The present study demonstrated rising DPR was associated with SAEs in APE. To the best of our knowledge, this is the first paper to explore the value of DPR in predicting prognosis in APE. Furthermore, a significant increase in the area under the ROC curve has been observed when DPR ≥ 4.55 as 1 point added to patients’ sPESI scores, suggesting more precise risk categorization compared to that of the sPESI score alone. These findings demonstrated the DPR may be a potential biomarker that may help identify patients with APE who are at higher risk of poor prognosis upon initial presentation. Furthermore, other meaningful findings worth being noted were as follows: First, NT-proBNP (r = 0,331, p < 0.001) and cTnI levels (r = 0.187, p = 0.023) were observed to be significantly correlated with DPR. Besides, our findings also demonstrated the pulmonary embolus position were correlated with DPR levels. Based on these findings, we postulated that the higher DPR value may be associated with the larger thrombus burden of APE patients. Second, the DPR and the pulmonary embolus position were proved to be independent predictors of in-hospital prognosis.
Elevated DPR can be regarded as increased D-dimer and a low platelet count status. Elevated D-dimer and thrombocytopenia have been observed to be associated with poor prognosis of APE in recent studies[8, 9, 13, 15–19]. But so far, no research has been done to explore the value of DPR in predicting the prognosis of APE.
Plasma D-dimer, as a degradation product of cross-linked fibrin, can well reflect the state of coagulation and fibrinolysis[3]. The correlation between D-dimer levels and the burden of PE has been proved in recent studies[6, 7, 20]. Keller K, et al[6] also confirmed the level of D-dimer could be used as a biomarker to identify the patients with right ventricular dysfunction (RVD) in normotensive APE. The cause of this phenomenon could be attributed to the position of the embolus[21, 22].Therefore, it can be speculated that patients with higher D-dimer may have more embolus burden of APE, leading to higher SAEs that was confirmed by Lobo JL, et al[23] and Song ZK, et al[24] studies. In addition, as an effective biomarker, D-dimer could significantly improve the predictive value of clinical predictive model[25, 26]. However, the D-dimer assay is not specific. Levels increase in patients with myocardial infarction, pneumonia, sepsis, cancer, and the postoperative state and those in the second or third trimester of pregnancy[1, 10]. Therefore, the prognostic value of D-dimer alone in SAEs is controversial[11, 12]. Geissenberger F, et al [11] found D-dimer could predict the severity of disease but not the prognosis in APE.
It’s well known that systemic inflammatory and hypercoagulable state play an important role in the pathophysiology of APE. Platelet hyperactivation can interact with inflammation and coagulation reaction, resulting in adverse prognostic events in patients with APE[13, 27]. Whether platelet count can be used as a marker of activation is currently controversial. Ozcan Cetin E, et al[28] reported that increased platelet was closely correlated with the RVD and disease severity in APE patients that are consistent with Telo S‘ research[29]. Contrarily, decreased platelet count has been shown to reflect an aggravated thrombocyte activity and that lead to destructive thrombotic response[30]. In clinical practice, Yardan T, et al[15] found the platelet significantly decreased in massive PE patients compared to low-risk groups and to be associated with RVD. The relationship between massive PE leading to cardiopulmonary resuscitation and increased D-dimer and decreased platelets has been confirmed by Leitner J, et al[17]. In this study, we found the elevated DPR caused by increased D-dimer and decreased platelets was associated with SAEs in APE. The reasons for this phenomenon may be attributed to the following aspects: first, we found that elevated DPR was significantly correlated with DVT and central thrombus, to a certain extent, reflecting thrombus burden in APE patients. Second, the correlation between DPR and NT-pro BNP was also confirmed. Elevated troponin and NT-pro BNP have been demonstrated to reflect the functional status of the right heart and be related to the prognosis in patients with APE[1, 18, 31]. Due to the limited number of cardiac ultrasound and taking into account the differences in the level of sonographers, this study cannot effectively reflect the state of right heart function by cardiac ultrasound. However, we excluded patients with a clear diagnosis of acute myocardial infarction and acute heart failure reducing impact on right heart function to a certain extent. Therefore, The DPR, as a simple, inexpensive and available index of prothrombotic status, seemed to be a potential predictor of in-hospital serious adverse outcomes.
Additionally, we sought to integrate DPR to the sPESI score to determine whether its prognostic utility could be enhanced with additional criteria reflective of prothrombotic status. Our integrative model demonstrated an increase in the area under the ROC curve for assessing SAEs (AUC: a), suggesting improved predictive value compared to that of the sPESI score alone. The sPESI model had been demonstrated to successfully predicts 30-day mortality in APE[32, 33]. We did not observe such a substantial improvement according to the sPESI score alone. We speculated the difference was caused by the following reasons: first, remedial thrombolysis and admission to the intensive care unit for invasive mechanical ventilation as adverse events were also included into SAEs that were only discussed during hospitalization, which may slightly underestimate the incidence of adverse events, while other studies looked at the mortality within 30 days[32]. On the other hand, cigarette smoking is an established risk factor for COPD[34], an important part of SPESI, but not all patients with a history of smoking were tested for lung function our study that may weaken the prediction accuracy of sPESI. But our integrative model can still accurately identify high-risk patients, showing that DPR is a potential effective predictor.
Clinical Implications
Considering that DPR is associated with the poor prognosis of acute PE, this parameter may be a useful indicator for identifying patients at high risk of adverse events. In our study, adding DPR to the sPESI score seems to play a contributive role in predicting in-hospital serious adverse events, and may provide a more accurate risk classification. Therefore, for patients with elevated DPR, we need to strengthen clinical monitoring and formulate individualized treatment plans in a timely manner based on changes in the patient’s condition.
Although it is necessary for further evaluation in prospective randomized trials, DPR should still be considered in the process of patient risk stratification and monitoring of treatment effects.