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SummaryPerioperative anticoagulant prophylaxis for postoperative venous thromboembolism (VTE) in neurosurgical patients has not gained wide acceptance due to the fear of intracranial bleeding. Physical methods give a worthwhile reduction of postoperative VTE but there still remains a substantial residual incidence. In other clinical indications, low molecular weight heparins have proven to be effective for prophylaxis of VTE when administered postoperatively, with the advantage of no bleeding enhancement during surgery.Therefore, we performed a multicentre, randomized, double-blind trial in neurosurgical patients to investigate the efficacy and safety of adding a low molecular weight heparin (LMWH), nadroparin, initiated postoperatively, to graduated compression stockings in the prevention of VTE. Deep-vein thrombosis was detected by mandatory venography. Bleeding was determined according to pre-defined objective criteria for major and minor episodes.An adequate bilateral venogram was obtained in 166 of 241 LMWH patients (68.9%) and 179 of 244 control patients (73.4%). A total of 31 of 166 LMWH patients (18.7%) and 47 of 179 control patients (26.3%) had VTE up to Day 10 postoperatively (p = 0.047). The relative risk reduction (RRR) was 28.9%. The rates for proximal deep-vein thrombosis/pulmonary embolism were 6.9% and 11.5% for the two groups, respectively (RRR: 40.2%; p = 0.065).Secondary analyses involved all VTE up to day 56 post-surgery which was detected in 33 patients of 241 in the LMWH group (13.7%) and 51 of 244 control patients (20.9%; RRR 34.5%; p = 0.018). The corresponding percentages for proximal deep-vein thrombosis/pulmonary embolism were 5.8% and 10.2% for the two groups, respectively, giving a RRR of 43.3%; p = 0.036. Major bleeding complications, during the treatment period, occurred in six low molecular weight heparin treated patients (2.5%) and in two control patients (0.8%); p = 0.087.A higher mortality was observed in the low molecular weight heparin group over the 56-day follow-up period (22 versus 10; p = 0.026). However, none of these deaths was judged by a blinded adjudication committee to be related to the study drug.In conclusion, this study demonstrates that the low molecular weight heparin, nadroparin, added to graduated compression stockings results in a clinically significant decrease in VTE without inducing any significant increase of major bleeding.

SummaryWe investigated sensitivity to activated protein C (APC) in 43 men, 42 women not using oral contraceptives (OC) and 38 women using OC containing 30.0-37.5 μg ethinyl estradiol. A commercially available kit was used. Men were more sensitive to APC as compared with women not using OC (p <0.005), but this difference seems not to be of clinical importance. Women using OC showed to be significantly less sensitive to APC, reflected by a lower APC-ratio, as compared with men (p <0.005) and women not using OC (p <0.05).So, in normal individuals the APC-sensitivity differs according to sex and estrogen intake. This should be taken into account when interpreting APC-ratios.

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