scholarly journals Blood-brain barrier permeability in survivors of immune-mediated thrombotic thrombocytopenic purpura: a pilot study

2021 ◽  
Author(s):  
Shih-Han Susan Huang ◽  
Katerina Pavenski ◽  
Ting-Yim Lee ◽  
Michael T Jurkiewicz ◽  
Aditya Bharatha ◽  
...  
Keyword(s):  
Platelet Count ◽  
Pilot Study ◽  
Thrombotic Thrombocytopenic Purpura ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Thrombocytopenic Purpura ◽  
Immune Mediated ◽  
Permeability Surface ◽  
Surface Product ◽  
Bbb Permeability

Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a rare, life-threatening disorder of systemic microthrombosis and organ ischemia. The etiology of chronic cerebrovascular outcomes in iTTP survivors is largely unknown. In this pilot study, we measured blood-brain barrier (BBB) permeability in iTTP patients at the start of remission and 6 months later. This prospective pilot study included 7 adult patients with incident iTTP. Eligibility criteria included ADAMTS13 activity <10% and detectable inhibitor at diagnosis. Patients were recruited from London Health Sciences Centre in Canada (2017-2019) within 3 days of hospital admission and followed for 6 months after remission (defined as normalization of platelet count and lactate dehydrogenase with no clinical signs or symptoms of microvascular injury for more than 30 days after the last plasma exchange). All patients had cerebral CT perfusion scans with BBB permeability surface product measurements. Patients (5 women, 2 men) had a mean age of 48 years (range 21-77). At diagnosis, patients had a mean platelet count of 22 (standard deviation [SD] 25) x109/L. At the start of remission, mean BBB permeability surface product was 0.91 (0.30) mL/min/100g. Six months later, the mean permeability surface product was 0.56 (0.22) mL/min/100g, with mean difference: -0.312 mL/min/100g (95% confidence interval: -0.4729 to -0.1510; p=0.0032). In this pilot study of iTTP patients, pathologically increased BBB permeability was evident and, though there was some improvement, this persisted 6 months after remission. Future work will explore the chronicity of these findings and their clinical implications.

Thrombotic Thrombocytopenic Purpura: Mechanism for Effectiveness of Plasmapheresis

1979 ◽  
Author(s):  
J. G. Kelton ◽  
P. B. Neame ◽  
I. Walker ◽  
A. G. Turpie ◽  
J. McBride ◽  
...  
Keyword(s):  
Platelet Count ◽  
Thrombotic Thrombocytopenic Purpura ◽  
The Other ◽  
Unknown Etiology ◽  
Normal Range ◽  
Antiplatelet Antibody ◽  
Thrombocytopenic Purpura ◽  
Serious Illness ◽  
Normal Platelet ◽  
Very High

Thrombotic thrombocytopenic purpura (TTP) is a rare but serious illness of unknown etiology. Treatment by plasmapheresis has been reported to be effective but the mechanism for benefit is unknown. We have investigated the effect of plasmapheresis in 2 patients with TTP by quantitating platelet associated IgG (PAIgG) levels prior to and following plasmapheresis. Both patients had very high levels of PAIgG at presentation (90 and A8 fg IgG/platelet respectively, normal 0-5). in both, the PAIgG levels progressively fell to within the normal range and the platelet count rose following plasmapheresis. One patient remained in remission with normal platelet counts and PAIgG levels. The other relapsed after plasmapheresis and the PAIgG level rose prior to the fall in platelet count. Plasmapheresis was repeated and resulted in normalization of both the platelet count and PAIgG level. It is suggested that plasmapheresis removes antiplatelet antibody or immune complexes which may be of etiological importance in this illness.

scholarly journals Dual Roles of Astrocyte-Derived Factors in Regulation of Blood-Brain Barrier Function after Brain Damage

2019 ◽  
Vol 20 (3) ◽  
pp. 571 ◽  
Author(s):  
Shotaro Michinaga ◽  
Yutaka Koyama
Keyword(s):  
Brain Damage ◽  
Blood Brain Barrier ◽  
Brain Barrier ◽  
Blood Brain ◽  
Secondary Damage ◽  
The Central Nervous System ◽  
Bbb Permeability ◽  
Novel Therapeutic Strategies ◽  
Glial Derived Neurotrophic Factor ◽  
Endothelial Growth Factors

The blood-brain barrier (BBB) is a major functional barrier in the central nervous system (CNS), and inhibits the extravasation of intravascular contents and transports various essential nutrients between the blood and the brain. After brain damage by traumatic brain injury, cerebral ischemia and several other CNS disorders, the functions of the BBB are disrupted, resulting in severe secondary damage including brain edema and inflammatory injury. Therefore, BBB protection and recovery are considered novel therapeutic strategies for reducing brain damage. Emerging evidence suggests key roles of astrocyte-derived factors in BBB disruption and recovery after brain damage. The astrocyte-derived vascular permeability factors include vascular endothelial growth factors, matrix metalloproteinases, nitric oxide, glutamate and endothelin-1, which enhance BBB permeability leading to BBB disruption. By contrast, the astrocyte-derived protective factors include angiopoietin-1, sonic hedgehog, glial-derived neurotrophic factor, retinoic acid and insulin-like growth factor-1 and apolipoprotein E which attenuate BBB permeability resulting in recovery of BBB function. In this review, the roles of these astrocyte-derived factors in BBB function are summarized, and their significance as therapeutic targets for BBB protection and recovery after brain damage are discussed.

scholarly journals Pseudogene ACTBP2 increases blood–brain barrier permeability by promoting KHDRBS2 transcription through recruitment of KMT2D/WDR5 in Aβ1–42 microenvironment

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Qianshuo Liu ◽  
Xiaobai Liu ◽  
Defeng Zhao ◽  
Xuelei Ruan ◽  
Rui Su ◽  
...  
Keyword(s):  
Blood Brain Barrier ◽  
Molecular Mechanisms ◽  
Rna Binding ◽  
Vital Role ◽  
Brain Barrier ◽  
Blood Brain ◽  
Bbb Permeability ◽  
Novel Target ◽  
And Function

AbstractThe blood–brain barrier (BBB) has a vital role in maintaining the homeostasis of the central nervous system (CNS). Changes in the structure and function of BBB can accelerate Alzheimer’s disease (AD) development. β-Amyloid (Aβ) deposition is the major pathological event of AD. We elucidated the function and possible molecular mechanisms of the effect of pseudogene ACTBP2 on the permeability of BBB in Aβ1–42 microenvironment. BBB model treated with Aβ1–42 for 48 h were used to simulate Aβ-mediated BBB dysfunction in AD. We proved that pseudogene ACTBP2, RNA-binding protein KHDRBS2, and transcription factor HEY2 are highly expressed in ECs that were obtained in a BBB model in vitro in Aβ1–42 microenvironment. In Aβ1–42-incubated ECs, ACTBP2 recruits methyltransferases KMT2D and WDR5, binds to KHDRBS2 promoter, and promotes KHDRBS2 transcription. The interaction of KHDRBS2 with the 3′UTR of HEY2 mRNA increases the stability of HEY2 and promotes its expression. HEY2 increases BBB permeability in Aβ1–42 microenvironment by transcriptionally inhibiting the expression of ZO-1, occludin, and claudin-5. We confirmed that knocking down of Khdrbs2 or Hey2 increased the expression levels of ZO-1, occludin, and claudin-5 in APP/PS1 mice brain microvessels. ACTBP2/KHDRBS2/HEY2 axis has a crucial role in the regulation of BBB permeability in Aβ1–42 microenvironment, which may provide a novel target for the therapy of AD.

scholarly journals Metastatic Breast Cancer with Extensive Osseous Metastasis Presenting with Symptomatic Immune Thrombocytopenic Purpura and Anemia: A Case Report and Review of the Literature

2015 ◽  
Vol 8 (2) ◽  
pp. 256-263 ◽  
Author(s):  
Jiaxin Niu ◽  
Teresa Goldin ◽  
Maurie Markman ◽  
Madappa N. Kundranda
Keyword(s):  
Breast Cancer ◽  
Platelet Count ◽  
Metastatic Breast Cancer ◽  
Immune Thrombocytopenic Purpura ◽  
English Literature ◽  
Metastatic Breast ◽  
Response To Therapy ◽  
Severe Thrombocytopenia ◽  
Thrombocytopenic Purpura ◽  
Immune Mediated

Background: Immune thrombocytopenic purpura (ITP) is a rare acquired bleeding disorder with an estimated incidence of 1 in 10,000 people in the general population. The association of ITP with breast cancer is an even rarer entity with very limited reports in the English literature. Case Presentation: We report a case of a 51-year-old female with no significant past medical history who presented with sudden onset of malaise, syncope, gingival bleed and epistaxis. She was found to have severe thrombocytopenia (platelet count 6,000/μl) and anemia (hemoglobin 7.2 g/dl). Her workup led to the diagnosis of metastatic ductal breast cancer with extensive bone metastasis. Bone marrow biopsy demonstrated myelophthisis which was initially thought to be consistent with her presentation of thrombocytopenia and anemia. Therefore, the patient was started on hormonal therapy for the treatment of her metastatic breast cancer. After 3 months of therapy, she did not improve and developed severe mucosal bleeding. Her clinical presentation was suspicious for ITP and immune-mediated anemia, and hence she was started on steroids and intravenous immunoglobulin. The patient had a dramatic response to therapy with normalization of her platelet count and hemoglobin within 2 weeks. Conclusion: To our knowledge, this is the first reported case of metastatic breast cancer presenting with symptomatic ITP and anemia, and both symptoms are postulated to be immune-mediated.

Dasatinib-induced immune mediated-thrombotic thrombocytopenic purpura

2018 ◽  
Vol 57 (2) ◽  
pp. 222-224 ◽  
Author(s):  
Esra Terzi Demirsoy ◽  
Ozgur Mehtap ◽  
Elif Birtas Atesoglu ◽  
Pinar Tarkun ◽  
Necmi Eren ◽  
...  
Keyword(s):  
Thrombotic Thrombocytopenic Purpura ◽  
Thrombocytopenic Purpura ◽  
Immune Mediated
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