COVID-19 Associated Thrombocytopenia in Children: An Emerging Issue
International Journal of Pediatrics-Mashhad. 2021;9(6):13635-13642
Thrombocytopenia is a risk factor for increased mortality and morbidity during the Coronavirus Disease 2019 (COVID-19) In patients with COVID-19, the mechanisms lead to thrombocytopenia seems to be multifactorial Thrombotic consumption of platelets in microvasculature, cytokine release, sepsis, and drug induced, direct infection of megakaryocytes and autoimmune destruction of platelets are the leading etiologies in COVID-19 and thrombocytopenia In this overview, the research was conducted by screening the relevant articles evaluating the COVID-19 associated thrombocytopenia in children An electronic search was performed in online databases of Scopus, EMBASE, Cochrane, Web of Science and Medline (via PubMed) with English language from December 2019 up to September 2020 Thrombocytopenia at admission in patients with SARS-CoV-2 infection is common, but delayed phase thrombocytopenia (occurring 2 weeks after beginning of symptoms) is uncertain The delayed phase thrombocytopenia in COVID-19 is more prevalent in infected case with low lymphocyte count at admission and has a significant correlation with higher mortality rate In majority of cases with COVID-19 and thrombocytopenia, the platelet count is mildly decreased Severe thrombocytopenia or a prompt decline in number of platelets often indicates immune mediated thrombocytopenia or in late terminal stages of this infection Thrombocytopenia is a significant finding in patients with severe type of COVID -19 Immune mediated platelet destruction might account for the delayed-phase thrombocytopenia in a group of patients, and can manifest as severe thrombocytopenia It is important for practitioners to be vigilant and aware of this hematologic abnormality
Immune Thrombocytopenic Purpura in a Patient With SARS-CoV-2 and Epstein-Barr Virus
A 35-year-old female was admitted to the hospital for menorrhagia and fatigue Initial labs revealed that the patient had severe thrombocytopenia and also tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) The main objective in this case is to describe the investigation that eventually led to a diagnosis of idiopathic thrombocytopenic purpura (ITP) in the setting of a SARS-CoV-2 coronavirus disease 2019 (COVID-19) infection and co-infection with Epstein-Barr virus (EBV) The majority of ITP cases are idiopathic and most are diagnosed and managed without hospital admission Admission and careful management were warranted in this particular case Interestingly, however, the patient did not have any respiratory complications associated with COVID-19 She was given 1 unit of platelets and subsequently received intravenous corticosteroids Platelet counts improved and the patient was discharged with a course of oral prednisone This case highlights the importance of understanding the differences between primary and secondary ITP
Is COVID-19 an Independent Risk Factor for Heparin-Induced Thrombocytopenia?
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes a viral respiratory illness initially described in Wuhan, China, and was declared a pandemic by World Health Organization (WHO) in 2020, and the disease is named coronavirus disease (COVID-19) SARS-CoV2 is known to cause fever, cough, fatigue, and acute respiratory distress syndrome As more patients become infected, extrapulmonary manifestations came to rise and hypercoagulability is one among those COVID-19 could predispose patients to both venous and arterial thromboembolic events which are commonly treated with unfractionated heparin or low molecular weight heparin (LMWH) The treatment of patients who develop heparin-induced thrombocytopenia (HIT) while being treated with heparin or LMWH for COVID-induced thromboembolic complications is challenging We describe a patient admitted to the hospital with COVID-19 pneumonia, found to have a cerebrovascular event treated with unfractionated heparin She also received therapeutic LMWH for anticoagulation on day 1 of presentation due to atrial fibrillation She was diagnosed with HIT and was found to have a pulmonary embolism, aortic arch mural thrombus, and arterial thrombi in the lower extremities As more recent studies showed HIT antibodies in COVID-19 patients who are naive for heparin-based products, COVID-19 may be an independent risk factor for the development of HIT The role of COVID-19 in the development of HIT is uncertain High vigilance is required to diagnose and initiate treatment for HIT early in the disease course as it can be life-threatening
Thrombocytopenia and Intracranial Venous Sinus Thrombosis after “COVID-19 Vaccine AstraZeneca” Exposure
Journal of Clinical Medicine. 2021;10(8):1599-1599
Background: As of 8 April 2021, a total of 2 9 million people have died with or from the coronavirus infection causing COVID-19 (Corona Virus Disease 2019) On 29 January 2021, the European Medicines Agency (EMA) approved a COVID-19 vaccine developed by Oxford University and AstraZeneca (AZD1222, ChAdOx1 nCoV-19, COVID-19 vaccine AstraZeneca, Vaxzevria, Covishield) While the vaccine prevents severe course of and death from COVID-19, the observation of pulmonary, abdominal, and intracranial venous thromboembolic events has raised concerns Objective: To describe the clinical manifestations and the concerning management of patients with cranial venous sinus thrombosis following first exposure to the “COVID-19 vaccine AstraZeneca” Methods: Patient files, laboratory findings, and diagnostic imaging results, and endovascular interventions of three concerning patients were evaluated in retrospect Results: Three women with intracranial venous sinus thrombosis after their first vaccination with “COVID-19 vaccine AstraZeneca” were encountered Patient #1 was 22 years old and developed headaches four days after the vaccination On day 7, she experienced a generalized epileptic seizure Patient #2 was 46 years old She presented with severe headaches, hemianopia to the right, and mild aphasia 13 days after the vaccination MRI showed a left occipital intracerebral hemorrhage Patient #3 was 36 years old and presented 17 days after the vaccination with acute somnolence and right-hand hemiparesis The three patients were diagnosed with extensive venous sinus thrombosis They were managed by heparinization and endovascular recanalization of their venous sinuses They shared similar findings: elevated levels of D-dimers, platelet factor 4 antiplatelet antibodies, corona spike protein antibodies, combined with thrombocytopenia Under treatment with low-molecular-weight heparin, platelet counts normalized within several days Conclusion: Early observations insinuate that the exposure to the “COVID-19 vaccine AstraZeneca” might trigger the expression of antiplatelet antibodies, resulting in a condition with thrombocytopenia and venous thrombotic events (e g , intracranial venous sinus thrombosis) These patients’ treatment should address the thrombo-embolic manifestations, the coagulation disorder, and the underlying immunological phenomena
SARS-CoV-2 receptor binding domain-specific antibodies activate platelets with features resembling the pathogenic antibodies in heparin-induced thrombocytopenia
Research Square. 2021
Severe COVID-19 is associated with unprecedented thromboembolic complications. We found that hospitalized COVID-19 patients develop immunoglobulin Gs (IgGs) that recognize a complex consisting of platelet factor 4 and heparin similar to those developed in heparin-induced thrombocytopenia and thrombosis (HIT), however, independent of heparin exposure. These antibodies activate platelets in the presence of TLR9 stimuli, stimuli that are prominent in COVID-19. Strikingly, 4 out of 42 antibodies cloned from IgG1 (+) RBD-binding B cells could activate platelets. These antibodies possessed, in the heavy-chain complementarity-determining region 3, an RKH or Y (5) motif that we recently described among platelet-activating antibodies cloned from HIT patients. RKH and Y (5) motifs were prevalent among published RBD-specific antibodies, and 3 out of 6 such antibodies tested could activate platelets. Features of platelet activation by these antibodies resemble those by pathogenic HIT antibodies. B cells with an RKH or Y (5) motif were robustly expanded in COVID-19 patients. Our study demonstrates that SARS-CoV-2 infection drives the development of a subset of RBD-specific antibodies that can activate platelets and have activation properties and structural features similar to those of the pathogenic HIT antibodies.
Cerebral Venous Sinus Thrombosis and Thrombotic Events After Vector-Based COVID-19 Vaccines: A Systematic Review and Meta-analysis
BACKGROUND AND OBJECTIVES There is accumulating evidence supporting an association between the "thrombosis and thrombocytopenia syndrome" (TTS) and adenovirus vector-based vaccines against SARS-CoV-2. Yet, TTS and TTS-associated cerebral venous sinus thrombosis (CVST) remain poorly characterized. We aim to systematically evaluate the proportion of CVST among TTS cases and assess its characteristics and outcomes. METHODS We performed a systematic review and meta-analysis of clinical trials, cohorts, case series and registry-based studies with the aim to assess (1) the pooled mortality rate of CVST, TTS-associated CVST, and TTS and (2) the pooled proportion of patients with CVST among patients with any thrombotic event and TTS. Secondary outcomes comprised clinical characteristics of patients with post-vaccination thrombotic event. This meta-analysis is reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and was written according to the Meta-analysis of Observational Studies in Epidemiology proposal. RESULTS Sixty-nine studies were included in the qualitative analysis comprising 370 patients with CVST out of 4182 patients with any thrombotic event associated with SARS-CoV-2 vector-based vaccine administration. Twenty-three studies were further included in quantitative meta-analysis. Among TTS cases, the pooled proportion of CVST was 51% (95%CI:36-66%; I(2)=61%). TTS was independently associated with a higher likelihood of CVST, when compared to non-TTS patients with thrombotic events after vaccination (OR:13.8; 95%CI:2.0-97.3; I(2)=78%). The pooled mortality rates of TTS and TTS-associated CVST were 28% (95%CI:21-36%) and 38% (95%CI:27-49%), respectively. Thrombotic complications developed within 2 weeks of exposure to vector-based SARS-CoV-2 vaccines (mean interval:10 days; 95%CI:8-12) and affected predominantly women (69%, 95%CI:60-77%), under the age of 45, even in the absence of pro-thrombotic risk factors. DISCUSSION Approximately one half of TTS cases present with CVST, while almost one third of TTS patients do not survive. Further research is required to identify independent predictors of TTS following adenovirus vector-based vaccination. REGISTRATION The pre-specified study protocol has been registered in the International Prospective Register of Ongoing Systematic Reviews PROSPERO (CRD42021250709).
Immune Thrombocytopenia Secondary to COVID-19: a Systematic Review
SN Compr. Clin. Med.. 2020
Immune thrombocytopenia, often known as immune thrombocytopenic purpura (ITP), has emerged as an important complication of COVID-19. A systematic review was done to analyze the clinical profile and outcomes in a total of 45 cases of new-onset ITP in COVID-19 patients described in literature until date. A comprehensive approach is essential for diagnosing COVID-19-associated ITP after excluding several concomitant factors that can cause thrombocytopenia in COVID-19. Majority of ITP cases (71%) were found to be elderly (> 50 years) and 75% cases had moderate-to-severe COVID-19. Three patients (7%) were in the pediatric age group. Reports of ITP in asymptomatic COVID-19 patients (7%) underscore the need for COVID-19 testing in newly diagnosed patients with ITP irrespective of COVID-19 symptoms amid this pandemic. ITP onset occurred in 20% cases 3 weeks after onset of COVID-19 symptoms, with many reports after clinical recovery. SARS-CoV-2-mediated immune thrombocytopenia can be attributed to the underlying immune dysregulation, susceptibility mutations in SOCS 1, and other mechanisms, including molecular mimicry, cryptic antigen expression, and epitope spreading. No bleeding manifestations were reported in 31% cases at diagnosis. Severe life-threatening bleeding was uncommon. One case of mortality was attributed to intracranial hemorrhage. Secondary Evans syndrome was diagnosed in one case. Good initial response to short course of glucocorticoids and intravenous immunoglobulin has been found with the exception of delayed lag response in one case. Thrombopoietin receptor agonist usage as a second-line agent has been noted in few cases for short duration with no adverse events. In the relatively short follow-up period, four relapses of ITP were found.
The Prognostic Value of Thrombocytopenia in COVID-19 Patients; a Systematic Review and Meta-Analysis
Archives of Academic Emergency Medicine. 2020;8(1):e75
INTRODUCTION Multiple lines of evidence have attested that decreased numbers of platelets may serve as a surrogate marker for poor prognosis in a wide range of infectious diseases. Thus, to provide a well-conceptualized viewpoint demonstrating the prognostic value of thrombocytopenia in COVID-19, we performed a meta-analysis of pertinent literature. METHODS The keywords "platelet" OR "thrombocytopenia" AND "COVID-19" OR "coronavirus 2019" OR "2019-nCoV" OR "SARS-CoV-2" were searched in National Library of Medicine Medline/PubMed and Scopus between December 30, 2019, and May 9, 2020 in English without any restriction. The initial search results were first screened by title and abstract, and then full texts of relevant articles representing information on the platelet count (main outcome) with a clinically validated deﬁnition of COVID-19 severity were ﬁnally selected. To assess the existence of bias in the included studies, the funnel plot and egger plot along with egger tests were used. Also, the heterogeneity among the included studies was tested using the Chi-square test. RESULTS The results of our meta-analysis of 19 studies, totaling 3383 COVID-19 patients with 744 (21.9%) severe cases, revealed that non-severe cases have a significantly higher number of platelets and showed that the probability of the emergence of thrombocytopenia is significantly higher in the severe cases with the pooled mean difference of -21.5 (%95 CI: -31.57, -11.43). CONCLUSION Decreased number of platelets more commonly associates with severe COVID-19; however, whether the emergence of thrombocytopenia may result in diseases severity or the severity of the disease may decrease platelets, is open to debate.
Mechanism of thrombocytopenia in COVID-19 patients
Annals of Hematology. 2020;:1-4
Since December 2019, a novel coronavirus has spread throughout China and across the world, causing a continuous increase in confirmed cases within a short period of time. Some studies reported cases of thrombocytopenia, but hardly any studies mentioned how the virus causes thrombocytopenia. We propose several mechanisms by which coronavirus disease 2019 causes thrombocytopenia to better understand this disease and provide more clinical treatment options.
Thrombocytopenia Is Associated with COVID-19 Severity and Outcome: An Updated Meta-Analysis of 5637 Patients with Multiple Outcomes
Laboratory Medicine. 2020
The COVID-19 pandemic is persistent worldwide. A prior meta-analysis suggested the association of thrombocytopenia (TCP) with more severe COVID-19 illness and high mortality. Considering newly published studies, we updated the previous meta-analysis to confirm and explain the association of TCP with COVID-19 severity and multiple outcomes. Twenty-four studies with 5637 patients with COVID-19 were included in this study. The weighted incidence of TCP in COVID-19 was 12.4% (95% confidence interval [CI], 7.9%-17.7%). Data synthesis showed that the platelet number was lower in patients with either more severe illness or poor outcomes and even lower in nonsurvivors, with weighted mean differences of -24.56 × 109/L, -22.48 × 109/L, and -49.02 × 109/L, respectively. The meta-analysis of binary outcomes (with and without TCP) indicated the association between TCP and 3-fold enhanced risk of a composite outcome of intensive care unit admission, progression to acute respiratory distress syndrome, and mortality (odds ratio [OR], 3.49; 95% CI, 1.57-7.78). Subgroup analysis by endpoint events suggested TCP to be significantly associated with mortality (OR, 7.37; 95% CI, 2.08-26.14). Overall, the present comprehensive meta-analysis indicated that approximately 12% of hospitalized patients with COVID-19 have TCP, which also represents a sign of more severe illness and poor outcomes.