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Blood, 15 May 2008, Vol. 111, No. 10, pp. 4958-4964. Prepublished online as a Blood First Edition Paper on February 6, 2008; DOI 10.1182/blood-2007-11-123620. This Article Full Text Full Text (PDF) Supplemental Videos All Versions of this Article: blood-2007-11-123620v1 111/10/4958    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Goerge, T. Articles by Wagner, D. D. Search for Related Content PubMed PubMed Citation Articles by Goerge, T. Articles by Wagner, D. D. Related Collections Hemostasis, Thrombosis, and Vascular Biology Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Inflammation induces hemorrhage in thrombocytopenia Tobias Goerge1,2,*, Benoit Ho-Tin-Noe1,2,*, Carla Carbo1,3, Charaf Benarafa1,4, Eileen Remold-O'Donnell1,4, Bing-Qiao Zhao1,2, Stephen M. Cifuni1, and Denisa D. Wagner1,2 1 Immune Disease Institute and 2 Department of Pathology, Harvard Medical School, Boston, MA; 3 Servei d'Hemoterapia-Hemostasia, Hospital Clinic, Universitat de Barcelona, Spain; and 4 Department of Pediatrics, Harvard Medical School, Boston, MA The role of platelets in hemostasis is to produce a plug to arrest bleeding. During thrombocytopenia, spontaneous bleeding is seen in some patients but not in others; the reason for this is unknown. Here, we subjected thrombocytopenic mice to models of dermatitis, stroke, and lung inflammation. The mice showed massive hemorrhage that was limited to the area of inflammation and was not observed in uninflamed thrombocytopenic mice. Endotoxin-induced lung inflammation during thrombocytopenia triggered substantial intra-alveolar hemorrhage leading to profound anemia and respiratory distress. By imaging the cutaneous Arthus reaction through a skin window, we observed in real time the loss of vascular integrity and the kinetics of skin hemorrhage in thrombocytopenic mice. Bleeding—observed mostly from venules—occurred as early as 20 minutes after challenge, pointing to a continuous need for platelets to maintain vascular integrity in inflamed microcirculation. Inflammatory hemorrhage was not seen in genetically engineered mice lacking major platelet adhesion receptors or their activators (IIbβ3, glycoprotein Ib [GPIb], GPVI, and calcium and diacylglycerol-regulated guanine nucleotide exchange factor I [CalDAG-GEFI]), thus indicating that firm platelet adhesion was not necessary for their supporting role. While platelets were previously shown to promote endothelial activation and recruitment of inflammatory cells, they also appear indispensable to maintain vascular integrity in inflamed tissue. Based on our observations, we propose that inflammation may cause life-threatening hemorrhage during thrombocytopenia. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: How do platelets prevent bleeding? Bernhard Nieswandt Blood 2008 111: 4835. [Full Text] [PDF] This article has been cited by other articles: S. J. Stanworth, P. Clarke, T. Watts, S. Ballard, L. Choo, T. Morris, M. F. Murphy, I. Roberts, and for the Platelets and Neonatal Transfusion Study G Prospective, Observational Study of Outcomes in Neonates With Severe Thrombocytopenia Pediatrics, November 1, 2009; 124(5): e826 - e834. [Abstract] [Full Text] [PDF] B.-Q. Zhao, A. K. Chauhan, M. Canault, I. S. Patten, J. J. Yang, M. Dockal, F. Scheiflinger, and D. D. Wagner von Willebrand factor-cleaving protease ADAMTS13 reduces ischemic brain injury in experimental stroke Blood, October 8, 2009; 114(15): 3329 - 3334. [Abstract] [Full Text] [PDF] B. Ho-Tin-Noe, C. Carbo, M. Demers, S. M. Cifuni, T. Goerge, and D. D. Wagner Innate Immune Cells Induce Hemorrhage in Tumors during Thrombocytopenia Am. J. Pathol., October 1, 2009; 175(4): 1699 - 1708. [Abstract] [Full Text] [PDF] J. Hirahashi, K. Hishikawa, S. Kaname, N. Tsuboi, Y. Wang, D. I. Simon, G. Stavrakis, T. Shimosawa, L. Xiao, Y. Nagahama, et al. Mac-1 (CD11b/CD18) Links Inflammation and Thrombosis After Glomerular Injury Circulation, September 29, 2009; 120(13): 1255 - 1265. [Abstract] [Full Text] [PDF] B. Ho-Tin-Noe, T. Goerge, and D. D. Wagner Platelets: Guardians of Tumor Vasculature Cancer Res., July 15, 2009; 69(14): 5623 - 5626. [Abstract] [Full Text] [PDF] G. Stoll, C. Kleinschnitz, and B. Nieswandt Molecular mechanisms of thrombus formation in ischemic stroke: novel insights and targets for treatment Blood, November 1, 2008; 112(9): 3555 - 3562. [Abstract] [Full Text] [PDF] B. Ho-Tin-Noe, T. Goerge, S. M. Cifuni, D. Duerschmied, and D. D. Wagner Platelet Granule Secretion Continuously Prevents Intratumor Hemorrhage Cancer Res., August 15, 2008; 68(16): 6851 - 6858. [Abstract] [Full Text] [PDF] D. D. Wagner and P. S. Frenette The vessel wall and its interactions Blood, June 1, 2008; 111(11): 5271 - 5281. [Abstract] [Full Text] [PDF] M. A. Blajchman, S. J. Slichter, N. M. Heddle, and M. F. Murphy New Strategies for the Optimal Use of Platelet Transfusions Hematology, January 1, 2008; 2008(1): 198 - 204. [Abstract] [Full Text] [PDF]

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