Simon Karpatkin, MD
Leading journal hails findings as ‘breakthrough’
Doctors Simon Karpatkin and Zongdong Li of the Department of Medicine and eight colleagues, all from the NYU Langone Medical Center, have published their discovery of a new mechanism dissolving thrombi and protecting against carotid artery blockage and cerebral stroke.
Their study, chosen as a plenary paper in the June 11, 2009 edition of the journal Blood was accompanied by a commentary, which states: “Li et al describe a surprising new role for thrombin: promoting the dissolution of platelet thrombi,” and characterize the findings as a “breakthrough.” Dr. Karpatkin is the director of the Division of Hematology in the Department of Medicine.
The journal Blood is published by the American Society of Hematology. According to the journal’s website, “with 1,250 articles published annually, [it has] an impact factor of 10.896, and an Immediacy Index of 2.458,” and “Blood is the most cited peer-reviewed publication in the field,” providing “an international forum for the publication of original articles describing basic laboratory, translational, and clinical investigations in hematology.” (http://bloodjournal.hematologylibrary.org/about/about.dtl)
ABSTRACT:
Anti-platelet integrin GPIIIa49-66 antibody (Ab) induces complement-independent platelet oxidative fragmentation and death by generation of platelet peroxide following NADPH oxidase activation. A C-terminal 385–amino acid fragment of ADAMTS-18 (a disintegrin metalloproteinase with thrombospondin motifs produced in endothelial cells) induces oxidative platelet fragmentation in an identical kinetic fashion as anti–GPIIIa49-66 Ab. Endothelial cell ADAMTS-18 secretion is enhanced by thrombin and activated by thrombin cleavage to fragment platelets. Platelet aggregates produced ex vivo with ADP or collagen and fibrinogen are destroyed by the C-terminal ADAMTS-18 fragment. Anti–ADAMTS-18 Ab shortens the tail vein bleeding time. The C-terminal fragment protects against FeCI3-induced carotid artery thrombosis as well as cerebral infarction in a postischemic stroke model. Thus, a new mechanism is proposed for platelet thrombus clearance, via platelet oxidative fragmentation induced by thrombin cleavage of ADAMTS-18.Blood, 11 June 2009, Vol. 113, No. 24, pp. 6051-6060. Prepublished online as a Blood First Edition Paper on February 13, 2009; DOI 10.1182/blood-2008-07-170571.
PLENARY PAPER
C-terminal ADAMTS-18 fragment induces oxidative platelet fragmentation, dissolves platelet aggregates, and protects against carotid artery occlusion and cerebral stroke
Zongdong Li1, Michael A. Nardi2, Yong-Sheng Li3, Wei Zhang1, Ruimin Pan1, Suying Dang1, Herman Yee4, David Quartermain3, Saran Jonas3, and Simon Karpatkin1
Departments of 1 Medicine, 2 Pediatrics, 3 Neurology, and 4 Pathology, New York University School of Medicine, NY
COMMENT:
Blood. 2009 Jun 11;113(24):6046-7.
Comment on: Blood. 2009 Jun 11;113(24):6051-60. Is thrombin the problem or (dis)solution?
Monash University.
PMID: 19520814
