Gram-negative bacteria release LPS, which activates Toll-like-receptor-4 (TLR4) in the host, initiating an inflammatory response to infection. Infection increases risk for thrombosis. Platelets contribute to defense from infection and to thrombosis. Experiments were designed to determine whether LPS, through TLR4 signaling, affects platelet phenotype. Platelet responses in wild-type (WT) mice and mice that lack the TLR4 gene (dTLR4) were compared following a single nonlethal injection of LPS (0.2 mg/kg iv). Compared with WT mice, mice without TLR4 had fewer circulating platelets with lower RNA content and were less responsive to thrombin-activated expression of P-selectin but were equally sensitive to aggregation or ATP secretion. One week following the LPS injection, the time it takes for the circulating platelet pool to turnover, the number of circulating platelets, thrombin-induced expression of P-selectin, and collagen-activated aggregation were increased comparably in both groups of mice. Therefore, the change of the platelet pool to an activated phenotype 1 wk after a single exposure to LPS appears to arise from a process that is independent of TLR4. The persistence of the effect 1 wk after the injection suggests that the changes reflect an action of LPS on megakaryocytes and their platelet progeny rather than on circulating platelets, which would have been cleared.

IMPORTANCE Guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) recommend intensive statin therapy and adding nonstatin therapy if low-density lipoprotein cholesterol (LDL-C) levels are 70 mg/dL or more. Compliance with guidelines is often low.OBJECTIVE To track LDL-C treatment patterns in the US over 2 years. DESIGN, SETTING, AND PARTICIPANTS GOULD is a prospective observational registry study involving multiple centers. Patients with ASCVD receiving any lipid-lowering therapy (LLT) were eligible. Between December 2016 and July 2018, patients were enrolled in 1 of 3 cohorts: (1) those currently receiving proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) and 2 groups not receiving PCSK9i drugs, with (2) LDL-C levels of 100 mg/dL or more or (3) LDL-C levels of 70 to 99 mg/dL. Patients had medical record reviews and telephone interviews every 6 months. Analysis was done on data collected as of October 5, 2020. MAIN OUTCOMES AND MEASURESThe primary outcome was the change in LLT use in 2 years. Secondary outcomes included the number of LDL-C measurements, LDL-C levels, and responses to structured physician and patient questionnaires over 2 years.RESULTS A total of 5006 patients were enrolled (mean [SD] age, 67.8 [9.9] years; 1985 women [39.7%]; 4312 White individuals [86.1%]). At 2 years, 885 (17.1%) had LLT intensification. In the cohorts with LDL-C levels of 100 mg/dL or more and 70 to 99 mg/dL, LLT intensification occurred in 403 (22.4%) and 383 (14.4%), respectively; statins were intensified in 115 (6.4%) and 168 (6.3%), ezetimibe added in 123 (6.8%) and 118 (4.5%), and PCSK9i added in 114 (6.3%) and 58 (2.2%), respectively. In the PCSK9i cohort, 508 of 554 (91.7%) were still taking PCSK9i at 2 years. Lipid panels were measured at least once over 2 years in 3768 patients (88.5%; PCSK9i cohort, 492 [96.1%]; LDL-C levels Ն100 mg/dL or more, 1294 [85.9%]; 70-99 mg/dL, 1982 [88.6%]). Levels of LDL-C fell from medians (interquartile ranges) of 120 (108-141) mg/dL to 95 (73-118) mg/dL in the cohort with LDL-C levels of 100 mg/dL or more, 82 (75-89) to 77 (65-90) mg/dL in the cohort with LDL-C levels of 70 to 99 mg/dL, and 67 (42-104) mg/dL to 67 (42-96) mg/dL in the PCSK9i cohort. Levels of LDL-C less than 70 mg/dL at 2 years were achieved by 308 patients (21.0%) and 758 patients (33.9%) in the cohorts with LDL-C levels of 100 mg/dL or more and 70 to 99 mg/dL, respectively, and 272 patients (52.4%) in the PCSK9i cohort. At 2 years, practice characteristics were associated with more LLT intensification (teaching vs nonteaching hospitals, 148 of 589 [25.1%] vs 600 of 3607 [16.6%]; lipid protocols or none, 359 of 1612 [22.3%] vs 389 of 2584 [15.1%]; cardiology, 452 of 2087 [21.7%] vs internal or family medicine, 204 of 1745 [11.7%] and other, 92 of 364 [25.3%]; all P < .001) and achievement of LDL-C less than 70 mg/dL (teaching vs nonteaching hospitals, 173 of 488 [35.5%] vs 823 of 2986 [27.6%]; lipid protocols vs none, 451 of 1411 [32.0%] vs 545 of 2063 [26.4%]; both P < .001; cardi...

BACKGROUND: Anticoagulation protocols used during mechanical circulatory support call for titration of antiplatelet agents. We compared the precision and reliability of 5 platelet function tests in healthy volunteers and donors on daily antiplatelet therapy to distinguish their efficacy for titrating antiplatelet therapy.

No abstract

Estrogen receptor beta (betaER) is the predominant estrogen receptor in platelets. Experiments were designed to define phenotypic changes in platelets with aging following deletion of betaER (betaERKO). Blood was collected from wild-type and betaERKO female mice at 4-7 (young) and 24-25 (aged) months of age. In young animals, total number of platelets, number of platelets containing RNA (reticulated platelets), aggregation, dense body adenosine triphosphate secretion, and alpha granular secretion were the same in both groups. With aging, total number of platelets decreased but reticulated platelets increased in betaERKO mice; aggregation and dense granule adenosine triphosphate secretion decreased whereas basal expression of fibrinogen receptors increased with age in wild-type and betaERKO mice. Basal expression of P-selectin and annexin V binding increased with aging only in betaERKO mice; thrombin did not increase expression in these mice. Therefore, deletion of betaER is associated with specific platelet functions, which are expressed only with age-associated reproductive senescence.