Impact of essential thrombocythemia on in-hospital outcomes and thrombotic complications in patients hospitalized with COVID-19: A national inpatient sample analysis (2016–2022)

Abstract Background: Essential thrombocythemia (ET) is a chronic myeloproliferative neoplasm characterized by elevated platelet counts and a predisposition to both thrombotic and hemorrhagic complications. While COVID-19 is independently associated with hypercoagulability and increased morbidity, the impact of coexisting ET on clinical outcomes among hospitalized COVID-19 patients remains poorly understood. Methods: We conducted a retrospective cohort study using the 2016–2022 National Inpatient Sample (NIS) to examine outcomes of patients hospitalized with a primary diagnosis of COVID-19 (ICD-10 U07.1). Patients with a concurrent diagnosis of essential thrombocythemia (ET; ICD-10 D47.3) were identified. Discharge weights were applied to generate nationally representative estimates. Baseline characteristics, in-hospital mortality, length of stay (LOS), hospital charges, and thromboembolic complications were compared between ET and non-ET patients. Multivariable logistic and linear regression models were used to adjust for demographics, comorbidities (Charlson Comorbidity Index [CCI]), and acute complications, including mechanical ventilation, septic shock, and acute kidney injury. Results: Among 5,934,565 patients hospitalized with COVID-19, 24,079 (0.4%) had ET. Compared to non-ET patients, the ET group was slightly younger (59.2 vs. 62.7 years, p<0.001), had a lower mean CCI (1.5 vs. 2.0, p<0.001), and a longer average LOS (11.3 vs. 8.1 days, p<0.001). ET patients also incurred higher mean hospitalization charges ($132,445 vs. $97,031, p<0.001). The in-hospital mortality rate was significantly lower in the ET group (9.6% vs. 11.3%, p<0.001). After adjustment for confounders, ET was independently associated with decreased odds of mortality (adjusted odds ratio [aOR] 0.87, 95% CI 0.78–0.98, p=0.023), reflecting a 12.9% relative reduction in mortality risk. Despite the lower mortality, ET patients experienced significantly worse thrombotic outcomes. After adjustment, ET was associated with increased odds of several thrombotic complications, including a 65.3% increase in pulmonary embolism (p<0.001), a 35% increase in ischemic stroke (p=0.006), and a 203% increase in arterial thrombosis (p<0.001). The risk of transient ischemic attack was marginally higher (4.5%) but not statistically significant (p=0.89). Interestingly, ET was associated with a non-significant 13.2% decrease in the odds of myocardial infarction (p=0.091). Adjusted analyses also demonstrated an average increase of 2.91 days in LOS and an additional $24,621 in total hospital charges for ET patients (p<0.001 for both). Conclusion: In this large, nationally representative cohort, patients with essential thrombocythemia (ET) hospitalized for COVID-19 experienced significantly higher rates of arterial and venous thrombotic complications, prolonged hospital stays, and increased healthcare costs compared to those without ET. Interestingly, ET was independently associated with a modest reduction in in-hospital mortality. This counterintuitive finding may be influenced by residual confounding, differences in baseline comorbidities, or unmeasured variations in clinical management, rather than a true protective effect of ET. These results emphasize the complex clinical profile of ET in the context of COVID-19 and underscore the need for further studies to clarify underlying mechanisms, validate these findings, and inform optimized risk stratification and management strategies for this vulnerable population.