4 μm, which mimic microcapillary networks. These precisely engineered microcapillaries retain RBCs with impaired deformability, such that stiffer RBCs occlude the wider upstream microcapillaries, while less stiff RBCs occlude the finer downstream microcapillaries. Second, the micropillar arrays are coupled with two side passageways, which mimic the arteriovenous anastomoses that act as shunts in the capillary bed. These side microfluidic anastomoses prevent microchannel blockage, and enable versatility and testing of clinical blood samples at near-physiologic hematocrit levels. Further, we define a new generalizable parameter, Occlusion Index (OI), which is an indicative index of RBC deformability and the associated microcapillary Occlusion. We demonstrate the promise of OcclusionChip in diverse pathophysiological scenarios that result in impaired RBC deformability, including mercury toxin, storage lesion, end-stage renal disease, malaria, and sickle cell disease (SCD). Hydroxyurea therapy improves RBC deformability and increases fetal hemoglobin (HbF%) in some, but not all, treated patients with SCD. HbF% greater than 8.6% has been shown to improve clinical outcomes in SCD. We show that OI associates with HbF% in 16 subjects with SCD. Subjects with higher HbF levels (HbF > 8.6%) displayed significantly lower OI (0.88% ± 0.10%, N = 6) compared with those with lower HbF levels (HbF ≤ 8.6%) who displayed greater OI (3.18% ± 0.34%, N = 10, p < 0.001). Moreover, hypoxic OcclusionChip assay revealed a significant correlation between hypoxic OI and subject-specific sickle hemoglobin (HbS) level in SCD. OcclusionChip enables versatile in vitro assessment of Microvascular Occlusion mediated by RBCs in a wide range of clinical conditions. OI may serve as a new parameter to evaluate the efficacy of treatments improving RBC deformability, including hemoglobin modifying drugs, anti-sickling agents, and genetic therapies.
Joshua Ruch - One of the best experts on this subject based on the ideXlab platform.
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catastrophic multiple organ ischemia due to an anti pr cold agglutinin developing in a patient with mixed cryoglobulinemia after treatment with rituximab
American Journal of Hematology, 2009Co-Authors: Joshua Ruch, Brandon Mcmahon, Glenn Ramsey, Hau C KwaanAbstract:Cold agglutinin disease occurring with cryoglobulinemia is a rare occurrence. Here, we report a patient with mixed cryoglobulinemia that was treated with rituximab and, after response, developed an anti-Pr cold agglutinin that manifested with hemolysis and Microvascular Occlusion causing mesenteric ischemia and cerebral infarction. Unlike previous reports of patients with cryoglobulinemia and cold agglutinin disease, our patient did not have a detectable cryoprecipitate when his cold agglutinin manifested.
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an igm lambda monoclonal antibody in a patient with anti pr cold agglutinin causing erythrocyte agglutination and catastrophic thrombosis
Blood, 2008Co-Authors: Hau C Kwaan, Joshua Ruch, Brandon Mcmahon, Ivy WeissAbstract:Erythrocyte agglutination causing Microvascular Occlusion is a rare albeit clinically significant event. This is seen in cold agglutinin disease and in cerebral malaria caused by Plasmodium falciparum. We studied a patient with autoimmune hemolytic anemia, characterized by massive hemolysis and the presence of both an anti-Pr antibody and a cold hemagglutinin. In addition, he suffered from catastrophic mesenteric ischemia necessitating surgical resection and extensive and multiple ischemia strokes. His surgical specimens, including colon, ileum and gall bladder, were studied with informed consent. Eluate from his agglutinated erythrocytes showed that he had an IgM lambda monoclonal antibody against the Pr antigen. The patient’s peripheral blood showed extensive erythrocyte agglutination that was worse at cold temperatures. H&E staining of the colon and ileum showed ischemia and necrosis with widespread Microvascular Occlusion caused by agglutinated erythrocytes. To characterize the intravascular agglutinated erythrocytes, immunoperoxidase staining was done and positive for IgM and lambda light chain and negative for IgG and kappa light chain. We thus concluded that the cold agglutinin on the intravascular agglutinated erythrocytes was an IgM lambda. To investigate why the circulating agglutinated erythrocytes resulted in widespread Microvascular Occlusion, we studied adhesive molecules including CD 62E (E-selectin), CD62P (P-selectin), CD54 (ICAM-1) and CD 106 (VCAM-1) and found all of them expressed on the agglutinated erythrocytes within the occluded vessels and on the endothelial cells of the involved vessels. The data suggests that the endothelial cells were activated at the site of vascular Occlusion, thereby promoting adhesion of the agglutinated erythrocytes to the vascular endothelium.
Shahid Ahmed - One of the best experts on this subject based on the ideXlab platform.
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acute pancreatitis during sickle cell vaso occlusive painful crisis
American Journal of Hematology, 2003Co-Authors: Shahid Ahmed, Anita K Siddiqui, Rina Siddiqui, Miriam Kimpo, Linda Russo, Joseph MattanaAbstract:Sickle cell disease is characterized by chronic hemolytic anemia and vaso-occlusive painful crisis. The vascular Occlusion in sickle cell disease is a complex process and accounts for the majority of the clinical manifestations of the disease. Abdominal pain is an important component of vaso-occlusive painful crisis and may mimic diseases such as acute appendicitis and cholecystitis. Acute pancreatitis is rarely included as a cause of abdominal pain in patients with sickle cell disease. When it occurs it may result form biliary obstruction, but in other instances it might be a consequence of microvessel Occlusion causing ischemia. In this series we describe four cases of acute pancreatitis in patients with sickle cell disease apparently due to Microvascular Occlusion and ischemic injury to the pancreas. All patients responded to conservative management. Acute pancreatitis should be considered in the differential diagnosis of abdominal pain in patients with sickle cell disease.