Thrombocytopenia and Mortality Risk in Patients With Atrial Fibrillation: An Analysis From the START Registry

Background: Thrombocytopenia is associated with increased mortality in the general population, but few data exist in patients with atrial fibrillation (AF) taking oral anticoagulants. We investigated factor determinants of thrombocytopenia in a large cohort of patients affected by AF and its association with total mortality. Methods and Results: Multicenter prospective cohort study, including 5215 patients with AF from the START (Survey on Anticoagulated Patients Register) registry, 3877 (74.3%) and 1338 (25.7%) on vitamin K or non\u2013vitamin K antagonist oral anticoagulants, respectively. Thrombocytopenia was defined by a platelet count <150 7109/L. Determinants of thrombocytopenia were investigated, and all-cause mortality was the primary survival end point of the study. Thrombocytopenia was present in 592 patients (11.4%). At multivariable logistic regression analysis, chronic kidney disease (odds ratio [OR], 1.257; P=0.030), active cancer (OR, 2.065; P=0.001), liver cirrhosis (OR, 7.635; P<0.001), and the use of diuretics (OR, 1.234; P=0.046) were positively associated with thrombocytopenia, whereas female sex (OR, 0.387; P<0.001) and the use of calcium channel blockers (OR, 0.787; P=0.032) were negatively associated. During a median follow-up of 19.2 months (9942 patient-years), 391 deaths occurred (rate, 3.93%/year). Mortality rate increased from 3.8%/year to 9.9%/year in patients with normal platelet count and in those with moderate-severe thrombocytopenia, respectively (log-rank test, P=0.009). The association between moderate-severe thrombocytopenia and mortality persisted after adjustment for CHA2DS2 VASc score (hazard ratio, 2.431; 95% CI, 1.254\u20134.713; P=0.009), but not in the fully adjusted multivariable Cox regression analysis model. Conclusions: Thrombocytopenia is common in patients with AF. Despite an increased incidence of mortality, thrombocytopenia was not associated with mortality at multivariable analysis. Thrombocytopenia may reflect the presence of comorbidities associated with poor survival in AF

Platelet aggregation studies : autologous platelet-poor plasma inhibits platelet aggregation when added to platelet-rich plasma to normalize platelet count

Adjusting platelet count (PC) in platelet-rich plasma (PRP) using platelet-poor plasma (PPP) is recommended for platelet aggregation (PA) studies, but it could also affect PA independently of the decrease in PC. Analysis of aggregation tracings from healthy controls showed that PC correlated with PA in 47 diluted-PRPs, but not in 104 undiluted- PRPs. Dilution of 9 PRPs with PPP progressively decreased PA, while dilution of washed platelets with buffer hardly affected PA. Apyrase partially prevented the inhibitory effect of PPP. Therefore, the practice of diluting PRP with PPP to adjust platelet count should be avoided because it artefactually inhibits P

Determination of total homocysteine in plasma: comparison of the Abbott Imx immunoassay with high performance liquid chromatography

Background and Objectives. The aim of this study was to compare the performance of a commercially available IMx immunoassay with that of a reversed-phase high performance liquid chromatography (HPLC) method for measuring plasma total homocysteine (tHcy). Methods. The levels of tHcy before and after oral methionine loading (ML) were measured in 135 healthy subjects and 39 patients scheduled for routine tHcy determination. The IMx method uses fluorescence polarization immunoassay (FPIA) technology. The HPLC-method includes derivatization with ABD-F and post-column fluorescence detection. Results. The imprecision was very low with both methods for both normal (11 \u3bcmol/L) and high (29 \u3bcmol/L) tHcy levels. The within and between-run coefficients of variation were < 5%. Both methods were able to discriminate between similar concentrations of tHcy both at normal and moderately high levels. There was a good correlation between measurements obtained with the two methods (r = 0.985, p = 0.001). The mean levels of tHcy measured with the IMx assay tended to be slightly higher than those with the HPLC both in the fasting state (mean difference = 0.8 \u3bcmol/L) and after ML (5.3 \u3bcmol/L). However only the difference in post-ML levels was statistically significant (p < 0.001). The percentage of patients with hyperhomocysteinemia identified with the two methods was similar. Interpretation and Conclusions. The IMx method compares well with an established HPLC method for measurement of fasting tHcy plasma levels

Effects of 5'-phosphate derivatives of 2-hexynyl adenosine and 2-phenylethynyl adenosine on responses of human platelets mediated by P2Y receptors

Newly synthesized mono-, di-, and triphosphate of 2-alkynyl adenosines showed very different behavior in human platelet P2Y receptor models, according to the different alkynyl chains. In fact, 2-hexynyladenosine di- (5) and triphosphate (7) induced platelet shape change and aggregation and inhibited PGE(1)-induced increase in platelet cyclic AMP. On the contrary, the corresponding 2-phenylethynyladenosine di- (6) and triphosphate (8) did not induce platelet shape change or aggregation, but inhibited platelet aggregation induced by ADP

Inhibition of platelet functions and thrombosis through selective or nonselective inhibition of the platelet P2 receptors with increasing doses of NF449 [4,4',4'',4'''-(carbonylbis(imino-5,1,3-benzenetriylbis-(carbonylimino)))tetrakis -benzene-1,3-disulfonic acid octasodium salt]

Our aim was to determine whether the newly described P2X1 antagonist NF449 [4,4\u2032,4\u2033,4\u2034-(carbonylbis(imino-5,1,3- benzenetriylbis(carbonylimino)))tetrakis-benzene-1,3-disulfonic acid octasodium salt] could selectively antagonize the platelet P2X1 receptor and how it affected platelet function. NF449 inhibited \u3b1,\u3b2- methyleneadenosine 5\u2032-triphosphate-induced shape change (IC50 = 83 \ub1 13 nM; n = 3) and calcium influx (pA2 = 7.2 \ub1 0.1; n = 3) (pIC50 = 6.95) in washed human platelets treated with apyrase to prevent desensitization of the P2X1 receptor. NF449 also antagonized the calcium rise mediated by the P2Y1 receptor, but with lower potency (IC50 = 5.8 \ub1 2.2 \u3bcM; n = 3). In contrast, it was a very weak antagonist of the P2Y12-mediated inhibition of adenylyl cyclase activity. Selective blockade of the P2X1 receptor with NF449 led to reduced collagen-induced aggregation, confirming a role of this receptor in platelet activation induced by collagen. Intravenous injection of 10 mg/kg NF449 into mice resulted in selective inhibition of the P2X 1 receptor and decreased intravascular platelet aggregation in a model of systemic thromboembolism (35 \ub1 4 versus 51 \ub1 3%) (P = 0.0061; n = 10) but without prolongation of the bleeding time (106 \ub1 16 versus 78 \ub1 7 s; n = 10) (N.S.; P = 0.1209). At a higher dose (50 mg/kg), NF449 inhibited the three platelet P2 receptors. This led to a further reduction in platelet consumption compared with mice injected with saline (13 \ub1 4 versus 42 \ub1 3%) (P = 0.0002; n = 5). NF449 also reduced dose-dependently the size of thrombi formed after laser-induced injury of mesenteric arterioles. Overall, our results indicate that NF449 constitutes a new tool to investigate the functions of the P2X1 receptor and could be a starting compound in the search for new antithrombotic drugs targeting the platelet P2 receptors. Copyrigh