A hypothesis about how to achieve anticoagulation without bleeding.

The hypothesis is set forth that a prothrombotic state is frequently caused by epinephrine-activated platelets initiating the intrinsic coagulation cascade by binding factor XII, a pathway which is enhanced by stasis. This pathway explains spontaneous non-injury related thrombosis in atrial fibrillation on the arterial side of the circulation and deep vein thrombosis/pulmonary embolism on the venous side of the circulation. Pharmacological interventions directed against targets in this pathway, for example factor XII, the putative factor XII receptor on activated platelets, and the α2-adrenoceptor on platelets, would be expected to provide effective anticoagulation for most clinical indications for anticoagulation without incurring the bleeding risk associated with pharmacological blockade of the extrinsic pathway, which is the limiting factor for conventional anticoagulants. Thrombotic stroke is another possible indication for such a treatment.