Objective: Pulmonary thrombosis is observed in severe acute respiratory syndrome coronavirus 2 pneumonia. Aim was to investigate whether subpopulations of platelets were programmed to procoagulant and inflammatory activities in coronavirus disease 2019 (COVID-19) patients with pneumonia, without comorbidities predisposing to thromboembolism. Approach and Results: Overall, 37 patients and 28 healthy subjects were studied. Platelet-leukocyte aggregates, platelet-derived microvesicles, the expression of P-selectin, and active fibrinogen receptor on platelets were quantified by flow cytometry. The profile of 45 cytokines, chemokines, and growth factors released by platelets was defined by immunoassay. The contribution of platelets to coagulation factor activity was selectively measured. Numerous platelet-monocyte (mean±SE, 67.9±4.9%, n=17 versus 19.4±3.0%, n=22; P <0.0001) and platelet-granulocyte conjugates (34.2±4.04% versus 8.6±0.7%; P <0.0001) were detected in patients. Resting patient platelets had similar levels of P-selectin (10.9±2.6%, n=12) to collagen-activated control platelets (8.7±1.5%), which was not further increased by collagen activation on patient platelets (12.4±2.5%, P =nonsignificant). The agonist-stimulated expression of the active fibrinogen receptor was reduced by 60% in patients ( P <0.0001 versus controls). Cytokines (IL [interleukin]-1α, IL-1β, IL-1RA, IL-4, IL-10, IL-13, IL, 17, IL-27, IFN [interferon]-α, and IFN-γ), chemokines (MCP-1/CCL2), and growth factors (VEGF [vascular endothelial growth factor]-A/D) were released in significantly larger amounts upon stimulation of COVID-19 platelets. Platelets contributed to increased fibrinogen, VWF (von Willebrand factor), and factor XII in COVID-19 patients. Patients (28.5±0.7 s, n=32), unlike controls (31.6±0.5 s, n=28; P <0.001), showed accelerated factor XII–dependent coagulation. Conclusions: Platelets in COVID-19 pneumonia are primed to spread proinflammatory and procoagulant activities in systemic circulation.

1. Medication errors are common in general practice and in hospitals. Both errors in the act of writing (prescription errors) and prescribing faults due to erroneous medical decisions can result in harm to patients. 2. Any step in the prescribing process can generate errors. Slips, lapses, or mistakes are sources of errors, as in unintended omissions in the transcription of drugs. Faults in dose selection, omitted transcription, and poor handwriting are common. 3. Inadequate knowledge or competence and incomplete information about clinical characteristics and previous treatment of individual patients can result in prescribing faults, including the use of potentially inappropriate medications. 4. An unsafe working environment, complex or undefined procedures, and inadequate communication among health-care personnel, particularly between doctors and nurses, have been identified as important underlying factors that contribute to prescription errors and prescribing faults. 5. Active interventions aimed at reducing prescription errors and prescribing faults are strongly recommended. These should be focused on the education and training of prescribers and the use of on-line aids. The complexity of the prescribing procedure should be reduced by introducing automated systems or uniform prescribing charts, in order to avoid transcription and omission errors. Feedback control systems and immediate review of prescriptions, which can be performed with the assistance of a hospital pharmacist, are also helpful. Audits should be performed periodically.

Background The global rate of intensive care unit (ICU) admission during the COVID-19 pandemic varies within countries and is among the main challenges for health care systems worldwide. Conflicting results have been reported about the response to coronavirus infection and COVID-19 outcomes in men and women. Understanding predictors of intensive care unit admission might be of help for future planning and management of the disease. Methods and findings We designed a cross-sectional observational multicenter nationwide survey in Italy to understand gender-related clinical predictors of ICU admission in patients with COVID-19. We

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Background-The current controversy on the potential cardioprotective effect of naproxen prompted us to evaluate the extent and duration of platelet, monocyte, and vascular cyclooxygenase (COX) inhibition by naproxen compared with low-dose aspirin. Methods and Results-We performed a crossover, open-label study of low-dose aspirin (100 mg/d) or naproxen (500 mg BID) administered to 9 healthy subjects for 6 days. The effects on thromboxane (TX) and prostacyclin biosynthesis were assessed up to 24 hours after oral dosing. Serum TXB 2 , plasma prostaglandin (PG) E 2 , and urinary 11-dehydro-TXB 2 and 2,3-dinor-6-keto-PGF 1␣ were measured by previously validated radioimmunoassays. The administration of naproxen or aspirin caused a similar suppression of whole-blood TXB 2 production, an index of platelet COX-1 activity ex vivo, by 94Ϯ3% and 99Ϯ0.3% (meanϮSD), respectively, and of the urinary excretion of 11-dehydro-TXB 2 , an index of systemic biosynthesis of TXA 2 in vivo, by 85Ϯ8% and 78Ϯ7%, respectively, that persisted throughout the dosing interval. Naproxen, in contrast to aspirin, significantly reduced systemic prostacyclin biosynthesis by 77Ϯ19%, consistent with differential inhibition of monocyte COX-2 activity measured ex vivo. Conclusions-The regular administration of naproxen 500 mg BID can mimic the antiplatelet COX-1 effect of low-dose aspirin. Naproxen, unlike aspirin, decreased prostacyclin biosynthesis in vivo. Key Words: aspirin Ⅲ naproxen Ⅲ thromboxanes Ⅲ epoprostenol Ⅲ platelets A spirin is the only nonsteroidal antiinflammatory drug (NSAID) known to react covalently with the cyclooxygenase (COX) channel of prostaglandin (PG) G/H synthase-1 and -2 (also referred to as COX-1 and COX-2) through a selective acetylation of a single serine residue (Ser 529 in human COX-1 and Ser 516 in human COX-2) that results in the permanent loss of the COX activity of the enzyme. 1,2 The consistency in dose requirement and saturability of the effects of aspirin in acetylating platelet COX-1, inhibiting thromboxane (TX) A 2 formation, and preventing atherothrombotic complications constitutes the best evidence that the antithrombotic effect of aspirin is largely caused by the suppression of platelet TXA 2 production. 3,4 However, it is uncertain whether other NSAIDs that act as competitive, reversible inhibitors of both COX-1 and COX-2 share an aspirin-like cardioprotective effect. This question has received considerable attention after publication of the Vioxx Gastrointestinal Outcome Research (VIGOR) trial, 5 a study of approximately 8000 patients with rheumatoid arthritis randomized to receive rofecoxib 50 mg/d or naproxen 500 mg BID with a mean duration of follow-up of 9 months. The rates of myocardial infarction were 0.5% and 0.1% in the rofecoxib-and naproxen-treated groups, respectively, raising the possibility of a thrombogenic effect of rofecoxib, a cardioprotective effect of naproxen, and/or the play of chance. 6 Six of 8 recent observational studies and a metaanalysis of these studies suggest that regular use...

Diabetes mellitus is associated with platelet hyperactivity, which leads to increased morbidity and mortality from cardiovascular disease. This is coupled with enhanced levels of thromboxane (TX), an eicosanoid that facilitates platelet aggregation. Although intensely studied, the mechanism underlying the relationship among hyperglycemia, TX generation, and platelet hyperactivity remains unclear. We sought to identify key signaling components that connect high levels of glucose to TX generation and to examine their clinical relevance. In human platelets, aldose reductase synergistically modulated platelet response to both hyperglycemia and collagen exposure through a pathway involving ROS/PLCγ2/PKC/p38α MAPK. In clinical patients with platelet activation (deep vein thrombosis; saphenous vein graft occlusion after coronary bypass surgery), and particularly those with diabetes, urinary levels of a major enzymatic metabolite of TX (11-dehydro-TXB 2 [TX-M]) were substantially increased. Elevated TX-M persisted in diabetic patients taking low-dose aspirin (acetylsalicylic acid, ASA), suggesting that such patients may have underlying endothelial damage, collagen exposure, and thrombovascular disease. Thus, our study has identified multiple potential signaling targets for designing combination chemotherapies that could inhibit the synergistic activation of platelets by hyperglycemia and collagen exposure. IntroductionAccelerated atherosclerosis and microvascular disease contribute to the morbidity and mortality associated with diabetes mellitus (DM) (1-3). Vascular inflammation, endothelial dysfunction associated with hyperglycemia, impaired fibrinolysis, and increased coagulation factors as well as abnormal platelet function are typical for DM, contributing to the increased thrombotic events and development of arteriosclerosis (4). Altered platelet function in DM, including altered adhesion and aggregation, may contribute to the pathogenesis of DM vascular complications by promoting microthrombus formation, contributing to enhanced risk of small vessel occlusions and accelerated atherothrombotic diseases (5, 6). Patients with type 2 DM (T2DM) exhibit platelet hyperreactivity both in vitro and in vivo, coupled with biochemical evidence of persistently increased thromboxane-dependent (TX-dependent) platelet activation (7,8). Despite many important studies, the mechanism by which platelets transduce glucose levels into enhanced TX generation independently of endothelial and other blood cell-derived factors remains unclear. Similarly, optimal antiplatelet therapy for DM patients remains to be achieved.Aldose reductase (AR) is the first enzyme of the polyol pathway, and it represents a minor source of glucose utilization, accounting for less than 3% of glucose consumption during euglycemia.

Background-Hypertensive patients with renovascular disease (RVD) may be exposed to increased oxidative stress, possibly related to activation of the renin-angiotensin system. Methods and Results-We measured the urinary excretion of 8-iso-prostaglandin (PG) F 2␣ and 11-dehydro-thromboxane (TX) B 2 as indexes of in vivo lipid peroxidation and platelet activation, respectively, in 25 patients with RVD, 25 patients with essential hypertension, and 25 healthy subjects. Plasma renin activity in peripheral and renal veins, angiotensin II in renal veins, cholesterol, glucose, triglycerides, homocysteine, and antioxidant vitamins A, C, and E were also determined. Patients were also studied 6 months after a technically successful angioplasty of the stenotic renal arteries. Urinary 8-iso-PGF 2␣ was significantly higher in patients with RVD (median, 305 pg/mg creatinine; range, 124 to 1224 pg/mg creatinine) than in patients with essential hypertension (median, 176 pg/mg creatinine; range, 48 to 384 pg/mg creatinine) or in healthy subjects (median, 123 pg/mg creatinine; range, 58 to 385 pg/mg creatinine). Urinary 11-dehydro-TXB 2 was also significantly higher in RVD patients compared with healthy subjects. In RVD patients, urinary 8-iso-PGF 2␣ correlated with 11-dehydro-TXB 2 (r s ϭ0.

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