Background: Studies have shown conflicting results when using thrombopoietin-related drugs (TPORD) for thromboembolic events (TEEs). Our study aimed to explore the correlation between TPORDs and TEEs.
Method: Drug-targeted Mendelian randomization (MR) and multivariate MR (MVMR) analysis were used to explore the causal relationship between TPORDs and TEEs such as venous thromboembolism (VTE), deep vein thrombosis (DVT), pulmonary embolism (PE), myocardial infarction (MI) and ischemic stroke (STR). At the same time, a real-world study was conducted by extracting adverse events (AEs) from the FDA Adverse Event Reporting System database included in AERSMine to further validate our findings.
Outcome: In drug-target MR, TPORDs were associated with VTE (OR = 1.193, 95% confidence interval (CI): 1.001-1.423, p = 0.049], DVT (OR = 1.321, 95% CI: 1.027-1.700, p = 0.030), MI (OR = 1.216, 95% CI: 1.010-1.464, p = 0.039), STR (OR = 1.224, 95% CI: 1.021-1.468, p = 0.029). VTE/DVT/STR remained stable in MVMR (VTE: OR = 1.3, 95% CI: 1.187-1.422, p < 0.001; DVT: OR = 1.465,95% CI:1.285-1.671, p < 0.001; STR: OR = 1.119, 95% CI: 1.018-1.229, p = 0.019) and real-world studies [lower bound of proportional reporting ratio (ROR) greater than 1]. The significance of myocardial infarction disappeared in MVMR (OR = 0.996, 95% CI: 0.894-1.109, p = 0.942) and in real-world studies (lower ROR lower than 1). There was no evidence of a causal relationship between TPORD and PE (OR = 1.244, 95% CI: 0.969-1.597, p = 0.087), but it generated a signal from a real-world study (lower bound of ROR greater than 1).
Conclusion: This study suggests that TPORDs may be associated with an increased risk of TEEs, particularly AEs leading to VTE/DVT/STR. In addition, the relationship between TPORDs and PE/MI is debatable and requires more research.
Keywords: Mendelian randomization analysis; pharmacovigilance; thromboembolism; thrombopoietin.
Examining Blood Clot Risk for Drugs: A Fusion of Genetic Research and Real-World Insights Why did this study be conducted? To investigate whether drugs used to treat low platelet counts increase the risk of thrombosis-related events. Platelets are essential for blood clotting, and a low platelet count increases the risk of bleeding. Drugs that stimulate platelet production were prescribed, and this study aims to elucidate their safety. Blood clot-related events, such as deep vein thrombosis and pulmonary embolism, are serious health problems that can lead to morbidity and mortality. For the sake of patient safety, it is critical to understand the possible link between these drugs and thrombosis-related events. What did the researchers do? To explore this question, we used a robust analytical method called Mendelian randomization (MR). MR uses genetic information to assess this link, helping researchers conclude whether the exposure (in this case, the drug) directly contributed to the outcome (blood clot-related event). They also examined real-world patient data, combining two different methods for a comprehensive analysis. What did the researchers find? We found that some of these platelet drugs may be associated with an increased risk of thrombosis-related events. However, it is important to note that these findings need to be further confirmed by more research and clinical studies. The complexity of medical research often means that preliminary observations must be confirmed through rigorous investigations. What do these findings mean? This study highlights the need for healthcare providers to closely monitor patients receiving these medications for any signs of thrombosis-related events. It also highlights the importance of further research to better understand the potential risks and benefits of these treatments. Ultimately, the goal is to provide physicians with more accurate information to make informed decisions about prescribing these medications, improving patient care, and minimizing potential risks.
© The Author(s), 2024.