Hypoprothrombinemia in the compensated form of hepatosplenic schistosomiasis: further studies

Manoukian, Nora; Borges, Durval Rosa

doi:10.1590/S0036-46651988000400005

Abstracts

Coagulation abnormality is frequently observed in schistosomiasis patients but its pathophysiology has not been established. We measured, by immunodiffusion. the prothrombin-antigen concentration in 56 individuals; of these 19 with demonstrated compensated form of hepatosplenic schistosomiasis, 17 with cirrhosis and 20 were control subjects. Transaminases, albumin, transthyretin, prothrombin time, antithrombin III, factor VII, and fibrinogen were also evaluated. All parameters were altered in the cirrhotic group but only albumin, prothrombin and antithrombin III levels were altered in the schistosomiasis group. Ninety percent of the patients with cirrhosis and sixty percent of the patients with schistosomiasis had abnormal plasma levels of albumin, transthyretin, prothrombin-antigen, and/or antithrombin III; an impaired hepatic synthesis was responsible for these results. Conversely forty percent of the schistosomiasis patients with normal plasma concentrations of both albumin and transthyretin had decreased mean plasma levels of both prothrombin and antithrombin III. These results suggest that either proth rombin and antithrombin III are more sensitive markers of impaired hepatic synthesis in schistosomiasis than are levels of albumin and transthyretin combined, or a low grade chronic consumption of clotting proteins also occurs. Considering the latter hypothesis it is possible that the thrombin formed would be inhibited by antithrombin III with the complexed thrombin-antithrombin III being cleared by the liver. Consequently the plasma levels of both prothrombin and antithrombin would be decreased, but the level of fibrinogen would be preserved.

Prothrombin; Antithrombin III; Schistosomiasis; Coagulopathy

Alterações na coagulação são frequentemente observadas em portadores da esquistossomose, mas sua fisiopatologia ainda não foi estabelecida. Medimos, por imunodifusão, a concentração da protrombina-antígeno em 56 indivíduos: 19 com a forma compensada da esquistossomose hepatoesplênica 17 com cirrose e 20 sadios. Foram também determinadas transaminases, albumina, transtiretina, tempo de protrombina, antitrombina III, fator VII e fibrinogênio. As médias de todos os parâmetros estavam alteradas no grupo cirrótico mas apenas as de albumina, protrombina e antitrombina III no grupo esquistossomótico. Noventa por cento dos portadores de cirrose e 60% dos portadores de esquistossomose tinham níveis plasmáticos diminuídos de albumina, transtiretina, protrombina e/ou antitrombina III; síntese hepática diminuída pode explicar estes resultados. Por outro lado, em 40% dos portadores de esqtiistossomose com concentrações plasmáticas de albumina e transtiretina normais as concentrações médias de protrombina e antitrombina III estavam diminuídas. Estes resultados sugerem que a protombina e antitrombina III são marcadores mais sensíveis de síntese hepática do que o conjunto albumina/transtiretina ou que um consumo crônico das proteínas da coagulação ocorra. Considerando esta última possibilidade é possível supor-se que a trombina formada seja inibida pela antitrombina III e o complexo trombina-antitrombina III depurado pelo fígado. Consequentemente os níveis plasmáticos de protrombina e antitrombina III diminuem mas o do fibrinogênio é preservado.

ORIGINAL ARTICLES

Hypoprothrombinemia in the compensated form of hepatosplenic schistosomiasis: further studies

Hipoprotrombinemia na forma-compensada da esquistossomose hepatoesplênica: novos estudos

Nora Manoukian; Durval Rosa Borges

Division of Gastroenterology, Department of Medicine "Escola Paulista de Medicina", São Paulo, SP., Brazil

^{Address for correspondence} Address for correspondence: Dr. Durval Rosa Borges Caixa Postal 20239. CEP 04034 São Paulo. SP., Brazil

SUMMARY

Coagulation abnormality is frequently observed in schistosomiasis patients but its pathophysiology has not been established. We measured, by immunodiffusion. the prothrombin-antigen concentration in 56 individuals; of these 19 with demonstrated compensated form of hepatosplenic schistosomiasis, 17 with cirrhosis and 20 were control subjects. Transaminases, albumin, transthyretin, prothrombin time, antithrombin III, factor VII, and fibrinogen were also evaluated.

All parameters were altered in the cirrhotic group but only albumin, prothrombin and antithrombin III levels were altered in the schistosomiasis group. Ninety percent of the patients with cirrhosis and sixty percent of the patients with schistosomiasis had abnormal plasma levels of albumin, transthyretin, prothrombin-antigen, and/or antithrombin III; an impaired hepatic synthesis was responsible for these results.

Conversely forty percent of the schistosomiasis patients with normal plasma concentrations of both albumin and transthyretin had decreased mean plasma levels of both prothrombin and antithrombin III. These results suggest that either proth rombin and antithrombin III are more sensitive markers of impaired hepatic synthesis in schistosomiasis than are levels of albumin and transthyretin combined, or a low grade chronic consumption of clotting proteins also occurs. Considering the latter hypothesis it is possible that the thrombin formed would be inhibited by antithrombin III with the complexed thrombin-antithrombin III being cleared by the liver. Consequently the plasma levels of both prothrombin and antithrombin would be decreased, but the level of fibrinogen would be preserved.

Key words: Prothrombin; Antithrombin III; Schistosomiasis; Coagulopathy.

RESUMO

Alterações na coagulação são frequentemente observadas em portadores da esquistossomose, mas sua fisiopatologia ainda não foi estabelecida. Medimos, por imunodifusão, a concentração da protrombina-antígeno em 56 indivíduos: 19 com a forma compensada da esquistossomose hepatoesplênica 17 com cirrose e 20 sadios. Foram também determinadas transaminases, albumina, transtiretina, tempo de protrombina, antitrombina III, fator VII e fibrinogênio.

As médias de todos os parâmetros estavam alteradas no grupo cirrótico mas apenas as de albumina, protrombina e antitrombina III no grupo esquistossomótico. Noventa por cento dos portadores de cirrose e 60% dos portadores de esquistossomose tinham níveis plasmáticos diminuídos de albumina, transtiretina, protrombina e/ou antitrombina III; síntese hepática diminuída pode explicar estes resultados.

Por outro lado, em 40% dos portadores de esqtiistossomose com concentrações plasmáticas de albumina e transtiretina normais as concentrações médias de protrombina e antitrombina III estavam diminuídas. Estes resultados sugerem que a protombina e antitrombina III são marcadores mais sensíveis de síntese hepática do que o conjunto albumina/transtiretina ou que um consumo crônico das proteínas da coagulação ocorra. Considerando esta última possibilidade é possível supor-se que a trombina formada seja inibida pela antitrombina III e o complexo trombina-antitrombina III depurado pelo fígado. Consequentemente os níveis plasmáticos de protrombina e antitrombina III diminuem mas o do fibrinogênio é preservado.

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1. ANDRADE, Z. A. & BRITO, P. A. - Evolution of schistosomal hepatic vascular lesion after specific chemoterapy. Amer. J. Trop. Med. Hyg., 30: 1223-1227, 1981.
2. BORGES, D. R.; VILELA, M. P. & GUERRA, C. C. C. - Haemostasis in schistosomiasis mansoni. Gen, 31: 165-177, 1977.
3. COLEMAN, M.; FINLAYSON, N.; BETTIGALE, R. E.; SA DULA, D.; COHN, M. & PASMANTIER, M. - Fibrinogen survival in cirrhosis: Improvement by "low dose" heparin. Ann. intern. Med.; 83: 79-81, 1975
4. COLMAN, R. W. & RUBIN, R. N. - Blood coagulation. In: ARIAS, J.; POPPER, H.; SCHAFTER, D. & SHAFRITZ, D. A., ed. - The liver: biology and pathobiology. New York, Raven Press, 1982. p. 761-769.
5. GORNALL, A. G.; BARDAWILL, C. J. & DAVID, M. A. - Determination of serum proteins by means of the biuret reaction. J. Biol. Chem., 177: 751-766. 1949.
6. HAIDER, M. & HAIDER, S. Q. - Assessment of protein caloric malnutrition. Clin. Chem., 30: 1286-1299, 1984.
7. HILL, P. G. & WELLS, T. N. C. - Bromocresol purple and the measurement of albumin. Ann. clin. Biochem., 20: 264-270, 1983.
8. KELLY, D. A. & TUDDENHAM, E. G. D. - Haemostatic problems in liver disease. Gut, 27: 339-349, 1986.
9. KESHGEGIAN, A. A. - Hypoalbuminemia associated with diffuse hyperglobulinemia in chronic diseases: lack of diagnostic specificity. Amer. J. clin. Path., 81: 477-481, 1984.
10. LOLLAR, P. & OWEN, W. G. - Clearance of thrombin from circulation in rabbits by high affinity binding sites on endothelium. J. clin. Invest., 66: 1222-1230, 1980.
11. LYRA, L. G.; REBOUÇAS, G. & ANDRADE, Z. A. - Hepatitis B surface antigen carrier state in hepatosplenic schistosomiasis. Gastroenterology, 71: 641-645, 1976.
12. MANOUKIAN, N. & BORGES, D. R. - Avaliação funcional e imunológica da protrombina na forma hepatoesplênica da esquistossomose e na cirrose hepática. Rev. paul. Med., 101: 182-185, 1983.
13. MANOUKIAN, N. & BORGES, D. R. - Pre-albumin, prekallikrein and prothrombin in hepatosplenic schistosomiasis: Increased turnover of the clotting proteins? Rev. Inst. Med. trop. S. Paulo, 26: 237-240, 1984
14. NEMERSON, Y. & CLYNE, L. P. - An assay for coagulation factor VII using factor VII depleted bovine plasma. J. Lab. clin. Med., 83: 301-303, 1974.
15. RAMOS, O. L.; SAAD, F. & LESER, W. P. - Portal hemodynamics and liver cell function in hepatic schistosomiasis. Gastroenterology, 47: 241-247, 1964.
16. SHERLOCK, S. - Hepatic cirrhosis. In: SHERLOCK, S. - Disease of the liver and biliary system. 7^th ed. Oxford, Blackwell Scientific Publication, 1985. p. 334-345.
17. SLEIGH, A. C.; HOFF, R.; MOTA, E. A.; SHERLOCK, I.; MOTT, K. E.; BARRETO, M. L.; MAGUIRE, J. H. & WELLER, T. H. - Three years prospective study of evolution of Manson's schistosomiasis in North East Brazil. Lancet, 2: 63-66, 1985.
18. STEINBERG, W. M.; GOLDSTEIN, S. S.; DAVIS, N. D.; SHAMMA'A, J. & ANDERSON, K. - Diagnosis assay in acute pancreatitis: a study of sensitivity and specificity. Ann. intern. Med., 102: 576-580, 1985.
19. VERSTRAETE, M.; VERMYLEN, S. & COLLEN, D. - Intravascular coagulation in liver disease. Ann. Rev. Med., 25: 447-455, 1974.
20. WINTROBE, M. M.; LEE, G. R.; BOGGS, D. R.; BITHELL, T. C; FOERSTER, J.; ATHENS, J. W. & LUKENS, J. N. - Blood coagulation. In: WINTROBE, M. M.; LEE, G. R.; BOGGS, D. R.; BITHELL, T. C.; FOERSTER, J.; ATHENS, J. W. & LUKENS, J. N. - Clinical haematology. 8^th ed. Philadelphia, Lea & Febiger, 1981. p. 405-452.

Address for correspondence:

Dr. Durval Rosa Borges

Caixa Postal 20239. CEP 04034 São Paulo. SP., Brazil

Publication Dates

Publication in this collection
10 Mar 2011
Date of issue
Aug 1988

History

Received
09 Mar 1988

This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

[1] 1. ANDRADE, Z. A. & BRITO, P. A. - Evolution of schistosomal hepatic vascular lesion after specific chemoterapy. Amer. J. Trop. Med. Hyg., 30: 1223-1227, 1981.

[2] 2. BORGES, D. R.; VILELA, M. P. & GUERRA, C. C. C. - Haemostasis in schistosomiasis mansoni. Gen, 31: 165-177, 1977.

[3] 3. COLEMAN, M.; FINLAYSON, N.; BETTIGALE, R. E.; SA DULA, D.; COHN, M. & PASMANTIER, M. - Fibrinogen survival in cirrhosis: Improvement by "low dose" heparin. Ann. intern. Med.; 83: 79-81, 1975

[4] 4. COLMAN, R. W. & RUBIN, R. N. - Blood coagulation. In: ARIAS, J.; POPPER, H.; SCHAFTER, D. & SHAFRITZ, D. A., ed. - The liver: biology and pathobiology. New York, Raven Press, 1982. p. 761-769.

[5] 5. GORNALL, A. G.; BARDAWILL, C. J. & DAVID, M. A. - Determination of serum proteins by means of the biuret reaction. J. Biol. Chem., 177: 751-766. 1949.

[6] 6. HAIDER, M. & HAIDER, S. Q. - Assessment of protein caloric malnutrition. Clin. Chem., 30: 1286-1299, 1984.

[7] 7. HILL, P. G. & WELLS, T. N. C. - Bromocresol purple and the measurement of albumin. Ann. clin. Biochem., 20: 264-270, 1983.

[8] 8. KELLY, D. A. & TUDDENHAM, E. G. D. - Haemostatic problems in liver disease. Gut, 27: 339-349, 1986.

[9] 9. KESHGEGIAN, A. A. - Hypoalbuminemia associated with diffuse hyperglobulinemia in chronic diseases: lack of diagnostic specificity. Amer. J. clin. Path., 81: 477-481, 1984.

[10] 10. LOLLAR, P. & OWEN, W. G. - Clearance of thrombin from circulation in rabbits by high affinity binding sites on endothelium. J. clin. Invest., 66: 1222-1230, 1980.

[11] 11. LYRA, L. G.; REBOUÇAS, G. & ANDRADE, Z. A. - Hepatitis B surface antigen carrier state in hepatosplenic schistosomiasis. Gastroenterology, 71: 641-645, 1976.

[12] 12. MANOUKIAN, N. & BORGES, D. R. - Avaliação funcional e imunológica da protrombina na forma hepatoesplênica da esquistossomose e na cirrose hepática. Rev. paul. Med., 101: 182-185, 1983.

[13] 13. MANOUKIAN, N. & BORGES, D. R. - Pre-albumin, prekallikrein and prothrombin in hepatosplenic schistosomiasis: Increased turnover of the clotting proteins? Rev. Inst. Med. trop. S. Paulo, 26: 237-240, 1984

[14] 14. NEMERSON, Y. & CLYNE, L. P. - An assay for coagulation factor VII using factor VII depleted bovine plasma. J. Lab. clin. Med., 83: 301-303, 1974.

[15] 15. RAMOS, O. L.; SAAD, F. & LESER, W. P. - Portal hemodynamics and liver cell function in hepatic schistosomiasis. Gastroenterology, 47: 241-247, 1964.

[16] 16. SHERLOCK, S. - Hepatic cirrhosis. In: SHERLOCK, S. - Disease of the liver and biliary system. 7^th ed. Oxford, Blackwell Scientific Publication, 1985. p. 334-345.

[17] 17. SLEIGH, A. C.; HOFF, R.; MOTA, E. A.; SHERLOCK, I.; MOTT, K. E.; BARRETO, M. L.; MAGUIRE, J. H. & WELLER, T. H. - Three years prospective study of evolution of Manson's schistosomiasis in North East Brazil. Lancet, 2: 63-66, 1985.

[18] 18. STEINBERG, W. M.; GOLDSTEIN, S. S.; DAVIS, N. D.; SHAMMA'A, J. & ANDERSON, K. - Diagnosis assay in acute pancreatitis: a study of sensitivity and specificity. Ann. intern. Med., 102: 576-580, 1985.

[19] 19. VERSTRAETE, M.; VERMYLEN, S. & COLLEN, D. - Intravascular coagulation in liver disease. Ann. Rev. Med., 25: 447-455, 1974.

[20] 20. WINTROBE, M. M.; LEE, G. R.; BOGGS, D. R.; BITHELL, T. C; FOERSTER, J.; ATHENS, J. W. & LUKENS, J. N. - Blood coagulation. In: WINTROBE, M. M.; LEE, G. R.; BOGGS, D. R.; BITHELL, T. C.; FOERSTER, J.; ATHENS, J. W. & LUKENS, J. N. - Clinical haematology. 8^th ed. Philadelphia, Lea & Febiger, 1981. p. 405-452.

Brasil

Brasil

Hypoprothrombinemia in the compensated form of hepatosplenic schistosomiasis: further studies

Hipoprotrombinemia na forma-compensada da esquistossomose hepatoesplênica: novos estudos

Abstracts

Publication Dates

History