European Journal of Cardiovascular Medicine

The main cause of morbidity and death worldwide, cardiovascular diseases (CVDs) impose a major healthcare burden on many different populations. Percutaneous coronary intervention (PCI), a minimally invasive technique that re-establishes blood flow in blocked coronary arteries, therefore improving survival rates and quality of life, marks a significant improvement in the treatment of acute coronary syndrome (ACS). Usually incorporating aspirin and a P2Y12 inhibitor to reduce thrombotic risks, including stent thrombosis (1, 2), post PCI dual-antiplatelet treatment (DAPT) is recommended in all guidelines with varying duration.

Notwithstanding with these developments, the care of thrombocytopenic patients undergoing PCI still presents a major challenge. Characterised by a platelet count below normal levels, thrombocytopenia can result from many aetiologies, including autoimmune diseases, pharmacological therapies, or chronic conditions. Pre-existing thrombocytopenia patients have increased bleeding risk because of poor clot formation; this risk is further increased by dual antiplatelet therapy (DAPT).

Particularly in those with platelet counts between 30,000 and 50,000/mm³, the interplay between hemorrhagic risk and ischaemic episode, compromises clinical decision-making. These patients have a paradox: antiplatelet drugs raise the risk of major hemorrhagic consequences even while they are absolutely essential for preventing thrombotic events like myocardial infarction and stent thrombosis. In contrast to persons with normal platelet counts, evidence shows that baseline thrombocytopenia in PCI patients corresponds with an elevated risk of major adverse cardiovascular events (MACE) and all-cause death (6).

Current recommendations provide inadequate and often contradicting advice for the management of thrombocytopenia following percutaneous coronary intervention (PCI). Some studies have proposed alternative antiplatelet strategies, such monotherapy with medicines such clopidogrel, following a short or ultra-short DAPT course (2) or reduced durations of dual antiplatelet therapy (DAPT). Supplementary therapies include using bare-metal stents (BMS) over drug-eluting stents (DES) in patients with a higher risk of haemorrhage (7) and radial access instead of femoral for PCI to lower vascular complications.

The aim of this study is to evaluate in real-world percutaneous coronary intervention situations the predictive effect of baseline thrombocytopenia on bleeding and cardiovascular outcomes. This study focusses on clinical and procedural data to close knowledge gaps in the management of thrombocytopenic patients and provide evidence-based strategies for balancing ishematic and hemorrhagic risks.

This prospective cohort study was performed at a tertiary care hospital in Northern India, SMS Medical College in Jaipur, under the Department of Cardiology From October 2023 to January 2025, the research period was fifteen months; the Institutional Ethics Committee approved it previously authoristically. All participants had informed permission before registration to improve ethical compliance and understanding of the study goals.

The study included 368 baseline thrombocytopenia patients undergoing percutaneous coronary intervention (PCI) with dual-antiplatelet therapy (DAPT) prescribed on discharge. Platelet counts let Thrombocytopenia were categorised as mild (100,000–150,000/mm¹), moderate (50,000– 100,000/mm¹), and severe (30,000–50,000/mm¹). Participants were adults (≥18 years) undergoing either elective or emergency PCI, with platelet levels within designated ranges. The study population were patients of both sexes independent of additional cardiovascular risk factors like diabetes mellitus, hypertension, dyslipidaemia, and smoking. Individuals were also deemed qualified for participation regardless of past PCI or myocardial infarction (MI) presenting with new onset ACS.

Patients were not included if their platelet counts were less than 30,000/mm¹ or exceeded 150,000/mm¹. Additional exclusion criteria included patients who were known case of hereditary thrombocytopenias, coagulopathies such haemophilia or von Willebrand disease, a past incidence of hemorrhagic stroke, or disorders that predispose individuals to gastrointestinal bleeding, such peptic ulcer disease or inflammatory bowel disease. Those with active cancer, decompensated liver failure, or chronic kidney disease needing renal replacement therapy were also excluded. The study also eliminated patients on medicines known to cause myelosuppression and those on thrombopoietin receptor agonists or anticoagulants. Those who objected to permission were not enrolled in the study.

Baseline information, including patient demographics, clinical history, and thrombocytopenia severity, was collected at enrolment of the patient. The data was collected from a structured questionnaire. Every patient underwent PCI and started DAPT including aspirin and a P2Y12 inhibitor (clopidogrel, prasugral, or ticagrelor). Patients were under observation during their hospital stay and then assessed at designated intervals of one, two, and six months following PCI. The follow-up included evaluating major adverse cardiovascular events (MACE), hemorrhagic complications, and other clinical outcomes.

Using Bleeding Academic Research Consortium (BARC) criteria Type1 to 5—which cover events like access site bleeding, post-procedural bleeding, brain haemorrhage, gastrointestinal bleeding, and other noteworthy bleeding events—bleeding complications were evaluated. A composite of mortality, myocardial infarction, coronary revascularisation, stroke, and hospitalisation owing to heart failure defined major adverse cardiovascular events (MACE). Target vessel revascularisation, in-hospital mortality, stent thrombosis, and post-PCI myocardial infarction were the side effects.

These endpoints were selected to fully depict the relationship between thrombocytopenia grade and it’s negative effects.

The relationships between the degree of thrombocytopenia and clinical outcomes were assessed statistically. Whereas categorical data were given as frequencies and percentages, continuous variables were compiled as mean ± standard deviation (SD). Chi-square test was used for categorical data; unpaired Student's t-test was used to investigate continuous variables between the two groups. Confounding factors—including those with a p-value of 0.05 from univariate analysis—were adjusted for using multivariate logistic regression. Platelet count thresholds predictive of hemorrhagic consequences were ascertained using receiver operating characteristic (ROC) curve analysis. Confidence intervals (CIs) were calculated at 95% for hazard ratios (HRs) and odds ratios (ORs), with a p-value of <0.05 signifying statistical significance. All analyses were performed with Microsoft Excel and SPSS (version 22.0).

Ethical issues were considered paramount throughout the study. Approval was secured from the Institutional Ethics Committee, and informed consent was collected in both Hindi and English to provide clarity from all participants.

This study aimed to evaluate the influence of thrombocytopenia severity on bleeding and cardiovascular outcomes in patients receiving PCI with DAPT. The methodical approach, coupled with ethical rigour, guarantees that the results yield significant insight into the management of this high-risk demographic of patients.

The study enrolled 368 patients, predominantly male (77.72%, n = 286), with a mean age of

62.33 years (SD: 10.82). The age range spanned from 37 to 101 years, with the majority of participants (53.13%, n = 195) aged between 61 and 80 years. Gender distribution across thrombocytopenia grades did not show significant variation (p = 0.44), ensuring a balanced representation of males and females. Additionally, the BMI was distributed uniformly across all thrombocytopenia grades, with a mean BMI of 22.12 (p = 0.63), indicating that the BMI was not associated with thrombocytopenia severity.

When stratified into thrombocytopenia severity, 64.4% of patients (n = 237) were classified as having mild thrombocytopenia, 28.2% (n = 104) had moderate thrombocytopenia, and 7.3% (n = 27) had severe thrombocytopenia. Analysis of major adverse cardiovascular events (MACE) demonstrated that the risk increased with the severity of thrombocytopenia. (Table 1) Patients with mild thrombocytopenia had a hazard ratio (HR) of 1.15 (95% CI: 1.01–1.32) in univariate analysis; however, this risk was no longer significant after multivariate adjustments (HR: 1.03, 95% CI: 0.87–1.21, p > 0.05). In contrast, moderate thrombocytopenia consistently showed an elevated risk across all models, with a final HR of 1.50 (95% CI: 1.28–1.76, p < 0.001) after adjusting for confounders. Patients with severe thrombocytopenia exhibited the highest risk for MACE, with an adjusted HR of 2.10 (95% CI: 1.72–2.58, p < 0.001), underscoring a strong, independent association with adverse cardiovascular outcomes. Figure 1 illustrates the trends in hazard ratios (HRs) for MACE Outcomes across different thrombocytopenia severity levels and statistical models.

Table 1. Risk Assessment of MACE and BARC Events Based on Thrombocytopenia Severity

MACE: Major Adverse Cardiovascular Events, BARC: Bleeding Academic Research Consortium-defined bleeding events, HR: Hazard Ratio; values > 1 indicate increased risk, CI (95%): Confidence Interval; indicates the range within which the true HR value is likely to lie, P-Value: Statistical significance; values < 0.05 indicate a significant association, Univariate Model: No adjustments for confounding factors, Model 1: Adjusted for age and sex, Model 2: Adjusted for clinical variables, including BMI, diabetes, and hypertension, Model 3: Fully adjusted model, including procedural outcomes such as stent thrombosis and post-PCI MI.

Fig 1. Trends in Hazard Ratios (HR) for MACE Across Thrombocytopenia Severity Levels and Models

Bleeding complications, assessed using the BARC criteria, followed a similar trend. (Table 1) The risk of bleeding complications increased proportionally with thrombocytopenia severity. For mild thrombocytopenia, the adjusted HR was 1.02 (95% CI: 0.87–1.19, p = 0.80), indicating no significant risk. However, moderate thrombocytopenia carried a significant risk, with an HR of 1.65 (95% CI: 1.43–1.90, p < 0.001). The highest bleeding risk was observed in patients with severe thrombocytopenia, with an adjusted HR of 2.70 (95% CI: 2.24–3.25, p

< 0.001). Figure 2 depicts the hazard ratios (HRs) for BARC Outcomes across varying thrombocytopenia grades analyzed through different statistical models.

Fig 2. Trends in Hazard Ratios (HR) for MACE Across Thrombocytopenia Severity Levels and Models

In-hospital mortality rates also increased with thrombocytopenia severity. The overall mortality rate was 4.3% (n = 16), but rates varied significantly across groups: 2.1% (n = 5) in the mild group, 6.7% (n = 7) in the moderate group, and 14.8% (n = 4) in the severe group.

Severe thrombocytopenia emerged as a significant predictor of in-hospital mortality, with an adjusted odds ratio (OR) of 4.12 (95% CI: 1.90–8.93, p < 0.001) compared to the mild thrombocytopenia group.

Secondary outcomes further highlighted the impact of thrombocytopenia severity. Stent thrombosis was observed in 3.8% of patients (n = 14), with severe thrombocytopenia accounting for 29% (n = 4) of these cases. Similarly, target vessel revascularization rates increased with thrombocytopenia severity, occurring in 2.5% (n = 6) of mild cases, 6.7% (n = 7) of moderate cases, and 11.1% (n = 3) of severe cases. Post-PCI myocardial infarction (MI) was reported in 6.2% of patients (n = 23), with patients in the severe thrombocytopenia group exhibiting a significantly higher adjusted OR of 3.50 (95% CI: 1.72–7.14, p < 0.001).

Subgroup analysis revealed notable associations between thrombocytopenia severity and patient characteristics. Smoking was significantly more prevalent in the moderate thrombocytopenia group (72.5%, p = 0.0065), with mean packs/year increasing in line with thrombocytopenia severity. Furthermore, a history of PCI and MI emerged as significant predictors of severe thrombocytopenia, with adjusted ORs of 2.76 (95% CI: 1.27–6.00) and

2.33 (95% CI: 1.08–5.01), respectively. Hypertension was also significantly associated with thrombocytopenia severity, affecting 27.4% of patients with mild thrombocytopenia, 53.9% of those with moderate thrombocytopenia, and 48.3% of those with severe thrombocytopenia (p < 0.001). Dyslipidemia showed a similar trend, being most prevalent in moderate and severe cases (p = 0.046).

Lipid profiles, while not significantly different across thrombocytopenia grades, revealed some trends. HDL cholesterol levels were notably lower in the severe thrombocytopenia group (mean: 35.75 mg/dL, p = 0.096), suggesting potential cardiovascular risks. Other lipid metrics, including triglycerides, total cholesterol, and LDL cholesterol, showed no significant associations with thrombocytopenia severity.

This study offers significant outlook into the relationship between the grade of thrombocytopenia and outcomes in patients receiving percutaneous coronary intervention while on dual antiplatelet therapy. These results correspond with and improve the current research, providing comprehensive insights into the dangers and therapeutic approaches associated with varying levels of grade of thrombocytopenia.

Hemorrhagic risks continue to be a significant issue for thrombocytopenic patients undergoing PCI with dual antiplatelet therapy (DAPT). Consistent with Long et al. (2020), who recorded ORs of 1.78 for cerebral bleeding and 1.44 for gastrointestinal bleeding in thrombocytopenic PCI patients, this study found a noteworthy correlation between severe thrombocytopenia and elevated risks of bleeding complications (HR: 2.70, p<0.001). Overgaard et al. (2008) demonstrated that thrombocytopenia independently predicted in- hospital bleeding complications, with significantly elevated rates in thrombocytopenic patients compared to those with normal platelet counts (1.7% vs. 0.8%, p<0.05) (8). These statistics highlight the neccessity for customised bleeding risk management, especially in those with severe thrombocytopenia.

The study's tiered approach to evaluating thrombocytopenia severity enhances comprehension of cardiovascular risks. Patients with severe thrombocytopenia showed the highest adjusted hazard ratio for major adverse cardiovascular events (MACE) (HR: 2.10, p<0.001), so validating the results of Ayoub et al. (2018), which indicated that persistent thrombocytopenia doubled the risk of adverse cardiovascular outcomes (OR: 2.30). A tendency also seen in the severe thrombocytopenic cohort of this study, which revealed a mortality rate of 14.8% (8), Overgaard et al. (2008) found higher in-hospital mortality rates in thrombocytopenic patients receiving urgent PCI (3.55% vs. 1.15%, p<0.001).

Recent studies imply that different DAPT strategies—especially for shorter durations—may reduce bleeding problems while preserving anti ischemic efficacy. Compared to 12-month DAPT, one month of dual antiplatelet therapy (DAPT) followed by clopidogrel monotherapy greatly decreased the incidence of serious bleeding (HR: 0.26, p=0.004). Shorter DAPT durations were noninferior to extended regimens for ischaemic outcomes and lowered bleeding risks in high-risk individuals, according per the XIENCE Short DAPT research (10). The findings especially apply to moderate thrombocytopenia since they imply that shorter DAPT lengths could offer a safer therapeutic interval.

Campo et al. (2012) showed that single antiplatelet treatment (SAPT) may be a good option for individuals with severe thrombocytopenia as this cohort showed no appreciable rise in ischaemic events. Their limited sample size (n=35) restricts the generalisability of their findings. The whole dataset of this study highlights the possibility for more exact treatment customisation and offers solid proof for stratified DAPT therapy. By assessing specific bleeding risks, risk stratification methods as the PRECISE-DAPT score improve clinical decision-making. In thrombocytopenic PCI patients, Prior to initiation of DAPT Costa et al. (2020) showed how well this score predicted bleeding episodes and optimised antiplatelet therapy. Although not specifically used in this work, including these approaches could help to better evaluate DAPT's risk-benefit ratio in thrombocytopenic groups.

These benefits notwithstanding, there are still flaws in the present evidence basis. The long- term effects going beyond six months are not clearly defined. Particularly in severe thrombocytopenia, the possibility of delayed unfavourable effects calls for longer follow-up tests. The lack of randomised controlled trials especially aiming at thrombocytopenia with DAPT hampers the formulation of a clear recommendation.

This study underscores the complex interplay between thrombocytopenia and adverse outcomes in patients undergoing PCI while on DAPT. The findings highlight that moderate and severe thrombocytopenia independently predict higher risks of bleeding complications and major adverse cardiovascular events (MACE). Severe thrombocytopenia, in particular, was associated with a markedly increased risk of in-hospital mortality and adverse clinical outcomes, emphasizing the need for careful management in this vulnerable population.

The evidence aligns with existing literature, which consistently shows that thrombocytopenia significantly exacerbates bleeding risks during DAPT. Moreover, emerging strategies such as abbreviated DAPT durations or the use of single antiplatelet therapy (SAPT) in selected high- risk patients offer promising avenues for mitigating these risks. Shortened DAPT regimens, as demonstrated in trials like STOPDAPT-2 and XIENCE Short DAPT, show potential for reducing bleeding without compromising ischemic outcomes, especially in moderate thrombocytopenia.

This study also underscores the importance of individualized treatment approaches. Stratifying patients based on thrombocytopenia severity and utilizing risk assessment tools like the PRECISE-DAPT score can aid in balancing the risks of bleeding and ischemia.

However, further research is needed, including long-term follow-up studies and randomized controlled trials, to refine management strategies and optimize outcomes.

Finally, this study provides a robust foundation for personalized antiplatelet therapy in thrombocytopenic patients undergoing PCI, offering valuable insights to guide clinical decision-making in this high-risk group. Effective management tailored to thrombocytopenia severity is critical to improving patient outcomes while minimizing treatment-associated risks.

1. Chen, Zhongxiu, Liu, Zheng, Li, Nan, Liu, Ran, Wang, Miye, Wang, Duolao, Li, Che n, Li, Kai, Luo, Fangbo, He, Yong, Impact of Thrombocytopenia on In-Hospital Outcome in Patients Undergoing Percutaneous CoronaryIntervention, Cardiovascular Therapeutics, 2021, 8836450, 9 pages, 2021. https://doi.org/10.1155/2021/8836450
2. Watanabe H, Domei T, Morimoto T, et al. Effect of 1-Month Dual Antiplatelet Therapy Followed by Clopidogrel vs 12-Month Dual Antiplatelet Therapy on Cardiovascular and Bleeding Events in Patients Receiving PCI: The STOPDAPT-2 Randomized Clinical Trial. JAMA. 2019;321(24):2414–2427. doi:10.1001/jama.2019.8145
3. Raphael CE, Spoon DB, Bell MR, Psaltis PJ, Kidd S, Loh SX, et al. Effect of preprocedural thrombocytopenia on prognosis after percutaneous coronary intervention. Mayo Clin Proc. 2016;91(8):1035–44. Available from: http://dx.doi.org/10.1016/j.mayocp.2016.05.008
4. Long, M., Ye, Z., Zheng, J. et al. Dual anti-platelet therapy following percutaneous coronary intervention in a population of patients with thrombocytopenia at baseline: a meta-analysis. BMC Pharmacol Toxicol 21, 31 (2020). https://doi.org/10.1186/s40360-020-00409-2
5. Ahsan MJ, Lateef N, Latif A, Malik SU, Batool SS, Fazeel HM, et al. A systematic review and meta-analysis of impact of baseline thrombocytopenia on cardiovascular outcomes and mortality in patients undergoing percutaneous coronary intervention. Catheter Cardiovasc Interv . 2021;97(6):E778–88. Available from: http://dx.doi.org/10.1002/ccd.29405
6. Park S, Ahn J-M, Kim TO, Park H, Cho S-C, Kang D-Y, et al. Incidence and impact of thrombocytopenia in patients undergoing percutaneous coronary intervention with drug-eluting stents. Am J Cardiol [Internet]. 2020;134:55–61. Available from: http://dx.doi.org/10.1016/j.amjcard.2020.07.059
7. Campo G, Marchesini J, Fileti L, Tebaldi M, Ferrari R. Medical and interventional management of patients with severe thrombocytopenia undergoing percutaneous coronary intervention. J Thromb Haemost 2012; 10: 153–6.
8. Overgaard CB, Ivanov J, Seidelin PH, Todorov M, Mackie K, Dzavík V. Thrombocytopenia at baseline is a predictor of inhospital mortality in patients undergoing percutaneous coronary intervention. Am Heart J. 2008;156(1):120–4. Available from: http://dx.doi.org/10.1016/j.ahj.2008.02.003
9. Ayoub K, Marji M, Ogunbayo G, Masri A, Abdel-Latif A, Ziada K, et al. Impact of chronic thrombocytopenia on in-hospital outcomes after percutaneous coronary intervention. JACC Cardiovasc Interv. 2018;11(18):1862–8. Available from: http://dx.doi.org/10.1016/j.jcin.2018.05.033
10. Mehran R, Cao D, Angiolillo DJ, Bangalore S, Bhatt DL, Ge J, et al. 3- or 1-month DAPT in patients at high bleeding risk undergoing everolimus-eluting Stent implantation. JACC Cardiovasc Interv . 2021;14(17):1870–83. Available from: http://dx.doi.org/10.1016/j.jcin.2021.07.016
11. Costa F, Valgimigli M, Steg PG, Bhatt DL, Hohnloser SH, Ten Berg JM, et al. Antithrombotic therapy according to baseline bleeding risk in patients with atrial fibrillation undergoing percutaneous coronary intervention: applying the PRECISE- DAPT score in RE-DUAL PCI. Eur Heart J Cardiovasc Pharmacother .2022;8(3):216–26. Available from: http://dx.doi.org/10.1093/ehjcvp/pvaa135