A Nomogram Model Containing Genetic Polymorphisms to Predict Risk of Pulmonary Embolism in Pregnant Women

Abstract

Introduction: Pulmonary embolism (PE), the most serious presentation of venous thromboembolism (VTE), is associated with a high rate of mortality and expense. Clinical studies on pregnant women with PE are scarce. The aim of this study was to analyze the clinical impact of fibrinolytic enzyme activation inhibitor-1 (PAI-1) 4G/5G genetic polymorphisms, methylenetetrahydrofolate reductase (MTHFR) rs1801131 (A1298C) and rs1801133 (C677T) genetic polymorphisms, and establish a predictive model for pregnant women.

Material and methods: Between September 2022 and August 2023, 53 pregnant women with PE were enrolled. Using the propensity score matching method, 106 consecutive pregnant women without VTE were 1:2 matched. The relevant patient data were collected, and the susceptibility genes for PE were detected to determine genetic polymorphisms, and PE susceptibility in pregnant women, as well as to develop predictive models.

Results: Our study showed that 4G/4G homozygous mutations increased the risk of pregnant PE fourfold (OR = 4.46, 95% CI = 1.59-12.50, P = 0.004), whereas the 4G allele mutation increased the risk twofold (OR = 2.33, 95% CI = 1.35-4.04, P = 0.002). A nomogram was established to predict the risk of pregnant women with PE by four predictive features including PAI-1 genetic polymorphisms, international normalized ratio (INR), antithrombin-III (AT-III) activity, and platelet count (PLT). The area under the curve (AUC) of the nomogram was 0.821 (0.744-0.898). The AUC of the internal validation group was 0.822 (0.674-0.971). Decision curve analysis revealed that the nomogram has a higher net benefit in the following threshold: probability interval of ≥15%.

Conclusion: The PAI-1 4G/4G genotype is an independent risk factor for pregnant women with PE; furthermore, the presence of the 4G allele can increase the risk of PE. The study established a nomogram to predict the risk of PE in pregnant women.

Keywords: PAI-1; genetic polymorphisms; nomogram model; pregnant women; pulmonary embolism.

Figure 1

Nomogram predicting PE in pregnant patients. (PAI-1 fibrinolytic enzyme activation inhibitor-1, INR International normalized ratio, AT-III Antithrombin III, PLT Platelet counts.).

Figure 2

(A) Calibration plot of the Nomogram for the probability of PE in pregnant patients. (B) DCA of the Nomogram of PE in pregnant patients. (C) ROC of PE in pregnant patients (model group). (D) ROC of PE in pregnant patients (validation group).