Incidence of thromboembolic events in non-small cell lung cancer patients treated with immune checkpoint inhibitors: A systematic review and meta-analysis.

ABSTRACT: The incidence of thromboembolic events (TEs) in non-small cell lung cancer (NSCLC) patients treated with immune checkpoint inhibitors (ICIs) has rarely been reported. The MEDLINE, EMBASE, and the Cochrane Library databases were searched. The primary outcome was the incidence of TEs, and the secondary outcome was the relationship between TEs and overall survival (OS) following ICI therapy. A subgroup analysis of TE incidents was performed according to the TE type and combination regimens. The I2 statistic was used to determine the heterogeneity, and funnel plots and Egger's test were used to assess publication bias. A total of 16,602 patients with NSCLC in 63 experimental arms were included in the analysis. The rate of TEs ranged from 0.1% to 13.8%, and the pooled overall incidence of all-grade TEs was 3% (95% confidence interval [CI], 2%-4%). The pooled rate of high-grade TEs was 1% (95% CI, 1%-2%). The venous and arterial TE rates were 3% (95% CI, 2%-4%) and 1% (95% CI, 1%-2%), respectively. Patients who received immunotherapy + chemoradiotherapy had the highest incidence of TEs (7%). The TE pooled rate was higher in patients treated with combined ICIs than in those treated with mono ICIs (4% vs. 2%). The OS was lower in patients with TEs than in those without TEs (hazard ratio, 1.4; 95% CI, 1.02%-1.92%). The incidence of TEs in NSCLC patients treated with ICIs was reasonable. Nonetheless, clinicians must be aware of potential thrombotic complications and treat them promptly.

Left atrial appendage occlusion: Percutaneous and surgical approaches in everyday practice.

Prophylactic left atrial appendage occlusion has been suggested as a means of reducing cardioembolism risk in patients with atrial fibrillation. Its clinical benefits have been discussed together with potential endocrine or hemodynamic adverse effects, with conflicting conclusions. We aimed to provide a thorough overview of the current literature and a recommendation for daily clinical decision-making. A comprehensive Medline search through PubMed was conducted to search for relevant articles, which were further filtered using the title and abstract. Sixty-five articles were selected as relevant to the topic. Concomitant left atrial appendage occlusion during cardiac surgery for other reasons is effective in terms of thromboembolism risk reduction in patients with a history of atrial fibrillation and higher CHA2DS2-VASc scores. Surgical occlusion is safe, and epicardial closure techniques are preferred. Thoracoscopic and transcatheter techniques are also feasible, and the individual treatment choice must be tailored to the patient. The concerns about endocrine imbalance or risk of heart failure after occlusion are not supported by evidence. Current evidence is conflicting with regard to hemodynamic consequences of appendage occlusion.

Thromboembolic risk of carfilzomib or bortezomib in combination with lenalidomide and dexamethasone for newly diagnosed multiple myeloma: A comparative systematic review and meta-analysis.

Thrombosis represents a frequent and potentially severe complication in individuals diagnosed with multiple myeloma (MM). These events can be driven by both the disease as well as the therapies themselves. Overall, available evidence is inconclusive about the differential thrombogenicity of carfilzomib/lenalidomide/dexamethasone (KRd) and bortezomib/lenalidomide/dexamethasone (VRd). This meta-analysis compares the risk for venous thromboembolism (VTE; including deep venous thrombosis and pulmonary embolism) and arterial thromboembolism (ATE; including myocardial infarction and ischemic stroke) with KRd versus VRd as primary therapy for newly diagnosed MM (NDMM). Out of 510 studies identified after deduplication, one randomized controlled trial and five retrospective cohort studies were included. We analyzed 2304 patients (VRd: 1380; KRd: 924) for VTE events and 2179 patients (VRd: 1316; KRd: 863) for ATE events. Lower rates of VTE were observed in the VRd group when compared with the KRd group (6.16% vs. 8.87%; odds ratio [OR], 0.53; 95% confidence interval [CI], 0.32-0.88; p = .01). Both treatment groups exhibited minimal ATE incidence, with no significant difference between them (0.91% vs. 1.16%; OR, 1.01; 95% CI, 0.24-4.20; p = .99). In view of potential biases from retrospective studies, heterogeneity of baseline population characteristics, and limited access to patient-level data (e.g., VTE risk stratification and type of thromboprophylaxis regimen used) inherent to this meta-analysis, additional research is warranted to further validate our findings and refine strategies for thrombosis prevention in MM.

Utilization and safety of off-label prothrombin complex concentrate (four-factor prothrombin complex concentrate) in a surgical population.

The aim of this study is to evaluate and describe the utilization and safety of 4F-PCC in a nonanticoagulated, surgical patient population at an academic, tertiary care center. This retrospective, single-center chart review evaluated nonanticoagulated adult patients at least 18 years of age who had at least one dose of 4F-PCC administered between 1 January 2017 and 30 September 2022 for a surgical or peri-procedural indication. Hemostatic efficacy following 4F-PCC administration was the primary outcome, assessed by subsequent blood product administration and hemoglobin and hematocrit reduction. Secondary outcomes included an assessment of thrombotic events within 30 days post-4F-PCC administration, in-hospital mortality, and the length of hospital stay. A total of 71 patients met the inclusion criteria, with 61 patients receiving 4F-PCC for cardiac surgery and 10 patients for other intraoperative or peri-procedural indications. The mean total 4F-PCC dose was 25.0 U/kg. For the primary outcome of hemostatic efficacy, 81% of patients had excellent hemostasis; however, blood product administration was reported in 95.8% of patients post-4F-PCC. Thromboembolic events occurred in 10 (14.1%) patients and 21.1% of patients expired prior to discharge in the total cohort. Off-label 4F-PCC use in nonanticoagulated patients is reported despite a lack of robust guidance for use. Following 4F-PCC administration, hemostatic efficacy based on hemoglobin and hematocrit changes was observed; however, blood product use was frequent, and 4F-PCC administration was not without risks, including thromboembolic complications such deep vein thrombosis (DVT), pulmonary embolism, and stroke. Further studies are needed to validate the off-label administration of 4F-PCC in nonanticoagulated patients.

Thromboembolism and Adjuvant Endocrine Therapy (AET) in Hormone Receptor-Positive Early Breast Cancer (EBC): Did Treatment Evolution Change Incidence of the Adverse Event? A Meta-Analysis.

The adjuvant endocrine therapy (AET) of HR+ EBC has been changing in recent years. Aromatase inhibitors (AIs) as an upfront strategy (or as part of a switch strategy) have been added to the choice of Tamoxifen (T) alone. Increased TE risk is well known in T-treated patients, while AIs have shown a reduced TE rate. By adding the cyclin dependent kinase 4/6 inhibitors (CDK4/6) to AIs, an increase in TE rate has been shown. We conducted this meta-analysis to evaluate the impact of the AETs on TE incidence. Twelve randomized phase III trials were included. Four trials evaluated the upfront strategy, 6 assessed the switch and 2 the combination with a CDK4/6 inhibitor. The new AETs did not significantly modify or affect the rate of TE events (OR 0.847, 95% CI, 0.528-1.366, P = .489). The OR for CDK4/6 inhibitor plus ET vs. ET was 3.635 (P = .002). Excluding the CDK4/6 inhibitors, the overall OR for AIs vs. T was 0.628 (P < .001), while it was 0.781 (P = .151) for switching T vs. continuing T for 5 years, and 0.52 (P < .0001) for the upfront strategies with AIs. The AIs alone or plus CDK4/6 inhibitors did not affect the rate of TE events. AIs as an upfront strategy is the safest AET, associated with the lowest TE incidence. The switch strategy increases TE rate, whereas the addition of CDK4/6 to the standard AET was shown to significantly increase TE events. The results of the currently ongoing trials with CDK4/6 inhibitors will help obtain additional data to evaluate any differences among the different CDK4/6 inhibitors and clarify the weight of TE adverse events in the benefit/risk balance of this new adjuvant strategy.

Thromboembolic events in patients who received adjuvant chemotherapy for gastric cancer: a single-center retrospective study.

BACKGROUND: Thromboembolic events (TEEs) are significant adverse events that can cause serious morbidities and mortality in cancer patients receiving chemotherapy. Patients with gastric cancer (GC) treated with palliative chemotherapy have been reported to experience a TEE incidence of 5-27%. However, very few reports have addressed TEEs in adjuvant chemotherapy (AC) for GC. METHODS: This study retrospectively analyzed 611 GC patients (stage II: 309, III: 302) who started AC with capecitabine/oxaliplatin (167 patients) or S-1 (444 patients) after undergoing curative resection between January 2013 and June 2020 at a single center. The incidence of TEEs during AC or within 1 year after AC completion was investigated, while analyzing the factors that influenced the TEEs' occurrence. RESULTS: TEEs were confirmed in 20 patients (3.3%), and TEEs occurred in almost all patients in the S-1 group (19 patients). The most common TEE types were cerebral infarction and pulmonary thromboembolism (five patients each). Although old age (≥ 70 years, p < 0.0001), S-1 treatment (p = 0.021), and hypertension (p = 0.017) were identified as significant risk factors for TEEs in univariate analysis, only old age showed a statistically significant correlation with TEEs' occurrence in multivariate analysis (odds ratio: 3.07; 95% confidence interval 1.11-8.48; p = 0.031). CONCLUSIONS: TEEs occurred in fewer patients with GC who had been treated with AC than patients who had received palliative chemotherapy in previous reports. However, elderly GC patients who are undergoing AC require more careful surveillance for possible TEEs, considering relatively higher incidence of them.

High-intensity interval training and thromboembolic events during chemotherapy for testicular cancer: a retrospective analysis from the Body & Cancer cohort.

Background: Men with testicular cancer receiving platinum-based chemotherapy have an increased risk of thromboembolic events, with incidence rates between 8-24%. A recent trial evaluating the effect of high-intensity interval training (HIIT) prematurely closed as three out of nine participants (33%) in the intervention group developed a thromboembolic event. The purpose of this retrospective cohort study was: 1) (primary) to evaluate the incidence of thromboembolic events in men receiving chemotherapy for testicular cancer who had participated in HIIT during a 6-week exercise program (Body & Cancer) 2) to describe the feasibility of this program.Material and methods: Forty men who had participated in at least one HIIT session from February 2007 to February 2020 were included. Electronic medical records were searched for incident thromboembolic events (arterial and venous) during Body & Cancer and up to one-year post-chemotherapy. Attendance, cardiorespiratory fitness (VO2-peak), and upper and lower extremity muscular strength (1 repetition maximum (RM)) were obtained from the Body & Cancer database.Results: One participant developed a thromboembolic event during Body & Cancer. No participants developed a thromboembolic event in the follow-up period. In all, data represent 160 HIIT sessions with a median attendance of eight sessions [range 1-19]. Statistically significant increases in upper and lower extremity strength were observed (8.6 (4.2 to 13.0) and 26.0 (14.9 to 37.0) kg, respectively). No significant increase in cardiorespiratory fitness was found (0.14 (-0.03 to 0.31) l/min).Conclusion: While conclusions on the safety of HIIT cannot be drawn, data from the present study do not support previous findings cautioning avoidance of HIIT due to a possible added risk of thromboembolic events in men receiving platinum-based chemotherapy for testicular cancer. Considering the potential for positive effects on cardiovascular outcomes associated with HIIT, future studies with robust design should be performed in this population to confirm these observations.

Effectiveness of perioperative anticoagulation interruption without heparin bridging on thromboembolic events in patients with atrial fibrillation undergoing elective invasive procedures: a systematic review protocol.

OBJECTIVE: This review will determine whether withholding heparin bridging is superior to bridging in patients with atrial fibrillation requiring temporary interruption of anticoagulation therapy in the perioperative period of an elective invasive procedure. INTRODUCTION: Atrial fibrillation is the most commonly diagnosed clinical arrhythmia. It is an important cause of cardioembolic events, requiring the use of oral anticoagulation in most patients. It is unclear whether heparin bridging during temporary interruption of anticoagulants has superior outcomes compared with no bridging in the perioperative setting. INCLUSION CRITERIA: This review will consider studies that compare adults aged 18 years or older; diagnosed with atrial fibrillation; undergoing elective invasive procedures; and who have had oral anticoagulants temporarily withheld with heparin bridging with patients without heparin bridging. Participants will be excluded if they had an alternative reason for anticoagulation or were admitted for emergency surgery. Outcomes will include arterial or venous thromboembolism (including stroke, transient ischemic attack, systemic embolism), major bleeding events, non-major bleeding events, length of hospital stay, and all-cause mortality. METHODS: The review will follow the JBI methodology for systematic reviews of effectiveness. Databases including MEDLINE, Embase, CINAHL, and CENTRAL will be searched for randomized and non-randomized trials from inception until the present. Two independent reviewers will screen citations by title and abstract, and again at full text. Risk of bias will be assessed using the JBI critical appraisal instrument, and data will be extracted using a modified extraction tool. Results will be synthesized using a random effects meta-analysis and presented in a forest plot. Heterogeneity will be tested for using the standard χ 2 and I2 tests. Overall certainty of evidence will be evaluated using the GRADE approach. REVIEW REGISTRATION: PROSPERO CRD42022348538.

Expression and Release of Tumor Cell Tissue Factor Triggers Recurrent Thromboembolism in a Patient with Endometrial Cancer.

Although cancer-associated thrombosis (CAT) is a frequent complication in patients with malignancies, its treatment remains a challenge in daily practice. Here, we report the clinical course of a 51-year-old woman presenting with a highly thrombogenic paraneoplastic coagulopathy. Despite therapeutic anticoagulation with various agents, including rivaroxaban, fondaparinux, and low-molecular-weight heparin, the patient suffered from recurrent venous and arterial thromboembolism. Locally advanced endometrial cancer was identified. Tumor cells showed strong expression of tissue factor (TF), and significant concentrations of TF-bearing microvesicles were detected in patient plasma. Coagulopathy was controlled only by continuous intravenous anticoagulation with the direct thrombin inhibitor, argatroban. Multimodal antineoplastic treatment, including neoadjuvant chemotherapy followed by surgery and postoperative radiotherapy, resulted in clinical cancer remission, which was paralleled by normalization of tumor markers, CA125 and CA19-9, D-dimer levels, and TF-bearing microvesicles. In summary, continuous anticoagulation with argatroban and multimodal anticancer treatment may be necessary to control TF-driven coagulation activation with recurrent CAT in endometrial cancer.

Assessment of Hormonal Contraceptive Utilization and Associated Odds of Hypercoagulopathy in Patients with Venous Malformations Using a National Claims Database.

BACKGROUND: Vascular anomalies that exhibit a slow velocity of blood flow, specifically venous malformations (VM), are associated with hypercoagulability. There is limited literature on the utilization of hormonal contraceptives (HCs) and the development of clotting events in female individuals diagnosed with VM. OBJECTIVE: We aimed to characterize HC utilization and associated odds of hypercoagulopathy in patients with VM of child-bearing age. METHODS: Using a national administrative claims database, we identified female patients with VM aged 15-49 years and a control population, matched for age and length of insurance enrollment, from 2016 to 2021. Multivariable logistic regression was used to estimate the odds of hypercoagulation events associated with HC use. RESULTS: Two hundred and sixty-seven (47.2%) patients with VM and 1284 (45.4%) control patients utilized HCs during the study period. Oral contraceptives were the most common HC for patients with and without VM (73.8% and 76.9% of those taking HCs, respectively), and estrogen-containing combination HCs (70.4% in patients with VM and 75.9% in controls) were more prevalent than progestin-only HCs in both populations. Despite a heightened baseline odds of hypercoagulopathy in patients with VM relative to patients without VM (odds ratio = 12.54; 95% confidence interval 7.73-20.3), HC use was not associated with an increased odds of hypercoagulation in the VM subpopulation (odds ratio = 0.82; 95% confidence interval 0.46-1.46). In contrast, tobacco use (odds ratio = 2.12; 95% confidence interval 1.09-4.12) and a history of coagulopathy (odds ratio = 3.92; 95% confidence interval 1.48-10.36) were predictive of thromboembolic events in the VM cohort. CONCLUSIONS: These findings suggest that patients with VM may safely use HCs with careful consideration of other risk factors for thromboses.

Perioperative management in chronically anticoagulated children undergoing tonsillectomy.

BACKGROUND: When undergoing tonsillectomy, patients at high risk of thrombosis who require chronic anticoagulation therapy pose a special challenge as bleeding may occur up to 2 weeks after surgery. Because of a lack of evidence-based data, there is no consensus on the best management for such patients. The objective of our study was to review perioperative anticoagulation bridging strategies in children undergoing tonsillectomy. METHODS: The study group were a retrospective series of patients on chronic anticoagulation therapy at high risk of a thromboembolic event, who underwent tonsillectomy from 2010 to 2021. Patients whose anticoagulation treatment was discontinued because of a low risk of thromboembolic events were excluded. RESULTS: Four patients met the inclusion criteria (age range, 1.5-16.1 years). All patients were admitted prior to surgery for bridging therapy with intravenous unfractionated heparin (UFH), drip-titrated to a therapeutic dose until 4-6 h prior to surgery. The estimated blood loss during surgery was minimal in all surgeries. Unfractionated heparin was readministered according to the hospital protocol on the night of surgery and titrated to a therapeutic dose. Warfarin was restarted within 2 days postsurgery for all patients. High-risk patients were kept in hospital until postoperative day 6-8 because of concern for delayed bleeding. One patient was noticed to have blood-tinged sputum requiring no intervention; none of the patients developed early or delayed hematemesis. CONCLUSIONS: Our data show that bridging therapy with UFH has been successful in chronically anticoagulated patients undergoing tonsillectomy. These patients require multidisciplinary care for the management of their pre- and postoperative course.

Prothrombin complex concentrates for the urgent reversal of apixaban and rivaroxaban: an Australian retrospective cohort study.

BACKGROUND: Direct acting oral anticoagulants (DOAC) are now commonly prescribed medications. Urgent reversal of their anticoagulant effect is sometimes required in emergency situations. In Australia, a specific reversal agent for factor Xa (FXa)-inhibitor DOAC is not available. Instead, two non-specific haemostatic agents, activated prothrombin complex concentrate (aPCC) and 3 factor-prothrombin complex concentrate (3F-PCC), are used off-label despite a paucity of evidence for their effectiveness or safety. AIMS: To provide further insight into the efficacy and safety of 3F-PCC and aPCC for the reversal of the anticoagulant effect of FXa inhibitor DOACs. METHODS: We conducted a single-centre retrospective cohort study to investigate the use of aPCC and 3F-PCC for patients on FXa-inhibitor DOAC who present with a significant bleeding event or who require urgent surgery. The primary outcome was haemostatic efficacy according to prespecified criteria. Safety outcomes included the thromboembolic event rate and all-cause mortality during the hospital admission. RESULTS: A total of 51 patients was included in the study (36 patients who had a spontaneous bleeding event and 15 non-bleeding patients who required urgent perioperative management). Thirty-one patients received aPCC and 20 patients received 3F-PCC. Haemostasis was adjudicated as effective in all assessable patients (n = 50; 100%). Thromboembolic events occurred in three patients who received aPCC and one patient who received 3F-PCC. All-cause mortality was 7.8% (four patients). CONCLUSIONS: Both aPCC and 3F-PCC are useful adjuncts for the management of patients who require urgent reversal of the anticoagulant effect of FXa-inhibitor DOAC. However, the risk of thromboembolism in this patient group requires careful consideration. Prospective, comparator studies are needed along with the development of guidelines that reflect the availability of haemostatic agents in Australia.

Update on the efficacy and safety of intravenous tranexamic acid in hip fracture surgery: a systematic review and meta-analysis.

AIM: The aim of this meta-analysis was to assess the safety and efficacy of tranexamic acid (TXA) in the management of hip fracture surgeries in comparison with placebo. METHODS: A systematic search was conducted from August 6, 2021. Eligible studies included randomized clinical trials and prospective studies comparing the use of intravenous TXA in patients treated for hip fractures, in comparison with placebo. Review Manager was used for the meta-analysis. RESULTS: Eighteen prospective studies including 14 RCTs met the eligibility criteria. The results favored the TXA group in the quantity of total blood loss (MD = - 196.91 mL, 95% CI - 247.59, - 146.23, I2 = 92%), intraoperative blood loss (MD = - 26.86 mL, 95% CI - 36.96, - 16.78, I2 = 62%), and rate of blood transfusion (OR 0.35, 95% CI 0.28, 0.42, I2 = 0%). TXA also exhibited higher hemoglobin level at day 1 (MD = 6.77 g/L, 95% CI 4.30, 9.24, I2 = 83%) and day 3 (MD = 7.02 g/L, 95% CI 3.30, 10.74, I2 = 82%) postoperatively. There was no significant difference found in the incidence of thromboembolic events from occurring between the two groups, such as deep vein thrombosis (OR 1.22, 95% CI 0.73, 2.02, I2 = 0%) and pulmonary embolism (OR 0.82, 95% CI 0.33, 2.05, I2 = 0%). CONCLUSION: Administration of intravenous TXA appears to reduce blood loss, rate of blood transfusions and pose no increased risk of thromboembolic events. Therefore, TXA should be considered by physicians when managing hip fracture patients.

Antithrombotic therapy and digestive endoscopy.

Antithrombotic therapy and digestive endoscopy Antithrombotic therapy comprises anticoagulation and antiplatelet treatment. The number of patients treated with various forms of antithrombotic therapy is growing. Procedures of digestive endoscopy are very frequently indicated by general practitioners and doctors of various specialisations. Interdisciplinary cooperation and mutual understanding are required in order for digestive endoscopy to be effective and safe. Hence, we present an overview based on recent European, British (1), and North American guidelines (2) for endoscopic procedures, with respect to guidelines for perioperative care in general (3). Antithrombotic therapy management in patients undergoing digestive endoscopy procedures is based on individual consideration of postprocedural bleeding (particularly a delayed one) on one hand, and thromboembolic risk on the other hand, ideally in cooperation with the physician prescribing antithrombotic therapy. Despite all efforts, patients taking antithrombotic medication are at a higher risk of postprocedural bleeding in comparison with those without this risk; this fact should be accepted by attending physicians and patients should be informed of it. Postprocedural bleeding is mostly manageable with a subsequent endoscopic procedure. By contrast, cerebral and cardiovascular thromboembolic complications are often life-threatening and not uncommonly disabling. One should always consider postponing an elective procedure in a patient with temporary antithrombotic therapy (after pulmonary embolism or after coronary stent insertion). Basic principles of administration of antithrombotic therapy in the context of an endoscopic procedure are described in Table 1. Digestive endoscopy procedures can be categorized according to postprocedural bleeding risk (Table 2). Postprocedural bleeding risk can be specifically reduced in some procedures (ERCP with papillary balloon dilation instead of sphincterotomy, mechanical securing of polypectomy base, etc.). Acetylsalicylic acid administered as secondary prevention (primary preventive indications are very narrow nowadays) should not be discontinued perioperatively (discontinuation is associated with an approximately threefold increase in thrombotic complications!). The riskiest procedures are the only exception in which discontinuation is explicitly requested by the digestive endoscopist. Reduction of dual antiplatelet therapy is better abandoned in high-risk patients - particularly those with recently implanted coronary stents (Table 3) - and postponement of an elective procedure should always be considered. Bridging of warfarin with low-molecular-weight heparin (LMWH) is not indicated routinely (in some cases, this practice increases the bleeding risk). Bridging with LMWH is appropriate in patients with high (or moderate) thromboembolic risk (Table 5). Furthermore, LMWH therapy carries specific risks, particularly in patients with renal function impairment (Table 4). In patients with a high thromboembolic risk, a statement of the physician indicating anticoagulation is always appropriate before an elective procedure (Table 6). Direct oral anticoagulants (DOACs) should not be administered on the day of the procedure, not even in one with a low risk (e.g., biopsy); a longer withdrawal is recommended in high-risk procedures (this cessation should not be bridged with LMWH given the rapid onset and elimination half-time) (Table 7). Recommencement of antithrombotic therapy after a high-risk endoscopic procedure should always be determined by the endoscopist and the recommended intervals should be considered minimal: 1-2 days after the procedure in the case of P2Y12 inhibitors; 2-3 days after the procedure in the case of DOACs; in the evening of the day of the procedure for warfarin with a maintenance (not saturation) dose; and 48 hours after the procedure in the case of LMWH at a therapeutic dose. Earlier administration of a lower-than-therapeutic dose of LMWH (twice a day per weight) can be considered in this context: prophylactic (once a day) or higher prophylactic (once a day per weight) doses. In general, a full anticoagulation effect should not be achieved earlier than approximately 48 hours after the procedure. The patient should be properly informed of the course of antithrombotic therapy before and after the endoscopic procedure, including a written form (a calendar can be downloaded online for this purpose).

Thromboembolism after COVID-19 Vaccination: A Systematic Review of Such Events in 286 Patients.

BACKGROUND: Development of vaccines with high efficacy against COVID-19 disease has ushered a new ray of hope in the fight against the pandemic. Thromboembolic events have been reported after administration of vaccines. We aim to systematically review thromboembolic events reported after COVID-19 vaccination. METHODS: The available literature was systematically screened for available data on thromboembolic events after COVID-19 vaccination. Data were extracted from selected studies and analyzed for site of thromboembolism as well as other risk factors. All data were pooled to determine cumulative incidence of thromboembolism at various sites after vaccination. RESULTS: A total of 20 studies were selected for the final analysis. The mean age of the population was 48.5 ± 15.4 years (females - 67.4%). The mean time to event after vaccination was 10.8 ± 7.2 days. Venous thrombosis (74.8%, n = 214/286) was more common than arterial thrombosis (27.9%, n = 80/286). Cerebral sinus thrombosis was the most common manifestation (28.3%, n = 81/286) of venous thrombosis followed by deep vein thrombosis (19.2%, n = 49/254). Myocardial infarction was common (20.1%, n = 55/274) in patients with arterial thrombosis followed by ischemic stroke (8.02%, n = 22/274). Concurrent thrombosis at multiple sites was noted in 15.4% patients. Majority of patients had thrombocytopenia (49%) and antiplatelet factor 4 antibodies (78.6%). Thromboembolic events were mostly reported after the AstraZeneca vaccine (93.7%). Cerebral sinus thrombosis was the most common among thromboembolic events reported after the AstraZeneca vaccine. Among the reported cases, mortality was noted in 29.9% patients. CONCLUSIONS: Thromboembolic events can occur after COVID-19 vaccination, most commonly after the AstraZeneca vaccine. Cerebral sinus thrombosis is the most common manifestation noted in vaccinated individuals.

Relationship between creatinine clearance and clinical outcomes in Chinese emergency patients with atrial fibrillation.

BACKGROUND: Few real-world data on the relation between creatinine clearance (CrCl) and adverse clinical outcomes in Chinese emergency department (ED) patients with nonvalvular atrial fibrillation (AF). METHODS: In this prospective, observational, multicenter AF study, enrolled AF patients presenting to an ED at 20 hospitals in China from November 2008 to October 2011, with a follow-up of 12 month. A total of 863 AF patients with CrCl data were analyzed, and patients were categorized as CrCl ≥ 80, 50 ≤ CrCl < 80, 30 ≤ CrCl < 50, and CrCl < 30(ml/min). Outcomes of analyses were all-cause death, cardiovascular death, thromboembolism (TE), and major bleeding. RESULTS: Among the whole patients, 126(14.6%) patients died during 12-month follow-up, 53(40.2%) among CrCl < 30 ml/min group, and 48(16.2%), 22(6.5%), and 3(3.2%) among 30 ≤ CrCl50, 50 ≤ Crl < 80, and CrCl ≥ 80 ml/min groups, respectively (p < 0.001). Cardiovascular death and TE rates also increased with decreasing CrCl. On multivariate analysis, patients with CrCl < 30 ml/min were associated with higher risks of all-cause death (HR 5.567; 95%CI1.618-19.876; p = .007) and higher cardiovascular death (HR11.939; 95%CI1.439-99.031; p = .022) as compared with CrCl≥80 ml/min category. Nevertheless, for TE and major bleeding risk, CrCl groups showed no significant difference after adjustment for variables in CHA2 DS2 -VASc score and status of warfarin prescription in our cohort. CONCLUSIONS: In Chinese ED nonvalvular AF patients, incidence rates of death increased with reducing CrCl across the whole range of renal function. CrCl < 30 ml/min was associated with all-cause death, cardiovascular death, but not for TE and major bleeding.

Hemorrhagic complications of cutaneous surgery for patients taking antithrombotic therapy: a systematic review and meta-analysis.

Cutaneous operations are generally safe procedures with minimal major risks. Excessive bleeding occasionally occurs, especially for patients taking antithrombotic medications. Conversely, stopping these medications before cutaneous surgery may increase the risk of a thromboembolic event. We aimed to synthesize the evidence regarding the risk of hemorrhage and thromboembolic events for patients undergoing cutaneous surgery while taking antithrombotic therapy. We performed a comprehensive search to identify randomized controlled trials and cohort studies that compared rates of hemorrhage and/or thromboembolic events between patients receiving antithrombotic therapy at cutaneous surgery and patients not receiving it. Odds ratio (OR) and risk difference for complications were calculated with random-effects models. Of 9214 patients taking anticoagulant or antiplatelet medications, 323 (3.5%) had hemorrhagic complications; of 21,696 control patients, 265 (1.2%) had hemorrhagic complications. Patients taking antithrombotic therapy had increased bleeding risk relative to control patients (OR 2.63 [95% CI 1.90-3.63]; P < 0.001) and an increased but less clinically important risk difference (OR 0.02 [95% CI 0.01-0.03]; P < 0.001) with high heterogeneity. No difference was observed in hemorrhage rates among patients whose antithrombotic therapy was stopped vs continued (OR 1.16 [95% CI 0.73-1.83]; P = 0.54). No difference was seen in rates of thromboembolic events among patients taking antithrombotic therapy vs control patients. However, two serious thromboembolic events were noted in a cohort of 59 patients whose antithrombotic therapy was stopped. Because of potentially devastating effects of thromboembolic events, the current accepted practice is indicated for continuation of antithrombotic therapy for patients undergoing cutaneous surgery.

Risk of venous and arterial thromboembolic events in women with advanced breast cancer treated with CDK 4/6 inhibitors: A systematic review and meta-analysis.

BACKGROUND: Cyclin-dependent kinase inhibitors (CDKIs) may increase the risk of thrombotic events of endocrine therapy (ET) in women with hormone-sensitive, HER2-negative advanced breast cancer (BC). Aim of our systematic review is the estimate of the risk of venous and arterial thromboembolism in women with advanced BC treated with CDKIs in phase III randomized controlled trials (RCTs). METHODS: Studies were identified by electronic search of MEDLINE, EMBASE and CENTRAL database until October 2021. Risk of bias was assessed according to Cochrane criteria. Differences in thrombotic outcomes among groups were expressed as pooled odds ratio (OR) and corresponding 95% confidence interval (CI), which were calculated using both a fixed-effects and a random-effects model. Statistical heterogeneity was evaluated using the I2 statistic. RESULTS: We included 7 phase III RCTs (4415 patients) for a total of 15 papers (7 were the first published paper and 8 the follow-up papers). Reporting of thrombotic events was at high risk of bias. Women with advanced BC treated with CDKIs and ET had a two to threefold increased risk of venous thromboembolic event (VTE) compared to ET plus placebo arm [OR 2.90 (95% CI 1.32, 6.37; I2 = 0%) in the main papers and OR 2.20 (95% CI 0.93, 5.20; I2 = 49%) in the follow-up papers]. Women with advanced BC treated with CDKIs and ET had a non-significant mild increased risk of arterial thromboembolic event compared to ET plus placebo arm [OR 1.22 (95% CI 0.47, 3.18 I2 = 0%)]. CONCLUSIONS: CDKIs in combination with endocrine therapy are associated with a two to threefold higher risk of VTE in comparison to endocrine therapy alone in women with advanced breast cancer, while the risk of arterial events is still to be defined.

Thirty-day mortality rates after immunotherapy initiation.

Background: The aim of this study was to determine the cause of death in patients who died within 30 days after the first dose of immunotherapy. Methods: The data of 1432 patients treated with immunotherapy in six tertiary referral hospitals were retrospectively analyzed. Results: It was determined that 34 (2%) of the patients died within 30 days after the first dose of immunotherapy. Death occurred in all patients who received palliative therapy, and most patients (88%) received immunotherapy as second- or subsequent-line of therapy. The most common cause of death was disease progression and thromboembolic events. Conclusion: Preliminary results of the current study might give some clues to define the patient population in whom the fatal side effects of immunotherapy might be encountered.