SUMMARY In 19 patients with unstable angina pectoris at rest, plasma levels of the platelet-derived proteins fl-thromboglobulin and platelet factor 4 were significantly elevated in blood samples obtained during or within 4 hours after episodes of angina, but were usually normal during quiescent intervals. Plasma levels of the arachidonic acid metabolite thromboxane B2 were less clearly related to angina, and there was no association of angina with levels of the coagulation product fibrinopeptide A. This demonstration of an association of platelet activation and secretion with unstable angina pectoris by radioimmunoassay of circulating platelet constituents offers a new approach to assessment of therapy in ischemic heart disease and suggests that agents that alter platelet function should be evaluated in patients with unstable angina.PATIENTS with ischemic heart disease represent a heterogeneous group in whom a variety of pathogenetic factors may be at work to reduce myocardial perfusion. Increasing evidence suggests that classic views of the pathogenesis of angina pectoris and myocardial infarction are oversimplifications. For example, coronary thrombosis is no longer thought to be the inevitable precursor of myocardial infarction.' Further, angina pectoris cannot always be attributed solely to reduction of blood flow through coronary arteries with fixed stenosis from atherosclerosis. With refined techniques of selective angiography, vasospasm has been identified as an important mechanism in variant angina2 and also in effort-induced angina3 and in myocardial infarction.4A critical role has been claimed for products of arachidonic acid metabolism in the control of coronary vasomotor tone. According to this hypothesis, vessel diameter is modulated by a balance between the vasoconstricting effects of thromboxane A2 (TxA2) generated by platelets and the vasodilating action of prostacyclin produced by the vessel wall.8 Thromboxane A2 also induces platelet aggregation, whereas prostacyclin is the most potent inhibitor of aggregation yet discovered.8 Turbulent flow, ulceration and hemorrhage into atherosclerotic plaques may promote platelet adhesion, TxA2 generation and release of other vasoactive substances.9 Reduced production of prostacyclin by diseased vessels would also favor vasoconstriction and platelet aggregation.

Objective: To compare Anti-Xa directed thromboprophylaxis using low molecular weight heparin (LMWH) (anti-Xa peak goal 0.2-0.5 IU/mL) to alternative anticoagulation strategies in critically ill COVID-19 patients. Methods: This was a retrospective, multicenter, single health-system study. Primary outcomes were thromboembolic events and clinically important bleeding events. Secondary outcomes included dosing comparisons between LMWH cohorts. Main Results: A total of 695 patients were included. No differences were found in the incidence of thrombotic events with any of the dosing strategies. The incidence of major bleeding was significantly higher in the standard dose thromboprophylaxis, intermediate dose subcutaneous heparin (SQH), and therapeutic anticoagulation cohorts. Forty-nine percent of patients within the anti-Xa directed group had their first anti-Xa peak at goal, while 43% were above goal. Patients who had levels above goal had dose modifications made, therefore anti-Xa directed LMWH resulted in significantly lower total daily doses compared to intermediate dose LMWH. Conclusions: Anti-Xa directed LMWH dosing provided comparable thromboprophylaxis with lower total daily doses of LMWH in critically ill COVID-19 patients. Further randomized controlled trials are needed to confirm our findings.

Background: Few studies have evaluated the early use of insulin glargine in the management of diabetic ketoacidosis (DKA) patients. Early insulin glargine use in DKA was safe and associated with a trend towards faster DKA resolution. Objectives: To evaluate the efficacy and safety of early insulin glargine administration for acute management of DKA in critically ill patients. Methods: This single-center retrospective cohort study included patients, who were >18 years of age with DKA, admitted to the intensive care unit (ICU) for at least 12 h, and received intravenous insulin infusion for at least 6 h. The primary endpoint was the association between the time to insulin glargine administration and time to DKA resolution. Linear and logistic regression analyses were performed. Results: Of the 913 patients evaluated, 380 were included in the study. The overall mean age was 45±17 years, 196 (51.6%) were female, and 262 (70%) patients had type 1 diabetes mellitus. The mean blood glucose level was 584.9±210 mg/dL, pH was 7.16±0.17, anion gap was 28.17±6.9 mEq/L, and serum bicarbonate level was 11.19±5.72 mEq/L. Every 6-h delay in insulin glargine administration was associated with a 26-min increase in time to DKA resolution (95% confidence interval [CI], 14.76–37.44; p<0.0001), 3.2-h increase in insulin infusion duration (95% CI, 28.8–36; p<0.0001), and 6.5-h increase in ICU LOS (95% CI, 5.04–7.92; p<0.0001). Conclusion: Early administration of insulin glargine is potentially safe and may be associated with a reduction in time to DKA resolution and shorter duration of insulin infusion.

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