The optimal procedure for withdrawal of warfarin in patients with deep vein thrombosis (DVT) is still not defined. Rebound thrombin generation, which occurs after the withdrawal of warfarin, has been said to be associated with early recurrence of DVT. The aim of this study was to compare two procedures for warfarin withdrawal after the first episode of DVT with respect to rebound thrombin generation. Forty-one consecutive patients were randomly assigned to abrupt withdrawal of warfarin (group A), or to an additional month of warfarin, at the fixed dose of 1.25 mg/day (group B). Plasma samples were withdrawn for the assay of prothrombin fragment F1+2 (F1+2), protein C, factor VII and International Normalized Ratio (INR), before any anticoagulant treatment (I), during initial heparin (II) and full dose warfarin (III), at the end of full dose warfarin (IV) and then 1 (V), 4 (VI), 5 (VII) and 9 (VIII) weeks after randomization. The mean duration of full-dose warfarin treatment, the mean warfarin dose and the mean INR during full-dose warfarin treatment were similar in the two groups. A decrease in F1+2 was observed during heparin and warfarin treatment (II, 1.7 nmol/ml; III, 1.0 nmol/ml; IV, 0.7 nmol/ml; versus I, 3.5 nmol/ml; P<0.01). After the withdrawal of warfarin, an increase in F1+2 was observed in both groups, but without significant statistical differences (group A: V, 1.2 nmol/ml; VI, 1.5 nmol/ml; VII, 1.6 nmol/ml; VIII, 1.1 nmol/ml; group B: V, 1.3 nmol/ml; IV, 1.5 nmol/ml; VII, 1.4 nmol/ml; VIII, 1.4 nmol/ml). No significant difference between the two groups was observed in the recovery of protein C and factor VII. Four patients experienced a recurrence of DVT, three in group B and one in group A. Our findings confirm that rebound thrombin generation occurs in patients with DVT after the withdrawal of warfarin. Rebound thrombin generation is not reduced by a low, fixed dose of warfarin.
Perioperative stroke is an ischemic or hemorrhagic cerebrovascular accident that can arise intraoperatively or from 3 to 30 days after surgery. This relatively rare complication deserves attention because of its high mortality and serious disability, the latter of which can lead to prolonged hospital stay as well as discharge to long-term care facilities. The aim of this article was to review the literature on perioperative stroke in general surgery, excluding carotid and cardiac surgeries because these have already been thoroughly investigated in previous papers.A search strategy was designed to identify all relevant studies on perioperative stroke in the English language. This search was restricted to papers published up to December 5, 2011. Studies were initially identified from the Medline/PubMed database, EMBASE and the Cochrane Database using the search terms 'surgery', 'perioperative stroke', 'risk factors', 'anticoagulation treatment' and 'antiplatelet treatment'.The incidence of perioperative stroke among patients who undergo nonvascular surgery is reported to be about 0.08-0.7%. This depends on the type and complexity of the surgical procedure along with patient risk factors. The reported perioperative mortality is 18-26%. One of the main issues is the management of patients taking anticoagulant or antiplatelet drugs, as the risk of bleeding has to be counterbalanced with the risk of arterial thrombosis due to discontinuation. Additionally, the presence of symptomatic carotid stenosis should be taken into account in the risk evaluation.To date, current guidelines are incomplete regarding the management of patients with vascular disease undergoing nonvascular surgery. It is recommended to stop oral anticoagulation approximately 5 days before major surgery to adequately allow the INR to normalize, and at the same time subcutaneous low-molecular-weight heparin or intravenous unfractionated heparin should be started. Regarding new anticoagulants, dabigatran does not need to be withheld for minor procedures. Currently, there are no clear recommendations on the use of rivaroxaban and apixaban. Data concerning the management of patients undergoing antiplatelet therapy are lacking. To date, neurologists discourage the perioperative withdrawal of aspirin (acetylsalicylic acid, ASA) especially in patients in secondary prevention. The 'Antiplatelet Agents in the Perioperative Management of Patients Trial' is ongoing to assess the safety and determine the optimal use of ASA in the perioperative management of patients undergoing general and abdominal surgery. In the meantime an individualized, accurate, multidisciplinary (surgical, neurological, cardiological and anesthesiological) risk/benefit assessment remains the best basis for treatment decision.
Venous thromboembolism (VTE), which includes pulmonary embolism and deep vein thrombosis, is a leading cause of morbidity and mortality worldwide. Based on new evidence, the management and treatment of VTE have changed over the years. For several decades, low molecular weight heparin and vitamin K antagonists have been the two cornerstones of anticoagulant therapy for VTE. Recently, the introduction in clinical practice of the new oral anticoagulants has radically changed the management of VTE for their easy use and their better efficacy and safety profile. Here, we report on recent evidence of 10 still controversial clinical questions concerning common diagnostic and therapeutic aspects of VTE.
