COVID-19 vaccine-induced immune thrombotic thrombocytopenia: A review of the potential mechanisms and proposed management

With over 600 million coronavirus (COVID-19) vaccine doses administered globally, adverse events are constantly monitored. Recently however, reports of thrombosis and thrombocytopenia following vaccination with the ChAdOx1 nCoV-19 vaccine have emerged. This paper aims to review the available literature and guidelines pertaining to vaccine-induced immune thrombotic thrombocytopenia (VITT) and the proposed guidelines, while offering a potential approach that unifies the available evidence. While the risk of VITT remains extremely low and the benefits outweigh the risks, experimental studies are needed to clarify the pathophysiology behind VITT and possibly decrease the risk of thrombosis and other adverse events occurring. However, treatment should not be delayed in suspected cases, and IV immunoglobulin and non-heparin anticoagulation should be initiated.

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Bleeding and Thrombotic Adverse Events in Hospitalized Patients Under Empiric Treatment for Suspected Heparin-Induced Thrombocytopenia While Awaiting Confirmatory Testing

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029621996473 ◽

2021 ◽

Vol 27 ◽

pp. 107602962199647

Author(s):

Kaitlyn C. Dykes ◽

Cassandra A. Johnson ◽

Jerald Z. Gong ◽

Steven E. McKenzie ◽

Holleh D. Husseinzadeh

Keyword(s):

Adverse Events ◽

Watchful Waiting ◽

Prediction Models ◽

Bleeding Event ◽

Retrospective Chart Review ◽

Bleeding Risk ◽

Heparin Induced Thrombocytopenia ◽

Empiric Treatment ◽

Heparin Anticoagulation ◽

Management Groups

Empiric management in suspected heparin-induced thrombocytopenia (HIT) is challenging due to imperfect prediction models, latency while awaiting test results and risks of empiric therapies. When there is high clinical suspicion for HIT, cessation of heparin and empiric non-heparin anticoagulation with FDA-approved argatroban is recommended. Alternatively off-label fondaparinux or watchful waiting have been utilized in clinical practice. Outcomes of patients empirically managed for HIT have not been compared directly in clinical trials and patients that ultimately do not have HIT are often overlooked. Clinicians need studies investigating empiric management to guide decision making in suspected HIT. In this study, adverse events (AE) were categorized and compared in patients being evaluated for HIT while undergoing empiric management by non-heparin anticoagulation with argatroban or fondaparinux, both at therapeutic or reduced doses, or watchful waiting with or without heparin. AE were defined as new thrombosis confirmed on imaging or new bleeding event after HIT was first suspected. A retrospective chart review of 312 patients tested for HIT at an academic hospital was conducted. 170 patients met inclusion criteria. Patients were excluded if the 4Ts score was < 4. The 4Ts score is a pretest probability for HIT based on thrombocytopenia degree, timing, alternative causes and presence of thrombosis. Included patients were divided according to management groups and compared with logistic regression analysis. Bleeding risk significantly differed between management groups (p = 0.002). Despite adjustment for bleeding risk, fondaparinux was associated with increased AE, (p = 0.03, OR = 5.81), while argatroban was not. There was no difference in AE based on time to initiation of empiric treatment and no advantage to reduced dosing with either anticoagulant. These findings challenge assumptions surrounding empiric HIT management.

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Effects of Probiotics on Diabetic Nephropathy: A Systematic Review

Current Clinical Pharmacology ◽

10.2174/1574884715666200303112753 ◽

2020 ◽

Vol 15 (3) ◽

pp. 234-242 ◽

Cited By ~ 1

Author(s):

Eugenia Vlachou ◽

Anastasia Ntikoudi ◽

Ourania Govina ◽

Maria Lavdaniti ◽

Nikolaos Kotsalas ◽

...

Keyword(s):

Systematic Review ◽

Diabetic Nephropathy ◽

Adverse Events ◽

Randomized Controlled Trials ◽

Positive Impact ◽

Experimental Studies ◽

Controlled Trials ◽

Extensive Literature ◽

Probiotic Supplementation ◽

Randomized Controlled

Background: Diabetic Nephropathy is a frequent complication of diabetes mellitus due to functional and structural modifications in multiple kidney compartments. Probiotics have risen lately as a forthcoming therapeutic intervention but they have not been systematically evaluated in diabetic nephropathy so far. The aim of this systematic review was to evaluate randomized controlled trials and experimental studies assessing the effect of probiotic supplements on diabetic nephropathy. Methods: An extensive literature search was conducted through electronic databases (PubMed, Scopus, Cinahl and Medline) with the Medical Subject Headings and entry terms of “diabetic nephropathy”, “diabetic renal disease” and “probiotics”. The search yielded 116 results, 9 of which met the inclusion criteria for this systematic review. Results: Most of the microorganisms used in the studies belonged to the Lactobacillus and Bifidobacterium genus. The dosage ranged from 2×107 to 6×1010 CFU/ g. The form of the probiotics varied across the studies (capsules, sachets, soy milk, kefir and honey). The majority of the studies demonstrated the benefits of probiotic supplementation on the reduction of inflammation, oxidative stress and on the amelioration of renal function biomarkers in subjects with diabetic nephropathy. No major gastrointestinal adverse events were observed during the intervention time with probiotics. Conclusion: : Findings of this systematic review demonstrate the positive impact of probiotics on Diabetic Nephropathy without any major adverse events. Moreover, future larger randomized controlled trials with bigger samples and longer follow-up time are deemed necessary for further valid results on the effectiveness of probiotic supplementation on Diabetic Nephropathy.

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Adverse Events of Mind-Body Interventions in Children: A Systematic Review

Children ◽

10.3390/children8050358 ◽

2021 ◽

Vol 8 (5) ◽

pp. 358

Author(s):

Meagan Lyszczyk ◽

Mohammad Karkhaneh ◽

Kerri Kaiser Gladwin ◽

Martha Funabashi ◽

Liliane Zorzela ◽

...

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Safety Assessment ◽

Experimental Studies ◽

Limited Knowledge ◽

Grade 3 ◽

Study Designs

Mind-body interventions (MBIs) are one of the top ten complementary approaches utilized in pediatrics, but there is limited knowledge on associated adverse events (AE). The objective of this review was to systematically review AEs reported in association with MBIs in children. In this systematic review the electronic databases MEDLINE, Embase, CINAHL, CDSR, and CCRCT were searched from inception to August 2018. We included primary studies on participants ≤ 21 years of age that used an MBI. Experimental studies were assessed for whether AEs were reported on or not, and all other study designs were included only if they reported an AE. A total of 441 were included as primary pediatric MBI studies. Of these, 377 (85.5%) did not explicitly report the presence/absence of AEs or a safety assessment. There were 64 included studies: 43 experimental studies reported that no AE occurred, and 21 studies reported AEs. There were 37 AEs found, of which the most serious were grade 3. Most of the studies reporting AEs did not report on severity (81.0%) or duration of AEs (52.4%). MBIs are popularly used in children; however associated harms are often not reported and lack important information for meaningful assessment.

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COVID-19 Vaccine-Related Thrombosis: A Systematic Review and Exploratory Analysis

Frontiers in Immunology ◽

10.3389/fimmu.2021.729251 ◽

2021 ◽

Vol 12 ◽

Author(s):

Clio Bilotta ◽

Giulio Perrone ◽

Valeria Adelfio ◽

Giovanni Francesco Spatola ◽

Maria Laura Uzzo ◽

...

Keyword(s):

Platelet Count ◽

Adverse Events ◽

Viral Vectors ◽

Descriptive Analysis ◽

Experimental Studies ◽

World Health ◽

Common Symptom ◽

Pathophysiological Mechanisms ◽

Critical Issues ◽

Health Organization

IntroductionThe World Health Organization declared the coronavirus disease 2019 (COVID-19) pandemic on March 11, 2020. Two vaccine types were developed using two different technologies: viral vectors and mRNA. Thrombosis is one of the most severe and atypical adverse effects of vaccines. This study aimed to analyze published cases of thrombosis after COVID-19 vaccinations to identify patients’ features, potential pathophysiological mechanisms, timing of appearance of the adverse events, and other critical issues.Materials and MethodsWe performed a systematic electronic search of scientific articles regarding COVID-19 vaccine-related thrombosis and its complications on the PubMed (MEDLINE) database and through manual searches. We selected 10 out of 50 articles from February 1 to May 5, 2021 and performed a descriptive analysis of the adverse events caused by the mRNA-based Pfizer and Moderna vaccines and the adenovirus-based AstraZeneca vaccine.ResultsIn the articles on the Pfizer and Moderna vaccines, the sample consisted of three male patients with age heterogeneity. The time from vaccination to admission was ≤3 days in all cases; all patients presented signs of petechiae/purpura at admission, with a low platelet count. In the studies on the AstraZeneca vaccine, the sample consisted of 58 individuals with a high age heterogeneity and a high female prevalence. Symptoms appeared around the ninth day, and headache was the most common symptom. The platelet count was below the lower limit of the normal range. All patients except one were positive for PF4 antibodies. The cerebral venous sinus was the most affected site. Death was the most prevalent outcome in all studies, except for one study in which most of the patients remained alive.DiscussionVaccine-induced thrombotic thrombocytopenia (VITT) is an unknown nosological phenomenon secondary to inoculation with the COVID-19 vaccine. Several hypotheses have been formulated regarding its physiopathological mechanism. Recent studies have assumed a mechanism that is assimilable to heparin-induced thrombocytopenia, with protagonist antibodies against the PF4–polyanion complex. Viral DNA has a negative charge and can bind to PF4, causing VITT. New experimental studies have assumed that thrombosis is related to a soluble adenoviral protein spike variant, originating from splicing events, which cause important endothelial inflammatory events, and binding to endothelial cells expressing ACE2.ConclusionFurther studies are needed to better identify VITT’s pathophysiological mechanisms and genetic, demographic, or clinical predisposition of high-risk patients, to investigate the correlation of VITT with the different vaccine types, and to test the significance of the findings.

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3-D reconstruction and analysis of mammalian mitotic spindle structure

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100123295 ◽

1992 ◽

Vol 50 (1) ◽

pp. 578-579

Author(s):

Kent McDonald ◽

David Mastronarde ◽

Rubai Ding ◽

Eileen O'Toole ◽

J. Richard McIntosh

Keyword(s):

Cross Sections ◽

Mitotic Spindle ◽

Experimental Studies ◽

Video Camera ◽

Three Dimensions ◽

Mitotic Spindles ◽

Black And White ◽

Reconstruction Methods ◽

Spindle Structure ◽

Tissue Culture Line

Mammalian spindles are generally large and may contain over a thousand microtubules (MTs). For this reason they are difficult to reconstruct in three dimensions and many researchers have chosen to study the smaller and simpler spindles of lower eukaryotes. Nevertheless, the mammalian spindle is used for many experimental studies and it would be useful to know its detailed structure.We have been using serial cross sections and computer reconstruction methods to analyze MT distributions in mitotic spindles of PtK cells, a mammalian tissue culture line. Images from EM negatives are digtized on a light box by a Dage MTI video camera containing a black and white Saticon tube. The signal is digitized by a Parallax 1280 graphics device in a MicroVax III computer. Microtubules are digitized at a magnification such that each is 10-12 pixels in diameter.

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