SARS-CoV-2 vaccination and immune thrombotic thrombocytopenic purpura.
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ABSTRACT:
SUBMITTER: Shah H
PROVIDER: S-EPMC8906888 | biostudies-literature | 2022 Apr
REPOSITORIES: biostudies-literature
Publications
SARS-CoV-2 vaccination and immune thrombotic thrombocytopenic purpura.
Shah Hridaya H Kim Ann A Sukumar Senthil S Mazepa Marshall M Kohli Ruhail R Braunstein Evan M EM Brodsky Robert A RA Cataland Spero S Chaturvedi Shruti S
Blood 20220401 16
Similar Datasets
Project description:•Data on caplacizumab use for thrombotic thrombocytopenic purpura (TTP) in Italy are missing.•Twenty-six Italian patients were treated with caplacizumab for an acute immune TTP episode.•Caplacizumab was effective in treating acute TTP in the Italian real-world clinical setting.•Two major bleeds leading to drug discontinuation were observed.
| S-EPMC10502422 | biostudies-literature
Project description:Immune thrombotic thrombocytopenic purpura (iTTP) is an autoimmune disorder of which the etiology is not fully understood. Autoantibodies targeting ADAMTS13 in iTTP patients have extensively been studied, the immunological mechanisms leading to the breach of tolerance remain to be uncovered. This review addresses the current knowledge on genetic factors associated with the development of iTTP and the interplay between the patient's immune system and environmental factors in the induction of autoimmunity against ADAMTS13. HLA-DRB1*11 has been identified as a risk factor for iTTP in the Caucasian population. Interestingly, HLA-DRB1*08:03 was recently identified as a risk factor in the Japanese population. Combined in vitro and in silico MHC class II peptide presentation approaches suggest that an ADAMTS13-derived peptide may bind to both HLA-DRB1*11 and HLA-DRB1*08:03 through different anchor-residues. It is apparent that iTTP is associated with the presence of infectious microorganisms, viruses being the most widely associated with development of iTTP. Infections may potentially lead to loss of tolerance resulting in the shift from immune homeostasis to autoimmunity. In the model we propose in this review, infections disrupt the epithelial barriers in the gut or lung, promoting exposure of antigen presenting cells in the mucosa-associated lymphoid tissue to the microorganisms. This may result in breach of tolerance through the presentation of microorganism-derived peptides that are homologous to ADAMTS13 on risk alleles for iTTP.
| S-EPMC8631936 | biostudies-literature
Project description:Thrombotic thrombocytopenic purpura (TTP) is a clearly defined entity of the thrombotic microangiopathies (TMA), a heterogeneous group of disorders characterized by microangiopathic hemolytic anemia with red cell fragmentation, thrombocytopenia and organ dysfunction due to disturbed microcirculation. TTP is characterized by a severe deficiency of ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), an enzyme responsible for physiological cleavage of von Willebrand factor (VWF). Organ dysfunction can be severe and life-threatening, and immediate start of appropriate therapy is necessary to avoid permanent damage or death. Until recently, therapeutic options were limited to symptomatic measures, which were not standardized or based on high scientific evidence. In recent years, not only considerable progress has been made in better diagnosis of TTP, but also new therapeutic strategies have been established. Initial treatment is still based on plasma exchange and symptomatic measures to protect organ function, but new concepts (immunosuppression, targeted anti-VWF or anti-complement therapy, replacement with recombinant enzymes) have recently demonstrated impressive advantages.
| S-EPMC6132833 | biostudies-literature
Project description:Survivors of immune-mediated thrombotic thrombocytopenic purpura (iTTP) are exposed to clinical relapses when a disintegrin and metalloproteinase with thrombospondin type 1 repeats, member 13 (ADAMTS13) activity decreases during follow-up. Although preemptive rituximab usually improves ADAMTS13 activity in this context, 15% of patients experience refractoriness or intolerance to rituximab and require alternative strategies. Here, we addressed whether cyclosporine A (CSA) could improve ADAMTS13 activity and prevent clinical relapses in this context. We treated preemptively with CSA 14 iTTP patients who were unresponsive (n = 11) or intolerant (n = 3) to rituximab. All patients had a severe ADAMTS13 deficiency (activity <20%) and otherwise in clinical remission. ADAMTS13 activity normalized in almost all patients (n = 13, 93%), after a median time of 2.5 months [IQR 1-6] following initiation. Median duration of CSA treatment was 17.5 months [IQR 10-34]. ADAMTS13 activity further declined to undetectable values during follow-up in five patients, but retreatment with rituximab or CSA allowed a recovery in ADAMTS13 activity in three cases. CSA could be stopped durably in two patients, while two others experienced an ADAMTS13 relapse. Severe but reversible side effects requiring cessation of the treatment occurred in two patients. CSA provides high and sustained response rates in patients who are refractory or intolerant to rituximab, with acceptable adverse events.
| S-EPMC10098822 | biostudies-literature
Project description:The discovery of a disintegrin-like and metalloproteinase with thrombospondin type 1 motif, member 13 (ADAMTS13) revolutionized our approach to thrombotic thrombocytopenic purpura (TTP). Inherited or acquired ADAMTS13 deficiency allows the unrestrained growth of microthrombi that are composed of von Willebrand factor and platelets, which account for the thrombocytopenia, hemolytic anemia, schistocytes, and tissue injury that characterize TTP. Most patients with acquired TTP respond to a combination of plasma exchange and rituximab, but some die or acquire irreversible neurological deficits before they can respond, and relapses can occur unpredictably. However, knowledge of the pathophysiology of TTP has inspired new ways to prevent early deaths by targeting autoantibody production, replenishing ADAMTS13, and blocking microvascular thrombosis despite persistent ADAMTS13 deficiency. In addition, monitoring ADAMTS13 has the potential to identify patients who are at risk of relapse in time for preventive therapy.
| S-EPMC5606001 | biostudies-literature
Project description: Not available
| S-EPMC10497387 | biostudies-literature
Project description:Recent advances have demonstrated that thrombotic thrombocytopenic purpura (TTP), characterized by widespread thrombosis in the arterioles and capillaries, is caused by deficiency of a circulating zinc metalloprotease, ADAMTS13. Two types of TTP are recognized: autoimmune TTP, caused by inhibitory antibodies of ADAMTS13, and hereditary TTP, caused by genetic mutations of ADAMTS13. This article reviews the characteristics and function of ADAMTS13, the mechanism by which ADAMTS13 deficiency may lead to thrombosis, and the causes of ADAMTS13 deficiency. It also discusses how the new knowledge may improve the diagnosis and treatment of this previously mysterious disorder.
| S-EPMC2426955 | biostudies-literature
Project description:ADAMTS13, a plasma metalloprotease that cleaves von Willebrand factor, is crucial for normal hemostasis. Acquired autoantibody-mediated deficiency of plasma ADAMTS13 results in a potentially fatal blood disorder, immune thrombotic thrombocytopenic purpura (iTTP). Plasma ADAMTS13 protease appears to exist in multiple conformations. Under physiological conditions, plasma ADAMTS13 exists predominantly in its "closed" conformation (or latent form), which may be activated by lowering pH, ligand binding, and binding of an antibody against the distal domains of ADAMTS13. In patients with iTTP, polyclonal antibodies target at various domains of ADAMTS13. However, nearly all inhibitory antibodies bind the spacer domain, whereas antibodies that bind the distal C-terminal domains may activate ADAMTS13 through removing its allosteric inhibition. Additionally, the anti-C-terminal antibodies may alter the potency of inhibitory antibodies towards ADAMTS13 activity. This review summarizes some of the most recent knowledge about the ADAMTS13 conformation and its mechanism of inhibition by its autoantibodies.
| S-EPMC9587499 | biostudies-literature
Project description:BackgroundThe prevalence, prognostic role, and diagnostic value of blood pressure in immune-mediated thrombotic thrombocytopenic purpura (iTTP) and other thrombotic microangiopathies (TMAs) remain unclear.MethodsUsing a national cohort of iTTP (n = 368), Shigatoxin-induced hemolytic uremic syndrome (n = 86), atypical hemolytic uremic syndrome (n = 84), and hypertension-related thrombotic microangiopathy (n = 25), we sought to compare the cohort's blood pressure profile to assess its impact on prognosis and diagnostic performances.ResultsPatients with iTTP had lower blood pressure than patients with other TMAs, systolic (130 [interquartile range (IQR) 118-143] vs 161 [IQR 142-180] mmHg) and diastolic (76 [IQR 69-83] vs 92 [IQR 79-105] mmHg, both p < 0.001). The best threshold for iTTP diagnosis corresponded to a systolic blood pressure <150 mmHg. iTTP patients presenting with hypertension had a significantly poorer survival (hazard ratio 1.80, 95% confidence interval 1.07-3.04), and this effect remained significant after multivariable adjustment (hazard ratio = 1.14, 95% confidence interval 1.00-1.30). Addition of a blood pressure criterion modestly improved the French clinical score to predict a severe A disintegrin and metalloprotease with thrombospondin type 1 deficiency in patients with an intermediate score (i.e., either platelet count <30 × 109/L or serum creatinine <200 µM).ConclusionsElevated blood pressure at admission affects the prognosis of iTTP patients and may help discriminate them from other TMA patients. Particular attention should be paid to blood pressure and its management in these patients.
| S-EPMC9115975 | biostudies-literature
Project description:Immune-mediated thrombotic thrombocytopenic purpura (iTTP) is a potentially life-threatening thrombotic microangiopathy caused by autoantibody-mediated severe ADAMTS13 deficiency. TTP should be suspected in patients with microangiopathic hemolytic anemia and thrombocytopenia without a definite cause. Early detection of iTTP and prompt treatment with plasma exchange and corticosteroids are essential. Rituximab administration should be considered for refractory or relapsed iTTP, and can be used as a first-line adjuvant or preemptive therapy. Treatment with caplacizumab, a novel anti-von Willebrand factor nanobody, resulted in a faster time to platelet count response, significant reduction in iTTP-related deaths, and reduced incidence of refractory iTTP. TTP survivors showed a higher rate of chronic morbidities, including cardiovascular disease and neurocognitive impairment, which can lead to a poor quality of life and higher mortality rate. Meticulous long-term follow-up of TTP survivors is crucial.
| S-EPMC9057674 | biostudies-literature