Tissue factor pathway inhibitor in childhood nephrotic syndrome
- 99 Downloads
- 7 Citations
Abstract
It is now recognised that the extrinsic tissue factor pathway is the main trigger to the coagulation system in vivo. Its main inhibitor, tissue factor pathway inhibitor (TFPI), has never been studied in childhood nephrotic syndrome. The aim of the study was to monitor the level of TFPI in childhood nephrotic syndrome. One hundred and thirty-nine nephrotic children were classified into the following groups: group 1 (n=25), in relapse and receiving no treatment; group 2 (n=37), in relapse but receiving steroid treatment; group 3 (n= 45), in early remission and on steroids; group 4 (n=24), in established remission and receiving no steroids; group 5 (n=8), steroid-resistant. The controls (n=84) were healthy and age-matched. There was significant elevation of total TFPI levels in groups 1 and 2 and 3; levels were comparable to those of the healthy controls in group 4. The highest levels of total TFPI were recorded in group 5. Like total TFPI, the levels of the free form of TFPI showed a statistically significant increase in groups 1, 2, 3 and 4, when compared with levels in healthy controls. The highest levels of free TFPI were recorded group 5. We concluded that the elevated levels of both the total and free TFPI in various phases of nephrotic syndrome add another natural anticoagulant mechanism, which will attenuate the hypercoagulability of childhood nephrotic syndrome.
Keywords
Nephrotic syndrome Tissue factor pathway inhibitor TFPI HaemostasisNotes
Acknowledgements
We are grateful to Mr. M.A. Hamid, Mr. Lugman A.G. El-Sid and Mrs. M.C. Aradillous for their technical assistance, to Mr. Amir Abdul Aziz for statistical help, and to Mrs. F. Chatila for her secretarial work. This work was supported by a grant (no. AT 18–73) from King Abdul Aziz City for Science and Technology (KACST), Riyadh, Saudi Arabia.
References
- 1.Livio M (1989) Hypercoagulability in the nephrotic syndrome. In: Remuzzi G, Rossi EC (eds) Haemostasis and the kidney. Butterworth, London, pp 145–152Google Scholar
- 2.Mehls O, Andrassy K, Koderisch J, Herzog U, Ritz E (1987) Hemostasis and thromboembolism in children with nephrotic syndrome: differences from adults. J Pediatr 110:862–8677PubMedGoogle Scholar
- 3.Andrassy K, Ritz F, Bommer J (1980) Hypercoagulability in the nephrotic syndrome. Klin Wochenschr 58:1029–1036PubMedGoogle Scholar
- 4.Robert A, Olmer M, Sampol J, Gugliotta JE, Casanova P (1987) Clinical correlation between hypercoagulability and thrombo-embolic phenomena. Kidney Int 31:830–835PubMedGoogle Scholar
- 5.Anand NK, Chand G, Talib VH, Chellani H, Pande J (1996) Haemostatic profile in nephrotic syndrome. Indian Pediatr 33:1005–1012PubMedGoogle Scholar
- 6.Schlegel N (1997) Thromboembolic risks and complications in nephrotic children. Semin Thromb Hemost 23:271–280PubMedGoogle Scholar
- 7.Citak A, Emre S, Sirin A, Bilge I, Nayr A (2000) Haemostatic problems and thromboembolic complications in nephrotic children. Pediatr Nephrol 14:138–142PubMedGoogle Scholar
- 8.Elidrissy ATH, Gader AMA (1985) Antithrombin III (ATIII) and fibrinogen levels in nephrotic syndrome in children. Haemostasis 15:384–388PubMedGoogle Scholar
- 9.Elidrissy ATH, Abdurrahman MB, Bahakim HM, Jones MD, Gader AMA (1991) Haemostatic measurements in childhood nephrotic syndrome. Eur J Pediatr 150:374–378PubMedGoogle Scholar
- 10.Al Mugeiren MM, Gader AMA, Al-Rasheed SA, Bahakim HM, Al-Momen AK, Al-Salloum A (1995) Platelet aggregometry—dose related responses to arachidonic acid in childhood nephrotic syndrome. Platelets 6:71–74Google Scholar
- 11.Oviasu E, Famodu AA, Ojeh EA (1998) Plasma viscosity in nephrotic Nigerians. Clin Hemorheol Microcirc 19:163–167PubMedGoogle Scholar
- 12.Sahu S, Nageswari K, Banerjee R, Puniyani RR (1998) Hemorheological changes in nephrotic syndrome. Clin Hemorheol Microcirc 19:17–20PubMedGoogle Scholar
- 13.Bohler T, Linderkamp O, Leo A, Wingen AM, Scharer K (1992) Increased aggregation with normal surface charge and deformability of red blood cells in children with nephrotic syndrome. Clin Nephrol 38:119–124PubMedGoogle Scholar
- 14.Tsukahara H, Haruki S, Hiraoka M, Hori C, Sudo M (1997) Persistent hypercholesterolaemia in frequently relapsing steroid-responsive nephrotic syndrome. J Paediatr Child Health 33:253–355PubMedGoogle Scholar
- 15.Al-Mugeiren MM, Gader AMA, Al-Rasheed SA, Bahakim HM, Al-Momen AK, Al-Salloum A (1996) The coagulopathy of nephrotic syndrome—a reappraisal of the role natural anticoagulants and fibrinolysis. Haemostasis 26:304–310PubMedGoogle Scholar
- 16.Yermiahu T, Shalev H, Landau D, Dvilansky A (1996) Protein C and protein S in pediatric nephrotic patients. Sangre (Barc) 41:155–157Google Scholar
- 17.Vigano-D’Angelo S, D’Angelo A, Kauffmann CE, Sholer C, Esmon CT, Comp PC (1987) Protein S deficiency occurs in the nephrotic syndrome. Ann Intern Med 107:42–47PubMedGoogle Scholar
- 18.Gouault-Heilmann M, Gadelha-Parente T, Levent M, Intrator L, Rostoker G, Lagrue G (1988) Total and free protein S in nephrotic syndrome. Thromb Res 49:37–42PubMedGoogle Scholar
- 19.Bajaj MS, Birktoft JJ, Steer SA, Bajaj SP (2001) Structure and biology of tissue factor pathway inhibitor. Thromb Haemost 86:959–972PubMedGoogle Scholar
- 20.Rapaport SI (1991) The extrinsic pathway inhibitor. A regulator of tissue factor dependent blood coagulation. Thromb Haemost 66:6–15PubMedGoogle Scholar
- 21.Broze GJJ (1995) Tissue factor pathway inhibitor. Thromb Haemost 74:90–93PubMedGoogle Scholar
- 22.Sandset PM, Warn-Cramer BJ, Rao LVM, Maki SL, Rapaport SI (1991) Depletion of extrinsic pathway inhibitor (EPI) sensitizes rabbits to disseminated intravascular coagulation induced with tissue factor: evidence supporting a physiologic role for EPI as a natural anticoagulant. Proc Natl Acad Sci USA 88:708–712PubMedGoogle Scholar
- 23.Sandset PM, Warn-Cramer BJ, Maki SL, Rapaport SI (1991) Immunodepletion of extrinsic pathway inhibitor sensitizes rabbits to endotoxin-induced intravascular coagulation and the generalized Shwartzman reaction. Blood 78:1496–1502PubMedGoogle Scholar
- 24.Day KC, Hoffman LC, Palmier MO, Kretzmer KK, Huang MD, Pyla EY, Spokas E, Broze JGJ, Warren TG, Wun TC (1990) Recombinant lipoprotein-associated coagulation inhibitor inhibits tissue thromboplastin-induced intravascular coagulation in the rabbit. Blood 76:1538–1545PubMedGoogle Scholar
- 25.Bregengard C, Nordfang O, Wildgoose P, Svendsen O, Hedner U, Diness V (1993) The effect of two-domain tissue factor pathway inhibitor on endotoxin-induced disseminated intravascular coagulation in rabbits. Blood Coagul Fibrinolysis 4:699–676Google Scholar
- 26.Holst J, Lindblad B, Bergqvist D, Nordfang O, Ostergaard PB, Peterson JG, Nielsen G, Hedner U (1994) Antithrombotic effect of recombinant truncated tissue factor pathway inhibitor (TFPI-161) in experimental venous thrombosis—a comparison with low molecular weight heparin. Thromb Haemost 71:214–219PubMedGoogle Scholar
- 27.Ellis BC, Stransky A (1961) A quick and accurate method for the determination of fibrinogen in plasma. J Lab Clin Med 58:477–488PubMedGoogle Scholar
- 28.Areins RAS, Moia M, Rivolta E, Ponticelli C, Mannucci PM (1999) High levels of tissue factor pathway inhibitor in patients with nephrotic proteinuria. Thromb Haemost 82:1020–1023Google Scholar
- 29.Malyszko JS, Malyszko J, Mysliwiec M (1999) Tissue factor and inhibitor of the blood coagulation pathway in nephrotic syndrome. Pol Arch Med Wewn 101:301–305PubMedGoogle Scholar
- 30.Warshawsky I, Bu G, Mast A, Saffitz JE, Broze GJ Jr, Schwartz AL (1995) The carboxy terminus of tissue factor pathway inhibitor is required for interacting with hepatoma cells in vitro and in vivo. J Clin Invest 95:1773–1781PubMedPubMedCentralGoogle Scholar
- 31.Palmier MO, Hall IJ, Reisch CM, Baidwin MK, Wilson AG, Wun TC (1992) Clearance of recombinant tissue factor pathway inhibitor (TFPI) in rabbits. Thromb Haemost 68:33–36PubMedGoogle Scholar
- 32.Narita M, Bu G, Olins GM, Higuchi DA, Herz J, Broze GJ Jr, Schwartz AL (1995) Two receptor systems are involved in the plasma clearance of tissue factor pathway inhibitor in vivo. J Biol Chem 270:24800–24804PubMedGoogle Scholar
- 33.Warshawsky I, Herz J, Broze GJ, Schwartz AL (1996) The low density lipo-protein receptor-related protein can function independently from heparin sulphate proteogylcans in tissue factor pathway inhibitor endocytosis. J Biol Chem 271:25873–25879PubMedGoogle Scholar
- 34.Eling M, Stephens AC, Oragui EE, Rivers RPA, Levin M (2001) Tissue factor pathway inhibitor (TFPI) levels in the plasma and urine of children with meningococcal disease. Thromb Haemost 85:240–244PubMedGoogle Scholar
- 35.Leurs PB, van Oerle R, Wolffenbuttel HR, Hamulyak K (1997) Increased tissue factor pathway inhibitor (TFPI) and coagulation in patients with insulin-dependent diabetes mellitus. Thromb Haemost 77:472–476PubMedGoogle Scholar
- 36.Alban S, Gastpar R (2001) Plasma levels of total and free tissue factor pathway inhibitor (TFPI) as individual pharmacological parameters of various heparins. Thromb Haemost 85:824–829PubMedGoogle Scholar
- 37.Hansen JB, Svensson B, Olsen R, Ezban M, Osterud B (2000) Heparin induces synthesis and secretion of tissue factor pathway inhibitor from endothelial cells in vitro. Thromb Haemost 83:937–943PubMedGoogle Scholar
- 38.Kemme MJ, Burggraaf J, Schoemaker RC, Cohen AF, Kluft C, Chia S, Webb DJ, Newby DE (2003) Local tissue factor pathway inhibitor release in the human forearm. Thromb Haemost 89:438–45PubMedGoogle Scholar
- 39.Novotny WF, Brown SG, Miletich JP, Rader DJ, Broze GJ Jr (1991) Plasma antigen levels of the lipoprotein-associated coagulation inhibitor in patient samples. Blood 78:387–393PubMedGoogle Scholar
- 40.Morishita E, Asakura H, Saito M, Yamazaki M, Ontachi Y, Mizutani T, Kato M, Matsuda T, Nakao S (2001) Elevated plasma levels of free-form of TFPI antigen in hypercholesterolemia patients. Atherosclerosis 154:203–212PubMedGoogle Scholar
- 41.Chesney RW (1999) The idiopathic nephrotic syndrome. Curr Opin Pediatr 11:158–161PubMedGoogle Scholar
- 42.Merouani A, Levy E, Mongeau JG, Robitaille P, Lambert M, Delvin EE (2003) Hyperlipidemic profiles during remission in childhood idiopathic nephrotic syndrome. Clin Biochem 36:571–574PubMedGoogle Scholar
- 43.Tkaczyk M, Owczarek D, Puczko-Nogal B, Makosiej R, Rogowska-Kalisz A, Ptasnik W, Finke D (2000) Activation of coagulation cascade in children during an idiopathic nephrotic syndrome relapse. Pol Merkuriusz Lek 8:226–227Google Scholar
- 44.Tkaczyk M, Baj Z (2002) Surface markers of platelet function in idiopathic nephrotic syndrome in children. Pediatr Nephrol 17:673–677PubMedGoogle Scholar
- 45.Schnaper HW (2001) Antithrombin III, protein S and coagulation in the nephrotic syndrome. Pediatr Nephrol 16:98PubMedGoogle Scholar
- 46.Loirat C, Hurtaud-Roux MF, Schlegel N, Brun P (1992) Thromboembolic complications in nephrotic syndrome. Pediatr Nephrol 6:C67Google Scholar
- 47.Svenson PJ, Dahlback B (1994) Resistance to activated protein C as a basis for venous thrombosis. N Engl J Med 330:517–522Google Scholar
- 48.Camisi S, Cavatoris F (1998) A case of deep vein thrombosis in idiopathic nephrotic syndrome with resistance to activated protein C. J Nephrol 11:76–77Google Scholar