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1.
Blood ; 2022 03 09.
Article in English | MEDLINE | ID: covidwho-1736329

ABSTRACT

The COVID-19 pandemic has resulted in the rapid development of a range of vaccines against SARS-CoV-2. Vaccine induced immune thrombocytopenia and thrombosis (VITT) is a rare but life-threatening complication of primarily adenoviral based vaccines, associated with the presence of antibodies to a PF4/polyanion neoepitope, measured by ELISA assays. Presented are serial anti-PF4/polyanion antibodies, platelet and D-dimer measurements in a large cohort of patients and their relation to relapse. 51% of patients using the Stago assay had a persistently positive anti-PF4/polyanion levels 100 days post diagnosis whilst 94% of patients monitored using the Immucor assay remain positive. The median duration of positivity of the PF4 assay is 87 days with 72% of patients remaining positive after a median duration of follow up of 105 days. The use of plasma exchange appeared to reduce anti-PF4/polyanion levels and increase platelet counts in the acute setting more rapidly than other therapies. The rate of relapse in this study was 12.6% with all relapsed cases showing persistently positive PF4 antibodies and falling platelet counts. Only one case had extension of their thrombosis. Overall, despite the persistence of PF4 antibodies in 72% of patients, the rate of relapse is low and does not appear to result in recrudescence of the aggressive clinical picture seen at index presentation. Monitoring of these patients in the UK cohort is ongoing and will aid definition of the natural history of this novel condition.

2.
Seminars in Hematology ; 2022.
Article in English | ScienceDirect | ID: covidwho-1692508

ABSTRACT

This review paper explores the potential psychiatric and psychological sequelae of vaccine-induced immune thrombotic thrombocytopenia, also called vaccine-induced immune thrombocytopenia and thrombosis (VITT). In the absence of any literature to date we have extrapolated data from similar conditions, particularly data pertaining to the critical care population. We discuss both the direct and indirect effects of thrombosis, likely psychiatric and psychological challenges during recovery, and ethical issues around vaccination. We have also suggested a comprehensive guide to the psychiatric assessment and management of patients presenting with VITT with the aim of early identification of problems and maximising rehabilitation potential and quality of life.

3.
Seminars in Hematology ; 2022.
Article in English | ScienceDirect | ID: covidwho-1671674

ABSTRACT

This chapter explores the clinical features of vaccine-induced immune thrombotic thrombocytopenia, also called vaccine-induced immune thrombocytopenia and thrombosis (VITT). Whilst the aetiology is distinct from other causes of thrombotic thrombocytopenia syndrome (TTS), presentation may be similar and hence the need for strict diagnostic criteria to ensure accurate and prompt diagnosis and early treatment. Studies have identified prognostic markers of the disease, directing therapy and management pathways, and mortality and morbidity from this rare but life-threatening and potentially disabling consequence of the ChAdOx1 nCov-19 vaccine has declined.

7.
J Thromb Haemost ; 20(1): 149-156, 2022 01.
Article in English | MEDLINE | ID: covidwho-1483925

ABSTRACT

Vaccine-induced immune thrombotic thrombocytopenia (VITT) is a rare but severe immunological reaction to the non-replicable adenoviral vector-based COVID-19 vaccines. Extreme activation of platelets and the coagulation system leads to a high risk of death from venous or arterial thrombosis or secondary hemorrhage. Public and clinician awareness has reduced mortality of VITT by nearly 90%. The World Health Organization provided a guideline in July 2021 on diagnosis and management of VITT (also called thrombosis with thrombocytopenia syndrome, or TTS). Since July 2021, new, clinically relevant information has become available. This update has been summarized by the authors in an informal process with recommendations for low resource environments. We provide new available evidence on VITT to empower clinicians to recognize VITT early, then effectively diagnose and treat the disorder to reduce morbidity and mortality. We strongly encourage production of clear management pathways for primary care settings and hospital settings.


Subject(s)
COVID-19 , Thrombocytopenia , Thrombosis , Vaccines , COVID-19 Vaccines , Humans , SARS-CoV-2 , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnosis , Thrombocytopenia/therapy
9.
Clin Med (Lond) ; 21(6): e600-e602, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-1468740

ABSTRACT

The COVID-19 pandemic has resulted in the development of highly effective vaccines that provide hope to the global community for reducing the spread of SARS-CoV-2 and limiting the mortality and morbidity caused by the disease. These vaccines have been produced using differing technologies, taken through clinical trials, and rolled out across the UK at unprecedented speed. However, the recent emergence of rare cases of life-threatening thrombosis in association with thrombocytopenia has threatened to derail one particular vaccine, the Oxford AstraZeneca ChAdOx1 vaccine, upon which many countries are dependent for their vaccination programmes. The story of how this situation has been managed in the UK at the height of the vaccine roll-out represents a remarkable collective endeavour on the part of the haematology community, working closely with other acute medical and surgical professionals within the NHS and the UK health regulatory bodies, to provide rapid expert guidance that has saved lives and helped keep the national vaccination programme on track.


Subject(s)
COVID-19 , Hematology , Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Thrombosis , Vaccines , COVID-19 Vaccines , Humans , Pandemics , SARS-CoV-2 , Thrombocytopenia/chemically induced , United Kingdom/epidemiology , Vaccination
10.
Br J Haematol ; 196(2): 351-355, 2022 01.
Article in English | MEDLINE | ID: covidwho-1373796

ABSTRACT

The COVID-19 pandemic has created many challenges in the management of immune thrombocytopenic purpura (ITP). The recommendation for avoidance of steroids by WHO led to the off-licence use, supported by NHS England, of thrombopoietin mimetics (TPO-RA) for newly diagnosed or relapsed ITP. This is a real-world prospective study which investigated the treatment patterns and outcomes in this setting. Twenty-four hospitals across the UK submitted 343 cases. Corticosteroids remain the mainstay of ITP treatment, but TPO-RAs were more effective. Incidental COVID-19 infection was identified in a significant number of patients (9·5%), while 14 cases were thought to be secondary to COVID-19 vaccination.


Subject(s)
COVID-19/epidemiology , Pandemics , Purpura, Thrombocytopenic, Idiopathic/therapy , Adolescent , Adrenal Cortex Hormones/administration & dosage , Adrenal Cortex Hormones/adverse effects , Adrenal Cortex Hormones/therapeutic use , Adult , Aged , Aged, 80 and over , Autoimmune Diseases/complications , COVID-19/blood , COVID-19 Vaccines/adverse effects , Combined Modality Therapy , Comorbidity , Connective Tissue Diseases/complications , Contraindications, Drug , Disease Management , Female , Hemorrhage/epidemiology , Hemorrhage/etiology , Hospitals, District/statistics & numerical data , Humans , Immunoglobulins, Intravenous/therapeutic use , Immunosuppressive Agents/therapeutic use , Male , Middle Aged , Neoplasms/complications , Off-Label Use , Platelet Transfusion , Prospective Studies , Purpura, Thrombocytopenic, Idiopathic/drug therapy , Purpura, Thrombocytopenic, Idiopathic/epidemiology , Purpura, Thrombocytopenic, Idiopathic/etiology , Tertiary Care Centers/statistics & numerical data , Thromboembolism/epidemiology , Thromboembolism/etiology , Thrombopoietin/agonists , Tranexamic Acid/therapeutic use , Treatment Outcome , United Kingdom/epidemiology , Young Adult
11.
N Engl J Med ; 385(18): 1680-1689, 2021 10 28.
Article in English | MEDLINE | ID: covidwho-1352005

ABSTRACT

BACKGROUND: Vaccine-induced immune thrombocytopenia and thrombosis (VITT) is a new syndrome associated with the ChAdOx1 nCoV-19 adenoviral vector vaccine against severe acute respiratory syndrome coronavirus 2. Data are lacking on the clinical features of and the prognostic criteria for this disorder. METHODS: We conducted a prospective cohort study involving patients with suspected VITT who presented to hospitals in the United Kingdom between March 22 and June 6, 2021. Data were collected with the use of an anonymized electronic form, and cases were identified as definite or probable VITT according to prespecified criteria. Baseline characteristics and clinicopathological features of the patients, risk factors, treatment, and markers of poor prognosis were determined. RESULTS: Among 294 patients who were evaluated, we identified 170 definite and 50 probable cases of VITT. All the patients had received the first dose of ChAdOx1 nCoV-19 vaccine and presented 5 to 48 days (median, 14) after vaccination. The age range was 18 to 79 years (median, 48), with no sex preponderance and no identifiable medical risk factors. Overall mortality was 22%. The odds of death increased by a factor of 2.7 (95% confidence interval [CI], 1.4 to 5.2) among patients with cerebral venous sinus thrombosis, by a factor of 1.7 (95% CI, 1.3 to 2.3) for every 50% decrease in the baseline platelet count, by a factor of 1.2 (95% CI, 1.0 to 1.3) for every increase of 10,000 fibrinogen-equivalent units in the baseline d-dimer level, and by a factor of 1.7 (95% CI, 1.1 to 2.5) for every 50% decrease in the baseline fibrinogen level. Multivariate analysis identified the baseline platelet count and the presence of intracranial hemorrhage as being independently associated with death; the observed mortality was 73% among patients with platelet counts below 30,000 per cubic millimeter and intracranial hemorrhage. CONCLUSIONS: The high mortality associated with VITT was highest among patients with a low platelet count and intracranial hemorrhage. Treatment remains uncertain, but identification of prognostic markers may help guide effective management. (Funded by the Oxford University Hospitals NHS Foundation Trust.).


Subject(s)
COVID-19 Vaccines/adverse effects , Purpura, Thrombocytopenic, Idiopathic/etiology , Thrombosis/etiology , Adolescent , Adult , Aged , Anticoagulants , Autoantibodies/blood , COVID-19/prevention & control , Female , Humans , Immunoglobulins, Intravenous/therapeutic use , Intracranial Hemorrhages/etiology , Intracranial Hemorrhages/mortality , Male , Middle Aged , Multivariate Analysis , Platelet Count , Platelet Factor 4/immunology , Prospective Studies , Purpura, Thrombocytopenic, Idiopathic/mortality , Purpura, Thrombocytopenic, Idiopathic/therapy , Risk Factors , Thrombosis/drug therapy , Thrombosis/mortality , United Kingdom/epidemiology , Young Adult
13.
Res Pract Thromb Haemost ; 5(5): e12529, 2021 Jun.
Article in English | MEDLINE | ID: covidwho-1274782
14.
J Thromb Haemost ; 19(8): 2007-2013, 2021 08.
Article in English | MEDLINE | ID: covidwho-1223529

ABSTRACT

INTRODUCTION: Vaccine-induced immune thrombocytopenia and thrombosis (VITT) following ChAdOx1 nCOV-19 vaccine has been described, associated with unusual site thrombosis, thrombocytopenia, raised D-dimer, and high-titer immunoglobulin-G (IgG) class anti-platelet factor 4 (PF4) antibodies. Enzyme-linked immunosorbent assays (ELISA) have been shown to detect anti-PF4 in patients with VITT, but chemiluminescence assays do not reliably detect them. ELISA assays are not widely available in diagnostic laboratories, and, globally, very few laboratories perform platelet activation assays. METHODS: Assays that are commercially available in the United Kingdom were evaluated for their ability to identify anti-PF4 antibodies in samples from patients with suspected VITT. Four IgG-specific ELISAs, two polyspecific ELISAs, and four rapid assays were performed on samples from 43 patients with suspected VITT from across the United Kingdom. Cases were identified after referral to the UK Expert Haematology Panel multidisciplinary team and categorized into unlikely, possible, or probable VITT. RESULTS AND DISCUSSION: We demonstrated that the HemosIL AcuStar HIT-IgG, HemosIL HIT-Ab, Diamed PaGIA gel, and STic Expert assays have poor sensitivity for VITT in comparison to ELISA. Where these assays are used for heparin-induced thrombocytopenia (HIT) diagnosis, laboratories should ensure that requests for suspected VITT are clearly identified so that an ELISA is performed. No superiority of IgG-ELISAs over polyspecific ELISAs in sensitivity to VITT could be demonstrated. No single ELISA method detected all possible/probable VITT cases; if a single ELISA test is negative, a second ELISA or a platelet activation assay should be considered where there is strong clinical suspicion.


Subject(s)
Laboratories , Platelet Factor 4 , COVID-19 Vaccines , Enzyme-Linked Immunosorbent Assay , Heparin , Humans , Immunoglobulin G , United Kingdom , Vaccination
16.
J Clin Pathol ; 74(11): 750-751, 2021 Nov.
Article in English | MEDLINE | ID: covidwho-873566

ABSTRACT

Thrombocytopenia is common in an intensive care unit (ICU) setting due to endogenous and iatrogenic factors. Despite that, thrombocytopenia in patients with severe COVID-19 infections is surprisingly uncommon. By examining the blood film of 20 ICU patients with COVID-19, we observed the presence of platelet aggregates and macrothrombocytes indicating increased platelet activity. We compared these findings with 20 blood films of non-severe COVID-19 cases where these findings were absent. These morphology features could be consistent with severe COVID-19 infection and is further evidence of the important role that platelets play when COVID-19 manifests with thrombotic complications or respiratory failure.


Subject(s)
Blood Platelets/pathology , Blood Platelets/virology , COVID-19/complications , Thrombosis/physiopathology , Thrombosis/virology , Aged , COVID-19/blood , Critical Care , Humans , Middle Aged , Platelet Count/methods , Thrombocytopenia/blood , Thrombocytopenia/physiopathology , Thrombocytopenia/virology , Thrombosis/blood
17.
Br J Haematol ; 189(6): 1038-1043, 2020 06.
Article in English | MEDLINE | ID: covidwho-186388

ABSTRACT

This document aims to provide practical guidance for the assessment and management of patients with thrombocytopenia, with a particular focus on immune thrombocytopenia (ITP), during the COVID-19 pandemic. The intention is to support clinicians and, although recommendations have been provided, it is not a formal guideline. Nor is there sufficient evidence base to conclude that alternative approaches to treatment are incorrect. Instead, it is a consensus written by clinicians with an interest in ITP or coagulation disorders and reviewed by members of the UK ITP forum.


Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , Purpura, Thrombocytopenic, Idiopathic , Adult , COVID-19 , Coronavirus Infections/epidemiology , Coronavirus Infections/etiology , Coronavirus Infections/therapy , Female , Humans , Male , Pneumonia, Viral/epidemiology , Pneumonia, Viral/etiology , Pneumonia, Viral/therapy , Practice Guidelines as Topic , Purpura, Thrombocytopenic, Idiopathic/congenital , Purpura, Thrombocytopenic, Idiopathic/epidemiology , Purpura, Thrombocytopenic, Idiopathic/therapy , SARS-CoV-2
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