Single-center nomogram estimates VTE risk in acute herpetic neuralgia

A retrospective study of 327 adults hospitalized with acute herpetic neuralgia found that 26 developed objectively confirmed venous thromboembolism during admission, an incidence of 7.95%. Researchers developed a nomogram combining fibrinogen, fibrin degradation products, pain intensity and an institutional thrombosis risk score to estimate the probability of in-hospital VTE. The model had an apparent area under the receiver operating characteristic curve of 0.853, with a 95% confidence interval of 0.764–0.941, and a bootstrap optimism-corrected concordance index of 0.834. The study, published in Frontiers in Neurology on 20 October 2026, provides a disease-specific risk estimate for hospitalized patients, but its single-center design, small number of events and lack of external validation limit its clinical reach.

The cohort comprised patients admitted to the Pain Department at Hengshui People’s Hospital in China between December 2020 and December 2023. Acute herpetic neuralgia was defined as pain occurring within 30 days after the appearance of a herpes zoster rash, with a Numerical Rating Scale score above 4. Eligible patients were at least 20 years old and had complete clinical and laboratory data from the index admission. The researchers excluded people with previous VTE, current anticoagulant or antiplatelet treatment, severe hepatic or renal dysfunction, known active malignancy, recent chemotherapy or radiotherapy, pregnancy or breastfeeding, and several unstable systemic conditions. Consequently, the findings describe a selected clinical population rather than all people with herpes zoster or neuralgia.

VTE outcomes were restricted to events occurring during the index hospitalization and confirmed by objective imaging. Deep vein thrombosis was diagnosed with compression or duplex ultrasonography, while pulmonary embolism was identified through computed tomography pulmonary angiography or, when that procedure was contraindicated, ventilation-perfusion scanning. Elevated D-dimer and clinical suspicion alone were not sufficient for diagnosis. The investigators collected demographic characteristics, comorbidities, laboratory measurements, pain scores and an admission thrombosis risk score from the first blood samples drawn after admission, before VTE diagnosis and before anticoagulant therapy. The thrombosis score was an institutional adaptation of the Caprini model, recorded as an aggregate from 0 to 8; individual Caprini items were not systematically documented.

Patients who developed VTE differed from those who did not in several baseline measures. Their median age was 75 years, compared with 65 years in the non-VTE group. Median fibrin degradation product concentration was 4.3 mg/L in the VTE group and 1.9 mg/L among those without VTE. Median Numerical Rating Scale scores were 8 and 7, respectively, and the median institutional thrombosis risk score was three in the VTE group and two in the non-VTE group. Elevated D-dimer, defined as a value above 0.5 mg/L fibrinogen-equivalent units, was present in 57.7% of patients with VTE and 13.3% of those without an event. These were observed group differences in a retrospective cohort, not evidence that any individual factor caused thrombosis.

To select candidate predictors, investigators used least absolute shrinkage and selection operator regression, commonly called LASSO, with 10-fold cross-validation to guide the regularization process. Ten variables were retained at the selected stage: sex, age, rheumatism and immunity, D-dimer, activated partial thromboplastin time, fibrinogen, fibrin degradation products, antithrombin III, Numerical Rating Scale score and thrombosis risk score. These variables were entered into multivariable logistic regression and refined through forward and backward stepwise selection based on the Akaike information criterion. Age correlated strongly with the institutional thrombosis risk score, at r = 0.627, because that assessment incorporated age; the age-related information was therefore largely captured by the score during variable selection. Fibrin degradation products had the strongest correlation with elevated D-dimer, at r = 0.582, and a weaker correlation with fibrinogen, at r = 0.357. Variance inflation factors for the four final predictors ranged from 1.018 to 1.534, indicating no meaningful multicollinearity within the model.

The final logistic regression associated three variables with higher adjusted odds of VTE and one with lower adjusted odds. Each 1 mg/L increase in fibrin degradation products was associated with an odds ratio of 1.48, with a 95% confidence interval of 1.282–1.737 and P less than 0.001. A one-point increase in the Numerical Rating Scale corresponded to an odds ratio of 1.584, with a 95% confidence interval of 1.05–2.538 and P = 0.039. Each additional point in the institutional thrombosis risk score was associated with an odds ratio of 2.05, with a 95% confidence interval of 1.455–2.947 and P less than 0.001. Fibrinogen was associated with lower odds, with an odds ratio of 0.477 per g/L, a 95% confidence interval of 0.275–0.798 and P = 0.006. These estimates describe conditional associations in the fitted model rather than interventions that would change a patient’s risk.

The inverse fibrinogen association requires particular caution. Fibrinogen was not significantly associated with VTE in the unadjusted analysis, with an odds ratio of 1.025 per g/L, a 95% confidence interval of 0.631–1.516 and P = 0.912. The inverse pattern emerged only after adjustment for fibrin degradation products and other correlated coagulation markers, which the authors considered more consistent with statistical suppression or negative confounding than with a directly protective biological effect. They also noted that fibrinogen is an acute-phase reactant and a substrate for fibrin formation, while citing inconsistent findings from previous studies about its relationship with VTE. Admission samples were obtained before VTE diagnosis and anticoagulant use, making treatment-related distortion unlikely. Likewise, severe pain might accompany reduced mobility and impaired venous flow, but bed-rest time and mobility status were not systematically recorded, so that proposed pathway could not be tested directly.

The four retained predictors were translated into a graphical nomogram that assigns points for fibrinogen, fibrin degradation products, Numerical Rating Scale score and the admission thrombosis risk score. Adding the assigned points yields an estimated probability of VTE during the index hospitalization. In the full cohort, the model’s apparent AUC was 0.853. Ten-fold cross-validation produced a C-index of 0.849, although its 95% confidence interval was wide, from 0.591 to 1.000, reflecting the limited number of events. Bootstrap validation with 1,000 repetitions yielded an optimism-corrected C-index of 0.834; the bootstrap distribution had a mean of 0.831 and a 95% confidence interval of 0.680–0.950. Because the model was developed on the full cohort of 327 patients rather than in a separate training sample, these results represent internal validation rather than evidence of performance in an independent population.

At the Youden-index cutoff of 0.094, the model identified 19 true positives and seven false negatives among the 26 patients with VTE, alongside 264 true negatives and 37 false positives among the 301 without VTE. Sensitivity was 0.731, with a 95% confidence interval of 0.522–0.884, and specificity was 0.877, with a 95% confidence interval of 0.835–0.912. Positive predictive value was 0.339, whereas negative predictive value was 0.974; overall accuracy was 0.865. The modest positive predictive value is consistent with the low base rate: most patients flagged as positive would not develop VTE. Calibration appeared close to the observed frequencies, with a Hosmer–Lemeshow chi-square value of 5.848 and P = 0.664, while decision-curve analysis indicated net benefit across most threshold probabilities.

Important limitations prevent the nomogram from being treated as a stand-alone diagnostic test. The retrospective, single-center design limits generalizability, and only 26 events occurred, creating substantial overfitting risk despite LASSO regularization and internal validation. Imaging was performed when clinically indicated rather than through universal screening, so asymptomatic events may have been missed and the reported incidence may be underestimated. Pharmacologic and mechanical prophylaxis was not systematically recorded, and residual confounding by prophylaxis therefore could not be excluded. Mobility data were unavailable, and the model could not be benchmarked against formally reconstructed Caprini, Padua or IMPROVE/IMPROVE-DD scores. The findings are therefore hypothesis-generating: larger multicenter prospective studies with standardized risk assessments, prophylaxis records and mobility data are needed before the model can be evaluated for routine clinical use.

Subject of Research: Development and internal validation of an in-hospital venous thromboembolism prediction model for adults with acute herpetic neuralgia

Article Title: Analysis of risk factors for venous thromboembolism in hospitalized patients with acute herpetic neuralgia and construction of a predictive nomogram model

Article References: Wang, C., Wang, G., Liu, B., Gao, Q., Du, C., & Li, L. (2026). Analysis of risk factors for venous thromboembolism in hospitalized patients with acute herpetic neuralgia and construction of a predictive nomogram model. Frontiers in Neurology, 17, Article 1877838. https://doi.org/10.3389/fneur.2026.1877838

Image Credits: AI Generated

DOI: 10.3389/fneur.2026.1877838

Keywords: acute herpetic neuralgia, venous thromboembolism, deep vein thrombosis, pulmonary embolism, prediction model, nomogram, fibrin degradation products, pain intensity, thrombosis risk score, clinical validation, Analysis, risk