Argatroban as a primary or secondary postoperative anticoagulant in patients implanted with ventricular assist devices.

BACKGROUND: We describe our experience with argatroban as a primary or secondary postoperative anticoagulant to heparin in patients receiving ventricular assist devices. METHODS: This is a retrospective review of all Abiomed (BVS5000, AB5000) and Thoratec (PVAD and IVAD) ventricular assist devices from May 2003 through May 2006 at a single institution. Postoperatively, patients received either heparin or argatroban as their anticoagulant. Patients in whom heparin-induced thrombocytopenia was suspected or confirmed were converted from heparin to argatroban. RESULTS: There were 33 Abiomed and Thoratec ventricular assist devices implanted. Thirteen patients received heparin as their primary postoperative anticoagulant; 8 of the 13 were converted to argatroban as a secondary anticoagulant (hep-arg), and 5 patients remained with heparin as their only anticoagulant. Twenty patients received argatroban as their primary and only postoperative anticoagulant. Thrombocytopenia occurred in 26 patients (79%) overall, 16 (80%) with argatroban only, 6 (75%) with hep-arg, and 4 (80%) with heparin only. Thromboembolic events occurred in 5 patients (15%) overall, 3 (15%) with argatroban only, 1 (13%) with hep-arg, and 1 (20%) with heparin only. Postoperative bleeding requiring reexploration occurred in 5 patients overall (15%), 1 with argatroban only (5%), 3 (38%) with hep-arg, and 1 (20%) with heparin only. Enzyme-linked immunosorbent assay heparin-induced thrombocytopenia tests were positive in 7 patients overall (21%), 5 (25%) with argatroban only, 2 (25%) with hep-arg, and 0 (0%) with heparin only. CONCLUSIONS: Argatroban is a comparable primary or secondary anticoagulant to heparin postoperatively in patients receiving ventricular assist devices.

Altered trafficking of Fas and subsequent resistance to Fas-mediated apoptosis occurs by a wild-type p53 independent mechanism in esophageal adenocarcinoma.

BACKGROUND: Decreased cell-surface expression of Fas (CD95) results in resistance to Fas-mediated apoptosis in esophageal adenocarcinoma (EA). Because p53 is known to increase transcription of Fas and also may induce trafficking of the protein to the plasma membrane, we investigated whether the loss of wild-type (wt)-p53 function accounts for our previous findings. MATERIALS AND METHODS: Surgical specimens of Barrett's Esophagus containing areas of dysplasia were immunostained for p53 and Fas protein expression. Three EA cell lines were transfected with a wt-p53 containing adenovirus to examine the effects of p53 overexpression. The p53 status of these EA cell lines was determined by sequence analysis. RESULTS: Regions of dysplasia where p53 protein accumulation was observed corresponded to areas of loss of Fas expression. Sequence analysis of the p53 coding sequence in three EA cell lines (Seg-1, Bic-1, and Flo-1) that retain Fas protein within the cytoplasm, demonstrated that Seg-1 contained wt-p53, but mutations were found in Flo-1 and Bic-1 cell lines. Adenoviral transduction of the cell lines with wt-p53 resulted in cell growth arrest in Seg-1 and Bic-1 and induced cell death in Flo-1, but did not result in an increase in Fas protein expression, cell-surface expression, or restoration of sensitivity to Fas-mediated apoptosis. CONCLUSIONS: These data suggest that decreased cell-surface expression of Fas and resistance to Fas-mediated apoptosis may occur independently of loss of wt p53 expression.