OBJECTIVE: To assess the effect of aging on the anticoagulant response to warfarin. DESIGN: Retrospective cohort study. SETTING: A university hospital outpatient anticoagulation clinic. PATIENTS: All patients (n = 530) monitored in the anticoagulation clinic over a 10-year period (1980 to 1990). The 530 study patients had a mean age of 61.5 (+/- 14.7) years (age range, 12 to 90 years). The patients were stratified into four age groups: younger than 50 years (n = 97); 50 to 59 years (n = 107); 60 to 69 years (n = 149); and 70 years or older (n = 177). MEASUREMENTS: For each patient, a dose-adjusted mean prothrombin time ratio was calculated by dividing the mean prothrombin time ratio by the mean daily warfarin dose. RESULTS: Older patients were more likely to be female (P less than 0.001), to have more medical problems (P less than 0.001), to be taking more medications (P less than 0.001), and to weigh less than younger patients (P less than 0.001). Across age groups, there were no significant differences in the use of medications that potentiated or inhibited the anticoagulant effects of warfarin. The prothrombin time ratio, when adjusted for dose, was significantly increased in older patients (P less than 0.001). The increased anticoagulant response to warfarin seen with increasing patient age persisted even after simultaneously controlling for relevant demographic and clinical variables in a multivariate model. Other factors significantly associated with an increased sensitivity to warfarin included use of a medication with a potentiating interactive effect with warfarin, female gender, and overall medication use. Increased body weight and duration of warfarin use exceeding 6 months were found to be inversely related to anticoagulant response. CONCLUSION: The anticoagulant response to warfarin is exaggerated with advancing age. This finding emphasizes the need for close monitoring of older patients treated with warfarin therapy.

Long-term oral anticoagulant therapy is critical to the optimal management of various thromboembolic and vascular disorders. To determine whether age is related to the development of bleeding complications in patients who are receiving long-term oral anticoagulant therapy, the records of 321 patients who were followed up in the university hospital outpatient anticoagulation clinic during an eight-year period were reviewed. During this period, 61 patients (19%) developed minor bleeding complications, and 14 patients (4.4%) developed major bleeding complications. In utilizing a life-table approach to adjust for varying lengths of follow-up, the risk of initial minor bleeding complications was found to be greatest within the first three months (14%). For major bleeding complications, risk increased throughout the first two years of anticoagulation clinic follow-up, with no particular period of greatest risk. No significant differences in the risk of initial minor or major bleeding complications were observed in the various age groups that were examined (less than 50, 50 to 59, 60 to 69, and greater than or equal to 70 years). A multivariate regression approach, controlling for several potentially confounding factors, confirmed the lack of an association of age with the risk of minor or major bleeding complications. The results of this retrospective follow-up study suggest that patient age, in and of itself, should not be considered a primary factor in assessing the risk of long-term oral anticoagulant therapy.

A dual radioisotope labeling technique was utilized to assess red cell survival differences between cells processed by either a bubble oxygenator (eight patients) or membrane oxygenator (eight patients) in 16 patients undergoing cardiopulmonary bypass surgery. Cells processed by a bubble oxygenator consistently had a shortened survival. The 30-minute recovery of cells was not significantly different between oxygenators in contradiction to some previous studies using plasma hemoglobin as an indicator of hemolysis. The results of this investigation confirm previous studies that a membrane oxygenator provides a survival advantage to red cells during cardiopulmonary bypass surgery.

Morphological and biochemical differences were demonstrated between prolymphocytic leukemia cells obtained from the spleen and peripheral blood of one patient. Peripheral blood prolymphocytes had consistently smaller nuclear-cytoplasmic ratios than did splenic prolymphocytes. Percoll gradient-purified prolymphocytes from the spleen synthesized abundant amounts of some membrane proteins which were hardly expressed by peripheral blood prolymphocytes. Peripheral blood prolymphocytes did not change their expression of membrane proteins during three days in culture. These findings are consistent with the view that prolymphocytic leukemia cells from the spleen exist, on the average, at an earlier stage of differentiation than do circulating leukemic cells, and that peripheral blood leukemic cells are frozen at a specific phase of differentiation.