Screening of Anticoagulant & Antithrombotic Drugs

Scope, rationale & organising framework

• What is screened — an experimental / methodology topic — the deliverable is the graded battery of in-vitro, ex-vivo & in-vivo assays that detect, quantify & rank a candidate's ability to inhibit coagulation, platelet activation/aggregation or established thrombi (thrombolysis), with parallel assessment of its bleeding liability — NOT clinical anticoagulant pharmacotherapy.
• Pathophysiological anchor — Virchow's triad — (1) stasis of flow, (2) hypercoagulability, (3) vessel-wall injury; every thrombosis model deliberately reproduces one, two or all three arms, which is why models differ by prothrombotic challenge, vessel type & species.
• Two thrombus phenotypes drive model choice — arterial ("white") thrombi — high shear, platelet-rich + little fibrin, modelled by wall injury/stenosis, predict antiplatelet efficacy; venous ("red") thrombi — low shear, fibrin-rich + few platelets, modelled by stasis/procoagulant, predict anticoagulant efficacy. The dichotomy is not strict.
• Hierarchy of testing (the cascade) — global in-vitro coagulation/platelet assays → ex-vivo tests on blood from dosed animals → in-vivo thrombosis models → bleeding-time (hemostasis) models — moving up increasing physiological relevance.
• Golden rule — validate in >1 model + a bleeding readout — models run in healthy animals lack the chronic human substrate (atherosclerosis, thrombophilia), so a new antithrombotic must be confirmed in more than one model and a hemostatic parameter included wherever possible — clinical usefulness is set by the safety/efficacy (bleeding-risk) ratio.