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Hematopoietic Growth Factors

Administration of granulocyte-colony-stimulating factor for allogeneic hematopoietic cell collection may induce the tissue factor-dependent pathway in healthy donors

Summary:

The hypercoagulable state caused by the use of recombinant human granulocyte colony-stimulating factor (rhG-CSF) has been cited in anecdotal reports. Since tissue factor (TF) is the main initiator of the coagulation cascade, we examined if rhG-CSF had an inductive effect on the TF-dependent pathway in 18 healthy donors receiving rhG-CSF (10 μg/kg/day × 5 days) for peripheral blood progenitor cell mobilization. After rhG-CSF, there were increases both in TF antigen (TF:Ag) (P=0.01) and TF procoagulant activity (TF:PCA) (P=0.06) plasma levels and in TF:Ag cytofluorimetric expression on CD33 (+) cells (P=0.04). Mean activities of FVIII and vWF also increased significantly. Thrombin time was slightly prolonged (P=0.06) due to significant increases in plasma D-dimer levels. In addition, while FIX activity remained stable, there were marked reductions in mean plasma FX and FII activities and a slight decrease in FVII activity that resulted in a significant prolongation of prothrombin time within normal ranges. In conclusion, the administration of rhG-CSF led to a ‘prothrombotic state’ via stimulation of TF and increased endothelial markers, such as F VIII and vWF. In the light of these findings, the use of rhG-CSF for stem cell mobilization should be undertaken cautiously in healthy donors with underlying thrombotic risk factors.

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References

  1. Anderlini P, Körbling M, Dale D et al. Allogeneic blood stem cell transplantation: consideration for donors. Blood 1997; 90: 903–908.

    CAS  Google Scholar 

  2. Anderlini P, Rizzo JD, Nugent ML et al. Peripheral blood stem cell donation: an analysis from the International Bone Marrow Transplant Registry (IBMTR) and European Group for Blood and Marrow Transplant (EBMT) databases. Bone Marrow Transplant 2001; 27: 689–692.

    Article  CAS  Google Scholar 

  3. Conti JA, Scher HI . Acute arterial thrombosis after escalated-dose methotrexate, vinblastine, doxorubicin and cisplatin chemotherapy with recombinant granulocyte colony-stimulating factor. Cancer 1992; 70: 2699–2702.

    Article  CAS  Google Scholar 

  4. Barbui T, Finazzi G, Grassi A, Marchioli R . Thrombosis in cancer patients treated with hematopoietic growth factors – a meta-analysis. Thromb Haemost 1996; 75: 368–371.

    CAS  PubMed  Google Scholar 

  5. Schimoda K, Okamura S, Harada N et al. Identification of a functional receptor for granulocyte colony-stimulating factor on platelets. J Clin Invest 1993; 9: 1310–1313.

    Article  Google Scholar 

  6. Kanaji T, Okamura T, Nagafuji K et al. Megakaryocytes produce the receptor for granulocyte colony stimulating factor. Blood 1995; 85: 3359–3360, (Letter).

    CAS  PubMed  Google Scholar 

  7. Kawachi Y, Watanabe A, Uchida T et al. Acute arterial thrombosis due to platelet aggregation in patient receiving granulocyte colony-stimulating factor. Br J Haematol 1996; 94: 413–416.

    Article  CAS  Google Scholar 

  8. Rappaport SI, Rao LVM . The tissue factor pathway: how it has become a ‘Prima Ballerina’. Thromb Haemost 1995; 74: 7–17.

    Google Scholar 

  9. Nemerson Y, Giesen PLA . Some thoughts about localization and expression of tissue factor. Blood Coagul Fibrinolysis 1998; 9: 45–47.

    Google Scholar 

  10. Rao LVM, Pendurthi UR . Tissue factor on cells. Blood Coagul Fibrinolysis 1998; 9: 27–35.

    CAS  Google Scholar 

  11. Falanga A, Marchetti M, Evangelista V et al. Neutrophil activation and haemostatic changes in healthy donors receiving granulocyte colony-stimulating factor. Blood 1999; 93: 2506–2514.

    CAS  PubMed  Google Scholar 

  12. Kuroiwa M, Okamura T, Kanaji T et al. Effects of granulocyte colony stimulating factor on the hemostatic system in healthy volunteers. Int J Hematol 1996; 63: 311–316.

    Article  CAS  Google Scholar 

  13. Falanga A, Marchetti M, Oldani E et al. Changes of hemostatic parameters in healthy donors administered rhG-CSF for allogeneic blood progenitor cells (PBPC) collection. Bone Marrow Transplant 1996; 17: 72a (Abstr.).

    Google Scholar 

  14. Nemerson, Y . Tissue factor in neutrophils. Thromb Haemost 2000; 83: 802.

    Article  CAS  Google Scholar 

  15. Bussolino F, Wang JM, Paola D et al. Granulocyte- and granulocyte macrophage-colony stimulating factors induce human endothelial cells to migrate and proliferate. Nature 1989; 337: 471–472.

    Article  CAS  Google Scholar 

  16. Blann AD, Taberner DA . A reliable marker for endothelial cell dysfunction: does it exist? Br J Haematol 1995; 90: 244–252.

    Article  CAS  Google Scholar 

  17. LeBlanc R, Roy J, Demers C et al. Prospective study of rhG-CSF effects on hemostasis in allogeneic blood stem cell donors. Bone Marrow Transplant 1999; 23: 991–996.

    Article  CAS  Google Scholar 

  18. Dahlback B . Resistance to activated protein C, the Arg506 to Gln mutation in the factor V gene, and venous thrombosis. Functional tests and DNA-based assays, pros and cons. Thromb Haemost 1995; 73: 739–742.

    Article  CAS  Google Scholar 

  19. Ozcan M . Changes in the natural anticoagulants following hematopoietic stem cell transplantation. Turk J Haematol 2000; 17: 138–142.

    Google Scholar 

  20. Lee KH, Lee JH, Choi SJ et al. Randomized comparison of two different schedules of granulocyte colony-stimulating factor administration after allogeneic bone marrow transplantation. Bone Marrow Transplant 1999; 24: 591–599.

    Article  CAS  Google Scholar 

  21. Lindemann A, Herrmann F, Oster W et al. Hematologic effects of recombinant human granulocyte colony stimulating factor in patients with malignancy. Blood 1989; 8: 2644–2651.

    Google Scholar 

  22. Morrison AE, Green RHA, Watson D et al. Hematological and immunological changes in sibling allogeneic peripheral blood progenitor cell donors. Blood 1997; 90: 391b (Abstr.).

    Google Scholar 

  23. Østerud B . The high responder phenomenon: enhancement of LPS induced tissue factor activity in monocytes by platelets and granulocytes. Platelets 1995; 6: 119–125.

    Article  Google Scholar 

  24. Bach RR, Moldow CF . Mechanism of tissue factor activation on HL-60 cells. Blood 1997; 89: 3270–3276.

    CAS  PubMed  Google Scholar 

  25. Albrecht S, Kotzsch M, Siegert G et al. Detection of circulating tissue factor and factor VII in a normal population. Thromb Haemost 1996; 75: 772–777.

    Article  CAS  Google Scholar 

  26. Fukuda C, Iijima K, Nakamura K . Measuring tissue factor (factor III) activity in plasma. Clin Chem 1989; 35: 1890–1897.

    Google Scholar 

  27. Hidekazu T, Nakamura S, Higure A . Neutrophils express tissue factor in a monkey model of sepsis. Surgery 2000; 127: 209–216.

    Article  Google Scholar 

  28. sterud B, Rao LVM, Olsen JO . Induction of tissue factor expression in whole blood: lack of evidence for the presence of tissue factor expression in granulocytes. Thromb Haemost 2000; 83: 861–867.

    Article  Google Scholar 

  29. Morton CT, Solovey A, Dandelet L . Enhanced expression of tissue factor (TF) by circulating endothelial cells following bone marrow transplantation. Blood 1998; 92: 173a (Abstr.).

    Google Scholar 

  30. Ozcan M, Morton CT, Solovey A et al. Whole blood tissue factor procoagulant activity remains during severe aplasia following bone marrow and peripheral blood stem cell transplantation. Thromb Haemost 2001; 85: 250–255.

    Article  CAS  Google Scholar 

  31. Ozcan M, Beksac M . Is there a relationship between rhG-CSF response to conditioning regimen and engraftment after bone marrow transplantation? Bone Marrow Transplant 1998; 21: 533–535.

    Article  CAS  Google Scholar 

  32. Kjalke M, Sorensen O, Niels B et al. Tissue factor expression by rabbit and human neutrophils. Thromb Haemost 1999; 94: 761 (Abstr.).

    Google Scholar 

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Acknowledgements

This study was supported by Ankara University Research Fund (99-09-00-006)

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Correspondence to M Özcan.

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Topcuoglu, P., Arat, M., Dalva, K. et al. Administration of granulocyte-colony-stimulating factor for allogeneic hematopoietic cell collection may induce the tissue factor-dependent pathway in healthy donors. Bone Marrow Transplant 33, 171–176 (2004). https://doi.org/10.1038/sj.bmt.1704341

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