[Bleeding complications due to anticoagulatoric therapy].

Anticoagulation is a standard treatment in patients with thrombosis and commonly used in surgical procedures for primary thrombosis prophylaxis. The occurrence of bleeding episodes is the predominant treatment complication. Although monitoring of hemostatic parameters reduces the risk of bleeding, bleedings occur in approximately 10% of patients.

Thrombin-induced interleukin 1beta synthesis in platelet suspensions: impact of contaminating leukocytes.

A controversial discussion as to whether human platelets are capable of regulated protein synthesis has been ongoing for over half a century. A previous study has suggested that human platelets synthesize large amounts of interleukin 1beta (IL-1beta) in response to external cues and in a physiologically significant manner. However, cytokines such as IL-1beta are generally considered to be products of leukocytes and it could not be completely excluded that contaminating leukocytes may have contributed to the IL-1beta results in platelet preparations.

Safety of phase I clinical trials with monoclonal antibodies in Germany--the regulatory requirements viewed in the aftermath of the TGN1412 disaster.

This review summarizes scientific, ethical and regulatory aspects of Phase I clinical trials with monoclonal antibodies. The current standard requirements for pre-clinical testing and for clinical study design are presented. The scientific considerations discussed herein are generally applicable, the view on legal requirements for clinical trials refer to the German jurisdiction only.

Platelet-dependent coagulation assays for factor VIII efficacy measurement after substitution therapy in patients with haemophilia A.

FVIII therapy for haemophilia A is safe and effective, with the problem of individually sufficient efficacy unsettled. Routine one-stage clotting assays and tests employing chromogenic substrates poorly detect individual haemostatic effects of FVIII due to artificial test conditions. In particular, the use of cell-free and diluted plasma samples neglect the crucial role of platelets for thrombin and fibrin formation.

Platelet-dependent thrombin generation assay for monitoring the efficacy of recombinant Factor VIIa.

Although the administration of recombinant coagulation factor VIIa (rFVIIa) is a well established treatment in haemophilia with inhibitory antibodies, monitoring the therapeutic efficacy is still a problem. This is because the complete haemostatic effect in vivo depends on negatively charged surfaces provided by exposed lipids from activated platelets which are not present in standard clinical assays using plasma. The thrombin generation assay, however, measures the endogenous thrombin potential (ETP) in platelet-rich plasma (PRP) and this assay might be useful for monitoring the haemostatic response to rFVIIa.