Expressions of tissue factor and tissue factor pathway inhibitor in patients with acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation

Abstract

This study examined the expressions of human serum tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) and their clinical significance. The serum TF and TFPI levels were detected by ELISA in 28 allo-HSCT recipients before and after the transplantation and the changes of TF and TFPI levels were dynamically monitored at different phases of the disease. No significant differences in the serum TF and TFPI levels were found in allo-HSCT recipients in the absence of aGVHD or with grade I aGVHD before and after the transplantation. The levels of serum TF and TFPI were substantially increased in the patients with gradeII aGVHD at the peak of aGVHD (P<0.05) and they were even higher in the patients with grade III–IV aGVHD (P<0.01). When the conditions became stable after treatment with immunosuppressive agents, the serum TFPI level was decreased to the baseline level (P>0.05) and the TF level was lowered but still higher than the baseline level (P<0.05). It was concluded that the levels of serum TF and TFPI were increased significantly in the patients with grade II–IV aGVHD after allo-HSCT and decreased markedly after the treatment. Monitoring the levels of serum TF and TFPI in the patients with allo-HSCT is important to predict the occurrence, outcome and prognosis of aGVHD.

Keywords

hematopoietic stem cell transplantation / graft-versus-host disease / tissue factor / tissue factor pathway inhibitor

References

[1] HattoriK., HiranoT., Yamakawa, et al.. Differential effects of anti-Fas ligand and anti TNF-A antibodies on acute graft vs host disease pathologies. Blood, 1998, 91(11): 4051-4055

[2] FalangaA., VignoliA., MarchettiM., et al.. Defibrotide reduces procoagulant activity and increases fibronolytic properties of endothelial cells. Leukemia, 2003, 17(8): 1636-1642

[3] CamererE., KolstoA.B., PrydzH.. Cell biology of tissue factor, the principal initiator of blood coagulation. Thromb Res, 1996, 81(1): 1-41

[4] PyoR.T., SatoY., MackmanN., et al.. Mice deficient in tissue factor demonstrate attenuated intimal hyperplasia in response to vascular injury and decreased smooth muscle cell migration. Thromb Haemost, 2004, 92(3): 451-458

[5] CarmelietP., MackmanN., MoonsL., et al.. Role of tissue factor in embryonic blood vessel development. Nature, 1996, 383(6595): 73-75

[6] RakJ., MilsomC., MayL., et al.. Tissue factor in cancer and angiogenesis: the molecular link between genetic tumor progression, tumor neovascularization, and cancer coagulopathy. Semin Thromb Hemost, 2006, 32(1): 54-70

[7] JaninA., DeschaumesC., DaneshpouyM., et al.. CD95 engagement induces disseminated endothelial cell apoptosis in vivo: immunopathologic implications. Blood, 2002, 99(8): 2940-2947

[8] ZhangZ.L., ShenT.Blood disease diagnosis and efficacy standards (the third version), 1999, Beijing, Science Press: 269-276

[9] ThomasE.D., StorbR., CliftR.A., et al.. Bone marrow transplantation. New Engl J Med, 1975, 292(4): 832-8434

[10] SuredaA., SchmitzN.. Allogeneic stem cell transplantation after reduced-intensity conditioning in lymphoid malignancies. Ann Hematol, 2003, 82(1): 1-13

[11] BleakleyM., RiddellS.R.. Molecules and mechanisms of the graft-versus-leukaemia effect. Nat Rev Cancer, 2004, 4(5): 371-380

[12] NajiA., DeschaseauxF., RacadotE., et al.. Induction of tissue factor expression on human umbilical vein endothelial cells by cell-specific HLA class I antibody. Transplant Proc, 2005, 37(6): 2892-2893

[13] GeX., KarrarA., EriczonB.G., et al.. Antibodies to liver sinusoidal endothelial cells modulate immune responses in liver transplantation. Transplant Proc, 2005, 37(8): 3335-3337

[14] EsmonC.T., FukudomeK., MatherT., et al.. Inflammation, sepsis, and coagulation. Haematologica, 1999, 84(3): 254-259

[15] EsmonC.T.. The interactions between inflammation and coagulation. Br J Haematol, 2005, 131(4): 417-430

[16] ShebuskiR.J., KilgoreK.S.. Role of Inflammatory mediators in thrombogenesis. Pharmacol Exp Ther, 2002, 300(3): 729-735

[17] ShamaL., MelisE., HickeyM.J., et al.. The cytoplasmic domain of tissue factor contributes to leukocyte recruitment and death in endotoxemia. Am J Pathol, 2004, 165(1): 331-403

[18] SpekC.A.. Tissue factor from just one of the coagulation factor to a major player in physiology. Blood Coagul Fibrinolysis, 2004, 15(Suppl1): S3-10

[19] ImamuraT.. Tissue factor expression at the site of inflammation: a cross-talk between inflammation and the blood coagulation system. Rinsho Byori, 2004, 52(4): 342-349

[20] SchmidE., MullerT.H., BudzinskiR.M., et al.. Lymphocyte adhesion to human endothelial cells induces tissue factor expression via a juxtacrine pathway. Thromb Haemost, 1995, 73(3): 421-428

[21] FriedlJ., PuhlmannM., BartlettD.L., et al.. Induction of permeability across endothelial cell monolayers by tumor necrosis factor (TNF) occurs via a tissue factor-dependent mechanism: relationship between the procoagulant and permeability effects of TNF. Blood, 2002, 100(4): 1334-1339

[22] LevyM.M., FinkM.P., MarshallJ.C., et al.. 2001 SCCM/ESICM/ACCP/ATS/SI international sepsis definitions conference. Crit Care Med, 2003, 31(4): 1250-1256

[23] GandoS., KameueT., MorimotoY., et al.. Tissue factor production not balanced by tissue factor pathway inhibitor in sepsis promotes poor prognosis. Crit Care Med, 2002, 30(8): 1729-1734

[24] EnkhbaatarP., OkajimaK., MurakamiK., et al.. Recombinant tissue factor pathway inhibitor reduces lipopolysaccharide induced pulmonary vascular lung injury by inhibiting leukocyte activation. Am J Respir Crit Care Med, 2000, 162(5): 1752-1759

[25] HansenJ.B., SvenssonB., OlsenR., et al.. Heparin induces synthesis and secretion of tissue factor pathway inhibitor from endothelial cells in vitro. Thromb Haemost, 2000, 83(6): 937-943