Your browser doesn't support javascript.
Show: 20 | 50 | 100
Results 1 - 20 de 40
Filter
2.
PLoS Med ; 19(2): e1003926, 2022 02.
Article in English | MEDLINE | ID: covidwho-1699720

ABSTRACT

BACKGROUND: Thromboses in unusual locations after the Coronavirus Disease 2019 (COVID-19) vaccine ChAdOx1-S have been reported, although their frequency with vaccines of different types is uncertain at a population level. The aim of this study was to estimate the population-level risks of hospitalised thrombocytopenia and major arterial and venous thromboses after COVID-19 vaccination. METHODS AND FINDINGS: In this whole-population cohort study, we analysed linked electronic health records from adults living in England, from 8 December 2020 to 18 March 2021. We estimated incidence rates and hazard ratios (HRs) for major arterial, venous, and thrombocytopenic outcomes 1 to 28 and >28 days after first vaccination dose for ChAdOx1-S and BNT162b2 vaccines. Analyses were performed separately for ages <70 and ≥70 years and adjusted for age, age2, sex, ethnicity, and deprivation. We also prespecified adjustment for anticoagulant medication, combined oral contraceptive medication, hormone replacement therapy medication, history of pulmonary embolism or deep vein thrombosis, and history of coronavirus infection in analyses of venous thrombosis; and diabetes, hypertension, smoking, antiplatelet medication, blood pressure lowering medication, lipid lowering medication, anticoagulant medication, history of stroke, and history of myocardial infarction in analyses of arterial thromboses. We selected further covariates with backward selection. Of 46 million adults, 23 million (51%) were women; 39 million (84%) were <70; and 3.7 million (8.1%) Asian or Asian British, 1.6 million (3.5%) Black or Black British, 36 million (79%) White, 0.7 million (1.5%) mixed ethnicity, and 1.5 million (3.2%) were of another ethnicity. Approximately 21 million (46%) adults had their first vaccination between 8 December 2020 and 18 March 2021. The crude incidence rates (per 100,000 person-years) of all venous events were as follows: prevaccination, 140 [95% confidence interval (CI): 138 to 142]; ≤28 days post-ChAdOx1-S, 294 (281 to 307); >28 days post-ChAdOx1-S, 359 (338 to 382), ≤28 days post-BNT162b2-S, 241 (229 to 253); >28 days post-BNT162b2-S 277 (263 to 291). The crude incidence rates (per 100,000 person-years) of all arterial events were as follows: prevaccination, 546 (95% CI: 541 to 555); ≤28 days post-ChAdOx1-S, 1,211 (1,185 to 1,237); >28 days post-ChAdOx1-S, 1678 (1,630 to 1,726), ≤28 days post-BNT162b2-S, 1,242 (1,214 to 1,269); >28 days post-BNT162b2-S, 1,539 (1,507 to 1,572). Adjusted HRs (aHRs) 1 to 28 days after ChAdOx1-S, compared with unvaccinated rates, at ages <70 and ≥70 years, respectively, were 0.97 (95% CI: 0.90 to 1.05) and 0.58 (0.53 to 0.63) for venous thromboses, and 0.90 (0.86 to 0.95) and 0.76 (0.73 to 0.79) for arterial thromboses. Corresponding aHRs for BNT162b2 were 0.81 (0.74 to 0.88) and 0.57 (0.53 to 0.62) for venous thromboses, and 0.94 (0.90 to 0.99) and 0.72 (0.70 to 0.75) for arterial thromboses. aHRs for thrombotic events were higher at younger ages for venous thromboses after ChAdOx1-S, and for arterial thromboses after both vaccines. Rates of intracranial venous thrombosis (ICVT) and of thrombocytopenia in adults aged <70 years were higher 1 to 28 days after ChAdOx1-S (aHRs 2.27, 95% CI: 1.33 to 3.88 and 1.71, 1.35 to 2.16, respectively), but not after BNT162b2 (0.59, 0.24 to 1.45 and 1.00, 0.75 to 1.34) compared with unvaccinated. The corresponding absolute excess risks of ICVT 1 to 28 days after ChAdOx1-S were 0.9 to 3 per million, varying by age and sex. The main limitations of the study are as follows: (i) it relies on the accuracy of coded healthcare data to identify exposures, covariates, and outcomes; (ii) the use of primary reason for hospital admission to measure outcome, which improves the positive predictive value but may lead to an underestimation of incidence; and (iii) potential unmeasured confounding. CONCLUSIONS: In this study, we observed increases in rates of ICVT and thrombocytopenia after ChAdOx1-S vaccination in adults aged <70 years that were small compared with its effect in reducing COVID-19 morbidity and mortality, although more precise estimates for adults aged <40 years are needed. For people aged ≥70 years, rates of arterial or venous thrombotic events were generally lower after either vaccine compared with unvaccinated, suggesting that either vaccine is suitable in this age group.


Subject(s)
COVID-19 Vaccines , Thrombocytopenia/etiology , Vaccination , Adult , Aged , Cohort Studies , England/epidemiology , Female , Humans , Incidence , Male , Middle Aged , SARS-CoV-2/pathogenicity , Thrombocytopenia/epidemiology , Vaccination/adverse effects
4.
Blood Adv ; 5(21): 4521-4534, 2021 11 09.
Article in English | MEDLINE | ID: covidwho-1511718

ABSTRACT

Heparin thromboprophylaxis is routinely administered during hospitalization for COVID-19. Because of the immune stimulation related to COVID-19, there is ongoing concern regarding a heightened incidence of heparin-induced thrombocytopenia (HIT). We performed a literature search using PubMed, EMBASE, Cochrane, and medRxiv database to identify studies that reported clinical and laboratory characteristics and/or the incidence of HIT in patients with COVID-19. The primary aim was to systematically review the clinical features and outcomes of patients with COVID-19 with confirmed HIT. The secondary objective was to perform a meta-analysis to estimate the incidence of HIT in hospitalized patients with COVID-19. A meta-analysis of 7 studies including 5849 patients revealed the pooled incidence of HIT in COVID-19 of 0.8% (95% confidence interval [CI], 0.2%-3.2%; I2 = 89%). The estimated incidences were 1.2% (95% CI, 0.3%-3.9%; I2 = 65%) vs 0.1% (95% CI, 0.0%-0.4%; I2 = 0%) in therapeutic vs prophylactic heparin subgroups, respectively. The pooled incidences of HIT were higher in critically ill patients with COVID-19 (2.2%; 95% CI, 0.6%-8.3%; I2 = 72.5%) compared with noncritically ill patients (0.1%; 95% CI, 0.0%-0.4%: I2 = 0%). There were 19 cases of confirmed HIT and 1 with autoimmune HIT for clinical and laboratory characterization. The median time from heparin initiation to HIT diagnosis was 13.5 days (interquartile range, 10.75-16.25 days). Twelve (63%) developed thromboembolism after heparin therapy. In conclusion, the incidence of HIT in patients with COVID-19 was comparable to patients without COVID-19, with higher incidences with therapeutic anticoagulation and in critically ill patients.


Subject(s)
COVID-19 , Thrombocytopenia , Venous Thromboembolism , Anticoagulants/adverse effects , Humans , SARS-CoV-2 , Thrombocytopenia/chemically induced , Thrombocytopenia/epidemiology
5.
Ann Rheum Dis ; 80(11): 1376-1384, 2021 11.
Article in English | MEDLINE | ID: covidwho-1462911

ABSTRACT

OBJECTIVES: There are no head-to-head trials of different dose escalation strategies of methotrexate (MTX) in RA. We compared the efficacy, safety and tolerability of 'usual' (5 mg every 4 weeks) versus 'fast' (5 mg every 2 weeks) escalation of oral MTX. METHODS: This multicentre, open-label (assessor blinded) RCT included patients 18-55 years of age having active RA with disease duration <5 years, and not on DMARDs. Patients were randomized 1:1 into usual or fast escalation groups, both groups starting MTX at 15 mg/week till a maximum of 25 mg/week. Primary outcome was EULAR good response at 16 weeks, secondary outcomes were ΔDAS28 and adverse effects (AE). Analyses were intention-to-treat. RESULTS: 178 patients with mean DAS28-CRP of 5.4(1.1) were randomized to usual (n=89) or fast escalation groups (n=89). At 16 weeks, there was no difference in good EULAR response in the usual (28.1%) or fast escalation (22.5%) groups (p=0.8). There was no difference in mean ΔDAS28-CRP at 8 weeks (-0.9, -0.8, p=0.72) or 16 weeks (-1.3, -1.3, p=0.98). Even at 24 weeks (extended follow-up), responses were similar. There were no inter-group differences in ΔHAQ, or MTX-polyglutamates 1-3 levels at 8 or 16 weeks. Gastrointestinal AE were higher in the fast escalation group over initial 8 weeks (27%, 40%, p=0.048), but not over 16 weeks. There was no difference in cytopenias, transaminitis, or drug discontinuation/dose reduction between the groups. No serious AE were seen. CONCLUSION: A faster MTX escalation strategy in RA was not more efficacious over 16-24 weeks, and did not significantly increase AE, except higher gastrointestinal AE initially. TRIAL REGISTRATION NUMBER: CTRI/2018/12/016549.


Subject(s)
Antirheumatic Agents/administration & dosage , Arthritis, Rheumatoid/drug therapy , Methotrexate/administration & dosage , Adolescent , Adult , Arthritis, Rheumatoid/physiopathology , Chemical and Drug Induced Liver Injury/epidemiology , Dose-Response Relationship, Drug , Drug Administration Schedule , Female , Gastrointestinal Diseases/chemically induced , Gastrointestinal Diseases/epidemiology , Humans , Leukopenia/chemically induced , Leukopenia/epidemiology , Male , Methotrexate/analogs & derivatives , Methotrexate/blood , Middle Aged , Polyglutamic Acid/analogs & derivatives , Polyglutamic Acid/blood , Thrombocytopenia/chemically induced , Thrombocytopenia/epidemiology , Treatment Outcome , Young Adult
7.
J Pediatr Hematol Oncol ; 43(7): 243-248, 2021 10 01.
Article in English | MEDLINE | ID: covidwho-1434557

ABSTRACT

Thrombocytopenia is noted in corona virus disease-2019 (COVID-19) with a prevalence of 5% to 41%, and has been observed to be associated with inferior outcomes. The pathogenesis of thrombocytopenia in COVID-19 is unique and differs from other viral syndromes in terms of clinical presentation and causative mechanisms. Platelets act as both targets and the initial defense against severe acute respiratory syndrome-coronavirus 2 and work in concert with the underlying thrombophilic mechanisms to modulate the final disease phenotype. Understanding these mechanisms may possibly allow targeting of a key component of COVID-19 pathogenesis. We provide a focused review of the current mechanisms implicated in development of thrombocytopenia in COVID-19 and therapeutic implications of the same.


Subject(s)
COVID-19/complications , SARS-CoV-2/isolation & purification , Thrombocytopenia/pathology , COVID-19/transmission , COVID-19/virology , Humans , Thrombocytopenia/epidemiology , Thrombocytopenia/virology
8.
BMJ ; 374: n1931, 2021 08 26.
Article in English | MEDLINE | ID: covidwho-1376469

ABSTRACT

OBJECTIVE: To assess the association between covid-19 vaccines and risk of thrombocytopenia and thromboembolic events in England among adults. DESIGN: Self-controlled case series study using national data on covid-19 vaccination and hospital admissions. SETTING: Patient level data were obtained for approximately 30 million people vaccinated in England between 1 December 2020 and 24 April 2021. Electronic health records were linked with death data from the Office for National Statistics, SARS-CoV-2 positive test data, and hospital admission data from the United Kingdom's health service (NHS). PARTICIPANTS: 29 121 633 people were vaccinated with first doses (19 608 008 with Oxford-AstraZeneca (ChAdOx1 nCoV-19) and 9 513 625 with Pfizer-BioNTech (BNT162b2 mRNA)) and 1 758 095 people had a positive SARS-CoV-2 test. People aged ≥16 years who had first doses of the ChAdOx1 nCoV-19 or BNT162b2 mRNA vaccines and any outcome of interest were included in the study. MAIN OUTCOME MEASURES: The primary outcomes were hospital admission or death associated with thrombocytopenia, venous thromboembolism, and arterial thromboembolism within 28 days of three exposures: first dose of the ChAdOx1 nCoV-19 vaccine; first dose of the BNT162b2 mRNA vaccine; and a SARS-CoV-2 positive test. Secondary outcomes were subsets of the primary outcomes: cerebral venous sinus thrombosis (CVST), ischaemic stroke, myocardial infarction, and other rare arterial thrombotic events. RESULTS: The study found increased risk of thrombocytopenia after ChAdOx1 nCoV-19 vaccination (incidence rate ratio 1.33, 95% confidence interval 1.19 to 1.47 at 8-14 days) and after a positive SARS-CoV-2 test (5.27, 4.34 to 6.40 at 8-14 days); increased risk of venous thromboembolism after ChAdOx1 nCoV-19 vaccination (1.10, 1.02 to 1.18 at 8-14 days) and after SARS-CoV-2 infection (13.86, 12.76 to 15.05 at 8-14 days); and increased risk of arterial thromboembolism after BNT162b2 mRNA vaccination (1.06, 1.01 to 1.10 at 15-21 days) and after SARS-CoV-2 infection (2.02, 1.82 to 2.24 at 15-21 days). Secondary analyses found increased risk of CVST after ChAdOx1 nCoV-19 vaccination (4.01, 2.08 to 7.71 at 8-14 days), after BNT162b2 mRNA vaccination (3.58, 1.39 to 9.27 at 15-21 days), and after a positive SARS-CoV-2 test; increased risk of ischaemic stroke after BNT162b2 mRNA vaccination (1.12, 1.04 to 1.20 at 15-21 days) and after a positive SARS-CoV-2 test; and increased risk of other rare arterial thrombotic events after ChAdOx1 nCoV-19 vaccination (1.21, 1.02 to 1.43 at 8-14 days) and after a positive SARS-CoV-2 test. CONCLUSION: Increased risks of haematological and vascular events that led to hospital admission or death were observed for short time intervals after first doses of the ChAdOx1 nCoV-19 and BNT162b2 mRNA vaccines. The risks of most of these events were substantially higher and more prolonged after SARS-CoV-2 infection than after vaccination in the same population.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Thrombocytopenia/epidemiology , Thromboembolism/epidemiology , Vaccination/statistics & numerical data , Adolescent , Adult , Aged , Aged, 80 and over , COVID-19/diagnosis , COVID-19/epidemiology , COVID-19 Vaccines/administration & dosage , England/epidemiology , Female , Humans , Male , Middle Aged , Pandemics , Risk Assessment , SARS-CoV-2 , Young Adult
9.
JAMA ; 326(4): 332-338, 2021 07 27.
Article in English | MEDLINE | ID: covidwho-1355843

ABSTRACT

Importance: Cases of cerebral venous sinus thrombosis in combination with thrombocytopenia have recently been reported within 4 to 28 days of vaccination with the ChAdOx1 nCov-19 (AstraZeneca/Oxford) and Ad.26.COV2.S (Janssen/Johnson & Johnson) COVID-19 vaccines. An immune-mediated response associated with platelet factor 4/heparin antibodies has been proposed as the underlying pathomechanism. Objective: To determine the frequencies of admission thrombocytopenia, heparin-induced thrombocytopenia, and presence of platelet factor 4/heparin antibodies in patients diagnosed with cerebral venous sinus thrombosis prior to the COVID-19 pandemic. Design, Setting, and Participants: This was a descriptive analysis of a retrospective sample of consecutive patients diagnosed with cerebral venous sinus thrombosis between January 1987 and March 2018 from 7 hospitals participating in the International Cerebral Venous Sinus Thrombosis Consortium from Finland, the Netherlands, Switzerland, Sweden, Mexico, Iran, and Costa Rica. Of 952 patients, 865 with available baseline platelet count were included. In a subset of 93 patients, frozen plasma samples collected during a previous study between September 2009 and February 2016 were analyzed for the presence of platelet factor 4/heparin antibodies. Exposures: Diagnosis of cerebral venous sinus thrombosis. Main Outcomes and Measures: Frequencies of admission thrombocytopenia (platelet count <150 ×103/µL), heparin-induced thrombocytopenia (as diagnosed by the treating physician), and platelet factor 4/heparin IgG antibodies (optical density >0.4, in a subset of patients with previously collected plasma samples). Results: Of 865 patients (median age, 40 years [interquartile range, 29-53 years], 70% women), 73 (8.4%; 95% CI, 6.8%-10.5%) had thrombocytopenia, which was mild (100-149 ×103/µL) in 52 (6.0%), moderate (50-99 ×103/µL) in 17 (2.0%), and severe (<50 ×103/µL) in 4 (0.5%). Heparin-induced thrombocytopenia with platelet factor 4/heparin antibodies was diagnosed in a single patient (0.1%; 95% CI, <0.1%-0.7%). Of the convenience sample of 93 patients with cerebral venous sinus thrombosis included in the laboratory analysis, 8 (9%) had thrombocytopenia, and none (95% CI, 0%-4%) had platelet factor 4/heparin antibodies. Conclusions and Relevance: In patients with cerebral venous sinus thrombosis prior to the COVID-19 pandemic, baseline thrombocytopenia was uncommon, and heparin-induced thrombocytopenia and platelet factor 4/heparin antibodies were rare. These findings may inform investigations of the possible association between the ChAdOx1 nCoV-19 and Ad26.COV2.S COVID-19 vaccines and cerebral venous sinus thrombosis with thrombocytopenia.


Subject(s)
COVID-19 Vaccines/adverse effects , Heparin/immunology , Platelet Factor 4/immunology , Sinus Thrombosis, Intracranial/complications , Thrombocytopenia/etiology , Adult , Antibodies/blood , Female , Heparin/adverse effects , Humans , Male , Middle Aged , Retrospective Studies , Sinus Thrombosis, Intracranial/immunology , Thrombocytopenia/epidemiology
10.
Rinsho Shinkeigaku ; 61(9): 594-601, 2021 Sep 28.
Article in Japanese | MEDLINE | ID: covidwho-1344506

ABSTRACT

Vaccines are important in managing the COVID-19 pandemic caused by SARS-CoV-2. Despite the very low incidence, severe cases of thrombosis with thrombocytopenia after COVID-19 vaccination termed as Thrombosis with Thrombocytopenia Syndrome (TTS) have been reported. TTS clinically resembles autoimmune heparin-induced thrombocytopenia. TTS can cause disability and even death. It usually presents 4-28 days after vaccination characterized by thrombocytopenia and progressive thrombosis, often causing cerebral vein/venous thrombosis (CVT) and splanchnic venous thrombosis. We should avoid all forms of heparin and platelet transfusion. While awaiting further information on the pathophysiological mechanism and treatment of TTS, clinicians should be aware of TTS with CVT in patients receiving COVID-19 vaccinations. This new syndrome of TTS is an active area of investigation globally. Here, we review the available literature.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Cerebral Veins , Sinus Thrombosis, Intracranial/etiology , Thrombocytopenia/etiology , Adult , COVID-19/virology , Female , Humans , Immunoglobulins, Intravenous/administration & dosage , Male , Middle Aged , SARS-CoV-2 , Sinus Thrombosis, Intracranial/diagnosis , Sinus Thrombosis, Intracranial/epidemiology , Sinus Thrombosis, Intracranial/therapy , Syndrome , Thrombocytopenia/diagnosis , Thrombocytopenia/epidemiology , Thrombocytopenia/therapy , Time Factors
13.
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
14.
JAMA ; 326(4): 332-338, 2021 07 27.
Article in English | MEDLINE | ID: covidwho-1293117

ABSTRACT

Importance: Cases of cerebral venous sinus thrombosis in combination with thrombocytopenia have recently been reported within 4 to 28 days of vaccination with the ChAdOx1 nCov-19 (AstraZeneca/Oxford) and Ad.26.COV2.S (Janssen/Johnson & Johnson) COVID-19 vaccines. An immune-mediated response associated with platelet factor 4/heparin antibodies has been proposed as the underlying pathomechanism. Objective: To determine the frequencies of admission thrombocytopenia, heparin-induced thrombocytopenia, and presence of platelet factor 4/heparin antibodies in patients diagnosed with cerebral venous sinus thrombosis prior to the COVID-19 pandemic. Design, Setting, and Participants: This was a descriptive analysis of a retrospective sample of consecutive patients diagnosed with cerebral venous sinus thrombosis between January 1987 and March 2018 from 7 hospitals participating in the International Cerebral Venous Sinus Thrombosis Consortium from Finland, the Netherlands, Switzerland, Sweden, Mexico, Iran, and Costa Rica. Of 952 patients, 865 with available baseline platelet count were included. In a subset of 93 patients, frozen plasma samples collected during a previous study between September 2009 and February 2016 were analyzed for the presence of platelet factor 4/heparin antibodies. Exposures: Diagnosis of cerebral venous sinus thrombosis. Main Outcomes and Measures: Frequencies of admission thrombocytopenia (platelet count <150 ×103/µL), heparin-induced thrombocytopenia (as diagnosed by the treating physician), and platelet factor 4/heparin IgG antibodies (optical density >0.4, in a subset of patients with previously collected plasma samples). Results: Of 865 patients (median age, 40 years [interquartile range, 29-53 years], 70% women), 73 (8.4%; 95% CI, 6.8%-10.5%) had thrombocytopenia, which was mild (100-149 ×103/µL) in 52 (6.0%), moderate (50-99 ×103/µL) in 17 (2.0%), and severe (<50 ×103/µL) in 4 (0.5%). Heparin-induced thrombocytopenia with platelet factor 4/heparin antibodies was diagnosed in a single patient (0.1%; 95% CI, <0.1%-0.7%). Of the convenience sample of 93 patients with cerebral venous sinus thrombosis included in the laboratory analysis, 8 (9%) had thrombocytopenia, and none (95% CI, 0%-4%) had platelet factor 4/heparin antibodies. Conclusions and Relevance: In patients with cerebral venous sinus thrombosis prior to the COVID-19 pandemic, baseline thrombocytopenia was uncommon, and heparin-induced thrombocytopenia and platelet factor 4/heparin antibodies were rare. These findings may inform investigations of the possible association between the ChAdOx1 nCoV-19 and Ad26.COV2.S COVID-19 vaccines and cerebral venous sinus thrombosis with thrombocytopenia.


Subject(s)
COVID-19 Vaccines/adverse effects , Heparin/immunology , Platelet Factor 4/immunology , Sinus Thrombosis, Intracranial/complications , Thrombocytopenia/etiology , Adult , Antibodies/blood , Female , Heparin/adverse effects , Humans , Male , Middle Aged , Retrospective Studies , Sinus Thrombosis, Intracranial/immunology , Thrombocytopenia/epidemiology
15.
Expert Rev Vaccines ; 20(8): 1027-1035, 2021 08.
Article in English | MEDLINE | ID: covidwho-1284828

ABSTRACT

INTRODUCTION: To combat COVID-19, scientists all over the world have expedited the process of vaccine development. Although interim analyses of clinical trials have demonstrated the efficacy and safety of COVID-19 vaccines, a serious but rare adverse event, thrombosis with thrombocytopenia syndrome (TTS), has been reported following COVID-19 vaccination. AREAS COVERED: This review, using data from both peer-reviewed and non-peer-reviewed studies, aimed to provide updated information about the critical issue of COVID-19 vaccine-related TTS. EXPERT OPINION: : The exact epidemiological characteristics and possible pathogenesis of this adverse event remain unclear. Most cases of TTS developed in women within 2 weeks of the first dose of vaccine on the receipt of the ChAdOx1 nCoV-19 and Ad26.COV2.S vaccines. In countries with mass vaccination against COVID-19, clinicians should be aware of the relevant clinical features of this rare adverse event and perform related laboratory and imaging studies for early diagnosis. Non-heparin anticoagulants, such as fondaparinux, argatroban, or a direct oral anticoagulant (e.g. apixaban or rivaroxaban) and intravenous immunoglobulins are recommended for the treatment of TTS. However, further studies are required to explore the underlying mechanisms of this rare clinical entity. PLAIN LANGUAGE SUMMARY: What is the context?Thrombosis with thrombocytopenia syndrome (TTS) usually develops within 2 weeks of the first doses of the ChAdOx1 nCoV-19 and Ad26.COV2.S COVID-19 vaccines.TTS mainly occurs in patients aged < 55 years and is associated with high morbidity and mortality.What is new?TTS mimics autoimmune heparin-induced thrombocytopenia and can be mediated by platelet-activating antibodies against platelet factor 4. Non-heparin anticoagulants, such as fondaparinux, argatroban, or a direct oral anticoagulant (e.g. apixaban or rivaroxaban) should be considered as the treatment of choice if the platelet count is > 50 × 109/L and there is no serious bleeding. Intravenous immunoglobulins and glucocorticoids may help increase the platelet count within days and reduce the risk of hemorrhagic transformation when anticoagulation is initiated.What is the impact?TTS should be a serious concern during the implementation of mass COVID-19 vaccination, and patients should be educated about this complication along with its symptoms such as severe headache, blurred vision, seizure, severe and persistent abdominal pain, painful swelling of the lower leg, and chest pain or dyspnea. The incidence of TTS is low; therefore, maintenance of high vaccination coverage against COVID-19 should be continued.


Subject(s)
COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Thrombocytopenia/chemically induced , Thrombosis/chemically induced , COVID-19/diagnosis , COVID-19/epidemiology , Humans , Thrombocytopenia/diagnosis , Thrombocytopenia/epidemiology , Thrombosis/diagnosis , Thrombosis/epidemiology
16.
J Autoimmun ; 122: 102685, 2021 08.
Article in English | MEDLINE | ID: covidwho-1281444

ABSTRACT

The involvement of viruses and SARS-CoV-2 in autoimmune diseases is well known. The recent demonstration that ChAdOx1 nCoV-19 Covid-19 (AstraZeneca) vaccine (ChA) favors the production of anti-platelet factor 4 (anti-PF4) antibodies, blood clots, and thrombocytopenia raises the question of whether other anti-CoViD-19 vaccines favor the same patterns of events. We assessed the frequency of severe adverse events (SAEs) documented in the EudraVigilance European database up to April 16, 2021 related to thrombocytopenia, bleeding, and blood clots in recipients of ChA compared to that of recipients of the BNT162b2 Covid-19 (Pfizer/BioNTech) vaccine (BNT). ChA administration was associated with a much higher frequency of SAEs in each AE Reaction Group as compared with that elicited by BNT. When considering AEs caused by thrombocytopenia, bleeding and blood clots, we observed 33 and 151 SAEs/1 million doses in BNT and ChA recipients, respectively. When considering patients with AEs related to cerebral/splanchnic venous thrombosis, and/or thrombocytopenia, we documented 4 and 30 SAEs and 0.4 and 4.8 deaths/1 million doses for BNT and ChA recipients, respectively. The highest risk following ChA vaccination is in young people and, likely, women of reproductive age, as suggested by hypothesized scenarios. In conclusion, the immune reaction promoted by ChA vaccine may lead to not only thrombocytopenia and cerebral/splanchnic venous thrombosis but also other thrombotic and thromboembolic SAEs. These events are not favored by BNT vaccine. Our study may help in the evaluation of the benefit/risk profile of the ChA vaccine considering the epidemic curve present in a country.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Hemorrhage/etiology , Thrombosis/etiology , Adolescent , Adult , Europe , Female , Hemorrhage/epidemiology , Humans , Male , Middle Aged , SARS-CoV-2 , Thrombocytopenia/epidemiology , Thrombocytopenia/etiology , Thrombosis/epidemiology , Young Adult
17.
PLoS One ; 16(6): e0252939, 2021.
Article in English | MEDLINE | ID: covidwho-1278183

ABSTRACT

BACKGROUND: Coagulopathy and thromboembolic events are among the complications of Corona Virus disease 2019 (COVID-19). Abnormal coagulation parameters in COVID-19 patients are important prognostic factors of disease severity. The aim of this study was to analyze coagulation profiles of hospitalized COVID-19 patients in Addis Ababa, Ethiopia. METHODS: This prospective cross-sectional study was conducted among 455 Covid-19 patients admitted at Millennium COVID-19 care and treatment center, Addis Ababa, Ethiopia from July 1- October 23, 2020. Prothrombin Time (PT), Activated Partial Thromboplastin Time (APTT) and International normalized ratio (INR) were determined on HUMACLOT DUE PLUS® coagulation analyzer (Wiesbaden, Germany). In all statistical analysis of results, p<0.05 was defined as statistically significant. RESULT: A prolonged prothrombin time was found in 46.8% of study participants with COVID-19 and a prolonged prothrombin time and elevated INR in 53.3% of study subjects with severe and 51% of critically COVID patients. Thrombocytopenia was detected in 22.1% of COVID-19 patients. 50.5% and 51.3% of COVID-19 patients older than 55 years had thrombocytopenia and prolonged APTT respectively. CONCLUSION: In this study, prolonged prothrombin time and elevated INR were detected in more than 50% of severe and critical COVID-19 patients. Thrombocytopenia and prolonged APTT were dominant in COVID-19 patients older than 55 years. Thus, we recommend emphasis to be given for monitoring of platelet count, PT, APTT and INR in hospitalized and admitted COVID-19 patients.


Subject(s)
COVID-19/diagnosis , Severity of Illness Index , Thrombocytopenia/epidemiology , Adolescent , Adult , Age Factors , Aged , Aged, 80 and over , COVID-19/blood , COVID-19/complications , COVID-19/mortality , Child , Child, Preschool , Critical Illness , Cross-Sectional Studies , Ethiopia/epidemiology , Hospitalization , Humans , International Normalized Ratio , Middle Aged , Partial Thromboplastin Time , Platelet Count , Prognosis , Prospective Studies , Prothrombin Time , Risk Factors , SARS-CoV-2/isolation & purification , Sex Factors , Thrombocytopenia/blood , Thrombocytopenia/diagnosis , Thrombocytopenia/etiology , Young Adult
18.
Nat Med ; 27(7): 1290-1297, 2021 07.
Article in English | MEDLINE | ID: covidwho-1263501

ABSTRACT

Reports of ChAdOx1 vaccine-associated thrombocytopenia and vascular adverse events have led to some countries restricting its use. Using a national prospective cohort, we estimated associations between exposure to first-dose ChAdOx1 or BNT162b2 vaccination and hematological and vascular adverse events using a nested incident-matched case-control study and a confirmatory self-controlled case series (SCCS) analysis. An association was found between ChAdOx1 vaccination and idiopathic thrombocytopenic purpura (ITP) (0-27 d after vaccination; adjusted rate ratio (aRR) = 5.77, 95% confidence interval (CI), 2.41-13.83), with an estimated incidence of 1.13 (0.62-1.63) cases per 100,000 doses. An SCCS analysis confirmed that this was unlikely due to bias (RR = 1.98 (1.29-3.02)). There was also an increased risk for arterial thromboembolic events (aRR = 1.22, 1.12-1.34) 0-27 d after vaccination, with an SCCS RR of 0.97 (0.93-1.02). For hemorrhagic events 0-27 d after vaccination, the aRR was 1.48 (1.12-1.96), with an SCCS RR of 0.95 (0.82-1.11). A first dose of ChAdOx1 was found to be associated with small increased risks of ITP, with suggestive evidence of an increased risk of arterial thromboembolic and hemorrhagic events. The attenuation of effect found in the SCCS analysis means that there is the potential for overestimation of the reported results, which might indicate the presence of some residual confounding or confounding by indication. Public health authorities should inform their jurisdictions of these relatively small increased risks associated with ChAdOx1. No positive associations were seen between BNT162b2 and thrombocytopenic, thromboembolic and hemorrhagic events.


Subject(s)
COVID-19 Vaccines/therapeutic use , COVID-19/prevention & control , Hemorrhage/epidemiology , Purpura, Thrombocytopenic, Idiopathic/epidemiology , Thrombocytopenia/epidemiology , Thromboembolism/epidemiology , Venous Thromboembolism/epidemiology , Adolescent , Adult , Aged , Case-Control Studies , Cohort Studies , Female , Humans , Incidence , Male , Middle Aged , Prospective Studies , SARS-CoV-2 , Scotland/epidemiology , Sinus Thrombosis, Intracranial/epidemiology , Young Adult
19.
Am J Emerg Med ; 49: 58-61, 2021 11.
Article in English | MEDLINE | ID: covidwho-1248779

ABSTRACT

BACKGROUND: Current vaccines for the Coronavirus Disease of 2019 (COVID-19) have demonstrated efficacy with low risk of adverse events. However, recent reports of thrombosis with thrombocytopenia syndrome (TTS) associated with adenovirus vector vaccines have raised concern. OBJECTIVE: This narrative review summarizes the current background, evaluation, and management of TTS for emergency clinicians. DISCUSSION: TTS, also known as vaccine-induced immune thrombotic thrombocytopenia, is a reaction associated with exposure to the ChAdOx1 nCoV-19 (Oxford-AstraZeneca) and AD26.COV2·S (Johnson & Johnson) vaccine, which may result in thrombocytopenia and thrombotic events. There are several case series of patients diagnosed with TTS, but the overall incidence is rare. TTS is characterized by exposure to one of the aforementioned vaccines 4-30 days prior to presentation, followed by thrombosis, mild-to-severe thrombocytopenia, and a positive platelet factor-4 (PF4)-heparin enzyme-linked immunosorbent assay (ELISA). Thrombosis typically involves atypical locations, including cerebral venous thrombosis and splanchnic vein thrombosis. Evaluation should include complete blood count, peripheral smear, D-dimer, fibrinogen, coagulation panel, renal and liver function, and electrolytes, as well as PF4-heparin ELISA if available. Consultation with hematology is recommended if suspected or confirmed. Treatment may include intravenous immunoglobulin and anticoagulation, while avoiding heparin-based agents and platelet transfusion. CONCLUSIONS: With increasing vaccine distribution, it is essential for emergency clinicians to be aware of the evaluation and management of this condition.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/prevention & control , Thrombocytopenia/chemically induced , Thrombosis/chemically induced , COVID-19/epidemiology , COVID-19 Vaccines/administration & dosage , Humans , Syndrome , Thrombocytopenia/diagnosis , Thrombocytopenia/epidemiology , Thrombosis/diagnosis , Thrombosis/epidemiology , Time Factors
20.
Eur J Haematol ; 107(2): 173-180, 2021 Aug.
Article in English | MEDLINE | ID: covidwho-1228750

ABSTRACT

Very rare cases of thrombosis associated with thrombocytopenia have occurred following the vaccination with AstraZeneca COVID-19 vaccine. The aim of this concise review is to summarize the current knowledge on the epidemiologic and pathogenic mechanisms of this syndrome named vaccine-associated immune thrombosis and thrombocytopenia (VITT). A practical patient management section will also be dealt with using information available from national and international scientific societies as well as expert panels. A literature search on the VITT syndrome was carried out in PubMed using appropriate MeSH headings. Overall, 40 VITT cases have been reported. Continuous pharmacovigilance monitoring is needed to collect more data on the real incidence and the pathogenesis of VITT syndrome. Such information will also help us to optimize the management this rare but often clinically severe thrombotic condition associated with COVID-19 vaccination.


Subject(s)
COVID-19 Vaccines/adverse effects , COVID-19/complications , SARS-CoV-2 , Thrombocytopenia/etiology , Thrombosis/etiology , Biomarkers , COVID-19/epidemiology , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , COVID-19 Vaccines/immunology , Cost of Illness , Disease Management , Disease Susceptibility , Humans , Patient Outcome Assessment , Risk Assessment , Risk Factors , SARS-CoV-2/immunology , Severity of Illness Index , Syndrome , Thrombocytopenia/diagnosis , Thrombocytopenia/epidemiology , Thrombocytopenia/therapy , Thrombosis/diagnosis , Thrombosis/epidemiology , Thrombosis/therapy
SELECTION OF CITATIONS
SEARCH DETAIL