Follow-up of thrombin generation after prostate cancer surgery: global test for increased hypercoagulability.

Recent studies provided evidence that evaluation of thrombin generation identifies patients at thrombotic risk. Thrombin generation has a central role in hemorrhage control and vascular occlusion and its measurement provides new metrics of these processes providing sufficient evaluation of an individual's hemostatic competence and response to anticoagulant therapy. The objective of the study is to assess a new measure of hypercoagulability that predisposes to venous thromboembolism in the postoperative period after radical prostatectomy. Pre- (day-1) and postoperative (hour 1, day 6, month 1 and 10) blood samples of 24 patients were tested for plasma thrombin generation (peak thrombin), routine hematology and hemostasis. Patients received low molecular weight heparin for thromboprophylaxis. Peak thrombin levels were higher in patients compared to controls at baseline (p<0.001), and elevated further in the early postoperative period (p<0.001). Longer general anesthesia and high body mass index were associated with increased thrombin generation after surgery (p = 0.024 and p = 0.040). D dimer and fibrinogen levels were higher after radical prostatectomy (p = 0.001 and p<0.001). Conventional clotting tests remained within the reference range. Our study contributed to the cognition of the hypercoagulable state in cancer patients undergoing pelvic surgery and revealed the course of thrombin generation after radical prostatectomy. Whilst it is unsurprising that thrombin generation increases after tissue trauma, further evaluation of this condition during the postoperative period would lead urologists to an international and well-supported consensus regarding thromboprophylaxis in order to provide better clinical outcome. Considering the routine evaluation of procoagulant activity and extending prophylactic anticoagulant therapy accordingly may potentially prevent late thrombotic events

Dasatinib inhibits coated-platelet generation in patients with chronic myeloid leukemia

Since the introduction of tyrosine kinase inhibitors, the overall survival of patients with chronic myeloid leukemia has markedly improved. However long term use of these drugs results in various adverse events. Treatment with second generation dasatinib is often complicated by hemorrhagic events. Previous lumi-aggregometry studies have shown impaired platelet function in patients on dasatinib therapy. Dual agonist activated platelets (coated-platelets) are also sensitive indicators of platelet function. We hypothesized that dual activation with convulxin and thrombin of platelets in a flow cytometric assay could be a more sensitive method for detecting platelet dysfunction as compared to single agonist studies used in lumi-aggregometer. Platelets of healthy volunteers incubated with dasatinib as well as platelets from patients on dasatinib therapy were investigated. Low therapeutic plasma level dasatinib concentrations at which a considerable reduction in coated-platelet generation was observed in vitro, did not cause detectable change in platelet aggregation response. Coated-platelet assay and lumi-aggregometry were also investigated at 0, 1 and 4 hours after drug administration in dasatinib treated CML patients. Significant decrease was observed at 1 hour in maximal aggregation by collagen. Although the aggregation curves became normalized by 4 hours, coated-platelet generation was still inhibited in dasatinib treated patients. Nilotinib, another second generation tyrosine kinase inhibitor, had no effect on aggregation and on coated-platelet formation neither in vitro nor in ex vivo samples. At therapeutic plasma levels coated-platelet assay is more sensitive than lumi-aggregometry studies for the demonstration of the inhibitory effect of dasatinib on platelet function

Routine test results of patients before and following radical prostatectomy.

1<p>Results are given as mean and ±SD or median and 25–75 percentile values, depending on the normality of the test results. P values are also calculated according to the distribution of the given data series and the option of paring: i.e. “preoperative results” to the “results of the controls” with unpaired t test (with Welch’s correction or Mann Whitney test); “postoperation results” to the “preoperative results” with Paired t test (and Wilcoxon signed rank test). Preoperative data were compared to controls and the results of the postoperative samples were compared to the preoperative ones (day-1).</p>2<p>reference range of the method applied.</p>3<p>mean±2SD of pooled control samples (n = 20) in the period of the study.</p>4<p>ND = not determined.</p><p>Bold letters indicate significant differences.</p

Specific test results of patients before and following radical prostatectomy.

1<p>Results are given as mean and ±SD or median and 25–75 percentile values, depending on the normality of the test results. P values are also calculated according to the distribution of the given data series and the option of pairing. Preoperative data were compared to controls and the results of the postoperative samples were compared to the preoperative ones (day-1).</p>2<p>limit of detection.</p>3<p>No LMWH therapy.</p><p>Bold letters indicate significant differences.</p

Thrombin generation parameters: Whiskers: 5–95 percentile graphs of peak thrombin (A), area under the curve (B), lag time (C) and peak time (D).

<p>Labels of significance: *p<0.05, **p<0.01, ***p<0.001.</p

Multiple loci influence erythrocyte phenotypes in the CHARGE Consortium

Erythrocyte measures are heritable and have important health implications, yet their genetic determinants are largely unknown. We performed genome-wide association analyses in 24,167 European-ancestry individuals for six erythrocyte traits and identified associations at 23 loci (P values 5×10(-8) to 1×10(-57)). Replication testing in an independent set of 9,456 European-ancestry individuals showed strong evidence of association in all 23 loci in meta-analysis of the discovery and replication cohorts. Our findings include previously identified loci (HBS1L/MYB, HFE, TMPRSS6, TFR2, SPTA1) and novel associations (EPO, TFRC, SH2B3, and 15 other loci). This study has identified novel determinants of erythrocyte traits, offering insight into common variants underlying variation in erythrocyte measures