Original Contribution


Platelet Count Does Not Predict Bleeding in Cirrhotic Patients: Results from the PRO-LIVER Study

  • The American Journal of Gastroenterology volume 113, pages 368375 (2018)
  • doi:10.1038/ajg.2017.457
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Thrombocytopenia is a hallmark for patients with cirrhosis and it is perceived as a risk factor for bleeding events. However, the relationship between platelet count and bleeding is still unclear.


We investigated the relationship between platelet count and major or clinical relevant nonmajor bleedings during a follow-up of 4 years.


A total of 280 cirrhotic patients with different degrees of liver disease (67% males; age 64±37 years; 47% Child–Pugh B and C) were followed up for a median of 1,129 (interquartile range: 800–1,498) days yielding 953.12 patient-year of observation. The annual rate of any significant bleeding was 5.45%/year (3.57%/year and 1.89%/year for major and minor bleeding, respectively). Fifty-two (18.6%) patients experienced a major (n=34) or minor (n=18) bleeding event, predominantly from gastrointestinal origin. Platelet counts progressively decreased with the worsening of liver disease and were similar in patients with or without major or minor bleeding: a platelet count ≤50 × 103/μl was detected in 3 (6%) patients with and in 20 (9%) patients without any bleeding event. Conversely, prothrombin time-international normalized ratio was slightly higher in patients with overall or major bleeding. On Cox proportional hazard analysis, only a previous gastrointestinal bleeding (hazard ratio (HR): 1.96; 95% confidence interval: 1.11–3.47; P=0.020) and encephalopathy (HR: 2.05; 95% confidence interval: 1.16–3.62; P=0.013) independently predicted overall bleeding events.


Platelet count does not predict unprovoked major or minor bleeding in cirrhotic patients.

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  1. 1.

    , , et al. Coagulation disorders and hemostasis in liver disease pathophysiology and critical assessment of current management. Hepatology 2006;44:1039–1046.

  2. 2.

    . Should the term coagulopathy in cirrhosis be abandoned? JAMA Intern Med 2015;175:862–863.

  3. 3.

    , . Clotting activation and hyperfibrinolysis in cirrhosis: implication for bleeding and thrombosis. Semin Thromb Hemost 2013;39:426–433.

  4. 4.

    , , et al. Bleeding and thrombosis in cirrhotic patients: what really matters? Dig Liver Dis 2012;44:275–279.

  5. 5.

    , , et al. Ongoing prothrombotic state in the portal circulation of cirrhotic patients. Thromb Haemost 1997;77:44–47.

  6. 6.

    , , et al. Enhanced expression of monocyte tissue factor in patients with liver cirrhosis. Gut 1998;43:428–432.

  7. 7.

    , , et al. Association between low-grade disseminated intravascular coagulation and endotoxemia in patients with liver cirrhosis. Gastroenterology 1995;109:531–539.

  8. 8.

    , , et al. An imbalance of pro- vs anti-coagulation factors in plasma from patients with cirrhosis. Gastroenterology 2009;137:2105–2111.

  9. 9.

    , , et al. Patients with liver cirrhosis suffer from primary haemostatic defects. Fact or fiction? J Hepatol 2011;55:1415–1427.

  10. 10.

    , , et al. Low-grade endotoxemia and platelet activation in cirrhosis. Hepatology 2017;65:571–581.

  11. 11.

    , , et al. Bleeding time does not predict gastrointestinal bleeding in patients with cirrhosis. The CALC Group. Coagulation Abnormalities in Liver Cirrhosis. J Hepatol 1996;24:574–580.

  12. 12.

    , , et al. Coagulation parameters and major bleeding in critically ill patients with cirrhosis. Hepatology 2016;64:556–568.

  13. 13.

    , , et al. Association of conventional haemostasis and coagulation tests with the risk of acute upper gastrointestinal bleeding in liver cirrhosis: a retrospective study. Gastroenterol Rep (Oxf) 2016;4:315–319.

  14. 14.

    , , et al. Bleeding after invasive procedures is rare and unpredicted by platelet counts in cirrhotic patients with thrombocytopenia. Eur J Intern Med 2017;38:79–82.

  15. 15.

    , , et al. von Willebrand factor and procoagulant imbalance predict outcome in patients with cirrhosis and thrombocytopenia. J Hepatol 2016;65:921–928.

  16. 16.

    , , Subcommittee on Control of Anticoagulation of the Scientific and Standardization Committee of the International Society on Thrombosis and Haemostasis. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in non-surgical patients. J Thromb Haemost 2005;3:692–694.

  17. 17.

    , , et al. Definition of major bleeding in clinical investigations of antihemostatic medicinal products in surgical patients. J Thromb Haemost 2010;8:202–204.

  18. 18.

    , , et al. Portal vein thrombosis relevance on liver cirrhosis: Italian Venous Thrombotic Events Registry. Intern Emerg Med 2016;11:1059–1066.

  19. 19.

    North Italian Endoscopic Club for the Study and Treatment of Esophageal Varices. Prediction of the first variceal hemorrhage in patients with cirrhosis of the liver and esophageal varices. A prospective multicenter study. N Engl J Med 1988;319:983–989.

  20. 20.

    , , et al. Prevention and management of gastroesophageal varices and variceal hemorrhage in cirrhosis. Hepatology 2007;46:922–938.

  21. 21.

    , , . Spontaneous bleeding or thrombosis in cirrhosis: What should be feared the most? World J Hepatol 2015;7:1818–1827.

  22. 22.

    , , Cooperative Study Group. Upper digestive bleeding in cirrhosis. Post-therapeutic outcome and prognostic indicators. Hepatology 2003;38:599–612.

  23. 23.

    , , . A clinical survey of bleeding, thrombosis, and blood product use in decompensated cirrhosis patients. Ann Hepatol 2012;11:686–690.

  24. 24.

    , , et al. Non-variceal gastrointestinal bleeding in patients with liver cirrhosis: a review. Dig Dis Sci 2012;57:2743–2754.

  25. 25.

    , , et al. Spontaneous intracranial hemorrhage in cirrhotic patients. Clin Neurol Neurosurg 2008;110:253–258.

  26. 26.

    , , . Liver cirrhosis and risk of intracerebral hemorrhage: a 9-year follow-up study. Stroke 2011;42:2615–2617.

  27. 27.

    , . Rebalanced hemostasis in patients with liver disease: evidence and clinical consequences. Blood 2010;116:878–885.

  28. 28.

    , . Thrombocytopenia in cirrhosis: impact of fibrinogen on bleeding risk. World J Hepatol 2017;9:318–325.

  29. 29.

    , , et al. Fibrinogen as an independent predictor of mortality in decompensated cirrhosis and bleeding. Hepatology 2017;65:1079–1080.

  30. 30.

    , . Treatment of patients with cirrhosis. N Engl J Med 2016;375:767–777.

  31. 31.

    , , et al. The 35-year odyssey of beta blockers in cirrhosis: any gender difference in sight? Pharmacol Res 2017;119:20–26.

  32. 32.

    , , . Inherited platelet disorders: thrombocytopenias and thrombocytopathies. Blood Transfus 2009;7:278–292.

  33. 33.

    , . Systematic review and meta-analysis of adverse events of low-dose aspirin and clopidogrel in randomized controlled trials. Am J Med 2006;119:624–638.

  34. 34.

    Under the auspices of the Italian Association for the Study of Liver Diseases (AISF) and the Italian Society of Internal Medicine (SIMI). Hemostatic balance in patients with liver cirrhosis: report of a consensus conference. Dig Liver Dis 2016;48:455–467.

  35. 35.

    , . Eltrombopag before procedures in patients with cirrhosis and thrombocytopenia. N Engl J Med 2012;367:2056.

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Author information

Author notes


  1. Department of Internal Medicine and Medical Specialties, Sapienza University of Rome, Rome, Italy

    • S Basili
    • , G Talerico
    •  & F Violi
  2. Department of Experimental Medicine, Sapienza University of Rome, Rome, Italy

    • V Raparelli
    •  & L Napoleone
  3. Clinica Medica I, Department of Internal Medicine S. Matteo, University Hospital Pavia, Pavia, Italy

    • G R Corazza
  4. Department of Medical and Surgical Sciences, University Magna Græcia of Catanzaro, Catanzaro, Italy

    • F Perticone
  5. Department of Medicine, University of Padova, Padova, Italy

    • D Sacerdoti
  6. Division of Gastroenterology, Casa Sollievo Sofferenza Hospital, IRCCS, San Giovanni Rotondo, Italy

    • A Andriulli
  7. Department of Internal Medicine and Specialities, DIBIMIS, University of Palermo, Palermo, Italy

    • A Licata
  8. Unit of Internal Medicine 2, Department of Medical and Surgical Science for Children and Adults, University of Modena and Reggio Emilia, Modena, Italy

    • A Pietrangelo
  9. Internal Medicine and Hepatology Unit, University Campus Bio-Medico, Rome, Italy

    • A Picardi
  10. Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy

    • G Raimondo


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Competing interests

Guarantor of the article: F. Violi, MD.

Specific author contributions: S. Basili: study design, patient recruitment, data analysis and interpretation, and writing the manuscript. V. Raparelli: data collection, patient recruitment, data analysis and interpretation, and writing the manuscript. L. Napoleone: patient recruitment and data entry. G. Talerico: patient recruitment and data entry. G.R. Corazza: patient recruitment and revision of the manuscript. F. Perticone, D. Sacerdoti, A. Andriulli, A. Licata, A. Pietrangelo, A. Picardi, and G. Raimondo: patient recruitment and revision of the manuscript. F. Violi: study conception and design, data interpretation, and writing the manuscript. F. Violi had full access to all the data in the study and had final responsibility for the decision to submit for publication.

Financial support: SAPIENZA University Research Project 2016.

Potential competing interests: None.

Corresponding author

Correspondence to F Violi.