[Successful treatment of venous thromboembolism with a Factor Xa inhibitor, edoxaban, in patients with lenalidomide-treated multiple myeloma].

Two multiple myeloma (MM) patients developed venous thromboembolism (VTE) while being treated with lenalidomide and low-dose dexamethasone. Aspirin is recommended for VTE prophylaxis when using lenalidomide/dexamethasone for MM patients with a standard risk of VTE. Despite aspirin administration, however, these two patients experienced VTE. Following VTE development, warfarin and then a Factor Xa inhibitor, edoxaban, were administered. The edoxaban treatment, especially, resulted in favorable and effective control of VTE. Considering these observations, Factor Xa inhibitors may in future become a preferred option for prevention and treatment of VTE when managing MM patients.

Evaluation of coagulant activity after mechanical heart valve replacement.

Long-term oral anticoagulant therapy is required for recipients of mechanical heart valves. In our hospital, the international normalized ratio of prothrombin time (PT-INR) has been set in the range 1.5-2.5 since October 2001. To evaluate whether coagulant activity is fully suppressed by this target range, coagulant activity was evaluated by measuring thrombin-antithrombin III complex (TAT) levels and valve-related complications were investigated retrospectively. Two hundred twenty-three patients who underwent mechanical valve replacement were enrolled in this study. PT-INR and TAT were measured at our outpatient clinic in March 2005 and valve-related complications since October 2001, when we started to control PT-INR in the range 1.5-2.5, were investigated. Under adequate warfarin control, there was no significant correlation between PT-INR and TAT, however nine patients who exhibited a PT-INR of less than 2.0 had high levels of TAT. And in atrial fibrillation (AF) patients after mitral valve replacement (MVR), the level of TAT was significantly high compared with sinus rhythm patients after atrial valve replacement. Valve-related complications were bleeding events at 2.75% per patient year and thromboembolism at 0.32% per patient year. Attention to complications of thromboembolism is necessary when the PT-INR is less than 2.0, especially in AF patients after MVR and in those with a thrombotic past history or high levels of TAT. The monitoring of TAT is useful in detecting potential coagulation factors and to determine the therapeutic range of warfarin that can normalize coagulant activity.

Dose-dependent inhibition of myointimal hyperplasia by orally administered rapamycin.

Myointimal hyperplasia (MIH) after vascular intervention is a major problem. Recent reports describing elimination of within-stent restenosis by means of rapamycin-eluting stents prompted us to examine the effect of systemic oral rapamycin on MIH induced by arterial trauma. We studied the effect of oral rapamycin on MIH after rabbit aorta balloon injury. Thirty-five New Zealand white rabbits (2.5-3 kg) had aortic injury and were given either no rapamycin (control), 0.1 (low dose) rapamycin mg/kg/day, or 0.4 mg/kg/day (high dose). Rapamycin was started 1 week before injury and continued for 3 (4 weeks total) or 6 weeks (7 weeks total) post-injury. Sections were analyzed to measure aortic intima/media area ratios (I:M) at either 3 or 6 weeks. At 3 weeks, the I:M (mean +/- SD) for controls was 0.53 +/- 0.1; for low dose, 0.17 +/- 0.13; and for high dose, 0.24 +/- 0.07 (p < 0.001 vs. control). At 6 weeks, the I:M for controls was 0.52 +/- 0.12; for low dose-4 weeks, 0.29 +/- 0.15; low dose-7 weeks, 0.33 +/- 0.07; and high dose-4 weeks, 0.47 +/- 0.16. At 6 weeks only the difference between the low dose-4 weeks and control I:M ratios was significant (p = 0.018). The results confirm earlier studies showing that systemic rapamycin inhibits MIH after arterial injury when drug therapy is started before injury. Therapy for 3 or 6 weeks after injury yields similar inhibition, indicating that exposure to the drug early in the response to injury is more important than prolonged exposure. We observed a paradoxical relation between dose and degree of MIH inhibition, with the low dose being more effective than the high dose at both time intervals studied. Overall, the results suggest that oral rapamycin therapy might be a useful adjunct to clinical interventions at risk for development of MIH.