Download PDF
Semin Thromb Hemost 2019; 45(05): 509-513
DOI: 10.1055/s-0039-1688570
Review Article
Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Tissue Factor-Negative Cell-Derived Microparticles Play a Distinctive Role in Hemostasis: A Viewpoint Review

Lawrence L. Horstman
1   University of Miami Miller School of Medicine, Miami, Florida
,
Robert F. McCauley
1   University of Miami Miller School of Medicine, Miami, Florida
,
Wenche Jy
1   University of Miami Miller School of Medicine, Miami, Florida
,
Yeon S. Ahn
1   University of Miami Miller School of Medicine, Miami, Florida
› Author Affiliations
Further Information

Publication History

Publication Date:
13 June 2019 (online)

    Permissions and Reprints

Abstract

Circulating cell-derived microparticles (MPs) exhibit procoagulant activity and have been investigated for a possible role in some human pathologies. However, their potential role in hemostasis has been neglected and often denied. This review brings to attention a specific body of direct clinical evidence supporting an important but distinctive role of MPs in hemostasis. Evidence for a role of MPs in hemostasis includes: (1) two congenital bleeding disorders attributed to impaired release of MPs; (2) two recent studies of trauma patients relating naturally elevated endogenous MPs at admission to reduced transfusion requirements and better outcomes; (3) a study of coronary surgery patients showing that elevated MP before surgery reduces transfusion requirements during surgery; and (4) a clinical study of patients with immune thrombocytopenia demonstrating that those with high circulating MP have reduced bleeding compared to patients with similar platelet counts but lower MP levels. Mechanisms involving potentiating the contact factor pathway are thought to play a key role and are probably synergistic with polyphosphate released from activated platelets at sites of endothelial injury. Hemostatic defect of patients with deficient MP-mediated coagulation resembles deficiency of FXI (hemophilia C), distinct from hemophilia A or B, so can be termed type C hemostasis. A better understanding of this proposed hemostatic pathway may lead to improved methods for controlling excessive bleeding in surgery, trauma, and other clinical settings.

Keywords

cell-derived microparticles - extracellular vesicles - hemostasis - contact pathway - coagulation
 

  • References

  • 1 Weyrich AS, Schwertz H, Mackman N. Platelet tissue factor comes of age. Blood 2007; 109 (12) 5069-5070
    CrossrefPubMedGoogle Scholar
  • 2 Panes O, Matus V, Sáez CG, Quiroga T, Pereira J, Mezzano D. Human platelets synthesize and express functional tissue factor. Blood 2007; 109 (12) 5242-5250
    CrossrefPubMedGoogle Scholar
  • 3 Bouchard BA, Mann KG, Butenas S. No evidence for tissue factor on platelets. Blood 2010; 116 (05) 854-855
    PubMedGoogle Scholar
  • 4 Biró E, Sturk-Maquelin KN, Vogel GM. , et al. Human cell-derived microparticles promote thrombus formation in vivo in a tissue factor-dependent manner. J Thromb Haemost 2003; 1 (12) 2561-2568
    CrossrefPubMedGoogle Scholar
  • 5 Osterud B, Bjorklid E. Tissue factor in blood cells and endothelial cells. Front Biosci (Elite Ed) 2012; 4: 289-299
    PubMedGoogle Scholar
  • 6 Ridger VC, Boulanger CM, Angelillo-Scherrer A. , et al. Microvesicles in vascular homeostasis and diseases. Position paper of the European Society of Cardiology (ESC) Working Group on Atherosclerosis and Vascular Biology. Thromb Haemost 2017; 117 (07) 1296-1316
    Article in Thieme ConnectPubMedGoogle Scholar
  • 7 Suades R, Padró T, Badimon L. The role of blood-borne microparticles in inflammation and hemostasis. Semin Thromb Hemost 2015; 41 (06) 590-606
    Article in Thieme ConnectPubMedGoogle Scholar
  • 8 Gilbert GE, Sims PJ, Wiedmer T, Furie B, Furie BC, Shattil SJ. Platelet-derived microparticles express high affinity receptors for factor VIII. J Biol Chem 1991; 266 (26) 17261-17268
    CrossrefPubMedGoogle Scholar
  • 9 Owens III AP, Mackman N. Microparticles in hemostasis and thrombosis. Circ Res 2011; 108 (10) 1284-1297
    CrossrefPubMedGoogle Scholar
  • 10 Mooberry MJ, Key NS. Microparticle analysis in disorders of hemostasis and thrombosis. Cytometry A 2016; 89 (02) 111-122
    CrossrefPubMedGoogle Scholar
  • 11 Brooks MB, Randolph J, Warner K, Center S. Evaluation of platelet function screening tests to detect platelet procoagulant deficiency in dogs with Scott syndrome. Vet Clin Pathol 2009; 38 (03) 306-315
    CrossrefPubMedGoogle Scholar
  • 12 Toti F, Satta N, Fressinaud E, Meyer D, Freyssinet JM. Scott syndrome, characterized by impaired transmembrane migration of procoagulant phosphatidylserine and hemorrhagic complications, is an inherited disorder. Blood 1996; 87 (04) 1409-1415
    CrossrefPubMedGoogle Scholar
  • 13 Stout JG, Bassé F, Luhm RA, Weiss HJ, Wiedmer T, Sims PJ. Scott syndrome erythrocytes contain a membrane protein capable of mediating Ca2+-dependent transbilayer migration of membrane phospholipids. J Clin Invest 1997; 99 (09) 2232-2238
    CrossrefPubMedGoogle Scholar
  • 14 Jy W, Horstman LL, Wang F, Duncan RC, Ahn YS. Platelet factor 3 in plasma fractions: its relation to microparticle size and thromboses. Thromb Res 1995; 80 (06) 471-482
    CrossrefPubMedGoogle Scholar
  • 15 Chou ML, Lin LT, Devos D, Burnouf T. Nanofiltration to remove microparticles and decrease the thrombogenicity of plasma: in vitro feasibility assessment. Transfusion 2015; 55 (10) 2433-2444
    CrossrefPubMedGoogle Scholar
  • 16 Castaman G, Yu-Feng L, Battistin E, Rodeghiero F. Characterization of a novel bleeding disorder with isolated prolonged bleeding time and deficiency of platelet microvesicle generation. Br J Haematol 1997; 96 (03) 458-463
    CrossrefPubMedGoogle Scholar
  • 17 Stormorken H, Holmsen H, Sund R. , et al. Studies on the haemostatic defect in a complicated syndrome. An inverse Scott syndrome platelet membrane abnormality?. Thromb Haemost 1995; 74 (05) 1244-1251
    Article in Thieme ConnectPubMedGoogle Scholar
  • 18 Misceo D, Holmgren A, Louch WE. , et al. A dominant STIM1 mutation causes Stormorken syndrome. Hum Mutat 2014; 35 (05) 556-564
    CrossrefPubMedGoogle Scholar
  • 19 Stormorken H, Sjaastad O, Langslet A, Sulg I, Egge K, Diderichsen J. A new syndrome: thrombocytopathia, muscle fatigue, asplenia, miosis, migraine, dyslexia and ichthyosis. Clin Genet 1985; 28 (05) 367-374
    PubMedGoogle Scholar
  • 20 Windeløv NA, Johansson PI, Sørensen AM. , et al. Low level of procoagulant platelet microparticles is associated with impaired coagulation and transfusion requirements in trauma patients. J Trauma Acute Care Surg 2014; 77 (05) 692-700
    CrossrefPubMedGoogle Scholar
  • 21 Matijevic N, Wang YW, Holcomb JB, Kozar R, Cardenas JC, Wade CE. Microvesicle phenotypes are associated with transfusion requirements and mortality in subjects with severe injuries. J Extracell Vesicles 2015; 4: 29338
    CrossrefPubMedGoogle Scholar
  • 22 Park MS, Xue A, Spears GM. , et al. Thrombin generation and procoagulant microparticle profiles after acute trauma: a prospective cohort study. J Trauma Acute Care Surg 2015; 79 (05) 726-731
    CrossrefPubMedGoogle Scholar
  • 23 Jy W, Gómez-Marín O, Salerno TA. , et al. Presurgical levels of circulating cell-derived microparticles discriminate between patients with and without transfusion in coronary artery bypass graft surgery. J Thorac Cardiovasc Surg 2015; 149 (01) 305-311
    CrossrefPubMedGoogle Scholar
  • 24 Jy W, Horstman LL, Arce M, Ahn YS. Clinical significance of platelet microparticles in autoimmune thrombocytopenias. J Lab Clin Med 1992; 119 (04) 334-345
    PubMedGoogle Scholar
  • 25 Fontana V, Jy W, Dudkiewicz P, Ahn E, Horstmann L, Ahn YS. Cell-derived microparticles in ITP patients with vs. without bleeding tendency. Blood 2007; 110 (11) 2092
    PubMedGoogle Scholar
  • 26 Giesen PLA, Nemerson Y. Tissue factor on the loose. Semin Thromb Hemost 2000; 26 (04) 379-384
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Van Der Meijden PE, Van Schilfgaarde M, Van Oerle R, Renné T, ten Cate H, Spronk HM. Platelet- and erythrocyte-derived microparticles trigger thrombin generation via factor XIIa. J Thromb Haemost 2012; 10 (07) 1355-1362
    CrossrefPubMedGoogle Scholar
  • 28 Rubin O, Delobel J, Prudent M. , et al. Red blood cell-derived microparticles isolated from blood units initiate and propagate thrombin generation. Transfusion 2013; 53 (08) 1744-1754
    CrossrefPubMedGoogle Scholar
  • 29 Aleman MM, Gardiner C, Harrison P, Wolberg AS. Differential contributions of monocyte- and platelet-derived microparticles towards thrombin generation and fibrin formation and stability. J Thromb Haemost 2011; 9 (11) 2251-2261
    CrossrefPubMedGoogle Scholar
  • 30 Lipets E, Vlasova O, Urnova E. , et al. Circulating contact-pathway-activating microparticles together with factors IXa and XIa induce spontaneous clotting in plasma of hematology and cardiologic patients. PLoS One 2014; 9 (01) e87692
    CrossrefPubMedGoogle Scholar
  • 31 Boknäs N, Faxälv L, Lindahl TL, Ramström S. Contact activation: important to consider when measuring the contribution of tissue factor-bearing microparticles to thrombin generation using phospholipid-containing reagents. J Thromb Haemost 2014; 12 (04) 515-518
    CrossrefPubMedGoogle Scholar
  • 32 Morrissey JH, Smith SA. Polyphosphate as modulator of hemostasis, thrombosis, and inflammation. J Thromb Haemost 2015; 13 (Suppl. 01) S92-S97
    CrossrefPubMedGoogle Scholar
  • 33 Gruber A. The role of the contact pathway in thrombus propagation. Thromb Res 2014; 133 (Suppl. 01) S45-S47
    PubMedGoogle Scholar
  • 34 Naito K, Fujikawa K. Activation of human blood coagulation factor XI independent of factor XII. Factor XI is activated by thrombin and factor XIa in the presence of negatively charged surfaces. J Biol Chem 1991; 266 (12) 7353-7358
    CrossrefPubMedGoogle Scholar
  • 35 Duga S, Salomon O. Congenital factor XI deficiency: an update. Semin Thromb Hemost 2013; 39 (06) 621-631
    Article in Thieme ConnectPubMedGoogle Scholar
  • 36 Wheeler AP, Gailani D. Why factor XI deficiency is a clinical concern. Expert Rev Hematol 2016; 9 (07) 629-637
    CrossrefPubMedGoogle Scholar
  • 37 Puy C, Rigg RA, McCarty OJ. The hemostatic role of factor XI. Thromb Res 2016; 141 (Suppl. 02) S8-S11
    CrossrefPubMedGoogle Scholar
  • 38 Mackman N, Tilley RE, Key NS. Role of the extrinsic pathway of blood coagulation in hemostasis and thrombosis. Arterioscler Thromb Vasc Biol 2007; 27 (08) 1687-1693
    CrossrefPubMedGoogle Scholar
  • 39 Gale AJ. Continuing education course #2: current understanding of hemostasis. Toxicol Pathol 2011; 39 (01) 273-280
    CrossrefPubMedGoogle Scholar
  • 40 Luddington R, Baglin T. Clinical measurement of thrombin generation by calibrated automated thrombography requires contact factor inhibition. J Thromb Haemost 2004; 2 (11) 1954-1959
    CrossrefPubMedGoogle Scholar
  • 41 Bidot L, Jy W, Bidot Jr C. , et al. Microparticle-mediated thrombin generation assay: increased activity in patients with recurrent thrombosis. J Thromb Haemost 2008; 6 (06) 913-919
    CrossrefPubMedGoogle Scholar
  • 42 Zubairova LD, Nabiullina RM, Nagaswami C. , et al. Circulating microparticles alter formation, structure, and properties of fibrin clots. Sci Rep 2015; 5: 17611
    CrossrefPubMedGoogle Scholar
  • 43 Levin G, Sukhareva E, Lavrentieva A. Impact of microparticles derived from erythrocytes on fibrinolysis. J Thromb Thrombolysis 2016; 41 (03) 452-458
    CrossrefPubMedGoogle Scholar
  • 44 Cho S, Jy W, Horstman LL, Bidot Jr C. , et al. Functional heterogeneity of red cell-derived microparticles from different sources: calcium ionophore vs. storage vs. extrusion. Blood 2016; 128: 3770
    CrossrefPubMedGoogle Scholar
  • 45 Azad M, Jy W, Horstman LL, Bidot Jr C. , et al. Evidence for anti-fibrinolytic activity of red cell-derived microparticles (RMP): a novel hemostatic action of RMP. Blood 2016; 128: 3769
    CrossrefPubMedGoogle Scholar
  • 46 Boulaftali Y, Ho-Tin-Noe B, Pena A. , et al. Platelet protease nexin-1, a serpin that strongly influences fibrinolysis and thrombolysis. Circulation 2011; 123 (12) 1326-1334
    CrossrefPubMedGoogle Scholar
  • 47 Key NS, Mackman N. Tissue factor and its measurement in whole blood, plasma, and microparticles. Semin Thromb Hemost 2010; 36 (08) 865-875
    Article in Thieme ConnectPubMedGoogle Scholar
  • 48 Polgar J, Matuskova J, Wagner DD. The P-selectin, tissue factor, coagulation triad. J Thromb Haemost 2005; 3 (08) 1590-1596
    CrossrefPubMedGoogle Scholar
  • 49 Vandendries ER, Furie BC, Furie B. Role of P-selectin and PSGL-1 in coagulation and thrombosis. Thromb Haemost 2004; 92 (03) 459-466
    Article in Thieme ConnectPubMedGoogle Scholar
  • 50 Hogg P. Disulfide exchange regulation of tissue factor de-encryption. Paper presented at: Third Symposium on Hemostasis with Focus on Factor VIIa and Tissue Factor 2006 , Chapel Hill, North Carolina (May 4–6)
    PubMedGoogle Scholar
  • 51 Steppich B, Mattisek C, Sobczyk D, Kastrati A, Schömig A, Ott I. Tissue factor pathway inhibitor on circulating microparticles in acute myocardial infarction. Thromb Haemost 2005; 93 (01) 35-39
    Article in Thieme ConnectPubMedGoogle Scholar
  • 52 Bajaj MS, Birktoft JJ, Steer SA, Bajaj SP. Structure and biology of tissue factor pathway inhibitor. Thromb Haemost 2001; 86 (04) 959-972
    Article in Thieme ConnectPubMedGoogle Scholar
  • 53 Maroney SA, Cunningham AC, Ferrel J. , et al. A GPI-anchored co-receptor for tissue factor pathway inhibitor controls its intracellular trafficking and cell surface expression. J Thromb Haemost 2006; 4 (05) 1114-1124
    CrossrefPubMedGoogle Scholar
  • 54 Salemink I, Blezer R, Willems GM, Galli M, Bevers E, Lindhout T. Antibodies to β2-glycoprotein I associated with antiphospholipid syndrome suppress the inhibitory activity of tissue factor pathway inhibitor. Thromb Haemost 2000; 84 (04) 653-656
    Article in Thieme ConnectPubMedGoogle Scholar
  • 55 Santizo F, Zenteno E, Pina-Canseco S. , et al. Lectin activity of the coagulation factor VIII/von Willebrand complex. Tohoku J Exp Med 2009; 217 (03) 209-215
    CrossrefPubMedGoogle Scholar
  • 56 Schmaier AH, McCrae KR. The plasma kallikrein-kinin system: its evolution from contact activation. J Thromb Haemost 2007; 5 (12) 2323-2329
    CrossrefPubMedGoogle Scholar
  • 57 Lopez E, Srivastava AK, Pati S, Holcomb JB, Wade CE. Platelet-derived microvesicles: a potential therapy for trauma-induced coagulopathy. Shock 2018; 49 (03) 243-248
    CrossrefPubMedGoogle Scholar
  • 58 Kim Y, Xia BT, Jung AD. , et al. Microparticles from stored red blood cells promote a hypercoagulable state in a murine model of transfusion. Surgery 2018; 163 (02) 423-429
    CrossrefPubMedGoogle Scholar
  • 59 Chang AL, Kim Y, Seitz AP, Schuster RM, Lentsch AB, Pritts TA. Erythrocyte-derived microparticles activate pulmonary endothelial cells in a murine model of transfusion. Shock 2017; 47 (05) 632-637
    CrossrefPubMedGoogle Scholar