Impact of Non-Alcoholic Fatty Liver Disease (NAFLD) on Platelet Count
Authors: Tomassetti Sarah , Yashar David , LaBarbera Katie 
Published: November 2021

Abstract
BACKGROUND: It is well established that alcohol use and chronic viral hepatitis negatively affect the peripheral platelet count. However, less is known about the effects of non-alcoholic fatty liver disease (NAFLD) on the peripheral platelet count.
Platelets are anucleate cells made in the bone marrow that are responsible for the initiation of the hemostatic system and ultimately the repair of damaged endothelium. Platelet production is stimulated by thrombopoietin (TPO), a glycoprotein made by the liver that regulates platelet production. Binding of TPO to its receptor, c-MPL, on platelets and megakaryocytes prevents apoptosis of megakaryocytes and increases their number, size, and ploidy. In the setting of liver disease, such as NAFLD, TPO production may be reduced, which could result in lower peripheral platelet counts.
NAFLD is a growing concern in the United States where the prevalence of NAFLD is estimated to be 25% and is expected to continue to rise over the next 10-15 years. NAFLD comprises a wide spectrum of disorders from simple steatosis to steatohepatitis. It is caused by excessive fat accumulation in the liver due to a dysregulation of fat synthesis and utilization resulting in oxidative stress. NAFLD is closely tied to insulin resistance. A subset of those with NAFLD develop progressive liver disease characterized by hepatocyte injury, inflammation, and ultimately cirrhosis. Hispanics have the highest prevalence and often have components of metabolic syndrome including obesity, systemic hypertension, dyslipidemia, and insulin resistance or diabetes. Studies show conflicting results as to the association of NAFLD and thrombocytopenia. Thus, the effect of NAFLD on the peripheral platelet count warrants further investigation.
METHODS: We performed a retrospective chart review of all patients aged greater than 18 years who presented to Harbor-UCLA Medical Center between October 1, 2015 and March 1, 2021 with the diagnosis of NAFLD based on imaging. Diagnosis was established based on radiologic evidence of NAFLD on abdominal ultrasound or computed tomography scan. Patients were excluded if they had cirrhosis, chronic viral hepatitis, splenomegaly, excessive alcohol consumption (≥ 30 g/day in men or ≥ 20 g/day in women), malignancy, consumption of drugs commonly associated with thrombocytopenia, or known immune thrombocytopenia. Platelet count, body mass index (BMI), bilirubin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), albumin, protein, cholesterol, triglycerides, prothrombin time (PT), partial thromboplastin time (PTT), and HbA1c were measured. Comorbid conditions including hypertension, obstructive sleep apnea (OSA), cardiovascular disease (CVD), and chronic kidney disease (CKD), were recorded.
RESULTS: There were a total of 587 patients with the diagnosis of NAFLD who met the inclusion criteria. 41.7% were female and 58.3% were male. Of these, 51.4% were Hispanic, 8.9% were White (European), 7.0% were African American, 2.7% were Asian, and 2.7% were Southeast Asian, and 27.3% were unknown. The average age was 49 years. The mean platelet count was 249.5 K/cumm. The mean BMI was 33.4. The mean AST was 60.23 (normal 15-41 U/L) and ALT was 20.23 U/L (normal 7-35 U/L). The mean bilirubin, albumin, protein, PT, and PTT were all within normal limits. The mean HbA1c was 6.89%. The mean total cholesterol was 178.81 mg/dL (normal 125-199mg/dL), HDL 44.07 mg/dL (normal &gt;40mg/dL), and LDL 101.65 mg/dL (normal &lt;99 mg/dL). Coexisting hypertension, CKD, CVD, and OSA occurred in 39.2%, 11.1%, 7.8%, and 4.4% respectively.
CONCLUSIONS: In this study, we found that NAFLD was not associated with thrombocytopenia. Further studies may be done to elucidate the impact of NAFLD on TPO levels and resulting peripheral platelet levels.

Disclosures
Tomassetti: Parexel: Research Funding; Novartis: Research Funding; Natera: Research Funding; Beigene: Research Funding; Rigel: Research Funding; Seagene: Research Funding.