Author/Editor		Blinc, A
Title		Transport of fibrinolytic agents as a rate-limiting step in fibrinolysis and thrombolysis
Type		članek
Source		In: Pathophysiological, clinical and laboratory aspects of thromboembolic disease. Proceedings of the 8th advanced teaching course in thrombosis and haemostasis; 2001 Mar 22-27; Kranjska gora. Ljubljana: University medical center, Department of angiology,
Publication year		2001
Volume		str. 153-65
Language		eng
Abstract		Transport of fibrinolytic agents into thrombi represents a rate-limiting step in therapeutic thrombolysis. Mathematical modeling predicts and experimental models demonstrate that effective delivery of fibrinolytic agents into clots is the most important determinant of fibrinolytic rate. Transport by diffusion is slow and limited by the need for a high concentration gradient. Transport by convection is more efficient and depends both on the intrinsic resistance of the thrombus and on the effective pressure gradient. Animal experiments indicate that delivery of activator into the thrombus accelerates fibrinolysis and that the fibrinolytic rate is dependent on the pressure gradient to which the clot is exposed. Clinical observations are consistent with a dominant role of transport in determining thrombolytic efficacy. Systemic thrombolysis is most successful in short clots exposed to a high pressure gradient; such as coronary artery thrombi in normotensive or hypertensive patients. Rapid lysis is also achieved by intrathrombic delivery of plasminogen activator into peripheral arterial clots and thrombosed dialysis access fistulas. In contrast, systemic thrombolysis is much less successful in clots that are exposed to an insufficient pressure gradient, such as venous thrombi or coronary artery thrombi of patients in cardiogenic shock.
Descriptors		THROMBOLYTIC THERAPY FIBRINOLYTIC AGENTS CLOT RETRACTION DRUG DELIVERY SYSTEMS MODELS, THEORETICAL TREATMENT OUTCOME