Démonstration de Faisabilité: Nonalcoholic Fatty Liver Disease May Cause Thrombocytopenia

Démonstration de faisabilité, in French, “proof of concept” in English, also known as proof of principle, is considered as a realization of a certain method or idea to demonstrate its feasibility or to verify that some concept or theory has practical potential. A proof of concept is usually small and may or may not be complete. I would like to propose that nonalcoholic fatty liver disease (NAFLD) leading into thrombocytopenia may now have sufficient evidence to provide a proof of concept.

Since 2014, we have been conducting prospective studies to assess the presence of thrombocytopenia (less than 100 × 10⁹/L platelets) in persons with NAFLD without overt liver cirrhosis.[1] [2] [3] [4] The concept was initially entertained by Dasanu et al in 2010.[5] To define the presence of NAFLD, several methods can be employed: liver biopsy, serologic determinations (Fibromax), and liver transient elastography (TE/Fibroscan). Employing serologic determinations, we initially found that 28% of people we identified to have NAFLD presented with less than 100 × 10⁹/L platelets.[1] Subsequently, employing both serologic determinations and transient elastography to define the presence of NAFLD, we found that 24% of those assessed had thrombocytopenia.[2] Interestingly, according to a group of researchers in Brazil, employing liver biopsy to define NAFLD, the prevalence of thrombocytopenia was 3%.[6] Since NAFLD is the hepatic component of insulin resistance, we assessed the association of thrombocytopenia and insulin resistance and found that, in the absence of NAFLD, insulin resistance by itself is not associated with thrombocytopenia.[3] It seems that changes in the intrahepatic circulation and/or structure are needed to induce the drop in platelet count. Strictly speaking, the cause of the thrombocytopenia we observe in NAFLD is unknown, but several explanations have been offered, such as a certain degree of hypersplenism, bone marrow hypoplasia, reduced peripheral blood cell survival, thrombopoietin deficiency, among others.[1] [2] [3] [4] [5] [6] Since hypersplenism may lead into granulocytopenia, we also explored the association of NAFLD, granulocytopenia, and thrombocytopenia and found that there is a significant association between these variables, thus suggesting that hypersplenism may somehow be involved in the origin of the cytopenias observed in people with NAFLD.[4]

As a result of the studies that have been conducted in this condition, we have learned that the salient features of the NAFLD-associated thrombocytopenia are: (1) it presents in around one-fifth of patients, depending on the method employed to define the liver damage; (2) it is associated with excess weight; (3) it is usually mild, with platelet count above 40 × 10⁹/L; (4) it is not associated to mucocutaneous bleeding; and (5) it does not need specific treatment to improve the platelet count.

Recognition that NAFLD may lead into mild thrombocytopenia means that a substantial number of unnecessary studies can be avoided in people being followed up for a mildly low platelet count. This concept may be particularly important in localities where the prevalence of insulin resistance is very high, and as a result the prevalence of NAFLD also high.

Publication History

Article published online:
11 October 2021

• References

• 1 Ruiz-Argüelles GJ, Velázquez-Sanchez-De-Cima S, Zamora-Ortiz G, Hernández-Reyes J, Ruiz-Delgado GJ. Nonalcoholic fatty liver disease may cause thrombocytopenia. Acta Haematol 2014; 132 (02) 159-162
• 2 Olivares-Gazca JC, Nuñez-Cortes AK, Méndez-Huerta MA, Cantero-Fortiz Y, Orea-Martínez JG, Ruiz-Argüelles GJ. More on the thrombocytopenia of the non-alcoholic fatty liver disease. Hematology 2017; 22 (05) 316-319
• 3 López-Trujillo MA, Olivares-Gazca JM, Cantero-Fortiz Y. et al. Nonalcoholic fatty liver disease and thrombocytopenia III: Its association with insulin resistance. Clin Appl Thromb Hemost 2019; 25: 1076029619888694
• 4 Rivera-Álvarez M, Córdova-Ramírez AC, Elías-De-La-Cruz GD. et al. Non-alcoholic fatty liver disease and thrombocytopenia IV: its association with granulocytopenia. Hematol Transfus Cell Ther 2021; (e-pub ahead of print) DOI: 10.1016/j.htct.2021.06.004.
• 5 Dasanu CA, Lamana S, Trikudanathan G. Thrombocytopenia, NAFLD, and metabolic syndrome: is there a link?. South Med J 2010; 103 (10) 1071
• 6 Panke CL, Tovo CV, Villela-Nogueira CA. et al. Evaluation of thrombocytopenia in patients with non-alcoholic fatty liver disease without cirrhosis. Ann Hepatol 2020; 19 (01) 88-91