title: Cellular microparticle and thrombogram phenotypes in the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study: correlation with coagulopathy.
abstract: BACKGROUND
  Trauma-induced coagulopathy following severe injury is associated with increased bleeding and mortality. Injury may result in alteration of cellular phenotypes and release of cell-derived microparticles (MP). Circulating MPs are procoagulant and support thrombin generation (TG) and clotting. We evaluated MP and TG phenotypes in severely injured patients at admission, in relation to coagulopathy and bleeding.
  
  
  METHODS
  As part of the Prospective Observational Multicenter Major Trauma Transfusion (PROMMTT) study, research blood samples were obtained from 180 trauma patients requiring transfusions at 5 participating centers. Twenty five healthy controls and 40 minimally injured patients were analyzed for comparisons. Laboratory criteria for coagulopathy was activated partial thromboplastin time (APTT) ≥ 35 sec. Samples were analyzed by Calibrated Automated Thrombogram to assess TG, and by flow cytometry for MP phenotypes [platelet (PMP), erythrocyte (RMP), leukocyte (LMP), endothelial (EMP), tissue factor (TFMP), and Annexin V positive (AVMP)].
  
  
  RESULTS
  21.7% of patients were coagulopathic with the median (IQR) APTT of 44 sec (37, 53), and an Injury Severity Score of 26 (17, 35). Compared to controls, patients had elevated EMP, RMP, LMP, and TFMP (all p<0.001), and enhanced TG (p<0.0001). However, coagulopathic PROMMTT patients had significantly lower PMP, TFMP, and TG, higher substantial bleeding, and higher mortality compared to non-coagulopathic patients (all p<0.001).
  
  
  CONCLUSIONS
  Cellular activation and enhanced TG are predominant after trauma and independent of injury severity. Coagulopathy was associated with lower thrombin peak and rate compared to non-coagulopathic patients, while lower levels of TF-bearing PMPs were associated with substantial bleeding.
authors.affiliation: Center for Translational Injury Research and Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, 6431 Fannin St. MSB 5.240, Houston, TX 77030, USA. Electronic address: Nena.Matijevic@uth.tmc.edu.
authors.forename: Nena
authors.initials: N
authors.lastname: Matijevic
authors.affiliation: Center for Translational Injury Research and Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, 6431 Fannin St. MSB 5.240, Houston, TX 77030, USA. Electronic address: Yao-Wei.W.Wang@uth.tmc.edu.
authors.forename: Yao-Wei W
authors.initials: YW
authors.lastname: Wang
authors.affiliation: Center for Translational Injury Research and Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, 6431 Fannin St. MSB 5.240, Houston, TX 77030, USA. Electronic address: Charles.E.Wade@uth.tmc.edu.
authors.forename: Charles E
authors.initials: CE
authors.lastname: Wade
authors.affiliation: Center for Translational Injury Research and Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, 6431 Fannin St. MSB 5.240, Houston, TX 77030, USA. Electronic address: John.Holcomb@uth.tmc.edu.
authors.forename: John B
authors.initials: JB
authors.lastname: Holcomb
authors.affiliation: Center for Translational Injury Research and Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, 6431 Fannin St. MSB 5.240, Houston, TX 77030, USA. Electronic address: Bryan.A.Cotton@uth.tmc.edu.
authors.forename: Bryan A
authors.initials: BA
authors.lastname: Cotton
authors.affiliation: Division of Trauma, Critical Care and Acute Care Surgery, School of Medicine, Oregon Health & Science University, 3181 Sam Jackson Rd SW, Mail Code L-611, Portland, OR 97035, USA. Electronic address: schreibm@ohsu.edu.
authors.forename: Martin A
authors.initials: MA
authors.lastname: Schreiber
authors.affiliation: Division of Trauma/Critical Care, Department of Surgery, College of Medicine, University of Cincinnati, 222 Piedmont Ave., Suite 7000, Cincinnati, OH 45219, USA. Electronic address: muskatp@ucmail.uc.edu.
authors.forename: Peter
authors.initials: P
authors.lastname: Muskat
authors.affiliation: Center for Translational Injury Research and Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, 6431 Fannin St. MSB 5.240, Houston, TX 77030, USA. Electronic address: Erin.E.Fox@uth.tmc.edu.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Fox
authors.affiliation: Center for Translational Injury Research and Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, 6431 Fannin St. MSB 5.240, Houston, TX 77030, USA. Electronic address: Deborah.J.deljunco@uth.tmc.edu.
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Del Junco
authors.affiliation: Center for Translational Injury Research and Division of Acute Care Surgery, Department of Surgery, Medical School, University of Texas Health Science Center at Houston, 6431 Fannin St. MSB 5.240, Houston, TX 77030, USA. Electronic address: Jessica.C.Cardenas@uth.tmc.edu.
authors.forename: Jessica C
authors.initials: JC
authors.lastname: Cardenas
authors.affiliation: Division of Clinical and Translational Sciences, Department of Internal Medicine, Medical School, Biostatistics/Epidemiology/Research Design Core,Center for Clinical and Translational Sciences and Division of Epidemiology, Human Genetics and Environmental Sciences, School of Public Health, University of Texas Health Science Center at Houston, 1100 Fannin St. UPB 1100.21, Houston, TX 77030, USA. Electronic address: Mohammad.H.Rahbar@uth.tmc.edu.
authors.forename: Mohammad H
authors.initials: MH
authors.lastname: Rahbar
authors.affiliation: Division of General Surgery, Department of Surgery, School of Medicine, University of California San Francisco, 1001 Potrero Ave. Room 3C-38, San Francisco, CA 94110, USA. Electronic address: mcohen@sfghsurg.ucsf.edu.
authors.forename: Mitchell Jay
authors.initials: MJ
authors.lastname: Cohen
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D001778:Blood Coagulation Disorders / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality / Q000628:therapy; D001803:Blood Transfusion; D055252:Cell-Derived Microparticles / Q000378:metabolism*; D005260:Female; D006470:Hemorrhage / Q000097:blood / Q000175:diagnosis / Q000209:etiology* / Q000401:mortality; D006801:Humans; D015601:Injury Severity Score; D008297:Male; D008875:Middle Aged; D010314:Partial Thromboplastin Time; D010641:Phenotype; D011237:Predictive Value of Tests; D011446:Prospective Studies; D012307:Risk Factors; D013916:Thrombelastography; D013917:Thrombin / Q000378:metabolism*; D013925:Thromboplastin / Q000378:metabolism; D014481:United States; D014947:Wounds and Injuries / Q000150:complications* / Q000175:diagnosis / Q000401:mortality; D055815:Young Adult
chemical_list: D015415:Biomarkers; D013925:Thromboplastin; D013917:Thrombin
keywords: Blood coagulation; Cell–derived microparticles; Hemorrhage; Thrombin; Trauma
references.citation: Semin Thromb Hemost. 2008 Oct;34(7):683-91
references.pmid: 19085769
references.citation: Thromb Haemost. 2001 Apr;85(4):639-46
references.pmid: 11341498
references.citation: J Trauma. 2008 Oct;65(4):748-54
references.pmid: 18849786
references.citation: Transfusion. 2009 Dec;49(12):2652-60
references.pmid: 19682336
references.citation: J Trauma Acute Care Surg. 2013 Jul;75(1 Suppl 1):S3-8
references.pmid: 23778508
references.citation: J Trauma Acute Care Surg. 2013 Jul;75(1 Suppl 1):S40-7
references.pmid: 23778510
references.citation: Arterioscler Thromb Vasc Biol. 2006 Dec;26(12):2594-604
references.pmid: 16990554
references.citation: Blood Cells Mol Dis. 2006 Mar-Apr;36(2):182-7
references.pmid: 16466949
references.citation: Br J Haematol. 2003 Dec;123(5):896-902
references.pmid: 14632781
references.citation: Thromb Haemost. 2002 Dec;88(6):943-9
references.pmid: 12529743
references.citation: Thromb Res. 2011 Jul;128(1):35-41
references.pmid: 21421259
references.citation: Am J Respir Crit Care Med. 2008 Dec 1;178(11):1148-55
references.pmid: 18723433
references.citation: Thromb Haemost. 2001 May;85(5):810-20
references.pmid: 11372673
references.citation: J Trauma. 2003 Jul;55(1):39-44
references.pmid: 12855879
references.citation: Semin Thromb Hemost. 2013 Feb;39(1):33-9
references.pmid: 23303566
references.citation: Platelets. 2008 Feb;19(1):9-23
references.pmid: 18231934
references.citation: Vox Sang. 2008 May;94(4):306-14
references.pmid: 18266780
references.citation: J Lab Clin Med. 1992 Apr;119(4):334-45
references.pmid: 1583382
references.citation: J Thromb Haemost. 2009 Aug;7(8):1421-3
references.pmid: 19500241
references.citation: Platelets. 1997;8(2-3):117-24
references.pmid: 20297932
references.citation: Thromb Res. 2010 Apr;125 Suppl 1:S42-5
references.pmid: 20189224
references.citation: Circ Res. 2011 May 13;108(10):1284-97
references.pmid: 21566224
references.citation: JAMA Surg. 2013 Feb;148(2):127-36
references.pmid: 23560283
references.citation: J Trauma. 2005 Mar;58(3):475-80; discussion 480-1
references.pmid: 15761339
references.citation: J Trauma. 2001 Oct;51(4):639-47
references.pmid: 11586152
references.citation: J Thromb Haemost. 2010 Nov;8(11):2571-4
references.pmid: 20831623
references.citation: J Am Coll Cardiol. 2005 May 3;45(9):1467-71
references.pmid: 15862420
references.citation: J Am Coll Surg. 1998 May;186(5):528-33
references.pmid: 9583692
references.citation: J Trauma. 2003 Jan;54(1):114-9; discussion 119-20
references.pmid: 12544906
references.citation: J Trauma. 2011 Jan;70(1):71-9; discussion 79-80
references.pmid: 21217484
references.citation: Thromb Haemost. 1998 Jun;79(6):1111-5
references.pmid: 9657433
references.citation: Blood. 2005 Feb 15;105(4):1515-22
references.pmid: 15486064
references.citation: Pathophysiol Haemost Thromb. 2002 Sep-Dec;32(5-6):249-53
references.pmid: 13679651
references.citation: J Thromb Haemost. 2011 Sep;9(9):1795-803
references.pmid: 21711444
references.citation: Arterioscler Thromb Vasc Biol. 2011 Jan;31(1):27-33
references.pmid: 21160065
references.citation: J Trauma. 2008 May;64(5):1211-7; discussion 1217
references.pmid: 18469643
references.citation: Surgery. 2012 Jun;151(6):831-6
references.pmid: 22316436
references.citation: Resuscitation. 2012 Apr;83(4):459-64
references.pmid: 22001613
references.citation: Thromb Haemost. 2007 Mar;97(3):425-34
references.pmid: 17334510
references.citation: Circulation. 2000 Feb 29;101(8):841-3
references.pmid: 10694520
references.citation: J Trauma. 2004 Apr;56(4):823-30; discussion 830-1
references.pmid: 15187749
references.citation: Ann Chir Gynaecol. 1992;81(3):322-5
references.pmid: 1456710
references.citation: Cell Tissue Res. 2009 Jan;335(1):143-51
references.pmid: 18989704
references.citation: J Thromb Haemost. 2013 Apr 2;:
references.pmid: 23551930
references.citation: Chest. 2007 Jun;131(6):1735-41
references.pmid: 17475637
references.citation: Blood. 1986 Jul;68(1):307-9
references.pmid: 3087440
references.citation: Thromb Res. 2009 Jul;124(3):281-7
references.pmid: 19041119
references.citation: Thromb Haemost. 2008 Jan;99(1):64-70
references.pmid: 18217136
references.citation: Thromb Res. 2012 May;129 Suppl 2:S27-9
references.pmid: 22424856