Characteristics of the amiodarone-warfarin interaction during long-term follow-up.

PURPOSE: Characteristics of the amiodarone-warfarin interaction during long-term follow-up were studied. METHODS: Medical records from patients seen in the anticoagulation clinic at the Hennepin County Medical Center between April 1998 and March 2003 were retrospectively reviewed. Patients were included if they were older than 18 years, used the anticoagulation clinic as their primary clinic for anticoagulation therapy, and were receiving combined amiodarone and warfarin therapy for at least one month. The primary study endpoint was the occurrence of International Normalized Ratios (INRs) of >5 at any time during combined warfarin-amiodarone therapy. The secondary endpoint was the frequency of warfarin dosage changes. RESULTS: A total of 70 patients met study inclusion criteria. Of these 70, 7 had amiodarone started before warfarin initiation. Of the 2434 INR values analyzed, 43% (n = 1043) were in the target therapeutic range, 34% (n = 820) were below target range, and 23% (n = 571) were above target range. A total of 102 INR values (4%) were above 5. The relative risk of having an INR of >5 for patients on concurrent warfarin and amiodarone versus those on warfarin alone was 1.366 (p = 0.005). INRs of >5 were most common during the first 12 weeks of combined therapy, with no subsequent large peaks evident. CONCLUSION: Among patients treated in an anticoagulation clinic, INR values of >5 were most common during the first 12 weeks of combined therapy with amiodarone and warfarin and necessitated reduction in warfarin dosage. No other notable changes in INR or amiodarone or warfarin dosage occurred throughout the remainder of the 80-week study period.

Sickle blood contains tissue factor-positive microparticles derived from endothelial cells and monocytes.

Blood microparticles (MPs) in sickle cell disease (SCD) are reportedly derived only from erythrocytes and platelets. Yet in SCD, endothelial cells and monocytes are activated and abnormally express tissue factor (TF). Thus, sickle blood might contain TF-positive MPs derived from these cells. With the use of flow cytometry to enumerate and characterize MPs, we found total MPs to be elevated in crisis (P =.0001) and steady state (P =.02) in subjects with sickle cell disease versus control subjects. These MPs were derived from erythrocytes, platelets, monocytes, and endothelial cells. Erythrocyte-derived MPs were elevated in sickle crisis (P =.0001) and steady state (P =.02) versus control subjects, as were monocyte-derived MPs (P =.0004 and P =.009, respectively). Endothelial and platelet-derived MPs were elevated in sickle crisis versus control subjects. Total TF-positive MPs were elevated in sickle crisis versus steady state (P =.004) and control subjects (P <.0001) and were derived from both monocytes and endothelial cells. Sickle MPs shortened plasma-clotting time compared with control MPs, and a TF antibody partially inhibited this procoagulant activity. Markers of coagulation were elevated in patients with sickle cell disease versus control subjects and correlated with total MPs and TF-positive MPs (P <.01 for both). These data support the concept that SCD is an inflammatory state with monocyte and endothelial activation and abnormal TF activity.