The Shear Stress of Busting Blood Clots

• Published in: The New England journal of medicine Vol. 367; no. 14; pp. 1361 - 1363
• Main Authors: Wootton, David M, Alevriadou, B. Rita
• Format: Journal Article
• Language: English
• Published: United States Massachusetts Medical Society 04.10.2012
• Subjects: Animal models; Animals; Blood coagulation; Drug Carriers; Drug dosages; Embolism; Fibrinolytic Agents - administration & dosage; Hemorheology; Hemorrhage; Humans; Hydrodynamics; Mice; Myocardial infarction; Nanoparticles; Shear stress; Thrombosis; Thrombosis - drug therapy; Tissue Plasminogen Activator - administration & dosage
• ISSN: 0028-4793; 1533-4406
• DOI: 10.1056/NEJMcibr1207994

Systemic delivery of tissue-type plasminogen activator (t-PA) to dissolve a thrombus after a heart attack or stroke is accompanied by the risk of hemorrhage. A recent study shows the use of nanoaggregates to target t-PA to the thrombus in mouse models of mesenteric injury and pulmonary embolism. “Clot-busting” fibrinolytic drugs are administered to patients who have had a heart attack or ischemic stroke. These drugs are delivered systemically or, when possible, locally through a catheter placed within the obstructed vessel. Korin and colleagues 1 found that if tissue-type plasminogen activator (t-PA) is packaged in a “shear-activated nanotherapeutic” (SA-NT) particle, local blood-flow profiles can distribute the drug to where it is needed most. The results of their study involving mouse models of acute arterial thrombosis and pulmonary embolism suggest that the total administered dose can be reduced by a factor of approximately 100, as compared with intravenously delivered t-PA. . . .