Reports Of Thromboembolic Events Research Articles

Thromboembolic events after Ad.26.COV2.S COVID-19 vaccine: Reports to the Vaccine Adverse Event Reporting System.

PurposeThe Food and Drug Administration (FDA) has identified a potential safety concern for thromboembolic events (TEEs) after Ad.26.COV2.S COVID‐19 Vaccine. We sought to characterize the frequency, severity, type, and anatomic location of TEEs reported to the Vaccine Adverse Event Reporting System (VAERS) following Ad.26.COV2.S.MethodsReports of TEEs after Ad.26.COV2.S were identified in VAERS, and demographics, clinical characteristics, and relevant medical history were summarized. For a subset of reports, physicians reviewed available medical records and evaluated clinical presentation, diagnostic evaluation, risk factors, and treatment. The crude reporting rate of TEEs was estimated based on case counts in VAERS and vaccine administration data.ResultsThrough February 28, 2022, FDA identified 3790 reports of TEEs after Ad.26.COV2.S. Median age was 56 years, and 1938 individuals (51.1%) were female. Most reports, 2892 (76.3%), were serious, including 421 deaths. Median time to onset was 12 days post‐vaccination. Obesity and ischemia were among the most commonly documented risk factors. Thrombocytopenia (platelet count less than 150 000/μl) was documented in 63 records (11.5%) and anti‐platelet 4 antibodies in 25 (4.6%). Medical review identified cases of severe clot burden (e.g., bilateral, saddle, or other massive pulmonary embolism with or without cor pulmonale; lower extremity thrombus involving the external iliac, common femoral, popliteal, posterior tibial, peroneal, and gastrocnemius veins). The crude reporting rate was ~20.7 cases of TEE per 100 000 doses of Ad.26.COV2.S administered.ConclusionsLife‐threatening or fatal TEEs have been reported after Ad.26.COV2.S, including bilateral massive pulmonary embolism or other severe clot burden.

Increased neutralization of SARS-CoV-2 Delta variant after heterologous ChAdOx1 nCoV-19/BNT162b2 versus homologous BNT162b2 vaccination

SummaryHeterologous SARS-CoV-2 vaccine approaches with a second mRNA-based vaccine have been favored in the recommendations of many countries over homologous vector-based ChAdOx1 nCoV-19 vaccination after reports of thromboembolic events and lower efficacy of this regimen. In the middle of 2021, the SARS-CoV-2 Delta variant of concern (VoC) has become predominant in many countries worldwide. Data addressing the neutralization capacity of a heterologous ChAdOx1 nCoV-19/mRNA-based vaccination approach against the Delta VoC in comparison to the widely used homologous mRNA-based vaccine regimen are limited. Here, we compare serological immune responses of a cohort of ChAdOx1 nCoV-19/BNT162b2-vaccinated participants with those of BNT162b2/BNT162b2 vaccinated ones and show that neutralization capacity against the Delta VoC is significantly increased in sera of ChAdOx1 nCoV-19/BNT162b2-vaccinated participants. This overall effect can be attributed to ChAdOx1 nCoV-19/BNT162b2-vaccinated women, especially those with more severe adverse effects leading to sick leave following second immunization.

Ischemic stroke after AstraZeneca (Covid-19) vaccination.

Vaccination against SARS-COV-2 is considered an effective preventive strategy to halt COVID-19 pandemic. Reports of thromboembolic events in vaccine recipients has jolted some of the European countries to pause the vaccination process temporarily. It is still unclear whether the events are actually due to the vaccines or it is just a coincidence. The gravity of events particularly in young and previously normal patients merits further research to reach some conclusion. Here we present a similar case who sustained ischemic stroke shortly after receiving the first dose of his vaccine.

Immune responses against SARS-CoV-2 variants after heterologous and homologous ChAdOx1 nCoV-19/BNT162b2 vaccination

Currently approved viral vector-based and mRNA-based vaccine approaches against coronavirus disease 2019 (COVID-19) consider only homologous prime-boost vaccination. After reports of thromboembolic events, several European governments recommended using AstraZeneca’s ChAdOx1-nCov-19 (ChAd) only in individuals older than 60 years, leaving millions of already ChAd-primed individuals with the decision to receive either a second shot of ChAd or a heterologous boost with mRNA-based vaccines. However, such combinations have not been tested so far. We used Hannover Medical School’s COVID-19 Contact Study cohort of healthcare professionals to monitor ChAd-primed immune responses before and 3 weeks after booster with ChAd (n = 32) or BioNTech/Pfizer’s BNT162b2 (n = 55). Although both vaccines boosted prime-induced immunity, BNT162b2 induced significantly higher frequencies of spike-specific CD4+ and CD8+ T cells and, in particular, high titers of neutralizing antibodies against the B.1.1.7, B.1.351 and P.1 variants of concern of severe acute respiratory syndrome coronavirus 2.

Thromboembolic events associated with immune checkpoint inhibitors: A real-world study of data from the food and drug administration adverse event reporting system (FAERS) database

BackgroundAlthough there have been a few studies reporting thromboembolic events (TEEs) in patients treated with immune checkpoint inhibitors (ICIs), the detailed profile of the TEEs and the prothrombotic effects of ICIs remain mostly unknown. MethodsData from January 2004 to December 2019 in the FAERS database were retrieved. We investigated the clinical characteristics of the TEEs and conducted disproportionality analysis by using reporting odds ratios (ROR) to compare ICIs with the full database and other anti-cancer agents. ResultsWe identified 1855 reports of TEEs associated with ICIs. Affected patients tended to be male (59.68%) and older than 65 (47.12%). The case-fatality rate of the reported TEEs was high (38%). The median time to onset (TTO) of all cases was 42 (interquartile range [IQR] 15–96) days and the median TTO of fatal cases (31 [IQR 13–73] days) was significantly shorter than non-fatal cases (50 [IQR 20–108] days, p = 0.000002). ICIs showed increased risks of VTE (ROR 2.81, 95% CI 2.69–2.95) and ATE (ROR 1.44, 95% CI 1.37–1.52) compared with the full database. Compared with protein kinase inhibitors, ICIs showed an increased risk of VTE (ROR 1.23, 95% CI 1.17–1.29), but only anti-PD-L1 showed an increased risk of cerebral ATE (ROR 1.38, 95% CI 1.08–1.76). Compared with chemotherapy, ICIs showed an increased risk of PE (ROR 1.14, 95% CI 1.07–1.21). ConclusionsOur study suggested ICIs tend to increase risks of VTE and ATE. The poor clinical outcome and early onset of these events should attract clinical attention.

Thrombosis with Thrombocytopenia Syndrome associated with viral vector COVID-19 vaccines

On March 11 2021, the European Medical Agency highlighted two relevant issues, after the decision by the Danish Health Authority to temporarily suspend its vaccination campaign with Vaxzevria (the COVID-19 vaccine by AstraZeneca) following the reports of thromboembolic events (TE) associated with the administration of the vaccine: 1) lack of evidence of a cause/effect relationship between the vaccine and TE; 2) the number of reported TE (30 in around 5,000,000 vaccinated people) was no higher than that expected [1].

Safety and Efficacy of Enoxaparin in Pregnancy: A Systematic Review and Meta-Analysis

IntroductionInternational guidelines support the use of low molecular weight heparins for the treatment of thromboembolism and thromboprophylaxis during pregnancy. However, evidence of the benefit and harm associated with specific low molecular weight heparins such as enoxaparin is dated. No current systematic review and meta-analysis describing the safety and efficacy of enoxaparin for thromboembolism and thromboprophylaxis during pregnancy exists.MethodsPubMed, Embase, and Cochrane databases were searched on August 17, 2018 for clinical trials or observational studies in pregnant women receiving enoxaparin; patients with a prosthetic heart valve were excluded. Risk ratios (RR) with 95% confidence intervals (CI) were calculated using a random effects model, and heterogeneity was measured using the I2 statistic.ResultsOf the 485 records identified in the search, 24 studies published clinical trials, and observational studies were found dating back to 2000. Only one observational cohort and one randomized control trial focused on the use of enoxaparin for thromboprophylaxis and therefore efficacy was not assessed; the other studies included women with recurrent pregnancy loss (15 studies), history of placental vascular complications (five studies), and recurrent in vitro fertilization failure (two studies) and were therefore analyzed in terms of safety only. Bleeding events were non-significantly more often reported for enoxaparin compared to untreated controls (RR 1.35 [0.88–2.07]) but less often reported for enoxaparin versus aspirin (RR 0.93 [0.62–1.39]); thromboembolic events, thrombocytopenia, and teratogenicity were rarely reported events; in patients with a history of recurrent pregnancy loss, encouragingly the rates of pregnancy loss were significantly lower for enoxaparin compared to untreated controls (RR 0.58 [0.34–0.96]) and enoxaparin + aspirin versus aspirin alone (RR 0.42 [0.32–0.56]) as well as observably lower for enoxaparin versus aspirin alone (RR 0.39 [0.15–1.01]), though significant heterogeneity was observed (I2 > 60).ConclusionLiterature on the efficacy and safety of enoxaparin for thromboembolism and thromboprophylaxis remains scanty, and therefore efficacy was not assessed; in terms of safety, when including other indications for enoxaparin in pregnancy, we found that enoxaparin was associated with significantly lower complications than aspirin. Given differences in study design and study heterogeneity, pregnancy loss results should be interpreted with caution. Moreover, reports of thromboembolic events, thrombocytopenia, and congenital malformations were rare.FundingSanofi.Electronic supplementary materialThe online version of this article (10.1007/s12325-019-01124-z) contains supplementary material, which is available to authorized users.

A randomized placebo-controlled trial of preoperative tranexamic acid among women undergoing elective cesarean delivery.

To study the efficacy and safety of preoperative intravenous tranexamic acid to reduce blood loss during and after elective lower-segment cesarean delivery. A single-blind, randomized placebo-controlled study was undertaken of women undergoing elective lower-segment cesarean delivery of a full-term singleton pregnancy at a center in Cairo, Egypt, between November 2013 and November 2014. Patients were randomly assigned (1:1) using computer-generated random numbers to receive either 1g tranexamic acid or 5% glucose 15 minutes before surgery. Preoperative and postoperative complete blood count, hematocrit values, and maternal weight were used to calculate the estimated blood loss (EBL) during cesarean, which was the primary outcome. Analyses included women who received their assigned treatment, whose surgery was 90 minutes or less, and who completed follow-up. Analyses included 100 women in each group. Mean EBL was significantly higher in the placebo group (700.3 ± 143.9 mL) than in the tranexamic acid group (459.4 ±7 5.4 mL; P<0.001). Only six women, all in the placebo group, experienced an EBL of more than 1000 mL. There were no reports of thromboembolic events up to 4 weeks postoperatively. Preoperative administration of tranexamic acid safely reduces blood loss during elective lower-segment cesarean delivery. Australian New Zealand Clinical Trials Registry:ACTRN12615000312549.

Thromboembolic events associated with immunoglobulin treatment

Due to an increasing number of reported thromboembolic events (TEE) after the administration of one intravenous immunoglobulin (IVIG) and one subcutaneous immunoglobulin (SCIG), pharmacovigilance and laboratory data were collected to analyse the root cause and assess the reporting frequency of TEEs for various IG products. Paul-Ehrlich-Institut retrospectively analysed 228 reports of TEEs associated with six different IG products and estimated annual TEE-reporting rates based on worldwide sale figures over a period of 6years (2006-2011). In addition, non-activated partial thromboplastin time (NAPTT) testing was performed to capture pro-coagulant potential of six IG products (four IVIG and two SCIG). For three IVIGs, the drug-related TEE-reporting rates remained stable from 2006 to 2011 (0-0·83 cases per 1000kg IVIG distributed). In contrast, the TEE rate of one IVIG increased significantly from 0·33 cases in 2006 to nearly nine cases in 2010 (P<0·001). The NAPTT testing of IG products with a low TEE rate revealed a NAPTT time >200s and a NAPTT ratio >0·8, whereas TEE-associated batches of IG products with an increased TEE rate had a NAPTT ratio <0·8. After modifications of manufacturing processes, a normalization of NAPTT results and a decrease in TEE rates could be demonstrated.

The use of recombinant activated factor VII in neurosurgery

Background Bleeding complications in neurosurgery often take alarming proportions without major hemodynamic effect or impairment of coagulation physiology because severe neurologic deficits are to be expected. Any measures used to stabilize or normalize coagulation are therefore of great interest. Administration of packed red cells, fresh frozen plasma, and platelet concentrates is associated with volume loading, which is suspected to multiply the secondary brain damage, for example, by the development of an edema. In this respect, the administration of rFVIIa may develop into a new option associated with low-volume administration. Case Descriptions We report on 5 neurosurgical patients to whom rFVIIa was given at doses of 51 to 202 μg/kg of body weight for the treatment of severe intraoperative bleeding (n = 3) or as prophylaxis of bleeding (n = 2). The operation was completed successfully in all patients after administration of rFVIIa, with stabilization of the coagulation status. Conclusion Therefore, reported cases constitute an approach in treatment and prophylaxis of bleeding complications in neurosurgery. There are reports of thromboembolic events in use of rFVIIa, particularly in unlabeled use. But according to our findings and current literature, there is no evidence of higher risk of thromboembolic adverse events in treatment with rFVIIa. However, the number of patients presented does not allow any final assessment to be made as to whether the properties of rFVIIa are of particular benefit for neurosurgical patients. Further studies with appropriate study design are required to verify effects observed in this investigation.

Atrial Fibrillation and Thromboembolism

Atrial Fibrillation and Thromboembolism