No abstract

Our study underlines that maximum PAI-1 plasma antigen levels not exceeding 120 ng/ml have a strong negative predictive value in the diagnosis of VOD and thus represent a helpful non-invasive tool for exclusion of VOD after HSCT.

Hypercoagulability is a key contributor to acute cardiovascular syndromes and to various microcirculatory disorders. The use of heparin-mediated extracorporeal low-density lipoprotein/fibrinogen precipitation (HELP) apheresis makes a controlled, immediately effective reduction of clotting factors possible, and induces subsequent positive effects on plasma viscosity, erythrocyte aggregation, and microcirculation. Oxygen supply to an ischemic artery can thus be increased without hemodilution, qualifying the HELP system as a possible therapeutic tool in the treatment of acute cardiovascular syndromes and microcirculatory disorders.

Clinical use of heart assist devices is often associated with thromboembolic complications. We hypothesized that platelets may be activated in patients receiving assist devices and examined expression of the platelet activation markers CD62, CD63, and thrombospondin using flow cytometry in eight patients with Novacor left ventricular assist system (LVAS) or Berlin Heart. Patients with end-stage heart failure had elevated expression of platelet activation markers before insertion of the assist device. While CD62 (P < 0.05) and thrombospondin expression (n.s.) decreased by the 14th postoperative day, the CD63 expression remained elevated (n.s.). A good correlation was found between CD62 and thrombospondin expression (r = 0.72). Bleeding time ex vivo indicated platelet dysfunction during the first 4 weeks after implantation. No relation between expression of platelet activation markers and bleeding time ex vivo were found. In conclusion, expression of the platelet activation markers CD62, CD63, and thrombospondin is increased in patients with end-stage heart failure before device placement and shows prolonged elevation during the assist period. Future studies in larger patient populations are necessary to identify new and specific markers of platelet activation in this clinical setting.

A recently published post-hoc analysis of a trial using high-dose antithrombin (AT) in septic patients (KyberSept) revealed significant reduction of lethality when no concomitant heparin was administered, whereas patients with the combination of heparin and AT did not benefit in terms of survival. Therefore, it seems feasible to study the capability of AT in prevention of microvascular thrombus formation to avoid concomitant application of heparin and AT. Using fluorescence microscopy and a light/dye-injury mouse ear model, the kinetics of thrombus formation were analyzed quantitatively in vivo upon single iv bolus of saline (control), heparin (100 IU/kg), hirudin (1 mg/kg) or AT (25, 50, 100 or 250 IU/kg) (N = 7 animals per group each). In controls, light/dye-injury induced complete thrombotic occlusion in all arterioles and venules studied. Heparin and hirudin prevented thrombotic vessel occlusion in 62% and 43% of arterioles and 11% and 28% of venules. AT-250 was found to be more effective than heparin and hirudin, because thrombus formation was completely banned in all arterioles and venules. AT-100 and AT-50 were also capable of significantly blocking thrombus formation in both arterioles and venules. In blood vessels, which finally clogged, the time for development of complete vessel occlusion was delayed after heparin, hirudin and AT-25, but in particular after AT-50 and AT-100. In conclusion, AT-mediated antithrombotic activity has been characterized in a model of phototoxicity-induced microvascular thrombosis formation, demonstrating that AT delays and prevents thrombus formation in arterioles and venules at least comparably effective as heparin and hirudin.