Platelet Function and Morphology in Patients with Sepsis and Septic Shock: A Retrospective Pilot Study

Abstract

Background: Sepsis remains a leading cause of mortality in the intensive care unit (ICU). Platelets (PLTs) are central to coagulation, inflammation, and the maintenance of endothelial integrity. Although thrombocytopenia is an established prognostic marker in sepsis, alterations in PLT function and morphology may provide additional insight into disease progression. Methods: This retrospective pilot study examined adult ICU patients diagnosed with sepsis or septic shock. Extracted data included demographic characteristics, clinical variables, and laboratory parameters. Platelet function was evaluated using impedance aggregometry and rotational thromboelastometry (ROTEM), while PLT morphology metrics were obtained from complete blood counts. Statistical analyses comprised Spearman’s rank correlation and logistic regression. Results: Twenty patients were included. Platelet aggregation was impaired across ASPI, ADP, and TRAP-6 assays despite normal PLT counts and morphology. ROTEM-derived measure of PLT contribution to clot strength was within normal ranges. No correlations were observed between PLT function and PLT morphology parameters. An inverse correlation was identified between ROTEM-derived PLT contribution to clot strength and SOFA score (r = −0.60, p = 0.03). Neither PLT function nor PLT morphology was associated with ICU mortality. Conclusions: Functional PLT deficits may occur in sepsis in the absence of structural abnormalities. ROTEM-derived PLT contribution to clot strength may inversely reflect sepsis severity. Platelet function parameters appear unlikely to predict short-term mortality in septic patients.

1. Introduction

Sepsis and septic shock remain leading causes of morbidity and mortality among critically ill patients admitted to intensive care unit (ICU) [1]. These conditions arise from a dysregulated host response to infection that results in life-threatening organ dysfunction. Septic shock represents a more severe subset, characterized by circulatory failure and metabolic derangements, and carries substantially higher mortality than sepsis alone [2]. Despite advances in antimicrobial therapy and supportive care, the complex and multifactorial pathophysiology of sepsis continues to challenge clinicians and researchers.

Within the intertwined immune and hemostatic disturbances of sepsis, PLTs have gained recognition as key mediators—not only in coagulation, but also in inflammation, immune modulation, and the preservation of endothelial integrity [3]. Thrombocytopenia, one of the most common hematologic abnormalities in sepsis, is well established as a marker of poor prognosis [4]. However, beyond quantitative measures such as PLT count, qualitative alterations in PLT function and alternations in morphology may provide deeper insight into the host response and the progression from sepsis to septic shock. Platelet dysfunction and morphological abnormalities are frequently observed in septic patients and have been associated with disease severity and adverse outcomes [5,6]. Parameters including PLT aggregation, activation markers, and mean platelet volume (MPV) have shown potential prognostic relevance, though their integration into routine clinical practice remains limited [7]. Despite growing interest in PLT biology in sepsis, relatively few studies have simultaneously assessed PLT function and morphology, particularly in real-world ICU settings [8].

The primary aim of this study was to evaluate PLT function and morphology in patients diagnosed with sepsis or septic shock. Secondary objectives included examining associations between different PLT function and morphology parameters, as well as exploring their relationships with disease severity and short-term mortality.

2. Materials and Methods

2.1. Study Design

This study used a retrospective cohort design and included patients admitted to the ICU of a large academic medical center with a primary admission diagnosis of sepsis or septic shock.

2.2. Study Population

The study population comprised adult patients (≥18 years) diagnosed with sepsis or septic shock according to the Sepsis-3 and Septic Shock-3 definitions, respectively. Inclusion criteria required the availability of PLT function test results. Patients were excluded if they had a known inherited PLT function disorder, were receiving antiplatelet agent (APA), or were pregnant.

2.3. Data Collection

Data were extracted from electronic medical records (AMMS, Asseco Medical Solutions, Rzeszów, Poland) and included demographic information, clinical variables, and laboratory results. Clinical data encompassed the diagnosis of sepsis or septic shock, anatomical source of infection, comorbidities, body mass index (BMI), the time interval (in hours) between the last dose of low-molecular-weight heparin (LMWH) and blood sampling for laboratory analysis, disease severity as assessed by the Sequential Organ Failure Assessment (SOFA) score, and ICU mortality. Platelet function was evaluated using multiple electrode impedance aggregometry (Multiplate^®, Roche Diagnostics International Ltd., Rotkreuz, Switzerland), and PLT contribution to clot strength was assessed with rotational thromboelastometry (ROTEM^®, TEM Innovations GmbH, Munich, Germany). Aggregometry was performed using three agonists: the ASPI test utilized arachidonic acid to stimulate cyclooxygenase-mediated thromboxane A₂ production; the ADP test employed adenosine diphosphate to activate platelet P2Y₁₂ receptors; and the TRAP-6 test used thrombin receptor-activating peptide 6 to engage thrombin receptors. The results from impedance aggregometry were expressed in aggregation units (AU). ROTEM-derived PLT contribution to clot strength was calculated as the difference in maximal clot firmness (MCF) between the assay evaluating the extrinsic coagulation pathway (EXTEM) and the assay evaluating fibrinogen/factor XIII function (FIBTEM). Platelet counts and morphology parameters were obtained from complete blood count (CBC) analysis and included plateletcrit, mean platelet volume (MPV), platelet distribution width (PDW), and platelet large-cell ratio (PLCR). Additionally, red blood cell distribution width (RDW) was retrieved. Biochemical markers included interleukin-6 (IL-6), procalcitonin (PCT), C-reactive protein (CRP), creatinine (Cr), blood urea nitrogen (BUN), urea, estimated glomerular filtration rate (eGFR), bilirubin, aspartate aminotransferase (AST), and alanine aminotransferase (ALT). Coagulation parameters encompassed both conventional coagulation tests (CCTs) and viscoelastic assays (ROTEM). Conventional coagulation tests included fibrinogen concentration (Clauss method), thrombin time (TT), prothrombin time (PT), prothrombin activity, international normalized ratio (INR), activated partial thromboplastin time (aPTT), and D-dimers (DD). All laboratory data were retrieved from the time of ICU admission.

2.4. Statistical Analysis

Statistical analyses were conducted using Stata 18 Basic Edition (Stata 18.0 Basic Edition, StataCorp LLC, College Station, TX, USA). Summary statistics for laboratory parameters were presented as medians (Me) with interquartile ranges (IQRs). Associations between PLT function and morphology parameters, as well as these parameters and severity of the sepsis, were assessed using Spearman’s rank correlation. Logistic regression was employed to evaluate the relationship between PLT parameters and the RDW and PLT ratio with ICU mortality. A p-value < 0.05 was considered statistically significant.

2.5. Ethical Considerations

Given the retrospective nature of the study, the Bioethics Committee of the Medical University of Silesia in Katowice determined that formal ethical approval was not required.

3. Results

Data for 20 patients were retrieved. The median age of patients was 63 (IQR 59–71) years. The majority of patients were women (60%, n = 12). Sepsis was diagnosed in nine (45%) patients, whereas septic shock was diagnosed in 11 (55%) patients. The anatomical sites of infection were as follows: abdomen—9 (45%), pneumonia—4 (20%), urinary tract infection—3 (15%), uterus—2 (10%), and blood stream infection—2 (10%). The frequency of comorbidities was as follows: hypertension—9 (45%) patients, obesity—5 (25%) patients, diabetes mellitus—4 (20%) patients, coronary artery disease—3 (15%) patients, chronic obstructive pulmonary disease—2 (10%) patients, and atrial fibrillation—2 (10%) patients. The median BMI in the study group was 28.2 (IQR 24.8–35.9) kg m⁻². Eight (40%) patients were receiving LMWH before ICU admission. The median time interval between LMWH administration and blood collection was 19.5 (IQR 11.0–36.0) hours. No patient was receiving APA. Because all patients who fulfilled Sepsis-3 criteria—either by scoring ≥2 SOFA points or by exhibiting an acute increase of ≥2 points—were admitted to the ICU without delay, and blood samples were obtained close to ICU admission, the timing of platelet function assessment closely reflected the early phase of sepsis and minimized temporal variability. The median SOFA score was 7.0 (IQR 6.0–7.0) points. The ICU mortality was 35%. The biochemical parameters and CCTs in the study group are presented in

Table 1. The biochemical and conventional coagulation parameters in the study group (n = 20).

Parameter	Value, Me 1 (IQR 2)	Reference Range
Interleukin 6 [pg mL−1]	137.0 (71.8–355.0)	<7.0
Procalcitonin [ng mL−1]	4.7 (1.7–19.4)	<0.5
C-reactive protein [mg L−1]	202.0 (124.0–322)	<5.0
Creatinine [mg dL−1]	1.02 (0.80–1.73)	0.51–0.95 (F)/0.67–1.17 (M)
Blood urea nitrogen [mg dL−1]	29.8 (19.7–48.1)	7.9–20.0
Urea [mg dL−1]	63.7 (42.2–103.0)	17.1–49.2
MDRD GFR 3 [mL min−1]	60.0 (38.9–60.0)	>60
Bilirubin [mg dL−1]	0.56 (0.36–1.33)	0.30–1.00
Aspartate aminotransferase [U L−1]	61.5 (33.4–126.0)	<35.0
Alanine aminotransferase [U L−1]	39.0 (17.4–70.5)	<35.0
Thrombin time [s]	15.9 (15.5–18.7)	10.3–16.6
Prothrombin time [s]	14.3 (13.2–16.9)	9.4–12.5
Prothrombin activity [%]	76.0 (61.0–82.0)	80.0–120.0
International normalized ratio	1.19 (1.09–1.41)	0.80–1.20
aPTT 4 [s]	34.5 (30.4–41.1)	25.4–36.9
Fibrinogen [mg dL−1]	415.0 (243.0–581.0)	200.0–393.0
D-dimers [ng mL−1]	4171.0 (1878.0–5841.0)	<500.0

¹ Median value. ² Interquartile range. ³ Modification of Diet in Renal Disease glomerular filtration rate. ⁴ Activated partial thromboplastin time. Abnormal results in bold.

.

The inflammatory parameters of the studied patients exceeded the upper range multiple times: 19.6 for IL-6, 9.4 for PCT, and 40.4 for CRP. Conventional coagulation tests showed slightly prolonged PT and decreased prothrombin activity, as well as a slightly increased fibrinogen concentration. The median RDW was 15.0 (IQR 14.2–16.9) %, whereas the median ratio of RDW to PLT was 0.079 (IQR 0.054–0.106).

The results for all PLT parameters are presented in

Table 2. The platelet function and platelet morphology parameters in the study group (n = 20).

Parameter	Value, Me 1 (IQR 2)	Reference Range
Aggregometry (ASPI 3 test) [U]	33 (22–72)	86.0–162.0; target for APA 4: 30–40
Aggregometry (ADP 5 test) [U]	38 (24–50)	53.0–140.0; target for APA: 19–46
Aggregometry (TRAP-6 6 test) [U]	63 (39–120)	97.0–182.0
EXTEM MCF 7-FIBTEM MCF [mm]	43 (39–46)	26–63
Platelets [×103 µL−1]	187 (150–270)	130–400
Plateletcrit [%]	0.21 (0.17–0.30)	0.17–0.35
Mean platelet volume [fL]	10.3 (9.7–11.0)	7.0–15.0
Platelet distribution width [%]	11.9 (10.5–13.8)	9.0–17.0
Platelet large-cell ratio [%]	27.5 (23.4–32.0)	19.5–43.8

¹ Median value. ² Interquartile range. ³ Arachidonic acid. ⁴ Antiplatelet agent. ⁵ Adenodiphosphate. ⁶ Thrombin receptor-activating protein 6. ⁷ Maximum clot firmness. Abnormal results in bold.

.

All PLT aggregometry parameters were grossly deranged and corresponded with the level of PLT aggregation in patients receiving APA. The PLT contribution to clot strength assessed using ROTEM was normal. The number of PLTs and all PLT morphological parameters were normal in the study group.

An analysis of the association between PLT aggregometry parameters and PLT contribution to clot strength (ROTEM) parameters, as well as these parameters and PLT morphology parameters, was performed (

Table 3. Associations between platelet function and platelet morphology parameters in the study group.

Association	Correlation Coefficient	p-Value
ASPI 1 vs. EXTEM MCF 2-FIBTEM MCF	0.21	0.48
ADP 3 vs. EXTEM MCF-FIBTEM MCF	0.52	0.07
TRAP-6 4 vs. EXTEM MCF-FIBTEM MCF	0.48	0.10
ASPI vs. MPV 5	0.22	0.43
ADP vs. MPV	0.39	0.17
TRAP-6 vs. MPV	−0.02	0.95
ASPI vs. PDW 6	0.08	0.78
ADP vs. PDW	0.03	0.92
TRAP-6 vs. PDW	−0.29	0.30
ASPI vs. PLCR 7	0.17	0.57
ADP vs. PLCR	0.29	0.31
TRAP-6 vs. PLCR	−0.11	0.69
EXTEM MCF-FIBTEM MCF vs. MPV	0.19	0.56
EXTEM MCF-FIBTEM MCF vs. PDW	−0.16	0.61
EXTEM MCF-FIBTEM MCF vs. PLCR	0.07	0.83

¹ Arachidonic acid. ² Maximum clot firmness. ³ Adenodiphosphate. ⁴ Thrombin receptor-activating protein 6. ⁵ Mean platelet volume. ⁶ Platelet distribution width. ⁷ Platelet large-cell ratio.

).

There were no correlations between the parameters of PLT function and PLT morphology. The association between ADP and EXTEM MCF-FIBTEM MCF was close to statistical significance (p = 0.07).

The associations between parameters of PLT function and PLT morphology with severity of sepsis (SOFA score) are presented in

Table 4. Associations between parameters of platelet function and platelet morphology and severity of sepsis in the study group.

Association	Correlation Coefficient	p-Value
ASPI 1 vs. SOFA 2	0.03	0.92
ADP 3 vs. SOFA	−0.05	0.87
TRAP-6 4 vs. SOFA	−0.26	0.34
EXTEM MCF 5- FIBTEM MCF vs. SOFA	−0.60	0.03
MPV 6 vs. SOFA	0.02	0.94
PDW 7 vs. SOFA	0.22	0.45
PLCR 8 vs. SOFA	0.07	0.80

¹ Arachidonic acid. ² Sequential Organ Failure Assessment. ³ Adenodiphosphate. ⁴ Thrombin receptor-activating protein 6. ⁵ Maximum clot firmness. ⁶ Mean platelet volume. ⁷ Platelet distribution width. ⁸ Platelet large-cell ratio. Statistically significant associations in bold.

.

We found negative correlation between EXTEM MCF-FIBTEM MCF and the SOFA score.

There were no correlations between PLT function or PLT morphology parameters and ICU mortality. There was also no correlation between the RDW and PLT ratio and ICU mortality—OR 0.25, 95% CI 0.0001–552.4, p = 0.72.

4. Discussion

Although the present pilot study focuses on PLT function and morphology in septic patients, there are many publications emphasizing the prognostic value of sole PLT count, and even more so its changes over time. A recent retrospective cohort study of 82 septic patients provided an important complementary perspective. In that study, survivors exhibited significantly higher PLT counts by day 14 of their ICU stay compared with non-survivors, and the day 14 PLT count demonstrated meaningful prognostic value, outperforming the SOFA score, with an area under the Receiver Operating Characteristic curve (AUROC) of 0.640 vs. 0.394, respectively. Moreover, a PLT count <224 × 10³ µL⁻¹ on day 14 emerged as an independent predictor of 28-day mortality [9].

The present retrospective cohort study investigated PLT function and PLT morphology in patients with sepsis and septic shock admitted to the ICU, with the aim of characterizing platelet dysfunction in this population and identifying potential associations between platelet parameters, sepsis severity, and short-term mortality. Despite the limited sample size, the findings offer several noteworthy insights that contribute to the evolving understanding of PLT dynamics in critical illness.

A key observation was the marked impairment in PLT aggregation across all impedance aggregometry assays (ASPI, ADP, TRAP-6), despite normal PLT counts and preserved morphology. This dissociation between function and structure mirrors the patterns observed in inherited PLT function disorders, where aggregation is severely impaired despite intact PLT morphology [10]. At the molecular level, this phenomenon is consistent with sepsis-associated alterations in PLT receptor expression and intracellular signaling pathways. Experimental studies have demonstrated the downregulation or shedding of key surface receptors, including GPIbα, GPVI, and P2Y12, mediated by ADAMTS family metalloproteinases, neutrophil-derived proteases, and endothelial activation products. Additionally, TLR4-dependent signaling triggered by circulating lipopolysaccharides can induce intracellular calcium dysregulation, impairing granule secretion and integrin activation. These mechanisms collectively contribute to a functional phenotype resembling “platelet exhaustion,” characterized by receptor desensitization, impaired signal transduction, and reduced responsiveness to agonists [3,11]. The concept is further supported by recent experimental and translational research demonstrating that inflammation profoundly alters PLT behavior at the receptor level. A recent study investigating PLT responses in both preclinical models of sterile inflammation and in sepsis patients provides important context for our findings. In that work, the authors identified a population of “inflammation-conditioned” PLTs that exhibited selective, receptor-specific defects in aggregation, with some signaling pathways remaining intact while others were markedly impaired. Notably, the authors also observed PLT hyperreactivity in sepsis patients, accompanied by a receptor-wise imbalance in aggregation responses. Importantly, the authors’ data suggested that this functional disbalance was at least partially driven by plasma components from sepsis patients, highlighting the role of circulating inflammatory mediators in modulating PLT responsiveness. These observations resonate with the present pilot study findings of severely impaired aggregation despite normal PLT morphology, and they reinforce the idea that PLT dysfunction in sepsis is not uniform but rather pathway-specific, shaped by the inflammatory milieu [12]. A recent prospective observational pilot study provided important complementary insight into this phenomenon [13]. In that study, hemostatic and immune PLT dysfunctions were already evident at ICU admission, even though thrombocytopenia developed only later during the clinical course. Using a multimodal assessment—including light transmission aggregometry, thromboelastography, platelet activation markers, platelet–leukocyte aggregates, and soluble CD40L—the authors demonstrated that PLT abnormalities were present at the earliest time point and correlated with sepsis severity, as reflected by higher SOFA scores and elevated PCT levels. These findings reinforce the notion that functional PLT impairment is an early event in sepsis, driven by inflammatory and immunologic dysregulation rather than by quantitative PLT loss. The parallels with the present pilot study are notable. A similar profound impairment in PLT aggregation was observed at ICU admission despite normal PLT counts and preserved morphology in the present study. The pilot study’s demonstration of early immune platelet dysfunction—manifested through altered platelet–leukocyte interactions and activation marker expression—provides a mechanistic framework that may help explain the aggregation defects we observed. Together, these findings suggest that PLT dysfunction in sepsis is multifaceted, involving both hemostatic and immune pathways, and that these abnormalities emerge before thrombocytopenia becomes clinically apparent. Importantly, the pilot study also showed that PLT dysfunction correlated with sepsis severity, particularly at the earliest time point. This aligns with the present pilot study observation of an inverse correlation between ROTEM-derived PLT contribution to clot strength and the SOFA score. Although no associations were identified between PLT parameters and ICU mortality in the present pilot study, the early functional abnormalities described in the pilot study support the idea that PLT dysfunction may serve as an early indicator of disease severity, even if its prognostic value for mortality remains uncertain in small cohorts. Recent clinical studies further support the idea that PLT abnormalities in sepsis extend beyond simple thrombocytopenia and may carry prognostic relevance. A prospective observational study evaluating PLT-derived indices as predictors of in-hospital mortality provides an important complementary perspective [14]. In that study of 114 septic patients, several PLT-based ratios were assessed at ICU admission, including the CRP-to-PLT ratio (CPR), PLT-to-lymphocyte ratio (PLR), PLT-to-white blood cell ratio (PWR), and PLT-to-creatinine ratio (PCR). Among these, CPR demonstrated the strongest prognostic performance, with an AUROC of 0.757 and an optimal cutoff of 0.886. C-reactive protein-to-platelet ratio remained an independent predictor of mortality in multivariate models, outperforming other PLT-related indices. These findings highlight that composite PLT-based biomarkers, which integrate inflammatory and hematologic information, may offer clinically meaningful prognostic value in sepsis. The contrast with the present pilot study findings is instructive. While no associations were observed between PLT function or morphology and ICU mortality in the present study, the external study suggests that PLT-derived indices—particularly those reflecting the interplay between inflammation and PLT count—may be more sensitive to early mortality risk. This discrepancy may reflect differences in study design, sample size, and the type of PLT parameters evaluated. The present pilot study focused on functional PLT assays and morphology at a single time point, whereas the PLT-based ratios in the external study captured broader systemic processes, including inflammation, immune activation, and organ dysfunction.

Notably, the aggregometry values recorded in the present cohort were comparable to those typically seen in individuals receiving APAs, despite the exclusion of such patients from the study. This finding further supports the hypothesis of sepsis-induced PLT hyporesponsiveness, potentially driven by sustained exposure to inflammatory cytokines (e.g., IL-6, TNF-α), circulating damage-associated molecular patterns (DAMPs), and thrombin-mediated PAR1 desensitization. The persistent activation of these pathways may lead to the internalization or conformational inactivation of integrin αIIbβ3, the final common mediator of PLT aggregation.

Interestingly, the PLT contribution to clot strength assessed using ROTEM remained within normal limits. This apparent discrepancy between aggregometry and viscoelastic testing likely reflects the distinct physiological processes each modality interrogates. While aggregometry evaluates agonist-dependent receptor activation and intracellular signaling, ROTEM primarily assesses the mechanical contribution of PLTs to clot firmness, which depends largely on integrin αIIbβ3–fibrin interactions and cytoskeletal contractility [15,16]. The preservation of ROTEM parameters suggested that PLT–fibrin crosslinking and cytoskeletal force generation remain relatively intact, even when receptor-mediated aggregation pathways are impaired. The near-significant correlation between ADP aggregometry and ROTEM-derived PLT contribution to clot strength (p = 0.07) suggests a partial overlap between these modalities. Platelet aggregation assays primarily reflect the function of specific activation pathways triggered by agonists such as ADP or collagen, whereas clot strength integrates multiple components, including fibrin formation, PLT–fibrin interactions, and the contribution of circulating coagulation factors. In sepsis, these processes may be differentially affected, leading to a dissociation between biochemical PLT signaling and the mechanical properties of the forming clot. This divergence may also reflect compensatory mechanisms activated during sepsis, such as increased fibrinogen levels, enhanced thrombin generation, or the upregulation of alternative PLT activation pathways that partially preserve clot firmness despite impaired receptor-mediated aggregation. Recognizing these distinct yet interconnected aspects of hemostasis may help explain the complex and sometimes paradoxical PLT behavior observed in septic patients. Further investigation in larger, prospective cohorts is therefore warranted.

The markedly elevated levels of inflammatory biomarkers (IL-6, PCT, CRP) confirm the intense inflammatory burden characteristic of sepsis and septic shock in the present study [17]. At the molecular level, IL-6 and other cytokines are known to modulate megakaryopoiesis, PLT turnover, and PLT transcriptomics, contributing to the emergence of a reprogrammed PLT phenotype with altered RNA content and protein expression. Conventional coagulation tests revealed mild coagulopathy, including prolonged PT and elevated fibrinogen and DD levels, consistent with a hypercoagulable state and ongoing fibrinolysis. These findings align with the established concept of sepsis-induced coagulopathy [18], driven by tissue factor overexpression, thrombin generation, suppression of the protein C pathway, and NET-mediated activation of coagulation.

A correlation was observed between sepsis severity and the ROTEM-derived parameter of PLT contribution to clot strength. However, contrary to initial expectations, no significant associations were found between PLT function or morphology and ICU mortality. There was also no correlation between the RDW and PLT ratio and ICU mortality, although some publications showed a good predictive value of the dynamic changes in this parameter in sepsis patients [19]. This may reflect the limited statistical power due to sample size constraints, or the multifactorial nature of sepsis-related mortality, in which PLT dysfunction represents only one of many contributing factors. Additionally, although the timing of PLT assessment relative to disease onset and progression may influence its prognostic relevance, this timing was mostly constant in our cohort—corresponding to the moment of acute organ failure.

Recent studies reinforce the relevance of viscoelastic testing and PLT dynamics in characterizing sepsis-associated coagulopathy and predicting clinical outcomes. Contemporary ROTEM and TEG investigations demonstrate that these modalities detect early coagulation disturbances that are not captured by conventional assays [20].

Several limitations of the study should be acknowledged. First, the small sample size limits both generalizability and statistical robustness. With only 20 patients, the statistical power is inherently constrained, and the results should therefore be viewed as preliminary rather than definitive. Secondly, while the lack of a control group prevents us from determining whether the observed impairment is specific to sepsis or reflects a broader response to critical illness, the consistent pattern observed across the present cohort still provides valuable preliminary insight into platelet dysfunction in this clinical context. Future studies incorporating appropriate control populations and locally derived reference ranges will be essential to confirm and extend these findings. Therefore, this study is best understood as a pilot exploratory investigation designed to generate hypotheses and identify potential trends that warrant further examination. Larger, adequately powered studies will be essential to validate these observations, refine effect estimates, and determine the generalizability of the patterns identified here. Thirdly, the retrospective design precludes causal inference and may introduce selection bias. Although the timing of LMWH administration was considered, its potential influence on platelet function cannot be entirely excluded. Finally, the absence of serial measurements precludes the evaluation of dynamic changes in PLT parameters over time, including potential shifts in PLT transcriptomic profiles, receptor expression, or intracellular signaling pathways as sepsis evolves.

5. Conclusions

This pilot study suggests that PLT functional impairments may occur independently of structural abnormalities in patients with sepsis and septic shock. Although an association was observed between ROTEM-derived PLT contribution to clot strength and disease severity, no PLT function or morphology parameter was significantly related to short-term mortality. These findings underscore the need for larger, prospective studies to further clarify the role of PLT dysfunction in the pathophysiology and clinical course of sepsis.