The Influence of Malnutrition on Outcomes in Primary Immune Thrombocytopenia

Background: Immune thrombocytopenia (ITP) is an acquired thrombocytopenia caused by autoantibodies against platelet antigens. It can be categorized into primary and secondary ITP based on etiology. Primary ITP (PITP) is a diagnosis of exclusion characterized by isolated thrombocytopenia caused by an auto-immune mediated platelet destruction with impaired platelet production. The pathogenesis of PITP is incompletely understood but has been thought to involve specific IgG autoantibodies directed against platelet membrane glycoproteins such as GPIIb/IIIa as well as autoreactive cytotoxic T cells directed against megakaryocytes. The specific inciting events have been linked to genetic and acquired factors such as chronic inflammation and immune stimulation. Deficiency of micronutrients and vitamins in malnutrition have been shown to alter immune tolerance, as they influence T-cell function and play important roles in clonal selection and development of regulatory t-cells. Malnutrition is a highly underrecognized condition among hospitalized patients in the United States. While obesity has been associated with adverse outcomes in patients with PITP, the influence of malnutrition has never been explored. This study aimed to explore the association between malnutrition and PITP.

Method: Using a retrospective cohort study design, we analyzed data from the 2016 - 2020 iterations of the National Inpatient Sample Database including adult patients (pts) aged 18 years or older with a primary discharge diagnosis of PITP. We excluded pts with missing data on sociodemographic and hospital characteristics, nutritional status, or assessed outcomes; pts with co-existing end stage liver and kidney disease; pts on hospice status and elective admissions. The independent variable was a secondary diagnosis of malnutrition identified using ICD-10 codes. The primary endpoint of the study was in-hospital mortality. The secondary endpoints included length of stay, total hospitalization costs, venous thromboembolism (VTE), minor and major bleeding. Baseline sociodemographic, hospital characteristics and outcomes were compared using Chi-Square (X²) for categorical variables and t-test for continuous variables. Multivariable logistic and linear regression models were fit to assess the relationship between malnutrition and PITP outcomes adjusting for potential confounders. Statistical significance was set at p<0.05.

Results: The sample included 9974 unweighted pts representing a weighted sample of 49869 adult PITP pts, of which 3.45% had a secondary diagnosis of malnutrition. The mean age (±SD) of the pts was 55.6 years (±20.31). Among pts with PITP, 57.93% were female, 63.75% were White, 15.30% Black, 16.90% Hispanic and 4.03 %Asian/Pacific Islander (PI). Overall, 13.95% had major bleed, and 1.04% venous thromboembolism. On bivariate analysis, there were a higher proportion of older pts (68.2 years vs 55.1 years, p<0.0001), Medicare pts (67.46% vs 39.99%; p<0.0001), White pts (70.62% vs 63.51%; p = 0.0186), and pts in the Midwest hospital region (25.29% vs 19.14%; p=0.0432) with malnutrition. After adjusting for confounders, malnutrition was associated with increased in-hospital mortality (aOR 3.66; 95% CI 1.82, 7.33), VTE (aOR 2.72; 95% CI 1.46, 5.11), mean length of stay (4.47; 95% CI 3.31, 5.63) and mean total hospitalization charge ($57630; 95% CI 32645, 82616). There were no statistically significant associations between malnutrition and major bleed (aOR 1.18; 95% CI 0.87, 1.60) or minor bleed (aOR 1.26; 95% CI 0.66, 2.41) in PITP pts.

Conclusion: In this nationally representative study, we found that malnutrition was associated with worse inpatient outcomes in patients with PITP including higher mortality, increased odds of VTE, longer hospital stays and increased healthcare costs. Early recognition through in-hospital nutritional assessments as well as a multidisciplinary based approach to nutritional intervention could improve outcomes in hospitalized patients with PITP.

No relevant conflicts of interest to declare.