MANAGEMENT AND PROGNOSIS OF LIFE-THREATENING BLEEDING DURING WARFARINTHERAPY

Background: The incidence of explicity defined life-threatening bleedi ng during warfarin sodium therapy is largely unknown, as are the progn osis for and treatment of patients who have such bleeding. In addition , the location of the source of the life-threatening bleeding and the risk factors associated with life-threatening bleeding are not well-de fined. Objectives: To determine the incidence of explicitly defined li fe-threatening bleeding during warfarin therapy, to identify the site of bleeding, to determine the risk factors for life-threatening bleedi ng, and to determine the risk of subsequent bleeding among patients re ceiving warfarin therapy. Methods: A cross-sectional prevalence study was conducted and data were combined with those obtained during prospe ctive observation of a dynamic cohort of patients followed up in 2 uni versity-affiliated and 3 Veterans Administration anticoagulation clini cs. Results: For this study, 1999 patients were followed up for 3865 p atient-years; 32 patients (11 women, 21 men, mean age of 69 years) met criteria for life-threatening bleeding, an incidence of 0.83 events/1 00 patient-years (95% confidence interval, 0.54-1.12). The most common indication for warfarin was to prevent thromboembolism because the pa tient had a mechanical heart valve (17/32 patients, 53%). The gastroin testinal tract was the definite or Likely site of bleeding in 21 (66%) of the 32 patients. The prothrombin lime ratio was longer than 2.0 or the international normalized ratio was longer than 4.5 in 16 (55%) of the 29 patients in whom a coagulation time was measured. Fourteen (44 %) of the 32 patients had a history of peptic ulcer disease or gastroi ntestinal bleeding. Warfarin was restarted in 26 (81%) of the 32 patie nts. Twenty-five of 26 patients were followed up for a median of 30 mo nths (range, 5-143 months); 14 (56%) of the 25 patients had a subseque nt bleeding event, with 8 (57%) of the 14 having 1 or more additional life-threatening bleeding events (1 fatal) after a median of 11.5 mont hs (range, 0.5-22 months). Conclusions: We conclude that in this cohor t: (1) the incidence of life-threatening bleeding was rare, (2) the ga strointestinal tract was the site of bleeding in two thirds of the pat ients who experienced life-threatening bleeding, (3) most patients who experienced life-threatening bleeding had multiple risk factors for b leeding, including excessive anticoagulation, and (4) the risk of subs equent bleeding was extremely high among the patients who continued to receive warfarin therapy.