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      Thrombotic Thrombocytopenic Purpura Following Pfizer-BioNTech COVID-19 Vaccination in a Patient With Multiple Myeloma: Case Report and Literature Review

      case-report
      1 , , 2 , 1 , 3 , 4 , 1
      ,
      Cureus
      Cureus
      caplacizumab, vitt, ttp, pfizer-biontech vaccine, covid-19 vaccine

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          Abstract

          The vaccines developed to prevent infection and mitigate morbidity and mortality in patients with COVID-19 demonstrated high efficacy in clinical trials but were associated with adverse events, most of which were mild and transient. However, some adverse events were rather serious, with grave prognoses. Of note, a few cases of autoimmune hematological conditions such as thrombotic thrombocytopenic purpura (TTP), immune thrombocytopenic purpura (ITP), and vaccine-induced immune thrombotic thrombocytopenia (VITT) were reported. TTP following Pfizer-BioNTech mRNA vaccination is exceptionally rare, with very scant literature. This case report describes an interesting case of a 61-year-old woman who presented 22 days after receiving the third dose of the Pfizer-BioNTech mRNA COVID-19 vaccine with malaise, bloody stools, and jaundice. Her medical history was significant for multiple myeloma previously treated with autologous bone marrow transplant and in remission with chemotherapy. She also had a history of chronic heart failure with preserved ejection fraction (HFpEF) and neuropathy treated with daily vitamins. The diagnosis was predicted by her classic presentation and was clinched by low ADAMTS13 activity. She was treated with plasmapheresis, steroids, and monoclonal antibodies. Intriguingly, her hospital stay was further complicated by an episode of generalized tonic-clonic seizure requiring intubation and mechanical ventilation for airway protection. Albeit infrequent, COVID-19 vaccine-associated TTP is associated with substantial morbidity and mortality. Hence, early diagnosis and treatment are essential in patients presenting with thrombocytopenia after COVID-19 vaccination.

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          mRNA vaccines — a new era in vaccinology

          mRNA vaccines represent a promising alternative to conventional vaccine approaches because of their high potency, capacity for rapid development and potential for low-cost manufacture and safe administration. However, their application has until recently been restricted by the instability and inefficient in vivo delivery of mRNA. Recent technological advances have now largely overcome these issues, and multiple mRNA vaccine platforms against infectious diseases and several types of cancer have demonstrated encouraging results in both animal models and humans. This Review provides a detailed overview of mRNA vaccines and considers future directions and challenges in advancing this promising vaccine platform to widespread therapeutic use.
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            High serum IFN-alpha activity is a heritable risk factor for systemic lupus erythematosus.

            Interferon alpha (IFN-alpha) levels are elevated in many patients with systemic lupus erythematosus (SLE); however it is not known whether high serum IFN-alpha activity is a cause or a result of the disease. We studied 266 SLE patients and 405 of their healthy relatives, and frequently found high serum IFN-alpha activity in both patients and healthy relatives as compared to healthy unrelated individuals. High IFN-alpha activity was clustered in specific families in both SLE patients and their healthy first-degree relatives, suggesting a heritable trait. Heritability was also supported by quantitative familial correlation of IFN-alpha activity, concordance in affected sib pairs and frequent transmission of the high IFN-alpha activity trait from parents to offspring. Autoantibodies to RNA-binding proteins and double-stranded DNA were associated with high IFN-alpha activity in SLE patients; however these autoantibodies were very uncommon in healthy family members and did not explain the observed familial correlations. The frequency of high IFN-alpha activity was similar across all studied ethnic backgrounds. These data suggest that high serum IFN-alpha activity is a complex heritable trait, which plays a primary role in SLE pathogenesis.
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              Real-world experience with caplacizumab in the management of acute TTP

              The cornerstone of life-saving therapy in immune-mediated thrombotic thrombocytopenic purpura (iTTP) has been plasma exchange (PEX) combined with immunomodulatory strategies. Caplacizumab, a novel anti–von Willebrand factor nanobody trialed in 2 multicenter randomized controlled trials (RCTs) leading to European Union and US Food and Drug Administration approval, has been available in the United Kingdom (UK) through a patient access scheme. Data were collected retrospectively from 2018 to 2020 for 85 patients (4 children) receiving caplacizumab from 22 UK hospitals. Patient characteristics and outcomes in the real-world clinical setting were compared with caplacizumab trial end points and historical outcomes in the precaplacizumab era. Eighty-four of 85 patients received steroid and rituximab alongside PEX; 26% required intubation. Median time to platelet count normalization (3 days), duration of PEX (7 days), and hospital stay (12 days) were comparable with RCT data. Median duration of PEX and time from PEX initiation to platelet count normalization were favorable compared with historical outcomes (P < .05). Thrombotic thrombocytopenic purpura (TTP) recurred in 5 of 85 patients; all had persistent ADAMTS13 activity < 5 IU/dL. Of 31 adverse events in 26 patients, 17 of 31 (55%) were bleeding episodes, and 5 of 31 (16%) were thrombotic events (2 unrelated to caplacizumab); mortality was 6% (5/85), with no deaths attributed to caplacizumab. In 4 of 5 deaths, caplacizumab was introduced >48 hours after PEX initiation (3-21 days). This real-world evidence represents the first and largest series of TTP patients, including pediatric patients, receiving caplacizumab outside of clinical trials. Representative of true clinical practice, the findings provide valuable information for clinicians treating TTP globally.
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                Author and article information

                Journal
                Cureus
                Cureus
                2168-8184
                Cureus
                Cureus (Palo Alto (CA) )
                2168-8184
                10 October 2023
                October 2023
                : 15
                : 10
                : e46784
                Affiliations
                [1 ] Hematology and Oncology, Greater Washington Oncology Associates, Silver Spring, USA
                [2 ] Cardiology, Texas A&M College of Medicine, Houston, USA
                [3 ] Internal Medicine, College of Medicine and Sagore Dutta Hospital, Kolkata, IND
                [4 ] Internal Medicine, Saraswathi Institute of Medical Sciences, Hapur, IND
                Author notes
                Article
                10.7759/cureus.46784
                10633882
                dee67f33-2966-4bc8-888c-4bf9a7d43941
                Copyright © 2023, Dan et al.

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 10 October 2023
                Categories
                Integrative/Complementary Medicine
                Internal Medicine
                Allergy/Immunology

                caplacizumab,vitt,ttp,pfizer-biontech vaccine,covid-19 vaccine

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