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The infection with the SARS-CoV-2 virus is associated with numerous systemic involvements. Besides the severe respiratory injuries and cardiovascular complications, it became obvious early on that this disease carries an increased risk of thromboembolic events, but a higher propensity for bleedings as well. We researched the medical literature over significant PubMed published articles debating on the prevalence, category of patients, the moment of occurrence, and evolution of venous thromboembolism (VTE), but also of venous and arterial "in situ" thrombosis (AT), and hemorrhagic events as well. Most researchers agree on an increased prevalence of thromboembolic events, ranging between 25 and 31% for VTE, depending on the analyzed population. For AT and hemorrhagic complications lower rates were reported, namely, about 2–3%, respectively, between 4.8 and 8%, occurring mostly in older patients, suffering from moderate/severe forms of COVID-19, with associated comorbidities. It is important to mention that patients suffering from hemorrhages frequently received thromboprophylaxis with anticoagulant drugs. As a consequence of thromboembolic and hemorrhagic complications which are both important negative prognostic factors, the evolution of patients infected with the SARS-CoV-2 virus is aggravated, determining an augmented morbidity and mortality of this population. [ABSTRACT FROM AUTHOR]

The infection with the SARS-CoV-2 virus is associated with numerous systemic involvements. Besides the severe respiratory injuries and cardiovascular complications, it became obvious early on that this disease carries an increased risk of thromboembolic events, but a higher propensity for bleedings as well. We researched the medical literature over significant PubMed published articles debating on the prevalence, category of patients, the moment of occurrence, and evolution of venous thromboembolism (VTE), but also of venous and arterial “in situ” thrombosis (AT), and hemorrhagic events as well. Most researchers agree on an increased prevalence of thromboembolic events, ranging between 25 and 31% for VTE, depending on the analyzed population. For AT and hemorrhagic complications lower rates were reported, namely, about 2–3%, respectively, between 4.8 and 8%, occurring mostly in older patients, suffering from moderate/severe forms of COVID-19, with associated comorbidities. It is important to mention that patients suffering from hemorrhages frequently received thromboprophylaxis with anticoagulant drugs. As a consequence of thromboembolic and hemorrhagic complications which are both important negative prognostic factors, the evolution of patients infected with the SARS-CoV-2 virus is aggravated, determining an augmented morbidity and mortality of this population.

Many potentially valuable drugs, including protein kinase inhibitors (PKI), risk being dropped from further development, without exploration of their clinical benefits, if early studies show these drugs to inhibit hERG channel and therefore, to have a potential for prolonging ventricular repolarisation (QT interval). This QT-phobia results from a perceived possibility of the clinical risks of QT-related ventricular proarrhythmia, further aggravated by uncertainties surrounding the regulatory evaluation of the risk and either approvability or restrictive labelling of the drug concerned. In reality, QT interval prolongation per se is only an imperfect surrogate of the proarrhythmia risk which is much smaller than perceived and compared to their other cardiovascular and non-cardiovascular risks. PKI-induced clinical hepatotoxicity, also evaluated on the basis of surrogate markers (serum transaminases and bilirubin) is another risk that far exceeds any risk arising from PKI-induced QT interval prolongation. This review of the currently approved 28 PKIs places the QT-phobia surrounding the development of PKIs in its perspective by juxta-positioning their potential to induce ventricular dysfunction, arterial thrombotic events and hepatotoxicity. Available evidence suggests that hERG channel may prove to be a valuable therapeutic target in oncology. Therefore, the development, approval and labelling of such vital oncology drugs requires careful assessment of their benefits and their risk/benefit generally, without being overtly consumed by their potential QT-liability, in terms of their more direct consequences on clinically relevant endpoints of morbidity, mortality and quality of life.

Purpose: The aim of this study was to evaluate the effect of intravitreal injection of aflibercept (IVA) on blood coagulation tests in neovascular age-related macular degeneration (AMD) patients.Methods: Thirty-four patients with neovascular AMD (study group) and 32 healthy individuals (control group) were enrolled. Prothrombin time (PT) and activated partial thromboplastin time (aPTT) were measured at different times in patients with neovascular AMD.Results: The levels of PT and aPTT after IVA were decreased at 1 month after the first injection and 1 month after the second injection compared to the baseline measurement in the study group.Conclusions: IVA may cause a decrease in the levels of PT and aPTT at 1 month after the first injection and 1 month after the second injection although these results are not statistically significant in our study. [ABSTRACT FROM AUTHOR]

Imatinib, the first-in-class BCR-ABL tyrosine kinase inhibitor (TKI), had been a revolution for the treatment of chronic myeloid leukemia (CML) and had greatly enhanced patient survival. Second- (dasatinib, nilotinib, and bosutinib) and third-generation (ponatinib) TKIs have been developed to be effective against BCR-ABL mutations making imatinib less effective. However, these treatments have been associated with arterial occlusive events. This review gathers clinical data and experiments about the pathophysiology of these arterial occlusive events with BCR-ABL TKIs. Imatinib is associated with very low rates of thrombosis, suggesting a potentially protecting cardiovascular effect of this treatment in patients with BCR-ABL CML. This protective effect might be mediated by decreased platelet secretion and activation, decreased leukocyte recruitment, and anti-inflammatory or antifibrotic effects. Clinical data have guided mechanistic studies toward alteration of platelet functions and atherosclerosis development, which might be secondary to metabolism impairment. Dasatinib, nilotinib, and ponatinib affect endothelial cells and might induce atherogenesis through increased vascular permeability. Nilotinib also impairs platelet functions and induces hyperglycemia and dyslipidemia that might contribute to atherosclerosis development. Description of the pathophysiology of arterial thrombotic events is necessary to implement risk minimization strategies.

Vasculitides, particularly those affecting small vessels, are known to complicate systemic lupus erythematosus (SLE); however, isolated venulitis of the mesenteric bed has rarely been reported. Here we relate the case of a 46-year-old woman with SLE who presented with acute abdominal pain due to artery thrombosis and extended splenic ischemia requiring splenectomy. The histological examination revealed diffuse venulitis in the absence of arterial vasculitis consistent with the definition of mesenteric inflammatory veno-occlusive disease (MIVOD). Furthermore, arterial wall thickening suggestive of uncomplicated atherosclerosis was observed. Two months later, the patient suffered of severe myocardial infarction (MI) resulting from thrombosis of the anterior interventricular coronary artery with otherwise no signs of coronary disease at coronarography. Extensive work-up to establish the cause of MI was negative, with the exception of marginal, isolated and transient elevation of cardiolipin IgG (14.5 GPL, n.v. 0–5 GPL). This patient’s SLE history is dramatically marked by the previously non-described association of MIVOD and two arterial thrombotic events (splenic and coronary) occurring within a two months period, and stresses the need of better understanding and prevention of vascular complications in SLE. [ABSTRACT FROM AUTHOR]

Background: Omalizumab is a monoclonal antibody, indicated for the treatment of severe allergic asthma. In Europe, there have been concerns about the cardiovascular safety of omalizumab. The objective of this study was to analyze the association between omalizumab and arterial thrombotic events in a spontaneous adverse drug reaction reporting database in the US. Methods and materials: Reports of arterial thrombotic events submitted to the US Food and Drug Administration's Adverse Event Reporting System (AERS) between 2004 and 2011 were retrieved and analyzed by the reporting odds ratio data mining algorithm. The reporting odds ratio of arterial thrombotic events for omalizumab was compared with specific asthma medications and all drugs in the AERS. Values ⩾2 were considered significant safety signals. The Medical Dictionary for Regulatory Activities Preferred Terms were used to identify arterial thrombotic events (eg, stroke, myocardial infarction). Results: In total, 293,783 reports of arterial thrombotic events were retrieved (about 2% of all adverse drug reaction reports), corresponding to 2274 asthma drug-arterial thrombotic events pairs (omalizumab, 222; inhaled corticosteroids [ICS], 131; long-acting beta-agonists [LABA], 102; single-device combination ICS-LABA, 506; inhaled short-acting beta-agonists [SABA], 475; oral SABA, 6; inhaled antimuscarinics [AMC], 477; single-device combination AMC-SABA, 127; xanthines, 50; leukotriene modifiers, 174; and mast cell stabilizers, 4). Reporting odds ratio and 95% confidence interval values for omalizumab compared with other asthma drugs and all drugs in AERS were 2.75 (2.39-316) and 1.09 (0.95-1.24), respectively. Omalizumab ranked second after ICS in the risk of arterial thrombotic events, followed by AMC, AMC-SABA, and ICS-LABA. Conclusion: Omalizumab is associated with higher than expected reporting of arterial thrombotic events in asthmatic patients. This hypothesis needs further testing in robust epidemiological studies [ABSTRACT FROM AUTHOR]

A B S T R A C T Thrombotic events are a major cause of morbidity and mortality in cancer. While the association of venous thromboembolic events with cancer is well documented, in recent years arterial events (i.e. acute myocardial infarction and ischemic strokes) have also emerged as relatively common complications among cancer patients. In hematological malignancies incorporating a heterogeneous group of diseases, the prediction of thrombosis occurrence and/or recurrence is challenging, due to unique disease characteristics. Furthermore, the treatment of thrombosis in these patients is often complicated because of disease- or therapy-related thrombocytopenia. In addition, patients with hematological cancers are poorly represented in randomized control clinical trials; hence, evidence-based guidelines are limited. This review will discuss the incidence of venous and arterial thrombotic events in common myeloid and lymphoproliferative diseases. Several new mechanisms contributing to cancer- associated thrombosis will be elaborated. The complicated issue of risk assessment and management of venous thrombosis in patients with hematological malignancies will be delineated., (© 2020 Elsevier Ltd. All rights reserved.)

Imatinib, the first-in-class BCR-ABL tyrosine kinase inhibitor (TKI), had been a revolution for the treatment of chronic myeloid leukemia (CML) and had greatly enhanced patient survival. Second- (dasatinib, nilotinib, and bosutinib) and third-generation (ponatinib) TKIs have been developed to be effective against BCR-ABL mutations making imatinib less effective. However, these treatments have been associated with arterial occlusive events. This review gathers clinical data and experiments about the pathophysiology of these arterial occlusive events with BCR-ABL TKIs. Imatinib is associated with very low rates of thrombosis, suggesting a potentially protecting cardiovascular effect of this treatment in patients with BCR-ABL CML. This protective effect might be mediated by decreased platelet secretion and activation, decreased leukocyte recruitment, and anti-inflammatory or antifibrotic effects. Clinical data have guided mechanistic studies toward alteration of platelet functions and atherosclerosis development, which might be secondary to metabolism impairment. Dasatinib, nilotinib, and ponatinib affect endothelial cells and might induce atherogenesis through increased vascular permeability. Nilotinib also impairs platelet functions and induces hyperglycemia and dyslipidemia that might contribute to atherosclerosis development. Description of the pathophysiology of arterial thrombotic events is necessary to implement risk minimization strategies.

Pulmonary vein thrombosis (PVT) is a challenging diagnosis and has been described in association with or as a complication of pulmonary tumors, lung surgeries, atrial myxoma, and after radiofrequency catheter ablation for atrial fibrillation. There are not many reported cases of PVT associated with medication use. We present a case of a 53-year-old male with a history of severe persistent asthma on omalizumab, who presented with shortness of breath and was found to have PVT on computed tomography scan of the chest. The hypercoagulable workup was normal, and the patient did not have a history of malignancy or pulmonary surgeries. Currently, available data suggest an association between omalizumab use and increased risk of arterial thrombotic events. However, on a literature search, we could not find any reported cases of PVT with omalizumab treatment., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Patients with cancer are at high risk for thrombotic events, which are known collectively as Trousseau's syndrome. Herein, we report a 66-year-old male patient who was diagnosed with terminal stage gastric cancer and liver metastasis and who had an initial clinical presentation of upper gastrointestinal bleeding. Acute ischemia of the left lower leg that resulted in gangrenous changes occurred during admission. Subsequent angiography of the left lower limb was then performed. This procedure revealed arterial thrombosis of the left common iliac artery with extension to the external iliac artery, the left common iliac artery, the posterior tibial artery, and the peroneal artery, which were occluded by thrombi. Aspiration of the thrombi demonstrated that these were not tumor thrombi. The interesting aspect of our case was that the disease it presented as arterial thrombotic events, which may correlate with gastric adenocarcinoma. In summary, we suggested that the unexplained thrombotic events might be one of the initial presentations of occult malignancy and that thromboprophylaxis should always be considered.