Seminars in Hematology
Volume 42, Issue 4 , Pages 239-247 , October 2005

Pathogenesis of Thrombosis in Essential Thrombocythemia and Polycythemia Vera: The Role of Neutrophils

  • Anna Falanga

      Affiliations

    • Hematology Division, Ospedali Riuniti, Bergamo, Italy.
    • Corresponding Author InformationAddress correspondence to Anna Falanga, Hematology Division, Ospedali Riuniti, Largo Barozzi, 1, Bergamo 24128, Italy.
  • ,
  • Marina Marchetti

      Affiliations

    • Hematology Division, Ospedali Riuniti, Bergamo, Italy.
  • ,
  • Tiziano Barbui

      Affiliations

    • Hematology Division, Ospedali Riuniti, Bergamo, Italy.
  • ,
  • C. Wayne Smith

      Affiliations

    • Baylor College of Medicine, Houston, TX.

References 

  1. Barbui T , Finazzi G , Barosi G . Chronic myeloid disorders, excluding CML . In:  Degos L ,  Linch DC ,  Löwenberg B editor. Textbook of Malignant Hematology . London, UK: Martin Dunitz; 1999;p. 847–869
  2. Gruppo Italiano Studio Policitemia Vera (GISP) . Polycythemia vera (The natural history of 1213 patients followed over 20 years) . Ann Intern Med . 1995;123:656–664
  3. Valla D , Casadevall N , Lacombe C , Varet B , Goldwasser E , Franco D , et al.   Primary myeloproliferative disorder and hepatic vein thrombosis . Ann Intern Med . 1985;103:329–334
  4. Marchioli R , Finazzi G , Landolfi R , Kutti J , Gisslinger H , Patrono C , et al.   Vascular and neoplastic risk in a large cohort of patients with polycythemia vera . J Clin Oncol . 2005;23:2224–2232
  5. Barbui T , Barosi G , Grossi A , Gugliotta L , Liberato LN , Marchetti M , et al.   Practice guidelines for the therapy of essential thrombocythemia. A statement from the Italian Society of Hematology, the Italian Society of Experimental Hematology and the Italian Group for Bone Marrow Transplantation . Haematologica . 2004;89:215–232
  6. Cortelazzo S , Viero P , Finazzi G , D’Emilio A , Rodeghiero F , Barbui T , et al.   Incidence and risk factors for thrombotic complications in a historical cohort of 100 patients with essential thrombocythemia . J Clin Oncol . 1990;8:556–562
  7. Pearson TC , Humphrey PRD , Thomas DJ , Wetherley-Mein G . Haematocrit, blood viscosity, cerebral blood flow and vascular occlusion . In:  Lowe GDO ,  Barbenel JC ,  Forbes CD editor. Clinical Aspects of Blood Viscosity and Cell Deformability . Berlin, Germany: Spriger-Verlag; 1981;p. 97–107
  8. Messinezy M , Nunan TO , Pearson TC . Brain perfusion in polycythemia using 99TcmHMPAO (Effect of treatment) . Eur J Haematol . 1993;51:120–121
  9. Kannel WB , Gordan T , Wolf PA , McNamara P . Hemoglobin and the risk of cerebral infarction (The Framingham study) . Stroke . 1972;3:409–420
  10. Cortelazzo S , Finazzi G , Ruggeri M , Vestri O , Galli M , Rodeghiero F , et al.   Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis . N Engl J Med . 1995;332:1132–1136
  11. Harrison CN , Campbel PJ , Buck G , Wheatley K , East CL , Bareford D , et al.   A randomized comparison of hydroxyurea with anagrelide in high-risk essential thrombocythemia . N Engl J Med . 2005;353:33–45
  12. Cortelazzo S , Marchetti M , Orlando E , Falanga A , Barbui T , Buchanan MR . Aspirin increases the bleeding side effects in essential thrombocythemia independent of the cyclooxygenase pathway (Role of the lypoxygenase pathway) . Am J Hematol . 1998;57:277–282
  13. Baxter EJ , Scott LM , Campbell PJ , East C , Fourouclas N , Swanton S , et al.   Acquired mutation of the tyrosine kinase JAK2 in human myeloproliferative disorders . Lancet . 2005;365:1054–1061
  14. Danesh J , Collins R , Appleby P , Peto R . Association of fibrinogen, C-reactive protein, albumin, or leukocyte count with coronary heart disease. Meta-analyses of prospective studies . JAMA . 1998;279:1148–1477
  15. Lowe G , Fowkes F , Dawes J , Donnan P , Lennie S , Housley E . Blood viscosity, fibrinogen, and activation of coagulation and leukocytes in peripheral arterial disease and the normal population in the Edinburg Artery Study . Circulation . 1983;87:1915–1920
  16. Falanga A , Marchetti M , Evangelista V , Manarini S , Oldani E , Giovanelli S , et al.   Neutrophil activation and hemostatic changes in healthy donors given granulocyte-colony stimulating factor . Blood . 1999;93:2506–2514
  17. Bokoch GM . Chemoattractant signaling and leukocyte activation . Blood Rev . 1985;86:1649–1660
  18. Lamy M , Deby-Dupont G . Is sepsis a mediator-inhibitor mismatch? . Intensive Care Med . 1995;21:254–255
  19. Weiss SJ . Tissue destruction by neutrophils . N Engl J Med . 1989;320:365–377
  20. Cassatella MA . Neutrophil-derived proteins (Selling cytokines by the pound) . Adv Immunol . 1999;73:369–509
  21. Scapini P , Lapinet-Vera JA , Gasperini S , Calzetti F , Bazzoni F , Cassatella MA , et al.   The neutrophil as a cellular source of chemokines . Immunol Rev . 2000;177:195–203
  22. Cloutier A , McDonald PP . Transcription factor activation in human neutrophils . Chem Immunol Allergy . 2003;83:1–23
  23. Girard D . Phenotypic and functional change of neutrophils activated by cytokines utilizing the common cytokine receptor gamma chain . Chem Immunol Allergy . 2003;83:64–80
  24. Tsukahara Y , Lian Z , Zhang X , Whitney C , Kluger Y , Tuck D , et al.   Gene expression in human neutrophils during activation and priming by bacterial lipopolysaccharide . J Cell Biochem . 2003;89:848–861
  25. Galligan C , Yoshimura T . Phenotypic and functional changes of cytokine-activated neutrophils . Chem Immunol Allergy . 2003;83:24–44
  26. Malcolm KC , Arndt PG , Manos EJ , Jones DA , Worthen GS . Microarray analysis of lipopolysaccharide-treated human neutrophils . Am J Physiol Lung Cell Mol Physiol . 2003;284:663–670
  27. Theilgaard-Monch K , Knudsen S , Follin P , Borregaard N . The transcriptional activation program of human neutrophils in skin lesions supports their important role in wound healing . J Immunol . 2004;172:7684–7693
  28. Kobayashi SD , Voyich JM , Braughton KR , Whitney AR , Nauseef WM , Malech HL , et al.   Gene expression profiling provides insight into the pathophysiology of chronic granulomatous disease . J Immunol . 2004;172:636–643
  29. Kobayashi SD , Voyich JM , Braughton KR , DeLeo FR . Down-regulation of proinflammatory capacity during apoptosis in human polymorphonuclear leukocytes . J Immunol . 2003;170:3357–3368
  30. Setiadi H , McEver RP . Signal-dependent distribution of cell surface P-selectin in clathrin-coated pits affects leukocyte rolling under flow . J Cell Biol . 2003;163:1385–1395
  31. Andrews RK , Berndt MC . Platelet physiology and thrombosis . Thromb Res . 2004;114:447–453
  32. Ahn KC, Jun AJ, Pawar P, Jadhav S, Napier S, McCarty OJ, et al. Preferential binding of platelets to monocytes over neutrophils under flow . Biochem Biophys Res Commun . 2005;329:345–355
  33. Ramachandran V , Williams M , Yago T , Schmidtke DW , McEver RP . Dynamic alterations of membrane tethers stabilize leukocyte rolling on P-selectin . Proc Natl Acad Sci U S A . 2004;101:13519–13524
  34. Seo SM , McIntire LV , Smith CW . Effects of IL-8, Gro-alpha, and LTB(4) on the adhesive kinetics of LFA-1 and Mac-1 on human neutrophils . Am J Physiol Cell Physiol . 2001;281:C1568–C1578
  35. Ma YQ , Plow EF , Geng JG . P-selectin binding to P-selectin glycoprotein ligand-1 induces an intermediate state of alphaMbeta2 activation and acts cooperatively with extracellular stimuli to support maximal adhesion of human neutrophils . Blood . 2004;104:2549–2556
  36. Lau D , Mollnau H , Eiserich JP , Freeman BA , Daiber A , Gehling UM , et al.   Myeloperoxidase mediates neutrophil activation by association with CD11b/CD18 integrins . Proc Natl Acad Sci U S A . 2005;102:431–436
  37. Stief TW . Regulation of hemostasis by singlet-oxygen (1DeltaO2*) . Curr Vasc Pharmacol . 2004;2:357–362
  38. Ishii H , Uchiyama H , Kazama M . Soluble thrombomodulin antigen in conditioned medium is increased by damage of endothelial cells . Thromb Haemost . 1991;65:618–623
  39. Vischer UM , Jornot L , Wolleheim CB , Theler JM . Reactive oxygen intermediates induce regulated secretion of von Willebrand factor from cultured human vascular endothelial cells . Blood . 1995;85:3164–3172
  40. Harlan JM , Killen PD , Harken LA , Striker GE , Wright DG . Neutrophil-mediated endothelial injury in vitro. Mechanisms of cell detachment . J Clin Invest . 1981;68:1394–1403
  41. Kolpakov V , D’Adamo MC , Salvatore L , Amore C , Mironov A , Iacoviello L , et al.   Neutrophils derived cathepsin G induces potentially thrombogenic changes in human endothelial cells (A scanning electron microscopy study in static and dynamic conditions) . Thromb Haemost . 1994;72:140–145
  42. Weksler BB , Jaffe EA , Brower MS , Cole OF . Human leukocyte cathepsin G and elastase specifically suppress thrombin-induced prostacyclin production in human endothelial cells . Blood . 1989;74:1627–1634
  43. Pintucci G , Iacoviello L , Castelli MP , Amore C , Evangelista V , Cerletti C , et al.   Cathepsin G-induced release of PAI-1 in the culture medium of endothelial cells (A new thrombogenic role for polymorphonuclear leukocytes?) . J Lab Clin Med . 1993;122:69–79
  44. Evangelista V , Piccardoni P , White JG , de Gaetano G , Cerletti C . Cathepsin G-dependent platelet stimulation by activated polymorphonuclear leukocytes and its inhibition by antiproteinases (Role of P-selectin-mediated cell-cell adhesion) . Blood . 1993;81:2947–2957
  45. Eckle I , Seitz R , Egbring R , Kolb G , Havemann K . Protein C degradation in vitro by neutrophil elastase . Biol Chem Hoppe Seyler . 1991;372:1007–1013
  46. Eckle I , Seitz R , Egbring R , Kolb G , Havemann K . Protein S degradation in vitro by neutrophil elastase . Scand J Clin Lab Invest . 1993;53:281–288
  47. Higuchi DA , Wun TC , Likert KM , Broze GJ . The effect of leukocyte elastase on tissue factor pathway inhibitor . Blood . 1992;79:1712–1719
  48. Jordan RE , Kilpatrick J , Nelson RM . Heparin promotes the inactivation of antithrombin by neutrophil elastase . Science . 1987;237:777–779
  49. Camire RM , Kalafatis M , Tracy PB . Proteolysis of factor V by cathepsin G and elastase indicates that cleavage at Arg1545 optimizes cofactor function by facilitating factor Xa binding . Biochemistry . 1998;37:11896–11906
  50. Owen CA , Campbell MA , Sannes PL , Boukedes SS , Campbell EJ . Cell surface-bound elastase and cathepsin G on human neutrophils focus and preserve catalytic activity of serine proteinases . J Cell Biol . 1995;131:775–789
  51. Evangelista V , Manarini S , Rotondo S , Martelli N , Polischuk R , McGregor JL , et al.   Platelet/polymorphonuclear leukocyte interaction in dinamic conditions (Evidence of adhesion cascade and cross-talk between P-selectin and the β2 integrin CD11b/CD18) . Blood . 1996;88:4185–4194
  52. de Gaetano G , Cerletti C , Evangelista V . Recent advances in platelet-polymorphonuclear leukocyte interaction . Haemostasis . 1999;29:41–49
  53. Engstad CS , Lia K , Rekdal ̌O , Olsen JO , ̌Osterud B . A novel biological effect of platelet factor 4 (PF4) (Enhancement of LPS-induced tissue factor activity in monocytes) . J Leukoc Biol . 1995;58:575–581
  54. Celi A , Pellegrini G , Lorenzet R , De Blasi A , Ready N , Furie BC , et al.   P-selectin induces the expression of tissue factor on monocytes . Proc Natl Acad Sci U S A . 1994;91:8767–8771
  55. Weyrich AS , Elstad MR , McEver RP , McIntyre TM , Moore KL , Morrissey JH , et al.   Activated platelets signal chemokine synthesis by human monocytes . J Clin Invest . 1996;97:1525–1534
  56. Nagata K , Tsuji T , Todoroki N , Katagiri Y , Tanoue K , Yamazaki H , et al.   Activated platelets induce superoxide anion release by monocytes and neutrophils through P-selectin (CD62) . J Immunol . 1993;151:3267–3273
  57. Neumann F-J , Marx N , Gawaz M , Gawaz M , Koch W , Pinkau T , et al.   Induction of cytokine expression in leukocytes by binding of thrombin-stimulated platelets . Circulation . 1997;95:2387–2394
  58. Gawaz M , Neumann F-J , Dickfeld T , Koch W , Laugwitz KL , Adelsberger H , et al.   Activated platelets induce monocyte chemotactic protein-1 secretion and surface expression of intercellular adhesion molecule-1 on endothelial cells . Circulation . 1998;98:1164–1171
  59. Li N , Goodall AH , Hjemdahl P . A sensitive flow cytometric assay for circulating platelet-leukocyte aggregates . Br J Haematol . 1997;99:808–816
  60. Burgaleta C , Gonzalez N , Cesar J . Increased CD11/18 expression and altered metabolic activity in polymorphonuclear leukocytes from patients with polycythemia vera and essential thrombocythemia . Acta Haematol . 2002;108:23–28
  61. Falanga A , Marchetti M , Evangelista V , Vignoli A , Licini M , Balicco M , et al.   Polymorphonuclear leukocyte activation and hemostasis in patients with essential thrombocythemia and polycythemia vera . Blood . 2000;96:4261–4266
  62. Falanga A , Ofosu FA , Cortelazzo S , Delaini F , Marziali S , Barbui T . Hemostatic system activation in patients with lupus anticoagulant and essential thrombocythemia . Semin Thromb Hemost . 1994;20:324–327
  63. Friedenberg WR , Roberts RC , David DE . Relationship of thrombohemorrhagic complications to endothelial cell function in patients with chronic myeloproliferative disorders . Am J Hematol . 1992;40:283–289
  64. Bellucci S , Ignatova E , Jaillet N , Boffa MC . Platelet hyperactivation in patients with essential thrombocythemia is not associated with vascular endothelial cell damage as judged by the level of plasma thrombomodulin, protein S, PAI-1, tPA and vWF . Thromb Haemost . 1993;70:736–742
  65. Ott I , Neumann F-J , Gawaz M , et al.   Increased neutrophil-platelet adhesion in patients with unstable angina . Circulation . 1996;94:1239–1246
  66. Jensen MK , de Nully Brown P , Lund BV , Nielsen OJ , Hasselbalch HC . Increased circulating platelet-leukocyte aggregates in myeloproliferative disorders is correlated to previous thrombosis, platelet activation and platelet count . Eur J Haematol . 2001;66:143–151
  67. Alvarez-Larràn A , Garcìa-Pagàn JC , Abraldes JG , et al.   Increased CD11b neutrophil expression in Budd-Chiari syndrome or portal vein thrombosis secondary to polycythaemia vera . Br J Haematol . 2004;124:329–335
  68. Villmow T , Kemkes-Matthes B , Matzdorff AC . Markers of platelet activation and platelet-leukocyte interaction in patients with myeloproliferative syndromes . Thromb Res . 2002;108:139–145
  69. Falanga A , Marchetti M , Vignoli A , Balducci D , Barbui T . Leukocyte-platelet interaction in patients with essential thrombocytemia and polycythemia vera . Exp Hematol . 2005;33:523–530

PII: S0037-1963(05)00083-1

doi: 10.1053/j.seminhematol.2005.05.023

Seminars in Hematology
Volume 42, Issue 4 , Pages 239-247 , October 2005