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.

We provide evidence that active blood flow surveillance and pre-emptive repair of subclinical stenosis reduce the thrombosis rate and prolong the functional life of mature forearm AVFs. We also show that Qa is a crucial indicator of access patency and a Qa >350 ml/min portends a superior outcome with pre-emptive action in AVFs.

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.

Abstract. Balloon angioplasty (PTA) is an established treatment modality for stenosis in dysfunctional arteriovenous fistulae (AVF), although most studies showing efficacy have been retrospective, uncontrolled, and nonrandomized. In addition, it is unknown whether correction of stenosis not associated with significant hemodynamic, functional, and clinical abnormality may improve survival in AVF. This study was a prospective controlled open trial to evaluate whether prophylactic PTA of stenosis not associated with access dysfunction improves survival in native, virgin, radiocephalic forearm AVF. Sixty-two stenotic, functioning AVF, i.e., able to provide adequate dialysis, were enrolled in the study: 30 were allocated to control and 32 to PTA. End points of the study were either AVF thrombosis or surgical revision due to reduction in delivered dialysis dose. Kaplan-Meier analysis showed that PTA improved AVF functional failure-free survival rates (P ϭ 0.012) with a fourfold increase in median survival and a 2.87-fold decrease in risk of failure. Cox proportional hazard model identified PTA as the only variable associated with outcome (P ϭ 0.012). PTA induced an increase in access blood flow rate (Qa) by 323 (236 to 445) ml/min (P Ͻ 0.001), suggesting that improved AVF survival is the result of increased Qa. PTA was also associated with a significant decrease in access-related morbidity by approximately halving the risk of hospitalization, central venous catheterization, and thrombectomy (P Ͻ 0.05). This study shows that prophylactic PTA of stenosis in functioning forearm AVF improves access survival and decreases access-related morbidity, supporting the usefulness of preventive correction of stenosis before the development of access dysfunction. It also strongly supports surveillance program for early detection of stenosis.

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Surgery is the traditional treatment for juxta-anastomotic stenoses in forearm arteriovenous fistulas (AVF), but percutaneous transluminal angioplasty (PTA) is a suitable alternative. No prospective comparative trials between the two have been reported to date, however. A retrospective analysis of prospectively, concurrently collected data was performed to compare the outcome and cost of surgery and PTA in the preemptive repair of juxta-anastomotic stenosis in lower forearm AVF. Sixty-four AVF with >50% venous juxta-anastomotic stenosis were considered: 21 were treated surgically (11 proximal neo-anastomosis and 10 polytetrafluoroethylene interposition graft) and 43 by PTA. After treatment, AVF were monitored by quarterly ultrasound dilution access blood flow measurement. End points were restenosis and procedure failure rate (re-intervention by another technique or access loss), and determinants were analyzed using Cox hazard model. Initial procedural success was 100% for surgery and 95% for PTA (P ‫؍‬ 0.539). Restenosis rate was 0.168 and 0.519 events/AVF-year for surgery and PTA, respectively (P ‫؍‬ 0.009). The type of procedure was the only variable that was significantly associated with restenosis, the adjusted relative risk being 2.77-fold higher (95% confidence interval 1.07 to 7.17; P ‫؍‬ 0.036) after PTA than surgery. The procedure failure rate was 0.110 and 0.097 events/AVF-year for surgery and PTA, respectively (P ‫؍‬ 0.736). The cost profile also was similar for the two procedures. This prospective comparative study confirms a higher restenosis rate after PTA than surgery, but with strict surveillance for restenosis, the two procedures show similar assisted primary patency and cost, suggesting that they should be considered equally valid, complementary alternatives in the preemptive treatment of juxtaanastomotic stenosis in forearm AVF.

SummaryBackground and objectives: Guidelines recommend systematically screening for stenosis using various methods, but no studies so far have compared all of the options. A prospective blinded study was performed to compare the performance of several bedside tests performed during dialysis in diagnosing angiographically proven Ͼ50% fistula stenosis. Design, setting, participants, & measurementsIn an unselected population of 119 hemodialysis patients with mature fistulas, physical examination (PE) was conducted; dynamic and derived static venous pressure (VAPR), blood pump flow/arterial pressure (Qb/AP) ratio, recirculation (R), and access blood flow (Qa) were measured; and angiography was performed.Results Angiography identified 59 stenotic fistulas: 43 stenoses were located upstream from the venous needle (inflow stenosis), 12 were located downstream (outflow stenosis), and 4 were located at both sites. The optimal tests for identifying an inflow stenosis were Qa Ͻ 650 ml/min and the combination of a positive PE "or" Qa Ͻ 650 ml/min (accuracy 80% and 81%, respectively), the latter being preferable because it was more sensitive (85% versus 65%, respectively) for a comparable specificity (79% versus 89%, respectively). The best tests for identifying outflow stenosis were PE and VAPR, with no difference between the two (accuracy 91% and 85%, sensitivity 75% and 81%, specificity 93% and 86%, respectively), the former being preferable because it was more reproducible, easier to perform, and applicable to all fistulas. ConclusionsThis study showed that fistula stenosis can be detected and located during dialysis with a moderate-to-excellent accuracy using PE and Qa measurement as screening procedures.