Platelets Accumulation In The Liver : A novel Mechanism Of Thrombocytopenia In Chronic Hepatic C Patients

Document Type : Original Article

Authors

1 Department of Tropical Medicine and Gastroenterology, Faculty of Medicine, Sohag University.

2 Department of, Pathology Department, Faculty of Medicine, Sohag University.

3 Department of, Tropical Medicine, and Gastroenterology Department, Faculty of Medicine, Sohag University.

Abstract

Background and aim: Thrombocytopenia is a common complication of chronicliver diseases and is due to various causes.The effect of thrombocytopenia on liver damage and the exact mechanisms that lead to thrombocytopenia in chronic liver disease and cirrhosis are still unclear. As Platelets Derived Growth Factor ß (PDGF-ß) is released from platelets (PLTs) upon activation. We tried to identify PLTs and PDGFR- ß in the liver to shed some light on the pathophysiology of thrombocytopenia and liver fibrosis in chronic hepatic C patients.
Patients and Methods: Analytical cross-sectional study was conducted on fiftypatients with proven chronic hepatitis C. All patients were referred to Tropical Medicine and Gastroenterology Department, Sohag University Hospital. Patients were categorized into two groups. Group 1 includes patients with PLT count less than 150000/µL (thrombocytopenia). Group 2 includes patients with normal PLT count (150000-450000/µL). All patients were subjected to full history taking, complete clinical examination, complete blood count, liver function tests. Liver biopsy was obtained for histological staging and grading. Immunohistochemical study of PLTs and PDGFR- ß were done using monoclonal antibodies against PLT's surface marker CD41 and PDGFR- ß.
Results: The included patients were 80 % males and 20 % females. Their mean agewas 44.42± 11.17 years. The mean average weighted score (AWS) of Imunohisto-chemical expression of CD41was significantly higher in thrombocytopenic group compared to normal PLTs group (5.8±2.86 vs 3.43±3.03; P<0.001). There was a significant negative correlation between CD41 expression and peripheral PLT count (r=-0.4; P=0.007). PDGFR- ß expression was significantly stronger in thrombocytopenic patients than patients with normal PLT count (6.9±3.6 vs 5.27±3.92; P=0.001). It showed also a significant negative correlation with peripheral PLT count (r=-0.34, P=0.045). Both CD41 and PDGFR- ß expression were significantly elevated in patients with advanced stage of fibrosis than in those
with earlier stages (7.26±5.23 vs 5.88±3.24; P=0.04 &9.2±2.7 vs 6.7±3.6; P Conclusion: The accumulation of PLTs in the liver in patients with chronic hepatitisC may be involved in thrombocytopenia and liver fibrosis.

Keywords

References

  1. Lavanchy D (2011): Evolving epidemiology of hepatitis C virus. Clin Microbiol Infect 17:107–115.
  2. Nagamine T, Ohtuka T, Takehara K, Arai T, Takagi H, Mori M (1996): Thrombocytopenia associated with hepatitis C viral infection. J Hepatol, 24:135-140.
  3. Peck-Radosavljevic  M.  (2000):  Thrombocytopenia  in  liver  disease.  Can  J Gastroenterol;14: 60-66.
  4. Hayashi H, Beppu T, Shirabe K (2014): Management of thrombocytopenia due to liver cirrhosis: a review. World J Gastroenterol 20(10): 2595–2605.
  5. Mannaioni PF, Di Bello MG, Masini E (1997): Platelets and inflammation: role of platelet-derived growth factor, adhesion molecules and histamine. Inflamm Res 46:4–18.
  6. Italiano JE Jr, Richardson JL, Patel-Hett S, Battinelli E, ZaslavskyA, Short S, et al.(2008) Angiogenesis is regulated by a novel mechanism: pro- and antiangiogenic proteins are organized into separate platelet a granules and differentially released. Blood 111:1227–1233.
  7. Mazzucco L, Medici D, Serra M, Panizza R, Rivara G, OrecchiaS, et al. (2004): The use of autologous platelet gel to treat difficult-to-heal wounds: a pilot study. Transfusion 44:1013–1018.
  8. Nash GF, Turner LF, Scully MF, Kakkar AK (2002): Platelets and cancer. Lancet Oncol 3: 425–430.
  9. Janowska-Wieczorek A, Wysoczynski M, Kijowski J, MarquezCurtis L, Machalinski B, Ratajczak J, et al. (2005): Microvesicles derived from activated platelets induce metastasis and angiogenesis in lung cancer. Int J Cancer 113:752–760.
  10. Iannacone M, Sitia G, Isogawa M,    Marchese P, Castro MG,Lowenstein PR, et al.

      (2005): Platelets mediate cytotoxic T lymphocyte induced liver damage. Nat Med 11:1167–9.

11.Lang PA, Contaldo C, Georgiev P, El-Badry AM, Recher M,Kurrer M, et al.(2008):

Aggravation of viral hepatitis by platelet-derived serotonin. Nat Med1 4:756–761.

12. Bashour FN, Teran JC, Mullen KD. (2000): Prevalence of peripheral blood cytopenias (hypersplenism) in patients with nonalcoholic chronic liver disease. Am J Gastroenterol.;95(10):2936–2939.

13. Atla PR (2012): Prevalence of cirrhosis in patients with thrombocytopenia who receive bone marrow biopsy. Saudi J Gastroenterol 18(4):257–262.

14. Dienstag JL, McHutchison JG (2006): American Gastroenterological Association technical review on the management of hepatitis C. Gastroenterology 130:213–64.

15. Aoki Y, Hirai K, Tanikawa K (1993): Mechanism of thrombocytopenia in liver cirrhosis: kinetics of indim-111 tropolone labeled in PLTs. Eur J Nucl Med 20:123– 129.

16. Noguchi H, Hirai K, Aoki Y, Sakata K, Tanikawa K (1995): Changes in platelet kinetics after a partial splenic arterial embolization in cirrhotic patients with hypersplenism. Hepatology 22: 1682–1688.

17. Kraiss LW, Raines EW, Wilcox JN (1993): Regional expression of the platelet-derived growth factor and its receptors in a primate graft model of vessel wall assembly. J Clin Invest 92: 338-348.

18. Pinzani M,Grappone C, Weber FL Jr (1994): Expression of platelet- derived growth factor in a model of acute liver injury. Hepatology 19:701-707.

19. Scheuer PJ, Desmet VJ, Gerber M, Hoofnagle JH, Manns M (1994): Classification of chronic hepatitis: diagnosis, grading and staging. Hepatology 19:1513–20.

20. Garcia-Suarez J, Burgaleta C, Hernanz N (2000). HCV-associated thrombocytopenia: clinical characteristics and platelet response after recombinant alpha2b-interferon therapy. Br J Haematol 110(1): 98–103.

21. BordinG, Ballare M, Zigrossi P (1995): A laboratory and thrombokinetic study ofHCV-associated       thrombocytopenia: a    direct   role      of HCV            in bone marrow exhaustion? ClinExp Rheumatol 13(Suppl 13): 39–43.

22. Nagamine  T, Ohtuka T, Takehara K, Arai T, Takagi H, Mori M. (1996):

     Thrombocytopenia associated with hepatitis C viral infection. J Hepatol, 24:135-140.

23. Kondo, R, Nomura, and Kage M (2013): Accumulation of platelets in the liver may be an importantcontributory factor to thrombocytopenia and liver fibrosis in chronic hepatitis C. J Gastroenterol 48:526–534.

24. Yan X, Xiong Y, Wu H, Liu Y, et al. (2017): Accumulation of platelets in the liver may be an important contributory factor to liver injury in chronic hepatitis B virus infection Int J ClinExp Pathol 10(6):6924-6929.

25. Sata M, Yano Y, Yoshiyama Y, Ide T, Kumashiro R, Suzuki H, et al. (1997): Mechanism of thrombocytopenia induced by interferon therapy for chronic hepatitis B. J Gastroenterol 32: 206–10.

26. Starlinger P and Assinger A (2016): Importance of platelet-derived growth factors in liver regeneration expert review of Gastroenterology and Hepatology 10 (5): 557-559.

27. Pawlotsky JM, Bouvier M, Fromont P et al. (1995): Hepatitis C virus infection and

     autoimmune thrombocytopenic purpura. J Hepatol 23(6): 635–639.

28. Chiao EY, Engels EA, Kramer JR, et al. (2009): Risk of immune thrombocytopenic purpura and autoimmune hemolytic anemia among 120 908 US veterans with hepatitis C virus infection. Arch Intern Med 169(4): 357–363.

29. Liang DY, Li CY (1995): Immunohistochemical study of the spleen in chronic immune thrombocytopenic Purpura. With special reference to hypoplastic follicles and foamy macrophages. Arch Pathol Lab Med 119(5): 533-537.

30. Hoffmeister  K M  (2011):  The  role  of lectins  and  glycans  in  platelet  clearance.

    Journal of thrombosis and haemostasis: 9 (Suppl 1): 35–43.

31. Tribulatti M V, Mucci J, Van Rooijen N, Leguizamon M S, Campetella O. (2005): The trans-sialidase from Trypanosoma cruzi induces thrombocytopenia during acute Chagas’ disease by reducing the platelet sialic acid contents. Infection and immunity 73: 201–207.

32. Rajendiran S, Lakshamanappa, H S, Zachariah B & Nambiar, S (2008): Desialylation

 Of plasma proteins in severe dengue infection: possible role of oxidative stress. TheAmerican journal of Tropical Medicine and Hygiene 79: 372–377.

33. Grozovsky, R., A.J. Begonja, K. Liu, G. Visner, J.H. Hartwig, H. Falet, and K.M. Hoffmeister. 2015. The Ashwell-Morell receptor regulates hepatic thrombopoietin production via JAK2-STAT3 signaling. Nat. Med. 21:47–54.

34. Ikeda N, Murata S, Maruyama T, Tamura T, et al. (2011): Platelet-derived adenosine 5’-triphosphate suppresses activation of human hepatic stellate cell - in vitro study. Hepatol research 42(1): 91–102.

35. Kodama  T,  Takehara  T,  Hikita  H  et  al.  (2010):  Thrombocytopenia  Exacerbates

Cholestasis-Induced Liver Fibrosis in Mice. Gastroenterology; 138 (7): 2487–7.

36. Ikura Y, Moromoto H, Masauki O, Histo J, Nasko I, and Masami S (1997): Expression of platelet-derived growth factor and its receptor in livers of patients with chronic liver disease. J Gastroenterol 32:496-501.

37. Burt AD (1993): Cellular and molecular aspects of hepatic fibrosis. J Pathol 170:105-

114.

Files

Share

How to cite

Statistics