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Blood activation is a coordinated physiological response involving the plasma cascades—specifically the coagulation, complement, and contact systems—along with cellular elements like platelets and leukocytes [3, 15]. This process is triggered by vascular injury or exposure to non-biological surfaces, such as those found in extracorporeal life support (ECLS) systems and medical implants [2, 5]. While essential for wound healing and defense against pathogens, pathological blood activation is a major driver of thrombosis, systemic inflammatory response syndrome (SIRS), and atherosclerotic cardiovascular diseases [1, 14]. Therapeutic strategies do not target 'blood activation' as a single entity; instead, they focus on specific molecular nodes like Thrombin, Factor Xa, or P2Y12 receptors to mitigate clinical risks [4, 12]. Additionally, in traditional medicine, 'blood activation' (Huoxue) refers to a therapeutic concept for resolving blood stasis, typically addressed by multi-target botanical compounds [1, 13].
Drugs modulate blood activation by inhibiting specific proteolytic enzymes in the coagulation or complement cascades, antagonizing surface receptors on platelets, or interfering with signaling pathways like MAPK and PI3K to prevent pathological thrombus formation and systemic inflammation.
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