title: Patients requiring interruption of long-term oral anticoagulant therapy: the use of fixed sub-therapeutic doses of low-molecular-weight heparin.
abstract: BACKGROUND
  We tested the efficacy and safety of fixed doses of low-molecular-weight heparin (LMWH) in patients requiring interruption of vitamin-K antagonist (VKA) because of invasive procedures.
  
  
  METHODS
  Preoperatively, patients discontinued VKA for 5 +/- 1 days; in those at low risk for thrombosis, LMWH was given at a prophylactic dosage of 3800 UI (nadroparin) or 4000 UI (enoxaparin) anti-factor (F) Xa once daily the night before the procedure. In patients at high risk for thrombosis, LMWH was started early after VKA cessation and given at fixed sub-therapeutic doses (3800 or 4000 UI anti-FXa twice daily) until surgery. Postoperatively, LMWH was reinitiated 12 h after procedure while VKA was reinitiated the day after. Heparin was continued until a therapeutic INR value was reached. The primary efficacy endpoints were the incidence of thromboembolism and major bleeding from VKA suspension (because of surgery) up to 30 +/- 2 days postprocedure.
  
  
  RESULTS
  A total of 328 patients (55.4% at low risk and 44.6% at high risk for thrombosis) were enrolled; 103 (31.4%) underwent major surgery and 225 (68.6%) non-major invasive procedures. Overall, thromboembolic events occurred in six patients (1.8%, 95% confidence interval 0.4-3.2), five belonging to the high-risk group and one belonging to the low-risk group. Overall, major bleeding occurred in seven patients (2.1%, 95 confidence interval 0.6-3.6), six patients belonged to the high-risk group and one belonged to the low-risk group; most of the events occurred in the high-risk group during major surgery.
  
  
  CONCLUSIONS
  LMWH given at fixed sub-therapeutic doses appears to be a feasible and safe approach for bridging therapy in chronic anticoagulated patients.
authors.affiliation: Cattedra ed U.O. di Ematologia con trapianto, Azienda Ospedaliera Universitaria Policlinico P. Giaccone, Palermo, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Malato
authors.forename: G
authors.initials: G
authors.lastname: Saccullo
authors.forename: L
authors.initials: L
authors.lastname: Lo Coco
authors.forename: D
authors.initials: D
authors.lastname: Caramazza
authors.forename: I
authors.initials: I
authors.lastname: Abbene
authors.forename: G
authors.initials: G
authors.lastname: Pizzo
authors.forename: A
authors.initials: A
authors.lastname: Casuccio
authors.forename: S
authors.initials: S
authors.lastname: Siragusa
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000008:administration & dosage* / Q000009:adverse effects; D004334:Drug Administration Schedule; D017984:Enoxaparin / Q000008:administration & dosage; D065427:Factor Xa Inhibitors; D005240:Feasibility Studies; D005260:Female; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D008297:Male; D008875:Middle Aged; D017762:Nadroparin / Q000008:administration & dosage; D019106:Postoperative Hemorrhage / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D011446:Prospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D013514:Surgical Procedures, Operative / Q000009:adverse effects*; D013923:Thromboembolism / Q000097:blood / Q000209:etiology / Q000517:prevention & control*; D013997:Time Factors; D014812:Vitamin K / Q000037:antagonists & inhibitors; D014859:Warfarin / Q000008:administration & dosage* / Q000009:adverse effects
chemical_list: D000925:Anticoagulants; D017984:Enoxaparin; D065427:Factor Xa Inhibitors; D006495:Heparin, Low-Molecular-Weight; D017762:Nadroparin; D014812:Vitamin K; D014859:Warfarin