Hyperfibrinolysis in hepatosplenic schistosomiasis.
PDF (813K)
Journal: 1997/March - Journal of Clinical Pathology
ISSN: 0021-9746
PUBMED: 9038736
Abstract:
OBJECTIVE
To evaluate the nature of accelerated fibrinolysis in hepatosplenic schistosomiasis.
METHODS
The biological activity of plasminogen (Plg), plasminogen activators (PA), alpha 2-antiplasmin (alpha 2-AP) and plasminogen activator inhibitor-1 (PAI-1) was determined by photometric analysis in 15 compensated and 35 decompensated patients with endemic Egyptian hepatosplenomegaly. Quantitative measurement of plasma concentrations of tissue t-PA, t-PA-PAI-1 complex, alpha 2-antiplasmin-plasmin complex (alpha 2-APP), fibrinogen degradation products (FbDP), D-dimers (D-D), thrombin-antithrombin complex (TAT) and prothrombin fragment (F 1 + 2) complexes, using double antibody sandwich enzyme linked immunosorbent assays and grading of the degree of hepatic insufficiency according to the Child-Pugh classification, were also carried out.
RESULTS
The progressive deterioration of liver function in schistosomal patients, which matched the severity of the disease, led to simultaneous defects in profibrinolytic (decreased Plg and increased PA and t-PA) and antifibrinolytic (decreased alpha 2-AP and PAI-1) factors-the latter defects being the most prominent-resulting in significant generation of plasmin (increased APP complexes) and therefore enhanced fibrinolysis (increased FbDP and D-dimer). The raised concentrations of FbDP, D-D, TAT and F 1 + 2 established its secondary nature.
CONCLUSIONS
These findings suggest that the amount of PAI-1 available to bind and neutralise circulating t-PA may be a critical factor in the progress of hyperfibrinolysis observed in hepatosplenic schistosomiasis, and that the pronounced reduction in its plasma concentration may be regarded as a potential warning indicator of haemostatic imbalance in decompensated schistosomal patients at high risk of variceal bleeding.
Open in
PUBMED | PMC | Google Scholar | Wikipedia
Relations:
Content
Citations
(5)
References
(30)
Diseases
(3)
Conditions
(2)
Chemicals
(2)
Organisms
(1)
Processes
(1)
Affiliates
(1)
Similar articles
Articles by the same authors
Discussion board
J Clin Pathol 49(12): 990-993
PMID: 9038736

Hyperfibrinolysis in hepatosplenic schistosomiasis.

Abstract

AIM: To evaluate the nature of accelerated fibrinolysis in hepatosplenic schistosomiasis. METHODS: The biological activity of plasminogen (Plg), plasminogen activators (PA), alpha 2-antiplasmin (alpha 2-AP) and plasminogen activator inhibitor-1 (PAI-1) was determined by photometric analysis in 15 compensated and 35 decompensated patients with endemic Egyptian hepatosplenomegaly. Quantitative measurement of plasma concentrations of tissue t-PA, t-PA-PAI-1 complex, alpha 2-antiplasmin-plasmin complex (alpha 2-APP), fibrinogen degradation products (FbDP), D-dimers (D-D), thrombin-antithrombin complex (TAT) and prothrombin fragment (F 1 + 2) complexes, using double antibody sandwich enzyme linked immunosorbent assays and grading of the degree of hepatic insufficiency according to the Child-Pugh classification, were also carried out. RESULTS: The progressive deterioration of liver function in schistosomal patients, which matched the severity of the disease, led to simultaneous defects in profibrinolytic (decreased Plg and increased PA and t-PA) and antifibrinolytic (decreased alpha 2-AP and PAI-1) factors-the latter defects being the most prominent-resulting in significant generation of plasmin (increased APP complexes) and therefore enhanced fibrinolysis (increased FbDP and D-dimer). The raised concentrations of FbDP, D-D, TAT and F 1 + 2 established its secondary nature. CONCLUSION: These findings suggest that the amount of PAI-1 available to bind and neutralise circulating t-PA may be a critical factor in the progress of hyperfibrinolysis observed in hepatosplenic schistosomiasis, and that the pronounced reduction in its plasma concentration may be regarded as a potential warning indicator of haemostatic imbalance in decompensated schistosomal patients at high risk of variceal bleeding.

Full text

Full text is available as a scanned copy of the original print version. Get a printable copy (PDF file) of the complete article (813K), or click on a page image below to browse page by page. Links to PubMed are also available for Selected References.
icon of scanned page 990
990
icon of scanned page 991
991
icon of scanned page 992
992
icon of scanned page 993
993

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Omran SA, Madkour BA, Essawy FM, Toima SM, el Kaliouby AH, Shams el Din AA. The pathogenesis of accelerated fibrinolysis in hepatosplenic schistosomiasis. Blood Coagul Fibrinolysis. 1992 Dec;3(6):819–822. [PubMed] [Google Scholar]
  • Omran SA, el-Bassiouni NE, Amer AM, Hussein AT. Fibrinolytic parameters during acute haematemesis in endemic hepatosplenomegaly. Blood Coagul Fibrinolysis. 1993 Dec;4(6):891–894. [PubMed] [Google Scholar]
  • Violi F, Ferro D, Basili S, Quintarelli C, Saliola M, Alessandri C, Cordova C, Balsano F. Hyperfibrinolysis increases the risk of gastrointestinal hemorrhage in patients with advanced cirrhosis. Hepatology. 1992 Apr;15(4):672–676. [PubMed] [Google Scholar]
  • Bertaglia E, Belmonte P, Vertolli U, Azzurro M, Martines D. Bleeding in cirrhotic patients: a precipitating factor due to intravascular coagulation or to hepatic failure? Haemostasis. 1983;13(5):328–334. [PubMed] [Google Scholar]
  • Francis RB, Jr, Feinstein DI. Clinical significance of accelerated fibrinolysis in liver disease. Haemostasis. 1984;14(6):460–465. [PubMed] [Google Scholar]
  • Boks AL, Brommer EJ, Schalm SW, Van Vliet HH. Hemostasis and fibrinolysis in severe liver failure and their relation to hemorrhage. Hepatology. 1986 Jan-Feb;6(1):79–86. [PubMed] [Google Scholar]
  • Leebeek FW, Kluft C, Knot EA, de Maat MP, Wilson JH. A shift in balance between profibrinolytic and antifibrinolytic factors causes enhanced fibrinolysis in cirrhosis. Gastroenterology. 1991 Nov;101(5):1382–1390. [PubMed] [Google Scholar]
  • Aoki N, Yamanaka T. The alpha2-plasmin inhibitor levels in liver diseases. Clin Chim Acta. 1978 Mar 1;84(1-2):99–105. [PubMed] [Google Scholar]
  • Booth NA, Anderson JA, Bennett B. Plasminogen activators in alcoholic cirrhosis: demonstration of increased tissue type and urokinase type activator. J Clin Pathol. 1984 Jul;37(7):772–777.[PMC free article] [PubMed] [Google Scholar]
  • Hersch SL, Kunelis T, Francis RB., Jr The pathogenesis of accelerated fibrinolysis in liver cirrhosis: a critical role for tissue plasminogen activator inhibitor. Blood. 1987 May;69(5):1315–1319. [PubMed] [Google Scholar]
  • Omran SA, el-Bassiouni NE, Hussein NA, Akl MM, Hussein AT, Mohamed AA. Disseminated intravascular coagulation in endemic hepatosplenic schistosomiasis. Haemostasis. 1995 Sep-Oct;25(5):218–228. [PubMed] [Google Scholar]
  • Pugh RN, Murray-Lyon IM, Dawson JL, Pietroni MC, Williams R. Transection of the oesophagus for bleeding oesophageal varices. Br J Surg. 1973 Aug;60(8):646–649. [PubMed] [Google Scholar]
  • Conn HO. A peek at the Child-Turcotte classification. Hepatology. 1981 Nov-Dec;1(6):673–676. [PubMed] [Google Scholar]
  • CLAUSS A. Gerinnungsphysiologische Schnellmethode zur Bestimmung des Fibrinogens. Acta Haematol. 1957 Apr;17(4):237–246. [PubMed] [Google Scholar]
  • Kluft C. Studies on the fibrinolytic system in human plasma: quantitative determination of plasminogen activators and proactivators. Thromb Haemost. 1979 Apr 23;41(2):365–383. [PubMed] [Google Scholar]
  • Stief TW, Lenz P, Becker U, Heimburger N. Determination of plasminogen activator inhibitor (PAI) capacity of human plasma in presence of oxidants: a novel principle. Thromb Res. 1988 May 15;50(4):559–573. [PubMed] [Google Scholar]
  • Silverstein RM. The determination of human plasminogen using Nalpha-CBZ-L-lysin p-nitrophenyl ester as substrate. Anal Biochem. 1975 May 12;65(1-2):500–506. [PubMed] [Google Scholar]
  • Teger-Nilsson AC, Friberger P, Gyzander E. Determination of a new rapid plasmin inhibitor in human blood by means of a plasmin specific tripeptide substrate. Scand J Clin Lab Invest. 1977 Sep;37(5):403–409. [PubMed] [Google Scholar]
  • Holvoet P, Cleemput H, Collen D. Assay of human tissue-type plasminogen activator (t-PA) with an enzyme-linked immunosorbent assay (ELISA) based on three murine monoclonal antibodies to t-PA. Thromb Haemost. 1985 Oct 30;54(3):684–687. [PubMed] [Google Scholar]
  • Koppert PW, Koopman J, Haverkate F, Nieuwenhuizen W. Production and characterization of a monoclonal antibody reactive with a specific neoantigenic determinant (comprising B beta 54-118) in degradation products of fibrin and of fibrinogen. Blood. 1986 Aug;68(2):437–441. [PubMed] [Google Scholar]
  • Koppert PW, Hoegee-de Nobel E, Nieuwenhuizen W. A monoclonal antibody-based enzyme immunoassay for fibrin degradation products in plasma. Thromb Haemost. 1988 Apr 8;59(2):310–315. [PubMed] [Google Scholar]
  • Pelzer H, Schwarz A, Heimburger N. Determination of human thrombin-antithrombin III complex in plasma with an enzyme-linked immunosorbent assay. Thromb Haemost. 1988 Feb 25;59(1):101–106. [PubMed] [Google Scholar]
  • Pelzer H, Schwarz A, Stüber W. Determination of human prothrombin activation fragment 1 + 2 in plasma with an antibody against a synthetic peptide. Thromb Haemost. 1991 Feb 12;65(2):153–159. [PubMed] [Google Scholar]
  • Booth NA, Bennett B. Plasmin-alpha 2-antiplasmin complexes in bleeding disorders characterized by primary or secondary fibrinolysis. Br J Haematol. 1984 Apr;56(4):545–556. [PubMed] [Google Scholar]
  • Savion N, Farzame N. Binding uptake and degradation of antithrombin III X protease complexes by cultured corneal endothelial cells. Exp Cell Res. 1984 Jul;153(1):50–60. [PubMed] [Google Scholar]
  • Booth NA, Anderson JA, Bennett B. Plasminogen activators in alcoholic cirrhosis: demonstration of increased tissue type and urokinase type activator. J Clin Pathol. 1984 Jul;37(7):772–777.[PMC free article] [PubMed] [Google Scholar]
  • Fitch P, Bennett B, Booth NA, Croll A, Ewen SW. Distribution of plasminogen activator inhibitor in normal liver, cirrhotic liver, and liver with metastases. J Clin Pathol. 1994 Mar;47(3):218–221.[PMC free article] [PubMed] [Google Scholar]
  • Suffredini AF, Harpel PC, Parrillo JE. Promotion and subsequent inhibition of plasminogen activation after administration of intravenous endotoxin to normal subjects. N Engl J Med. 1989 May 4;320(18):1165–1172. [PubMed] [Google Scholar]
  • Amer AM, el Defrawi IE, el Sherif NH, el Khayat HR. Is the coagulopathy of hepatosplenic schistosomiasis immune-related? Blood Coagul Fibrinolysis. 1994 Oct;5(5):789–793. [PubMed] [Google Scholar]
  • Sprengers ED, Princen HM, Kooistra T, van Hinsbergh VW. Inhibition of plasminogen activators by conditioned medium of human hepatocytes and hepatoma cell line Hep G2. J Lab Clin Med. 1985 Jun;105(6):751–758. [PubMed] [Google Scholar]
  • Rijken DC, van Hinsbergh VW, Sens EH. Quantitation of tissue-type plasminogen activator in human endothelial cell cultures by use of an enzyme immunoassay. Thromb Res. 1984 Jan 15;33(2):145–153. [PubMed] [Google Scholar]
Department of Haematology, Theodor Bilharz Research Institute, Imbaba, Giza, Egypt.
Department of Haematology, Theodor Bilharz Research Institute, Imbaba, Giza, Egypt.
Copyright notice
Abstract
AIM: To evaluate the nature of accelerated fibrinolysis in hepatosplenic schistosomiasis. METHODS: The biological activity of plasminogen (Plg), plasminogen activators (PA), alpha 2-antiplasmin (alpha 2-AP) and plasminogen activator inhibitor-1 (PAI-1) was determined by photometric analysis in 15 compensated and 35 decompensated patients with endemic Egyptian hepatosplenomegaly. Quantitative measurement of plasma concentrations of tissue t-PA, t-PA-PAI-1 complex, alpha 2-antiplasmin-plasmin complex (alpha 2-APP), fibrinogen degradation products (FbDP), D-dimers (D-D), thrombin-antithrombin complex (TAT) and prothrombin fragment (F 1 + 2) complexes, using double antibody sandwich enzyme linked immunosorbent assays and grading of the degree of hepatic insufficiency according to the Child-Pugh classification, were also carried out. RESULTS: The progressive deterioration of liver function in schistosomal patients, which matched the severity of the disease, led to simultaneous defects in profibrinolytic (decreased Plg and increased PA and t-PA) and antifibrinolytic (decreased alpha 2-AP and PAI-1) factors-the latter defects being the most prominent-resulting in significant generation of plasmin (increased APP complexes) and therefore enhanced fibrinolysis (increased FbDP and D-dimer). The raised concentrations of FbDP, D-D, TAT and F 1 + 2 established its secondary nature. CONCLUSION: These findings suggest that the amount of PAI-1 available to bind and neutralise circulating t-PA may be a critical factor in the progress of hyperfibrinolysis observed in hepatosplenic schistosomiasis, and that the pronounced reduction in its plasma concentration may be regarded as a potential warning indicator of haemostatic imbalance in decompensated schistosomal patients at high risk of variceal bleeding.
Collaboration tool especially designed for Life Science professionals.Drag-and-drop any entity to your messages.