Browsing by Author "Haatainen, Hanna-Kaisa"

Hemostasis is a highly regulated process, which enables the repair of damaged blood vessels by clotting but also keeps the blood fluid and removes blood clots when they are no longer needed. There is a variety of medical conditions that could lead to hemostatic malfunction, manifesting in thrombosis and/or bleeding. The aim of this study was to get acquainted with these conditions and the fundamental laboratory methods for screening hemostasis. Another goal was to study APAC variants in these selected test methods. APACs are semisynthetic molecule complexes consisting of human serum albumin (HSA) core and tailored number of covalently bound UFH chains. In several animal models, APACs have established both antiplatelet (AP) and anticoagulant (AC) functions. They target and act locally at the vascular injury site. We used 7 APAC variants differing at their coupling level of UFH (CL). We chose test methods to assess the intrinsic and common coagulation pathways, the activity and concentration of thrombin in clotting plasma, interactions between different agents in coagulation and the ability of collagen to induce platelet activation and aggregation. The chosen methods were Activated Partial Thromboplastin Time (APTT), thrombin time, Rotational Tromboelastometry (ROTEM), the Calibrated Automated Thrombogram (CAT) and Collagen-induced Platelet Aggregation in Platelet-rich plasma (Aggregometer, AggRAM). Generally, all studied APAC variants show dose-dependent inhibition of coagulation that is at least similar, but mostly more efficient compared with plain UFH. At the concentration corresponding to clinically relevant heparin concentration (3 µg/ml), APACs prolong the coagulation globally. At low concentrations they are more potent anticoagulants and thrombin inhibitors than UFH and also inhibit platelet procoagulant activity (PCA). Further studies are needed, however, the results support data that APACs are promising targets for the future drug development.