Zhang L, Xu SQ, Zhu YJ, Dong L, Yin L, Xiao JC, Cheng DL, Wang RF, Zhou CZ. Association of severe thrombocytopenia with prognosis following transjugular intrahepatic portosystemic shunt in cirrhotic patients with portal hypertension. World J Gastrointest Surg 2026; 18(7): 120610 [DOI: 10.4240/wjgs.v18.i7.120610]
Corresponding Author of This Article
Chun-Ze Zhou, MD, Assistant Professor, School of Graduate, Bengbu Medical University, No. 2600 Donghai Avenue, Bengbu 233030, Anhui Province, China. zhouchunze@ustc.edu.cn
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Zhang L, Xu SQ, Zhu YJ, Dong L, Yin L, Xiao JC, Cheng DL, Wang RF, Zhou CZ. Association of severe thrombocytopenia with prognosis following transjugular intrahepatic portosystemic shunt in cirrhotic patients with portal hypertension. World J Gastrointest Surg 2026; 18(7): 120610 [DOI: 10.4240/wjgs.v18.i7.120610]
World J Gastrointest Surg. Jul 27, 2026; 18(7): 120610 Published online Jul 27, 2026. doi: 10.4240/wjgs.v18.i7.120610
Association of severe thrombocytopenia with prognosis following transjugular intrahepatic portosystemic shunt in cirrhotic patients with portal hypertension
Liu Zhang, Shi-Qi Xu, Chun-Ze Zhou, School of Graduate, Bengbu Medical University, Bengbu 233030, Anhui Province, China
Liu Zhang, Shi-Qi Xu, Yi-Jiang Zhu, Li Dong, Liang Yin, De-Lei Cheng, Chun-Ze Zhou, Department of Interventional Radiology, The First Affiliated Hospital of University of Science and Technology of China, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei 230001, Anhui Province, China
Jin-Chang Xiao, The Affiliated Hospital of Xuzhou Medical University, Xuzhou 221006, Jiangsu Province, China
Rui-Feng Wang, The Second Affiliated Hospital of Anhui Medical University, Hefei 230001, Anhui Province, China
Co-corresponding authors: Rui-Feng Wang and Chun-Ze Zhou.
Author contributions: Zhou CZ contributed to the study conception and design, Wang RF participated in the data analysis and manuscript revision, and they are co-corresponding authors; Cheng DL provided academic guidance and supervision for this work; Zhang L, Zhu YJ, Yin L, Dong L and Xiao JC contributed to material preparation, data collection and analysis; Zhang L and Xu SQ contributed to the first draft of the manuscript as co-first authors; all authors commented on previous versions of the manuscript, read and approved the final manuscript.
AI contribution statement: Grammarly and DeepL were used for language polishing and Chinese-to-English translation assistance. DeepSeek was used to help refine the phrasing and structure of certain sections, particularly in the introduction and discussion. All AI-generated content was thoroughly reviewed, fact-checked, substantially revised, and rewritten by the authors to ensure scientific accuracy and originality. The study design, inclusion/exclusion criteria, statistical analysis plan, and interpretation of clinical results were performed entirely by the authors. No AI image generation tools were used.
Supported by the National Natural Science Foundation of China, No. 82370748; the Scientific Research Foundation of the Education Department of Anhui Province, No. 2022AH040189; and the Anhui Provincial Health Commission Scientific Research Project, No. AHWJ2024Aa10141.
Institutional review board statement: The study protocol was conducted in accordance with the ethical principles of the Declaration of Helsinki and was approved by the Institutional Ethics Committee of the First Affiliated Hospital of the University of Science and Technology of China (approval No. 2024-RE-404).
Informed consent statement: Given the retrospective and fully anonymized nature of this study, the requirement for informed consent was waived by the Institutional Ethics Committee.
Conflict-of-interest statement: The authors declare that they have no conflict of interest.
STROBE statement: The authors have read the STROBE Statement—a checklist of items, and the manuscript was prepared and revised according to the STROBE Statement-a checklist of items.
Data sharing statement: The datasets generated and analyzed during this study are available from the corresponding author upon reasonable request.
Corresponding author: Chun-Ze Zhou, MD, Assistant Professor, School of Graduate, Bengbu Medical University, No. 2600 Donghai Avenue, Bengbu 233030, Anhui Province, China. zhouchunze@ustc.edu.cn
Received: March 4, 2026 Revised: March 20, 2026 Accepted: April 10, 2026 Published online: July 27, 2026 Processing time: 145 Days and 17.9 Hours
Abstract
BACKGROUND
Cirrhotic portal hypertension (CPH) is frequently complicated by variceal bleeding and ascites, for which transjugular intrahepatic portosystemic shunt (TIPS) represents a key therapeutic intervention. Thrombocytopenia (TCP) is prevalent in these patients; however, the prognostic significance of severe TCP, defined as a platelet count < 50 × 109/L, on TIPS outcomes remains unclear.
AIM
To evaluate the impact of severe TCP (platelet count < 50 × 109/L) on mortality and bleeding risk following TIPS.
METHODS
This multicenter, retrospective cohort study included CPH patients who underwent TIPS between 2014 and 2023 and were stratified into non-severe and severe TCP groups. Overall survival (OS) served as the primary outcome. To reduce potential confounding, we conducted 1:1 propensity score matching (PSM).
RESULTS
A total of 434 patients were analyzed (131 with severe TCP and 303 with non-severe TCP). Prior to PSM, the severe TCP group had significantly worse 90-day [hazard ratio (HR) = 2.65] and 1-year (HR = 2.18) survival. After PSM (n = 90 per group), however, no significant difference in survival was observed at any time point. Multivariate analysis further confirmed that severe TCP was not independently associated with OS after adjustment via PSM. Severe TCP was linked to a higher incidence of minor bleeding (47.1% vs 33.5%, P = 0.026) but showed no association with moderate-to-severe or procedural bleeding.
CONCLUSION
Severe TCP is not an independent predictor of mortality after TIPS once liver disease severity is accounted for. Baseline liver dysfunction, not platelet count, is the principal determinant of post-TIPS survival. Clinicians should prioritize comprehensive assessment of liver function over platelet levels when evaluating prognosis in TIPS candidates.
Core Tip: In this multicenter study of 434 cirrhotic patients, severe thrombocytopenia (< 50 × 109/L) was initially associated with poorer survival after transjugular intrahepatic portosystemic shunt (TIPS), but this association vanished after adjusting for liver disease severity using propensity score matching. Although severe thrombocytopenia correlated with an increased risk of minor bleeding, it was not linked to moderate-to-severe or procedural hemorrhage. These findings challenge conventional assumptions by demonstrating that baseline liver dysfunction, not platelet count, is the key driver of post-TIPS prognosis. Clinicians should therefore focus on comprehensive liver function evaluation rather than platelet thresholds when assessing TIPS candidates.
Citation: Zhang L, Xu SQ, Zhu YJ, Dong L, Yin L, Xiao JC, Cheng DL, Wang RF, Zhou CZ. Association of severe thrombocytopenia with prognosis following transjugular intrahepatic portosystemic shunt in cirrhotic patients with portal hypertension. World J Gastrointest Surg 2026; 18(7): 120610
The global prevalence of cirrhosis has risen markedly, increasing from 36.9 million cases in 1990 to 58.4 million in 2021[1]. Major risk factors include viral hepatitis, alcohol-related liver disease, non-alcoholic fatty liver disease, and autoimmune liver diseases. These etiologies drive liver fibrogenesis through distinct pathophysiological pathways, ultimately culminating in cirrhotic portal hypertension (CPH). As the most common and clinically severe complication of cirrhosis, CPH is defined by a pathological elevation in portal venous pressure resulting from increased intrahepatic vascular resistance combined with extrahepatic hemodynamic changes, particularly splanchnic vasodilation and a hyperdynamic circulatory state[2]. This chronic, progressive syndrome may result in life-threatening complications, including variceal bleeding and refractory ascites, which are associated with high hospitalization rates and impose a substantial burden on healthcare systems worldwide[3-5].
Transjugular intrahepatic portosystemic shunt (TIPS) has become a highly effective, minimally invasive procedure for managing CPH[6,7]. By creating a low-resistance shunt between the portal and hepatic venous systems, TIPS effectively decompresses the portal circulation at its most critical sites and plays a central role in preventing variceal rebleeding and treating refractory ascites[8,9]. Despite its efficacy, outcomes after TIPS are heterogeneous and strongly depend on the patient’s baseline physiological reserve, particularly the severity of liver dysfunction and associated systemic derangements[10].
Among these derangements, thrombocytopenia (TCP) is one of the most common hematologic abnormalities in patients with CPH, affecting the vast majority of this population[11]. Consequently, platelet count (PLT) is widely regarded as a reliable, non-invasive surrogate marker of portal hypertension severity and overall prognosis in cirrhotic patients[12]. Severe TCP, typically defined as a PLT count below 50 × 109/L, is traditionally viewed as a major contraindication to invasive procedures due to concerns about an elevated bleeding risk. This concern is reflected in clinical guidelines issued by organizations such as the American Gastroenterological Association[13,14]. This poses a significant clinical dilemma, particularly in acute scenarios like active variceal bleeding, where clinicians must balance the potential life-saving benefit of TIPS against the perceived bleeding risk and the impracticality of rapidly correcting severe TCP[15].
However, the true impact of pre-existing severe TCP on outcomes after TIPS remains controversial, with limited and conflicting evidence in the literature. This uncertainty challenges the conventional view and aligns with the “rebalanced hemostasis” theory in cirrhosis, which posits that deficiencies in procoagulant factors are often offset by concurrent reductions in anticoagulant proteins and enhanced primary hemostatic mechanisms. According to this theory, a low PLT does not necessarily translate into a proportionally higher bleeding risk[16]. Some clinical studies reflect this complexity; for instance, Chen et al[17] found no significant association between TCP and adverse events following TIPS, although their study design may have been subject to potential confounding. In contrast, other research, including studies that incorporate PLT into prognostic models such as the platelet-albumin-bilirubin (PALBI) grade, has shown that lower platelet levels correlate with worse survival, underscoring their potential prognostic value[18]. This inconsistency in the existing literature creates a substantial knowledge gap, making it difficult for clinicians to accurately risk-stratify patients with severe TCP[19]. Therefore, this large-scale, multicenter retrospective study was designed to definitively assess the role of severe TCP in patients with CPH undergoing TIPS.
Previous studies on TCP and TIPS outcomes have yielded conflicting results, largely due to small sample sizes, single-center designs, or inadequate control for confounding factors. Our multicenter study, with a larges sample size and rigorous propensity score matching (PSM), reduces selection bias and provides more robust evidence. Additionally, our patient cohort, drawn from three major medical centers in China, represents a diverse population with varied cirrhosis etiologies, including hepatitis B virus (HBV), which is highly prevalent in Asia, thereby offering insights particularly relevant to regions with similar disease patterns. By performing comprehensive multivariate analyses using four distinct liver function scoring systems, we systematically evaluated the independent role of TCP across different prognostic frameworks.
MATERIALS AND METHODS
Study design and patients
This retrospective, multicenter cohort study consecutively enrolled patients with CPH who underwent TIPS procedures between April 2014 and April 2023 at three major medical centers in China: The First Affiliated Hospital of the University of Science and Technology of China (USTC), the Second Affiliated Hospital of Anhui Medical University, and the Affiliated Hospital of Xuzhou Medical University. The study was approved by the Institutional Ethics Committee of the First Affiliated Hospital of USTC (approval No. 2024-RE-404; approval date: October 16, 2024). Informed consent was waived owing to the retrospective design and anonymized nature of the data analysis.
Inclusion criteria: (1) Age between 18 and 80 years; and (2) Clinical diagnosis of CPH with complications such as esophageal or gastric variceal bleeding or ascites.
Exclusion criteria: (1) Prior splenectomy before TIPS; (2) Receipt of platelet transfusions or thrombopoietin-stimulating agents within 7 days before TIPS and/or use of a thrombopoietin receptor agonist within 2 months before TIPS; (3) Comorbid hematological disorders; (4) Missing critical baseline data, including PLT count, Child-Pugh score, PALBI grade, and model for end-stage liver disease sodium (MELD-Na) score; (5) Loss to follow-up within 3 months after the procedure; and (6) Concurrent liver cancer or other malignancies. The diagnosis of cirrhosis was established based on clinical history, radiological imaging findings, and/or liver biopsy results.
TIPS procedure
All TIPS procedures were performed by experienced interventional radiologists at the participating centers using a standardized protocol. The procedure began with puncture of the right internal jugular vein, followed by catheterization of the hepatic vein. A shunt was then created between the hepatic and portal veins using a transjugular liver access set (RUPS-100, Cook Inc., United States). After measuring the pre-shunt portal pressure gradient (PPG), the tract was dilated and an 8-10 mm polytetrafluoroethylene-covered stent (Viatorr, W. L. Gore Associates, United States; or Fluency, C.R. Bard, United States) was deployed. The stent was subsequently dilated to the intended diameter. The procedure was considered complete once the PPG was successfully reduced to a target of ≤ 12 mmHg or achieved a ≥ 50% reduction from baseline.
Data collection and definitions
We extracted comprehensive baseline data from electronic medical records, including demographic characteristics (age, sex), etiology of cirrhosis, clinical indications for TIPS, laboratory results (complete blood count, liver and renal function tests, coagulation profile), and established prognostic scoring systems. These included the Child-Pugh score, which assesses cirrhosis severity based on bilirubin, albumin, prothrombin time (PT), ascites, and encephalopathy; the MELD and MELD-Na scores, which are laboratory-based predictors of 3-month mortality[20]; and the ALBI and PALBI scores, which provide simpler, objective assessments of liver function[11,18,21]. Follow-up visits were conducted at 1 month, 3 months, 6 months, and 12 months after TIPS and annually thereafter, supplemented by telephone interviews every 3 months. The last follow-up occurred in June 2024. The primary endpoint was overall survival (OS). Secondary endpoints included 30-day, 90-day, and 1-year survival, as well as procedure-related and post-procedure bleeding events.
Severe TCP was defined as a PLT < 50 × 109/L within one week before the TIPS procedure[22-24]. Patients were accordingly stratified into the severe TCP group (PLT < 50 × 109/L) and the non-severe TCP group (PLT ≥ 50 × 109/L). Bleeding events were classified according to the International Society on Thrombosis and Haemostasis (ISTH) criteria[25]. Per ISTH definitions, major bleeding includes fatal bleeding, symptomatic bleeding in a critical site, or bleeding associated with a hemoglobin drop of ≥ 2 g/dL or transfusion of ≥ 2 units of red blood cells. In this study, severe and clinically significant non-major bleeding events were grouped into a “moderate-to-severe bleeding” category. All other bleeding events were classified as “minor bleeding”. Procedure-related bleeding was defined as any bleeding occurring during the TIPS procedure or within the first 3 days postoperatively.
Statistical analysis
Continuous variables were compared using Student’s t-test or the Mann-Whitney U test, and categorical variables were analyzed with the χ2 test or Fisher’s exact test, as appropriate. Data are presented as mean ± SD, median (interquartile range), or n (%). Missing non-critical data were imputed using multiple imputation. To minimize selection bias, 1:1 PSM was conducted with a caliper width of 0.02. Matching variables included age, sex, etiology, TIPS indication, white blood cell count, hemoglobin, and Child-Pugh score. Balance between groups after matching was assessed using the standardized mean difference. Survival curves were estimated using the Kaplan-Meier method and compared with the log-rank test. Cox proportional hazards models were employed to identify independent predictors of OS. Four multivariate Cox regression models were constructed, each incorporating a different liver function scoring system, Child-Pugh, MELD, PALBI, and ALBI, to evaluate the robustness of the findings across distinct prognostic frameworks. Multicollinearity was assessed using the variance inflation factor. Statistical significance was defined as a two-tailed P value < 0.05. All analyses were performed using SPSS (version 27.0) and R software (version 4.4.0).
RESULTS
Patient characteristics
A total of 825 patients who underwent TIPS were initially screened, and 434 were included in the final analysis after applying the exclusion criteria (Figure 1). The cohort included 291 males (67.1%) and 143 females (32.9%). Of these, the severe TCP group (n = 131) comprised 95 males (72.5%) and 36 females (27.5%), whereas the non-severe TCP group (n = 303) included 196 males (64.7%) and 107 females (35.3%). HBV infection was the most common etiology of cirrhosis, accounting for 66.6% of cases. Most patients (70.3%, 305/434) had Child-Pugh class B or higher. The primary indication for TIPS was gastrointestinal bleeding (70.3%, 305/434), followed by recurrent or refractory ascites (29.7%, 129/434).
Before matching, the 131 patients with severe TCP exhibited significantly greater evidence of advanced liver disease and hematologic suppression compared with the 303 patients with non-severe TCP. Specifically, the severe TCP group had higher MELD scores (10.6 ± 4.5 vs 8.5 ± 5.0; P < 0.001) and PALBI scores (-1.8 ± 0.4 vs -2.5 ± 0.5; P < 0.001), as well as lower hemoglobin levels (median 72.0 g/L vs 84.0 g/L), reduced white blood cell counts (median 2.6 × 109/L vs 4.0 × 109/L), prolonged PT (15.8 seconds vs 14.3 seconds; P < 0.001), prolonged activated partial thromboplastin time (APTT) (39.5 seconds vs 34.0 seconds; P < 0.001), and elevated international normalized ratio (INR) (median 1.3 vs 1.2). After 1:1 PSM, 90 patients were matched in each group (n = 90 per group). In the matched cohort, baseline characteristics, including age, sex, etiology, TIPS indication, and Child-Pugh score, were well balanced by design. This balance was reflected in the substantial reduction in standardized mean differences across all covariates, resulting in two comparable groups for outcome analysis (Table 1 and Supplementary Table 1).
Table 1 The baseline characteristics, mean ± SD/n (%)/median (interquartile range).
The median follow-up duration was 23.5 months (range: 0.1-82.1 months), with 21.1 months in the severe TCP group and 24.5 months in the non-severe TCP group. In the pre-matched cohort, patients with severe TCP had significantly worse survival outcomes. Kaplan-Meier analysis showed a 1-year survival rate of 82.8% in the severe TCP group vs 92.0% in the non-severe TCP group [hazard ratio (HR) = 2.18, 95% confidence interval (CI): 1.21-3.94, P = 0.009]. This difference persisted over the long term, with OS also significantly lower in the severe TCP group (HR = 1.70, 95%CI: 1.08-2.66, P = 0.021) (Figure 2A-D). The corresponding 5-year survival rates were 63.9% in the severe TCP group and 69.8% in the non-severe TCP group.
Figure 2 Kaplan-Meier survival analysis.
A-D: Pre-matched cohort: 30-day survival after transjugular intrahepatic portosystemic shunt (TIPS) in both groups (A); 90-day survival after TIPS in both groups (B); 1-year survival after TIPS in both groups (C); Overall survival after TIPS in both groups (D); E-H: Post-matched cohort: 30-day survival after TIPS in both groups (E); 90-day survival after TIPS in both groups (F); 1-year survival after TIPS in both groups (G); Overall survival after TIPS in both groups (H). TCP: Thrombocytopenia.
After PSM, however, this survival disadvantage was entirely eliminated. In the matched cohort, no statistically significant differences in survival were observed at any time point. The 1-year survival rates were nearly identical, 86.7% in the severe TCP group and 85.6% in the non-severe TCP group (HR = 1.08, 95%CI: 0.49-2.37, P = 0.845). Likewise, the OS curves for the two groups overlapped closely, showing no significant difference (HR = 1.21, 95%CI: 0.69-2.14, P = 0.509) (Figure 2E-H). The 5-year survival rate was 76.7% for the severe TCP group and 68.9% for the non-severe TCP group.
These results were further confirmed by multivariate Cox regression analyses. As shown in Supplementary Table 2, all variance inflation factor values were well below 5, indicating no substantial multicollinearity among predictors. In the pre-matched cohort, severe TCP emerged as an independent predictor of mortality in three of the four models. Specifically, in model 1 (Child-Pugh score), independent predictors included age, severe TCP status, creatinine, and Child-Pugh score. In model 2 (MELD score), age, severe TCP status, and MELD score were independently associated with death. In model 4 (ALBI score), age, severe TCP status, creatinine, and ALBI score remained significant predictors (Table 2). In contrast, in the post-matched cohort, severe TCP was not independently associated with OS in any of the four multivariate models. Instead, consistent independent predictors of mortality across models included older age (e.g., model 1: HR = 1.041, P = 0.003), higher baseline creatinine (e.g., model 1: HR = 1.011, P = 0.002), and greater severity of liver dysfunction, as reflected by Child-Pugh score (HR = 1.287, P = 0.006), MELD score (HR = 1.113, P = 0.004), PALBI score (HR = 2.164, P = 0.014), or ALBI score (HR = 3.886, P < 0.001) (Table 3). During follow-up, 80 patients died. The most frequent causes of death were hepatic encephalopathy (37.5%) and liver failure (35.0%). Competing risk analysis further confirmed that severe TCP was not associated with an increased risk of death specifically from gastrointestinal bleeding (Supplementary Table 3).
Table 2 Uni- and multivariable Cox regression analyses of the pre-matched cohort.
Analysis of hemorrhagic complications revealed distinct patterns according to bleeding severity. In the full cohort, 19 patients (4.4%) experienced procedure-related bleeding. This complication was infrequent and unrelated to baseline PLT, occurring in 6 of 131 patients (4.6%) in the severe TCP group and 13 of 303 patients (4.3%) in the non-severe TCP group (P = 1.000). During long-term follow-up, bleeding outcomes were ascertained in 311 patients; the remaining 123 patients were lost to follow-up for this endpoint (44 in the severe TCP group and 79 in the non-severe TCP group). Among these 311 patients, 145 (46.6%) experienced at least one bleeding event (“all-cause bleeding”). The cumulative incidence of any bleeding did not differ significantly between groups (54.0% vs 43.6%, P = 0.103). Importantly, the rate of clinically significant moderate-to-severe bleeding events, observed in 40 patients overall (12.9%), was also similar between the severe TCP and non-severe TCP groups (14.9% vs 12.1%, P = 0.495). In contrast, minor bleeding occurred more frequently in the severe TCP group: It affected 41 of 87 patients (47.1%) with severe TCP, compared with 75 of 224 patients (33.5%) in the non-severe TCP group (χ2 = 4.988, P = 0.026), as indicated in Table 4.
This large multicenter retrospective study demonstrates that severe TCP is not an independent predictor of mortality following TIPS in patients with CPH. Although unadjusted analyses suggested worse survival among patients with severe TCP, this association disappeared after adjustment for confounding factors, particularly the severity of underlying liver disease, using PSM. Our findings indicate that established prognostic indicators of liver dysfunction, including the MELD and Child-Pugh scores, along with age and renal function, are the primary determinants of survival after TIPS. We also found that while severe TCP was not associated with an increased risk of procedure-related or moderate-to-severe bleeding, it was linked to a higher incidence of minor bleeding complications.
Our findings challenge the prevailing view that severe TCP is an unfavorable prognostic indicator in patients undergoing invasive procedures such as TIPS[13,24]. The initial observation of worse survival among patients with severe TCP is consistent with prior studies implicating low PLTs in adverse short-term outcomes, for example, those incorporating the PALBI score or focusing on patients with acute-on-chronic liver failure, a condition driven by systemic inflammation[26-28]. However, the key strength of our study lies in the use of PSM, which revealed that this apparent association is likely attributable to confounding. As our data demonstrate, patients with more severe TCP also exhibited poorer liver function (including higher MELD and PALBI scores) and more pronounced coagulation abnormalities, including prolonged PT and APTT and elevated INR, prior to matching. These factors are themselves well-established predictors of mortality[11]. The coexistence of severe TCP with impaired liver function and coagulopathy may reflect underlying endothelial dysfunction in cirrhosis[29-31]. Chronic inflammation and oxidative stress damage liver sinusoidal endothelial cells, reducing nitric oxide bioavailability. This not only exacerbates intrahepatic vascular resistance but also promotes platelet adhesion and aggregation on the injured endothelial surface, leading to microthrombus formation and subsequent impairment of hepatic microcirculation[30,32,33]. Platelet consumption within the hepatic microvasculature may therefore directly contribute to peripheral TCP, strongly suggesting that severe TCP is a consequence, not a cause, of the underlying vascular pathology. Indeed, once patients were adequately matched for the severity of liver disease (using Child-Pugh score and other relevant covariates), the apparent prognostic impact of PLT on survival disappeared entirely. This indicates that severe TCP serves as a marker of advanced disease rather than a direct driver of post-TIPS mortality. Our results align with another study that found no independent association between TCP and adverse outcomes after adjusting for confounders[11]. Furthermore, multivariate regression analyses in the post-matched cohort consistently support this interpretation: Severe TCP was never an independent predictor of mortality in any of the four models, whereas established indicators of liver and renal dysfunction remained significant across all models.
Consistent with a substantial body of evidence, our multivariate analyses confirmed the prognostic significance of conventional liver function scores (Child-Pugh, MELD, ALBI, and PALBI) in the post-TIPS interval[21,34]. The ALBI and PALBI scores, which exclude subjective variables, performed particularly well, further supporting their utility in risk stratification[35,36]. Similarly, the identification of age and baseline creatinine as independent risk factors aligns with previous reports, underscoring the multifactorial nature of post-TIPS prognosis. Systemic factors such as sarcopenia (often age-related) and renal insufficiency play crucial roles in this context[37,38].
Regarding bleeding risk, our finding that severe TCP does not increase the risk of procedure-related or moderate-to-severe bleeding corroborates several recent studies challenging the predictive value of PLT and routine coagulation tests for clinically significant bleeding in cirrhosis[38,39]. In cirrhosis, rebalanced hemostasis is characterized by pro-hemostatic adaptations, such as elevated von Willebrand factor, that can offset TCP[40]. However, the increased risk of minor bleeding (e.g., mucocutaneous bleeding) observed in the severe TCP group highlights the critical role of platelets in primary hemostasis and the repair of small vessel injuries. This risk may be exacerbated by extrahepatic vascular dysfunction seen in advanced cirrhosis. Splanchnic vasodilation and hyperdynamic circulation lead to microcirculatory changes, including increased vascular permeability and vessel wall fragility[30,41,42]. These alterations make patients more susceptible to mucocutaneous bleeding, particularly in the gastrointestinal mucosa, when PLTs fall to critically low levels. Although not life-threatening, these events may significantly impact patient quality of life and warrant clinical attention[43,44].
The primary strength of our study lies in its large multicenter design and the use of PSM to minimize selection bias, thereby enhancing the validity of our findings. Nevertheless, several limitations warrant consideration. As a retrospective analysis, the study remains vulnerable to inherent biases despite statistical adjustments. Although PSM improved baseline comparability, certain markers of liver disease severity, including MELD score, PALBI score, and INR, still differed significantly between groups (Table 1), suggesting potential residual confounding. Additionally, the reduced sample size after matching may have limited the statistical power of our regression models to detect more modest associations. The cohort was drawn exclusively from centers in China, which may restrict the generalizability of our results to other populations with different etiologies of liver disease. Furthermore, as a multicenter study conducted over a decade, unmeasured variations in operator experience and minor institutional protocol changes over time could have introduced additional confounding, even though a standardized procedural framework was applied throughout. We also did not evaluate other clinically relevant outcomes, such as post-TIPS complications (e.g., hepatic encephalopathy), health-related quality of life, or healthcare costs. Lastly, a substantial proportion of patients were lost to follow-up for bleeding outcomes, which may introduce selection bias and affect the reliability of our conclusions regarding bleeding risk.
Future prospective
Future prospective multicenter studies are needed to validate our findings in diverse populations with varying etiologies of cirrhosis. Mechanistic investigations that assess platelet function, not merely PLT, in cirrhotic patients undergoing TIPS, potentially using viscoelastic testing to evaluate global hemostatic status, would provide deeper insights into the role of TCP in this setting. Interventional trials are also warranted to determine whether improving liver function, for example, through nutritional support or better management of complications, leads to better outcomes in severely thrombocytopenic patients, rather than targeting PLT elevation alone. Additionally, evaluating post-TIPS health-related quality of life, incidence of hepatic encephalopathy, and cost-effectiveness in relation to baseline PLTs would offer a more comprehensive assessment of clinical impact.
CONCLUSION
Severe TCP is not an independent risk factor for mortality after TIPS. Patient outcomes are primarily driven by the severity of underlying liver and renal dysfunction. Although severe TCP may be associated with a higher risk of minor (trivial) bleeding, it should not preclude TIPS when the procedure is clinically indicated for managing life-threatening complications of portal hypertension. Future prospective studies are needed to validate these findings and to define optimal management strategies for this patient subgroup.
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