Abstract
This study aimed to investigate the conditions of patients with peripherally inserted central catheter (PICC) placements, analyze the risk factors influencing thrombosis in PICC-placed patients, and formulate more accurate and effective PICC management strategies. A total of 147 patients undergoing PICC placements were selected as the study subjects. Clinical data were collected, and the patients were divided into thrombosis and non-thrombosis groups. Detect levels of bilirubin, white blood cells, venous pressure, heparin concentration, blood flow, citric acid, and platelets. Pearson chi-square test, Spearman correlation analysis, as well as univariate and multivariate logistic regression were employed to analyze independent risk factors. Among the 147 patients with PICC placements, there were 84 males and 63 females. Thrombosis occurred in 116 cases, with an incidence rate of 78.91%. Pearson chi-square test showed a significant correlation between citric acid, blood flow, platelets and frailty (P < .001) with thrombosis formation. Spearman correlation analysis revealed a significant correlation between citric acid (ρ = −0.636, P < .001), blood flow (ρ = 0.584, P < .001), platelet count (ρ = 0.440, P < .001), frailty (ρ = −0.809, P < .001) and thrombosis in PICC placement patients. Univariate logistic regression analysis indicated a significant correlation between thrombosis formation and citric acid (OR = 0.022, 95% CI = 0.006–0.08, P < .001), blood flow (OR = 33.973, 95% CI = 9.538–121.005, P < .001), platelet count (OR = 22.065, 95% CI = 5.021–96.970, P < .001), frailty (OR = 0.003, 95% CI = 0.001–0.025, P < .001). Multivariate logistic regression analysis also showed a significant correlation between thrombosis formation and citric acid (OR = 0.013, 95% CI = 0.002–0.086, P < .001), blood flow (OR = 35.064, 95% CI = 6.385–192.561, P < .001), platelet count (OR = 4.667, 95% CI = 0.902–24.143, P < .001), frailty (OR = 0.006, 95% CI = 0.001–0.051, P < .001). However, gender (OR = 0.544, 95% CI = 0.113–2.612, P = .447), age (OR = 4.178, 95% CI = 0.859–20.317, P = .076), bilirubin (OR = 2.594, 95% CI = 0.586–11.482, P = .209), white blood cells (OR = 0.573, 95% CI = 0.108–3.029, P = .512), venous pressure (OR = 0.559, 95% CI = 0.129–2.429, P = .438), and heparin concentration (OR = 2.660, 95% CI = 0.333–21.264, P = .356) showed no significant correlation with thrombosis formation. Patients with PICC placements have a higher risk of thrombosis, citric acid, blood flow, platelet count and frailty are the main risk factors.
Keywords: peripherally inserted central catheter, risk factors, thrombosis
1. Introduction
Peripherally Inserted Central Catheter (PICC) is a medical device inserted into a patient major blood vessels for the administration of fluids, medications, or blood withdrawal. This catheter is typically inserted into a vein to allow rapid and efficient access to the circulatory system.[1,2] PICC placed through the veins of the human body, can establish a long-term venous route for critically ill patients. Due to its peripheral vein insertion point, broad vascular selectivity, high success rate, minimal trauma, lower infection risk, ease of care, rapid infusion capabilities, and the ability to monitor cardiac function parameters, PICC has become a common intervention for patients requiring long-term intravenous therapy.[3] The peripherally inserted central catheter (PICC) via peripheral vein puncture is a commonly used intervention for patients requiring long-term intravenous therapy in clinical settings. It effectively reduces puncture frequency, alleviates patient discomfort, and facilitates clinical rescue efforts.[4] However, the placement of a PICC is a risky process, and long-term PICC use can lead to catheter-related complications,[5] potentially causing vessel wall damage and thrombus formation.[6]
Sodium citrate is the salt of citric acid and sodium. It is a white crystalline powder that dissolves in water, exhibiting alkaline properties.[7] Sodium citrate is commonly used in the collection and preservation of blood samples as an anticoagulant. Its application as a buffering agent helps maintain the stability of biological specimens, such as in enzyme reactions and PCR. The use of sodium citrate in anticoagulant therapy, particularly in patients with kidney disease, may be a focal point of research. This anticoagulation method is typically employed to prevent the formation of blood clots and may find widespread application in therapeutic processes like dialysis.[8–10] Citric acid is an organic acid, presenting as a colorless crystalline solid that is soluble in water.[11] The application of citric acid in pharmaceuticals includes its use as a buffering agent, pH regulator, and solvent.[12]
A thrombus is a solid clot formed in the blood, typically within blood vessels. These clots may be composed of platelets and clotting proteins aggregated during the coagulation process, sometimes also including red blood cells.[13] Thrombi may occur on the surface of blood vessels (venous thrombi) or within blood vessels (arterial thrombi).[14] Thrombus formation is an adverse reaction that may occur in the veins surrounding the catheter or inside the catheter itself, with the position and length of the catheter potentially influencing the risk of thrombus formation.[15] The occurrence of thrombi causes suffering for patients and presents challenges for subsequent clinical treatment, adversely affecting patient prognosis. Therefore, analyzing factors influencing thrombosis in patients with PICC placements is beneficial for early prevention, reducing the incidence of thrombosis, and improving patient outcomes. This study investigates the incidence of thrombosis in patients with PICC placements in our hospital, analyzes the risk factors for thrombosis in PICC-placed patients, and proposes corresponding preventive measures to contribute evidence-based information to clinical practice.
2. Materials and methods
2.1. General information
A total of 147 patients undergoing peripherally inserted central catheter (PICC) placements were selected as the study population, including 84 males and 63 females. Inclusion criteria: first-time placement and maintenance of a PICC catheter, and completeness of patient medical records. Exclusion criteria: immunodeficiency, preexisting allergies or intolerance before catheter placement, and the use of specific medications.
2.2. Data collection
2.2.1. Clinical data.
A self-designed survey form was used to collect information on the gender (male/female), age (<60/≥60), bilirubin (high/low), white blood cells (high/low), venous pressure (high/low), heparin concentration (high/low), blood flow (high/low), citric acid levels (high/low), platelets(high/low), frailty(Yes/No) of the study subjects.
2.2.2. Thrombosis investigation.
Thrombosis occurrence was recorded for all 147 patients.
2.3. Data analysis
Data analysis was performed using Statistical Package for the Social Sciences statistical software. Statistical Package for the Social Sciences is a professional statistical software widely used for data analysis in social sciences, biomedical research, and business fields. Pearson chi-square test was employed to analyze the relationship between clinical parameters and thrombosis occurrence in PICC-placed patients. Spearman correlation analysis was used to assess the correlation between clinical parameters and thrombosis in PICC-placed patients. Univariate and multivariate logistic regression analyses were conducted to calculate the odds ratios (OR) for each variable, identifying independent risk factors. A significance level of P < .05 was considered statistically significant.
3. Results
3.1. Pearson chi-square analysis of thrombosis occurrence in PICC-placed patients
Pearson chi-square analysis was conducted to examine factors related to thrombosis occurrence in PICC-placed patients. The results showed a significant correlation between citric acid, blood flow, platelets and frailty (P < .001) with thrombus formation. Gender (P = .350), age (P = .448), bilirubin (P = .587), white blood cell count (P = .790), venous pressure (P = .210), and heparin concentration (P = .088) showed no statistical significance in relation to thrombus formation (Table 1).
Table 1.
Factors associated with thrombosis in patients with PICC were analyzed by χ2 test.
| Parameters | PICC induced thrombosis | P | ||
|---|---|---|---|---|
| Yes | No | |||
| Gender | ||||
| Male | 84 | 64 (43.5%) | 20 (13.6%) | .350 |
| Female | 63 | 52 (35.4%) | 11 (7.5%) | |
| Age | ||||
| <60 | 67 | 51 (34.7%) | 16 (10.9%) | .448 |
| ≥60 | 80 | 65 (44.2%) | 15 (10.2%) | |
| Bilirubin | ||||
| High | 79 | 61 (41.5%) | 18 (12.2%) | .587 |
| Low | 68 | 55 (37.4%) | 13 (8.8%) | |
| White blood cells | ||||
| High | 116 | 91 (61.5%) | 25 (17.0%) | .790 |
| Low | 31 | 25 (17.0%) | 6 (4.1%) | |
| Venous pressure | ||||
| High | 57 | 48 (32.7%) | 9 (6.1%) | .210 |
| Low | 90 | 68 (46.3%) | 22 (15.0%) | |
| Heparin concentration | ||||
| High | 16 | 10 (6.8%) | 6 (4.1%) | .088 |
| Low | 131 | 106 (72.1%) | 25 (17.0%) | |
| Citric acid | ||||
| High | 99 | 96 (65.3%) | 3 (2.0%) | <.001* |
| Low | 48 | 20 (13.6%) | 28 (19.0%) | |
| Blood flow | ||||
| High | 53 | 25 (17.0%) | 28 (19.0%) | <.001* |
| Low | 94 | 91 (61.9%) | 3 (2.0%) | |
| Platelets | <.001* | |||
| High | 75 | 46 (31.3%) | 29 (19.7%) | |
| Low | 72 | 70 (47.6%) | 2 (1.4%) | |
| Frailty | <.001* | |||
| Yes | 123 | 115 (78.2%) | 8 (5.4%) | |
| No | 24 | 1 (0.7%) | 23 (15.6%) | |
3.2. Spearman analysis of factors influencing thrombosis in PICC-placed patients
Spearman analysis was further conducted to confirm the factors influencing thrombosis occurrence in PICC-placed patients. Citric acid (ρ = −0.636, P < .001), blood flow (ρ = 0.584, P < .001), platelet count (ρ = 0.440, P < .001), frailty (ρ = −0.809, P < .001) showed a significant correlation with thrombus formation. Gender (ρ = 0.77, P = .3520), age (ρ = 0.063, P = .451), bilirubin (ρ = 0.045, P = .590), white blood cell count (ρ = −0.022, P = .792), venous pressure (ρ = −0.103, P = .213), and heparin concentration (ρ = 0.141, P = .089) showed no statistical significance in relation to thrombus formation (Table 2).
Table 2.
Spearman correlation analysis of factors associated with thrombosis in patients with PICC.
| Parameters | PICC induced thrombosis | |
|---|---|---|
| ρ | P | |
| Gender | 0.77 | .352 |
| Age | 0.063 | .451 |
| Bilirubin | 0.045 | .590 |
| White blood cells | -0.022 | .792 |
| Venous pressure | -0.103 | .213 |
| Heparin concentration | 0.141 | .089 |
| Citric acid | -0.636 | <.001* |
| Blood flow | 0.584 | <.001* |
| Platelets | 0.440 | <.001* |
| Frailty | -0.809 | <.001* |
3.3. Univariate logistic regression analysis of factors influencing thrombosis in PICC-placed patients
Univariate logistic regression analysis was performed to assess the significant impact of variables on the probability of thrombus formation. The results showed that citric acid (OR = 0.022, 95% CI = 0.006–0.08, P < .001), blood flow (OR = 33.973, 95% CI = 9.538–121.005, P < .001), platelet count (OR = 22.065, 95% CI = 5.021–96.970, P < .001), frailty (OR = 0.003, 95% CI = 0.001–0.025, P < .001) were significantly correlated with thrombus formation. Gender (OR = 1.477, 95% CI = 0.650–3.360, P = .352), age (OR = 1.359, 95% CI = 0.614–3.008, P = .448), bilirubin (OR = 1.248, 95% CI = 0.560–2.781, P = .560–2.781), white blood cell count (OR = 0.874, 95% CI = 0.323–2.363, P = .790), venous pressure (OR = 0.580, 95% CI = 0.245–1.368, P = .213), and heparin concentration (OR = 2.544, 95% CI = 0.845–7.657, P = .097) showed no significant correlation with thrombus formation (Table 3).
Table 3.
Univariate logistic regression analysis of factors associated with thrombosis in patients with PICC.
| Parameters | PICC induced thrombosis | |||
|---|---|---|---|---|
| OR | 95% CI | P | ||
| Gender | Male | 1 | .352 | |
| Female | 1.477 | 0.650–3.360 | ||
| Age | <60 | 1 | .448 | |
| ≥60 | 1.359 | 0.614–3.008 | ||
| Bilirubin | High | 1 | .587 | |
| Low | 1.248 | 0.560–2.781 | ||
| White blood cells | High | 1 | .790 | |
| Low | 0.874 | 0.323–2.363 | ||
| Venous pressure | High | 1 | .213 | |
| Low | 0.580 | 0.245–1.368 | ||
| Heparin concentration | High | 1 | .097 | |
| Low | 2.544 | 0.845–7.657 | ||
| Citric acid | High | 1 | <.001* | |
| Low | 0.022 | 0.006–0.081 | ||
| Blood flow | High | 1 | <.001* | |
| Low | 33.973 | 9.538–121.005 | ||
| Platelets | High | 1 | <.001* | |
| Low | 22.065 | 5.021–96.970 | ||
| Frailty | Yes | 1 | <.001* | |
| No | 0.003 | 0.001–0.025 | ||
3.4. Multivariate logistic regression analysis of factors influencing thrombosis in PICC-placed patients
Multivariate logistic regression analysis was conducted to explore the impact of multiple factors on the probability of thrombus formation in PICC-placed patients, considering the interaction effects of various factors. The results of the multivariate logistic regression analysis indicated that citric acid (OR = 0.013, 95% CI = 0.002–0.086, P < .001), blood flow (OR = 35.064, 95% CI = 6.385–192.561, P < .001) platelet count (OR = 4.667, 95% CI = 0.902–24.143, P < .001), frailty (OR = 0.006, 95% CI = 0.001–0.051, P < .001) were significantly correlated with thrombus formation. Gender (OR = 0.544, 95% CI = 0.113–2.612, P = .447), age (OR = 4.178, 95% CI = 0.859–20.317, P = .076), bilirubin (OR = 2.594, 95% CI = 0.586–11.482, P = .209), white blood cell count (OR = 0.573, 95% CI = 0.108–3.029, P = .512), venous pressure (OR = 0.559, 95% CI = 0.129–2.429, P = .438), and heparin concentration (OR = 2.660, 95% CI = 0.333–21.264, P = .356) showed no significant correlation with thrombus formation (Table 4).
Table 4.
Multivariate logistic regression analysis of factors associated with thrombosis in patients with PICC.
| Parameters | PICC induced thrombosis | ||
|---|---|---|---|
| OR | 95% CI | P | |
| Gender | 0.544 | 0.113–2.612 | .447 |
| Age | 4.178 | 0.859–20.317 | .076 |
| Bilirubin | 2.594 | 0.586–11.482 | .209 |
| White blood cells | 0.573 | 0.108–3.029 | .512 |
| Venous pressure | 0.559 | 0.129–2.429 | .438 |
| Heparin concentration | 2.660 | 0.333–21.264 | .356 |
| Citric acid | 0.013 | 0.002–0.086 | <.001* |
| Blood flow | 35.064 | 6.385–192.561 | <.001* |
| Platelets | 4.667 | 0.902–24.143 | <.001* |
| Frailty | 0.006 | 0.001–0.051 | <.001* |
4. Discussion
PICC involves percutaneous puncture of veins, inserting various catheters into blood vessels or the heart, and provides a direct and convenient pathway for measuring various physiological parameters, offering a rapid and effective means of accessing the circulatory system.[16] Peripherally inserted central catheter (PICC) is suitable for patients requiring intravenous nutrition or drug therapy, monitoring central venous pressure in critically ill patients, those with renal failure, and patients with acute circulatory failure. PICCs are also well-suited for patients requiring rapid and large-volume fluid administration.[17] While PICCs are widely used in clinical settings as an adjunctive means of fluid administration, thrombosis is one of the common complications in patients with PICC placement.[18] Thrombus formation can have a significant impact on subsequent patient treatment, emphasizing the importance of early preventive measures in reducing the incidence of thrombosis and improving patient prognosis. The results of this study demonstrate a significant correlation between citric acid and blood flow with thrombus formation in PICC-placed patients.
Thrombus formation is a physiological phenomenon characterized by the solidification of blood formed during the abnormal activation of the coagulation system.[19] Under normal circumstances, blood remains in a liquid state, but when blood vessels are damaged, the coagulation system is activated to prevent excessive blood loss. However, in certain situations, abnormal activation of the coagulation system may occur, leading to thrombus formation, which can be pathological.[20] The process of central venous catheterization, such as that with a peripherally inserted central catheter (PICC), may cause vascular wall damage, stimulating blood clotting and promoting thrombus formation. Foreign bodies or injuries on the surface of the PICC may lead to the aggregation of platelets and coagulation proteins, forming a thrombus. During catheter placement, local inflammatory reactions and tissue damage may occur, causing endothelial cell damage and activating platelets and coagulation factors, thereby increasing the risk of thrombus formation.[21–23] Acid-base balance has a certain impact on the coagulation system, and an imbalance may alter the activity of coagulation factors, affecting the coagulation properties of blood and making it more prone to thrombus formation, especially in cases where the vascular wall is damaged. Changes in acid-base balance may affect the rheological properties of blood, including viscosity and flowability, thereby influencing the risk of thrombus formation. Any obstruction or narrowing in the veins can cause an increase in venous pressure, potentially leading to slowed blood flow and an increased risk of thrombus formation.
Citric acid is an organic acid found in citrus fruits, and its salt, citrate, is commonly used in the food industry, pharmaceuticals, and other fields.[24,25] In medicine and biochemistry, citric acid has properties that act as an anticoagulant, influencing the activity of coagulation factors and slowing down the rate of blood coagulation. This action may be related to antithrombotic effects since coagulation is a crucial step in thrombus formation. The relationship between citric acid and its anticoagulant effect typically involves the regulation of the coagulation process, where it may affect the activity of thrombin, a key enzyme in the coagulation process. By influencing the activity of thrombin, citric acid may help prevent excessive blood clotting. Citric acid may also exert anticoagulant effects by inhibiting the activity of certain coagulation factors, slowing down or preventing coagulation cascade reactions, thus maintaining normal blood flow.[26] Higher citric acid concentrations exhibit better anticoagulant effects and are less likely to form thrombi.
Under normal circumstances, blood maintains a flowing state in blood vessels to ensure the delivery of oxygen, nutrients, and other necessary substances to various parts of the body. Normal blood flow contributes to the stability of the endothelial cells lining the blood vessel walls and is crucial for maintaining the normal functioning of organs and tissues.[27] Rapid blood flow may impact the endothelium, which is a single-cell-thick membrane inside the blood vessel wall that plays a key role in the stability of the blood vessel wall and blood flow.[28] Particularly in areas where blood vessels bend or bifurcate, rapid blood flow may cause blood flow impact, exerting physical pressure and damage to endothelial cells. After endothelial cell damage, the permeability of the blood vessel wall may increase, releasing signaling substances. These factors may attract white blood cells and platelets and may also promote the deposition of lipids on the blood vessel wall.[29] Lipid deposition can form atheromatous plaques, and the inflammatory process inside the plaque may lead to plaque instability. In some cases, components such as platelets and fibrin may aggregate at the plaque site, forming a thrombus.[30] The results of this study indicate that faster blood flow is associated with a higher thrombus formation rate. Rapid blood flow impacts the endothelium, leading to endothelial damage, lipid deposition, and subsequent thrombus formation.
Frailty may lead to a decline in physical activity, and a lack of exercise can result in blood stasis in the vessels. Prolonged periods of immobility, often accompanied by malnutrition, can lead to insufficient nutrients in the blood, affecting the balance of coagulation and anticoagulation mechanisms and increasing the risk of thrombosis.[31] Frailty is commonly associated with chronic diseases such as cardiovascular disorders, diabetes, and chronic inflammation. These underlying conditions themselves may elevate the risk of thrombosis.
5. Limitations and prospects
The sample size in this study is relatively small, which may limit the generalizability of the results. The data are sourced from a single medical center, introducing potential limitations due to the variability in patient populations and management practices across different healthcare facilities. Larger-scale, multicenter studies are warranted to validate the findings of this study and gain a more comprehensive understanding of the characteristics and risk factors among patients in diverse medical settings. Further investigations into the specific mechanisms underlying the relationship between citric acid, blood flow, and thrombosis formation are needed to deepen our understanding of their roles in this process. Based on additional research findings, the development of more accurate and personalized management guidelines for patients with PICC is crucial to minimize the risk of thrombosis.
6. Conclusion
The risk of thrombosis is higher in PICC-placed patients, with citric acid and blood flow identified as major risk factors. Maintaining normal blood flow, reducing vascular damage, and balancing the coagulation system can help prevent thrombus formation. Clinical attention should be heightened, and early prevention measures based on the patient actual condition should be implemented to reduce the risk of thrombosis in PICC-placed patients, ultimately improving patient prognosis.
Author contributions
Conceptualization: Xiaoli Gao.
Data curation: Xiaoli Gao, Xihua Mi, Shiyang Hou, Chunbo Kang.
Formal analysis: Xiaoli Gao, Xihua Mi, Shiyang Hou, Chunbo Kang.
Methodology: Xiaoli Gao, Xihua Mi, Shiyang Hou, Chunbo Kang.
Supervision: Xiaoli Gao.
Software: Xihua Mi.
Writing – original draft: Xiaoli Gao, Shiyang Hou, Chunbo Kang.
Writing – review & editing: Shiyang Hou, Chunbo Kang.
Abbreviations:
- OR
- odds ratios
- PICC
- peripherally inserted central catheter
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
The authors have no funding and conflicts of interest to disclose.
This study was approved by the ethics committee of Beijing Rehabilitation Hospital Affiliated to Capital Medical University.
How to cite this article: Gao X, Mi X, Hou S, Kang C. Analysis of factors related to thrombosis in patients with PICC placements. Medicine 2024;103:5(e37168).
Contributor Information
Xiaoli Gao, Email: gaoxiaoli1121@163.com.
Xihua Mi, Email: 459054538@qq.com.
Shiyang Hou, Email: housy123456@163.com.
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