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1.
Int J Infect Dis ; 119: 130-139, 2022 Jun.
Article in English | MEDLINE | ID: covidwho-1814522

ABSTRACT

OBJECTIVES: To meta-analyse the clinical manifestations, diagnosis, treatment, and mortality of vaccine-induced immune thrombotic thrombocytopenia (VITT) after adenoviral vector vaccination. METHODS: Eighteen studies of VITT after ChAdOx1 nCoV-19 or Ad26.COV2.S vaccine administration were reviewed from PubMed, Scopus, Embase, and Web of Science. The meta-analysis estimated the summary effects and between-study heterogeneity regarding the incidence, manifestations, sites of thrombosis, diagnostic findings, and clinical outcomes. RESULTS: The incidence of total venous thrombosis after ChAdOx1 nCoV-19 vaccination was 28 (95% CI 12-52, I2=100%) per 100,000 doses administered. Of 664 patients included in the quantitative analysis (10 studies), the mean age of patients with VITT was 45.6 years (95% CI 43.8-47.4, I2=57%), with a female predominance (70%). Cerebral venous thrombosis (CVT), deep vein thrombosis (DVT)/pulmonary thromboembolism (PE), and splanchnic vein thrombosis occurred in 54%, 36%, and 19% of patients with VITT, respectively. The pooled incidence rate of CVT after ChAdOx1 nCoV-19 vaccination (23 per 100,000 person-years) was higher than that reported in the pre-pandemic general population (0.9 per 100,000 person-years). Intracranial haemorrhage and extracranial thrombosis accompanied 47% and 33% of all patients with CVT, respectively. The antiplatelet factor 4 antibody positivity rate was 91% (95% CI 88-94, I2=0%) and the overall mortality was 32% (95% CI 24-41, I2=69%), and no significant difference was observed between heparin- and non-heparin-based anticoagulation treatments (risk ratio 0.84, 95% CI 0.47-1.50, I2=0%). CONCLUSIONS: Patients with VITT after SARS-CoV-2 vaccination most frequently presented with CVT following DVT/PE and splanchnic vein thrombosis, and about one-third of patients had a fatal outcome. This meta-analysis should provide a better understanding of VITT and assist clinicians in identifying VITT early to improve outcomes and optimise management.


Subject(s)
COVID-19 , Purpura, Thrombocytopenic, Idiopathic , Thrombocytopenia , Thrombosis , Vaccines , Venous Thrombosis , COVID-19/prevention & control , COVID-19 Vaccines/adverse effects , Female , Humans , Male , Middle Aged , Purpura, Thrombocytopenic, Idiopathic/epidemiology , Purpura, Thrombocytopenic, Idiopathic/etiology , SARS-CoV-2 , Thrombocytopenia/etiology , Thrombosis/epidemiology , Thrombosis/etiology , Venous Thrombosis/chemically induced , Venous Thrombosis/etiology
2.
BMJ ; 377: e069590, 2022 04 06.
Article in English | MEDLINE | ID: covidwho-1779333

ABSTRACT

OBJECTIVE: To quantify the risk of deep vein thrombosis, pulmonary embolism, and bleeding after covid-19. DESIGN: Self-controlled case series and matched cohort study. SETTING: National registries in Sweden. PARTICIPANTS: 1 057 174 people who tested positive for SARS-CoV-2 between 1 February 2020 and 25 May 2021 in Sweden, matched on age, sex, and county of residence to 4 076 342 control participants. MAIN OUTCOMES MEASURES: Self-controlled case series and conditional Poisson regression were used to determine the incidence rate ratio and risk ratio with corresponding 95% confidence intervals for a first deep vein thrombosis, pulmonary embolism, or bleeding event. In the self-controlled case series, the incidence rate ratios for first time outcomes after covid-19 were determined using set time intervals and the spline model. The risk ratios for first time and all events were determined during days 1-30 after covid-19 or index date using the matched cohort study, and adjusting for potential confounders (comorbidities, cancer, surgery, long term anticoagulation treatment, previous venous thromboembolism, or previous bleeding event). RESULTS: Compared with the control period, incidence rate ratios were significantly increased 70 days after covid-19 for deep vein thrombosis, 110 days for pulmonary embolism, and 60 days for bleeding. In particular, incidence rate ratios for a first pulmonary embolism were 36.17 (95% confidence interval 31.55 to 41.47) during the first week after covid-19 and 46.40 (40.61 to 53.02) during the second week. Incidence rate ratios during days 1-30 after covid-19 were 5.90 (5.12 to 6.80) for deep vein thrombosis, 31.59 (27.99 to 35.63) for pulmonary embolism, and 2.48 (2.30 to 2.68) for bleeding. Similarly, the risk ratios during days 1-30 after covid-19 were 4.98 (4.96 to 5.01) for deep vein thrombosis, 33.05 (32.8 to 33.3) for pulmonary embolism, and 1.88 (1.71 to 2.07) for bleeding, after adjusting for the effect of potential confounders. The rate ratios were highest in patients with critical covid-19 and highest during the first pandemic wave in Sweden compared with the second and third waves. In the same period, the absolute risk among patients with covid-19 was 0.039% (401 events) for deep vein thrombosis, 0.17% (1761 events) for pulmonary embolism, and 0.101% (1002 events) for bleeding. CONCLUSIONS: The findings of this study suggest that covid-19 is a risk factor for deep vein thrombosis, pulmonary embolism, and bleeding. These results could impact recommendations on diagnostic and prophylactic strategies against venous thromboembolism after covid-19.


Subject(s)
COVID-19 , Pulmonary Embolism , Venous Thromboembolism , Venous Thrombosis , Anticoagulants/adverse effects , COVID-19/complications , COVID-19/epidemiology , Cohort Studies , Hemorrhage/chemically induced , Hemorrhage/etiology , Humans , Pulmonary Embolism/epidemiology , Pulmonary Embolism/etiology , Pulmonary Embolism/prevention & control , Risk Factors , SARS-CoV-2 , Venous Thromboembolism/chemically induced , Venous Thrombosis/chemically induced , Venous Thrombosis/etiology
6.
Radiology ; 302(2): 319-325, 2022 02.
Article in English | MEDLINE | ID: covidwho-1360579

ABSTRACT

This case series reports six patients (four men and two women; median age, 38 years; interquartile range, 26-48 years) who presented with vaccine-induced thrombocytopenia and thrombosis beginning 3-26 days after receiving the first dose of the ChAdOx1 nCoV-19 (AstraZeneca) vaccine for COVID-19. The patients were admitted to a general hospital between 9 and 31 days after the first dose. All patients had strongly detected antiplatelet factor 4 antibodies and severe thrombosis. Laboratory features included thrombocytopenia and elevated d-dimer levels. Thrombotic events were predominantly venous; two patients had arterial or mixed arterial and venous thrombosis. All patients recovered after receiving intravenous immunoglobulin and nonheparin-based anticoagulation. © RSNA, 2021 An earlier incorrect version appeared online. This article was corrected on August 18, 2021.


Subject(s)
/adverse effects , Diagnostic Imaging/methods , Thrombocytopenia/chemically induced , Thrombocytopenia/diagnostic imaging , Venous Thrombosis/chemically induced , Venous Thrombosis/diagnostic imaging , Adult , Anticoagulants/therapeutic use , COVID-19/prevention & control , Female , Fibrin Fibrinogen Degradation Products , Humans , Immunoglobulins, Intravenous/therapeutic use , Lung/diagnostic imaging , Male , Middle Aged , Retrospective Studies , SARS-CoV-2 , Thrombocytopenia/drug therapy , Venous Thrombosis/drug therapy
8.
Nat Commun ; 12(1): 4663, 2021 08 02.
Article in English | MEDLINE | ID: covidwho-1338537

ABSTRACT

Vaccine-induced thrombotic thrombocytopenia with cerebral venous thrombosis is a syndrome recently described in young adults within two weeks from the first dose of the ChAdOx1 nCoV-19 vaccine. Here we report two cases of malignant middle cerebral artery (MCA) infarct and thrombocytopenia 9-10 days following ChAdOx1 nCoV-19 vaccination. The two cases arrived in our facility around the same time but from different geographical areas, potentially excluding epidemiological links; meanwhile, no abnormality was found in the respective vaccine batches. Patient 1 was a 57-year-old woman who underwent decompressive craniectomy despite two prior, successful mechanical thrombectomies. Patient 2 was a 55-year-old woman who developed a fatal bilateral malignant MCA infarct. Both patients manifested pulmonary and portal vein thrombosis and high level of antibodies to platelet factor 4-polyanion complexes. None of the patients had ever received heparin in the past before stroke onset. Our observations of rare arterial thrombosis may contribute to assessment of possible adverse effects associated with COVID-19 vaccination.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/immunology , Cerebral Infarction/chemically induced , Purpura, Thrombocytopenic, Idiopathic/chemically induced , SARS-CoV-2/immunology , Thrombosis/chemically induced , Autoantibodies/blood , Autoantibodies/immunology , COVID-19/virology , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Cerebral Infarction/diagnostic imaging , Computed Tomography Angiography/methods , Female , Humans , Magnetic Resonance Imaging/methods , Middle Aged , Platelet Factor 4/immunology , Purpura, Thrombocytopenic, Idiopathic/diagnostic imaging , SARS-CoV-2/physiology , Thrombosis/diagnostic imaging , Tomography, X-Ray Computed/methods , Vaccination/adverse effects , Venous Thrombosis/chemically induced , Venous Thrombosis/diagnostic imaging
9.
J Korean Med Sci ; 36(27): e197, 2021 Jul 12.
Article in English | MEDLINE | ID: covidwho-1308264

ABSTRACT

We used the nationwide claims database to calculate the incidence of thrombotic events and predict their overall 2-week incidence. From 2006 to 2020, the incidence of deep vein thrombosis (DVT), pulmonary embolism (PE), and disseminated intravascular coagulation (DIC) tended to increase. Unlike intracranial venous thrombosis (ICVT) and intracranial thrombophlebitis (ICTP), which showed no age difference, other venous embolism, and thrombosis (OVET), DIC, DVT, and PE were significantly more common in over 65 years. The overall 2-week incidence of ICVT was 0.21/1,000,000 (95% confidence interval [CI], 0.11-0.32). ICTP, OVET, DIC, DVT and PE were expected to occur in 0.08 (95% CI, 0.02-0.14), 7.66 (95% CI, 6.08-9.23), 5.95 (95% CI, 4.88-7.03), 13.28 (95% CI, 11.92-14.64), 14.09 (95% CI, 12.80-15.37) per 1,000,000, respectively. To date, of 8,548,231 patients vaccinated with ChAdOx1 nCoV-19 in Korea, two had confirmed thrombosis with thrombocytopenia syndrome within 2 weeks. The observed incidence of ICVT after vaccination was 0.23/1,000,000.


Subject(s)
COVID-19 Vaccines/adverse effects , Disseminated Intravascular Coagulation/chemically induced , Pulmonary Embolism/chemically induced , Thromboembolism/chemically induced , Vaccination/adverse effects , Venous Thrombosis/chemically induced , Aged , Causality , Cerebrovascular Disorders/epidemiology , Disseminated Intravascular Coagulation/epidemiology , Female , Humans , Incidence , Intracranial Thrombosis/epidemiology , Male , Middle Aged , Models, Theoretical , Pulmonary Embolism/epidemiology , Republic of Korea/epidemiology , Thrombocytopenia/chemically induced , Thrombocytopenia/epidemiology , Thromboembolism/epidemiology , Venous Thrombosis/epidemiology
10.
Am J Case Rep ; 22: e932946, 2021 Jun 12.
Article in English | MEDLINE | ID: covidwho-1266948

ABSTRACT

BACKGROUND The COVID-19 pandemic is an ongoing cause of the current global healthcare crisis. Several vaccines were approved for use by emergency vaccination campaigns worldwide. At present, there are very few reports of COVID-19 vaccine-induced immune-thrombotic thrombocytopenia, a variant of heparin-induced thrombocytopenia (HIT), in comparison to the massive number of vaccinated people worldwide. CASE REPORT A 59-year-old woman presented to the Emergency Department with a 3-day history of sudden-onset left leg pain 7 days after receiving her first dose of BNT162b2 mRNA COVID-19 (Pfizer-BioNTech). She was diagnosed with deep vein thrombosis (DVT) and pulmonary embolism (PE) and found to have a positive HIT screen with optical density (OD) of 0.6 via ELISA test. She was hospitalized for 4 days and discharged home with an oral anticoagulant (rivaroxaban). CONCLUSIONS This case report describes a possible link between BNT162b2 mRNA COVID-19 (Pfizer-BioNTech) vaccination and thromboembolism. However, further data are needed to support such an association.


Subject(s)
COVID-19 , Pulmonary Embolism , Vaccines , Venous Thrombosis , COVID-19 Vaccines , Female , Humans , Middle Aged , Pandemics , Pulmonary Embolism/chemically induced , RNA, Messenger , SARS-CoV-2 , Venous Thrombosis/chemically induced
14.
Kardiologiia ; 60(6): 15-29, 2020 07 07.
Article in English, Russian | MEDLINE | ID: covidwho-688942

ABSTRACT

Introduction Coronavirus pneumonia not only severely affects the lung tissue but is also associated with systemic autoimmune inflammation, rapid overactivation of cytokines and chemokines known as "cytokine storm", and a high risk of thrombosis and thromboembolism. Since there is no specific therapy for this new coronavirus infection (COVID-19), searching for an effective and safe anti-inflammatory therapy is critical.Materials and methods This study evaluated efficacy and safety of pulse therapy with high doses of glucocorticosteroids (GCS), methylprednisolone 1,000 mg for 3 days plus dexamethasone 8 mg for another 3-5 days, in 17 patients with severe coronavirus pneumonia as a part of retrospective comparative analysis (17 patients in control group). The study primary endpoint was the aggregate dynamics of patients' condition as evaluated by an original CCS-COVID scale, which included, in addition to the clinical status, assessments of changes in the inflammation marker, C-reactive protein (CRP); the thrombus formation marker, D-dimer; and the extent of lung injury evaluated by computed tomography (CT). Patients had signs of lung injury (53.2 % and 25.6 %), increases in CRP 27 and 19 times, and a more than doubled level of D-dimer (to 1.41 µg/ml and 1.15 µg/ml) in the active therapy and the control groups, respectively. The GCS treatment group had a more severe condition at baseline.Results The GCS pulse therapy proved effective and significantly decreased the CCS-COVID scores. Median score difference was 5.00 compared to the control group (р=0.011). Shortness of breath considerably decreased; oxygen saturation increased, and the NEWS-2 clinical status scale scores decreased. In the GCS group, concentration of CRP significantly decreased from 134 mg/dl to 41.8 mg/dl (р=0.009) but at the same time, D-dimer level significantly increased from 1.41 µg/ml to 1.98 µg/ml (р=0.044). In the control group, the changes were nonsignificant. The dynamics of lung injury by CT was better in the treatment group but the difference did not reach a statistical significance (р=0.062). Following the GCS treatment, neutrophilia increased (р=0.0001) with persisting lymphopenia, and the neutrophil/lymphocyte (N/L) ratio, a marker of chronic inflammation, increased 2.5 times (р=0.006). The changes in the N/L ratio and D-dimer were found to correlate in the GCS pulse therapy group (r =0.49, p=0.04), which underlined the relationship of chronic autoimmune inflammation with thrombus formation in COVID-19. No significant changes were observed in the control group. In result, four patients developed venous thromboembolic complications (two of them had pulmonary artery thromboembolism) after the GCS pulse therapy despite the concomitant antiplatelet treatment at therapeutic doses. Recovery was slower in the hormone treatment group (median stay in the hospital was 26 days vs 18 days in the control group, р=0.001).Conclusion Pulse therapy with high doses of GCS exerted a rapid anti-inflammatory effect but at the same time, increased the N/L ratio and the D-dimer level, which increased the risk of thromboembolism.


Subject(s)
Betacoronavirus , Coronavirus Infections , Pandemics , Pneumonia, Viral , Steroids/adverse effects , Venous Thrombosis , COVID-19 , Coronavirus Infections/drug therapy , Humans , Inflammation , Pneumonia, Viral/drug therapy , Retrospective Studies , SARS-CoV-2 , Venous Thrombosis/chemically induced
15.
AJNR Am J Neuroradiol ; 41(8): 1370-1376, 2020 08.
Article in English | MEDLINE | ID: covidwho-608376

ABSTRACT

Despite the severity of coronavirus disease 2019 (COVID-19) being more frequently related to acute respiratory distress syndrome and acute cardiac and renal injuries, thromboembolic events have been increasingly reported. We report a unique series of young patients with COVID-19 presenting with cerebral venous system thrombosis. Three patients younger than 41 years of age with confirmed Severe Acute Respiratory Syndrome coronavirus 2 (SARS-Cov-2) infection had neurologic findings related to cerebral venous thrombosis. They were admitted during the short period of 10 days between March and April 2020 and were managed in an academic institution in a large city. One patient had thrombosis in both the superficial and deep systems; another had involvement of the straight sinus, vein of Galen, and internal cerebral veins; and a third patient had thrombosis of the deep medullary veins. Two patients presented with hemorrhagic venous infarcts. The median time from COVID-19 symptoms to a thrombotic event was 7 days (range, 2-7 days). One patient was diagnosed with new-onset diabetic ketoacidosis, and another one used oral contraceptive pills. Two patients were managed with both hydroxychloroquine and azithromycin; one was treated with lopinavir-ritonavir. All patients had a fatal outcome. Severe and potentially fatal deep cerebral thrombosis may complicate the initial clinical presentation of COVID-19. We urge awareness of this atypical manifestation.


Subject(s)
Betacoronavirus , Coronavirus Infections/complications , Intracranial Thrombosis/etiology , Pneumonia, Viral/complications , Venous Thrombosis/etiology , Adult , Azithromycin/therapeutic use , COVID-19 , Coronavirus Infections/drug therapy , Female , Humans , Hydroxychloroquine/therapeutic use , Male , Pandemics , Pneumonia, Viral/drug therapy , Ritonavir/therapeutic use , SARS-CoV-2 , Venous Thrombosis/chemically induced , Young Adult
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