title: Low molecular weight heparin and compression stockings in the prevention of venous thromboembolism in neurosurgery.
abstract: Perioperative 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 controls 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 = 0.36. 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 = 0.87. 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.
authors.affiliation: Center for Hemostasis, Thrombosis, Atherosclerosis and Inflammation Research, Academic Medical Center, Amsterdam.
authors.forename: M T
authors.initials: MT
authors.lastname: Nurmohamed
authors.forename: A M
authors.initials: AM
authors.lastname: van Riel
authors.forename: C M
authors.initials: CM
authors.lastname: Henkens
authors.forename: M M
authors.initials: MM
authors.lastname: Koopman
authors.forename: G T
authors.initials: GT
authors.lastname: Que
authors.forename: P
authors.initials: P
authors.lastname: d'Azemar
authors.forename: H R
authors.initials: HR
authors.lastname: Büller
authors.forename: J W
authors.initials: JW
authors.lastname: ten Cate
authors.forename: J A
authors.initials: JA
authors.lastname: Hoek
authors.forename: J
authors.initials: J
authors.lastname: van der Meer
authors.forename: C
authors.initials: C
authors.lastname: van der Heul
authors.forename: A G
authors.initials: AG
authors.lastname: Turpie
authors.forename: S
authors.initials: S
authors.lastname: Haley
authors.forename: A
authors.initials: A
authors.lastname: Sicurella
authors.forename: M
authors.initials: M
authors.lastname: Gent
mesh_terms: D000925:Anticoagulants / Q000009:adverse effects / Q000627:therapeutic use*; D001458:Bandages; D003131:Combined Modality Therapy; D004311:Double-Blind Method; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D017762:Nadroparin / Q000009:adverse effects / Q000627:therapeutic use*; D009493:Neurosurgery; D011183:Postoperative Complications / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*; D011655:Pulmonary Embolism / Q000209:etiology / Q000401:mortality / Q000517:prevention & control; D013924:Thrombophlebitis / Q000209:etiology / Q000401:mortality / Q000517:prevention & control*
chemical_list: D000925:Anticoagulants; D017762:Nadroparin