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      Recommendations for the clinical and laboratory diagnosis of VITT against COVID‐19: Communication from the ISTH SSC Subcommittee on Platelet Immunology

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          Abstract

          Vaccine administration is under way worldwide to combat the current COVID‐19 pandemic. The newly developed vaccines are highly effective with minimal adverse effects. Recently, the AstraZeneca ChadOx1 nCov‐19 vaccine has raised public alarm with concerns regarding the rare, but serious, development of thrombotic events, now known as vaccine‐induced immune thrombotic thrombocytopenia (VITT). These thrombotic events appear similar to heparin‐induced thrombocytopenia, both clinically and pathologically. In this manuscript, the ISTH SSC Subcommittee on Platelet Immunology outlines guidelines on how to recognize, diagnose and manage patients with VITT.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Chaolin Huang, Yeming Wang, Xingwang Li … (2020)
          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study

            Julie Helms, Charles Tacquard, François Séverac … (2020)
            Little evidence of increased thrombotic risk is available in COVID-19 patients. Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.
            Article 0 comments Cited 1430 times – based on 0 reviews     Review now
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              Thrombotic Thrombocytopenia after ChAdOx1 nCov-19 Vaccination

              Andreas Greinacher, Thomas Thiele, Theodore Warkentin … (2021)
              Background Several cases of unusual thrombotic events and thrombocytopenia have developed after vaccination with the recombinant adenoviral vector encoding the spike protein antigen of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) (ChAdOx1 nCov-19, AstraZeneca). More data were needed on the pathogenesis of this unusual clotting disorder. Methods We assessed the clinical and laboratory features of 11 patients in Germany and Austria in whom thrombosis or thrombocytopenia had developed after vaccination with ChAdOx1 nCov-19. We used a standard enzyme-linked immunosorbent assay to detect platelet factor 4 (PF4)–heparin antibodies and a modified (PF4-enhanced) platelet-activation test to detect platelet-activating antibodies under various reaction conditions. Included in this testing were samples from patients who had blood samples referred for investigation of vaccine-associated thrombotic events, with 28 testing positive on a screening PF4–heparin immunoassay. Results Of the 11 original patients, 9 were women, with a median age of 36 years (range, 22 to 49). Beginning 5 to 16 days after vaccination, the patients presented with one or more thrombotic events, with the exception of 1 patient, who presented with fatal intracranial hemorrhage. Of the patients with one or more thrombotic events, 9 had cerebral venous thrombosis, 3 had splanchnic-vein thrombosis, 3 had pulmonary embolism, and 4 had other thromboses; of these patients, 6 died. Five patients had disseminated intravascular coagulation. None of the patients had received heparin before symptom onset. All 28 patients who tested positive for antibodies against PF4–heparin tested positive on the platelet-activation assay in the presence of PF4 independent of heparin. Platelet activation was inhibited by high levels of heparin, Fc receptor–blocking monoclonal antibody, and immune globulin (10 mg per milliliter). Additional studies with PF4 or PF4–heparin affinity purified antibodies in 2 patients confirmed PF4-dependent platelet activation. Conclusions Vaccination with ChAdOx1 nCov-19 can result in the rare development of immune thrombotic thrombocytopenia mediated by platelet-activating antibodies against PF4, which clinically mimics autoimmune heparin-induced thrombocytopenia. (Funded by the German Research Foundation.)
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                Author and article information

                Contributors
                Ishac Nazy:
                ORCID: https://orcid.org/0000-0002-5695-4343
                nazyi@mcmaster.ca , @ishacgaby
                Tamam Bakchoul:
                ORCID: https://orcid.org/0000-0002-6797-6812
                tamam.bakchoul@med.uni-tuebingen.de , tamambakchoul@yahoo.com
                Journal
                Journal ID (nlm-ta): J Thromb Haemost
                Journal ID (iso-abbrev): J Thromb Haemost
                Journal ID (doi): 10.1111/(ISSN)1538-7836
                Journal ID (publisher-id): JTH
                Title: Journal of Thrombosis and Haemostasis
                Publisher: John Wiley and Sons Inc. (Hoboken )
                ISSN (Print): 1538-7933
                ISSN (Electronic): 1538-7836
                Publication date (Electronic): 20 May 2021
                Publication date (Print): June 2021
                Volume: 19
                Issue: 6 ( doiID: 10.1111/jth.v19.6 )
                Pages: 1585-1588
                Affiliations
                [ 1 ] Department of Medicine Michael G. DeGroote School of Medicine McMaster University Hamilton ON Canada
                [ 2 ] McMaster Centre for Transfusion Research Hamilton ON Canada
                [ 3 ] Department of Thrombosis and Haemostasis Giessen University Hospital Giessen Germany
                [ 4 ] Cardeza Foundation for Hematological Research Thomas Jefferson University Philadelphia PA USA
                [ 5 ] Haematology Department The Canberra Hospital Canberra ACT Australia
                [ 6 ] John Curtin School of Medical Research ANU Canberra ACT Australia
                [ 7 ] Transfusion Medicine Medical Faculty of Tuebingen University of Tuebingen Tuebingen Germany
                [ 8 ] Centre for Clinical Transfusion Medicine Tuebingen ZKT gGmbH Tuebingen Germany
                [ 9 ] Norwegian National Unit for Platelet Immunology University Hospital of North Norway Tromso Norway
                [ 10 ] Versiti BloodCenter of Wisconsin Pediatric Hematology/Oncology Medical College of Wisconsin Milwaukee WI USA
                [ 11 ] Dana‐Farber/Boston Children's Cancer and Blood Disorders Center Harvard Medical School Boston MA USA
                [ 12 ] Institute for Clinical and Experimental Transfusion Medicine Medical Faculty of Tuebingen University Hospital of Tuebingen Tuebingen Germany
                Author notes
                [*] [* ] Correspondence

                Ishac Nazy, Department of Medicine, Michael G. DeGroote School of Medicine, McMaster University, HSC 3H53, 1280 Main Street West, L8S 4K1 Hamilton, ON, Canada.

                Email: nazyi@ 123456mcmaster.ca

                Tamam Bakchoul, Universitätsklinikum Tübingen, Transfusion Medicine, Otfried‐Müller, 72076 Tübingen, Germany.

                Emails: tamam.bakchoul@ 123456med.uni-tuebingen.de , tamambakchoul@ 123456yahoo.com

                Author information
                https://orcid.org/0000-0002-5695-4343
                https://orcid.org/0000-0002-3104-3818
                https://orcid.org/0000-0001-7302-0449
                https://orcid.org/0000-0002-6797-6812
                Article
                Publisher ID: JTH15341
                DOI: 10.1111/jth.15341
                PMC ID: 8250233
                PubMed ID: 34018298
                SO-VID: 4087ffff-c5f6-4af9-b584-71680f9f0624
                Copyright © © 2021 International Society on Thrombosis and Haemostasis
                License:

                This article is being made freely available through PubMed Central as part of the COVID-19 public health emergency response. It can be used for unrestricted research re-use and analysis in any form or by any means with acknowledgement of the original source, for the duration of the public health emergency.

                History
                Date revision received : 09 April 2021
                Date received : 30 March 2021
                Date accepted : 12 April 2021
                Page count
                Figures: 1, Tables: 0, Pages: 4, Words: 1855
                Categories
                Subject: Recommendations and Guidelines
                Subject: Isth Ssc Communication
                Custom metadata
                source-schema-version-number 2.0
                cover-date June 2021
                details-of-publishers-convertor Converter:WILEY_ML3GV2_TO_JATSPMC version:6.0.4 mode:remove_FC converted:02.07.2021

                ScienceOpen disciplines: Hematology
                Keywords: astrazeneca chadox1 ncov‐19 vaccine,covid‐19,platelet activation,thrombocytopenia,thrombosis
                Data availability:
                ScienceOpen disciplines: Hematology
                Keywords: astrazeneca chadox1 ncov‐19 vaccine, covid‐19, platelet activation, thrombocytopenia, thrombosis

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