Hip fractures significantly impact the health and quality of life in the elderly. The prevalence of CKD is rising among this demographic. As kidney function declines, there's an observed increase in fracture rates in older individuals, especially following falls[2]. ROD, a major public health concern in aging populations, further complicates the management of hip fractures in CKD patients. This condition not only intensifies the severity of fractures but also challenges post-fracture recovery, significantly affecting overall patient health[3]. Elderly patients with hip fractures and CKD often experience severe pain and reduced mobility, leading to prolonged recovery periods. The combination of these conditions, particularly decreased mobility and the systemic effects of CKD, not only impairs overall health but also markedly elevates the risk of DVT as an additional complication. DVT is not only a frequent complication in older individuals with hip fractures, but it's also one of the most common complications in hospitalized patients, leading to disability and even death in severe cases[11]. Despite improvements in medical diagnostics reducing DVT rates, it remains a concern. Recent studies show 19.5% to 32% of hip fracture patients have DVT before surgery[12]. Our study found a 34.4% preoperative DVT rate in elderly hip fracture patients, a significant figure. Key reasons include the older age group's inherent risk, the hip's vulnerability to DVT, and the added risk from coexisting CKD, which may increase DVT likelihood.[13]. Although there are existing studies exploring the risk factors of DVT preoperatively in elderly patients with hip fractures, and some have even identified CKD as a risk factor for DVT in these patients, research specifically targeting the population of elderly hip fracture patients who already have CKD remains limited[7, 13]. There is still a research gap in understanding the risk factors of DVT in this particular demographic.
The prevalence of CKD is steadily increasing in the general population, and it frequently coexists as a comorbidity in patients who suffer from hip fractures[14]. In previous studies, it was established that patients with CKD faced a heightened risk of preoperative DVT occurrence compared to those with normal kidney function[15-16]. After total joint arthroplasty, Li et al. observed that CKD can elevate the risk of both total and symptomatic DVT. Specifically, they reported a relative risk of 2.68 for DVT in patients with stage 3/4 CKD. Besides, in their report, Lutz et al. noted that the risk of thromboembolic disease was 2.5 times higher in individuals with mild renal dysfunction and 5.5 times higher in those with severe renal dysfunction when compared to patients with normal kidney function. In patients with CKD, the hemostatic system undergoes various alterations. This includes changes in platelet function and levels of coagulation factors, leading to a hypercoagulable state and thereby increasing the risk of thrombus formation. Moreover, CKD often coexists with other conditions such as hypertension and diabetes, which are themselves risk factors for thrombosis[17]. Despite the established links between CKD and an increased risk of DVT in such patients, there remains a significant gap in the literature specifically addressing the cumulative risk factors for DVT in elderly patients with hip fractures and CKD. This study aims to fill this critical gap by systematically evaluating the various preoperative risk factors that contribute to the incidence of lower limb DVT in this specific patient population. Understanding these unique risk factors is essential for developing targeted preventive strategies and improving patient outcomes in this vulnerable group.
In our current study, we observed that out of 180 participants, 62 individuals, or 34.4%, experienced DVT. Our logistic regression analysis indicated that older age, higher WBC, and elevated D-dimer levels were associated with an increased risk of DVT. Specifically, the cut-off values for predicting DVT, as determined by ROC curve analysis, were found to be 73 years for age, 9.5 x 10^9/μL for WBC count, and 3.3 ng/mL for D-dimer levels.
D-dimer is a blood test used to assess the risk of DVT. It is a product of fibrin breakdown in blood clots. Thrombin cleaves fibrinogen into fibrin monomers, which then form fibrin polymers. Factor XIIIa cross-links D domains, and plasmin breaks down fibrin, releasing D-dimer[18]. In DVT diagnosis, D-dimer level measurement is key. Normal D-dimer often excludes DVT, but high levels aren't specific and may be caused by other factors like infections or trauma. Therefore, high D-dimer necessitates further evaluation with clinical symptoms and additional diagnostic methods[19]. This research revealed that in patients who suffer from both elderly hip fractures and CKD, those diagnosed with DVT exhibit significantly higher levels of D-dimer compared to those not afflicted with DVT. The establishment of a threshold level at 3.3 ng/mL for D-dimer is a key finding of this study. Exceeding this threshold suggests a heightened risk of DVT in such patients, thereby necessitating closer monitoring and potentially more aggressive preventative strategies for those whose D-dimer levels surpass this critical value. A number of previous studies have established a significant correlation between elevated D-dimer levels and the occurrence of preoperative DVT in patients with hip fractures[20-22]. Furthermore, studies have also revealed a relationship between heightened D-dimer levels and an increased risk of DVT in individuals afflicted with CKD, emphasizing the broader relevance of D-dimer as an indicator in diverse health conditions[23]. The findings from these studies are consistent with the results of our own research. This might be due to elevated levels of D-dimer, a fibrin degradation product indicative of increased fibrinolytic activity typically spurred by clot formation, serving as a predictive biomarker for DVT and reflecting thrombotic processes within the body. Consequently, in clinical practice, heightened vigilance for the potential occurrence of DVT is imperative in these patients exhibiting raised D-dimer levels.
Advanced age is commonly considered a significant risk factor for the occurrence of DVT[24-25]. Barco et al. conducted a comprehensive study involving 24,911 patients who were objectively diagnosed with a first episode of lower-limb DVT, demonstrating that the risk of DVT depends on a combination of factors including age, gender, and other VTE risk factors[24]. Another study by Stein et al. emphasized the impact of an aging population on the rate ratios for the diagnosis of DVT. This research indicated that over a span of 21 years, the rate of DVT diagnosis increased exponentially[26]. These findings underscore the significant role that age plays in the incidence of DVT, which is consistent with our research. In addition to this, our study also found that when the age of the patients included in this study exceeded 73 years, the risk of developing DVT significantly increased. As individuals age, a combination of factors comes into play, including the stiffening of blood vessels, potentially leading to a reduction in blood flow, especially in the veins of the lower limbs. This diminished flow rate can result in prolonged blood stagnation within the veins, consequently increasing the likelihood of clot formation. Furthermore, the aging process can lead to functional impairment in vascular endothelial cells and alterations in the mechanisms governing blood coagulation, further contributing to the heightened risk of clot formation. Additionally, age-related changes in blood components, such as an elevation in fibrinogen levels, can enhance susceptibility to clot formation, thereby elevating the overall risk of developing DVT. Therefore, clinical management should emphasize age-specific risk assessment and tailored preventive measures to address this elevated risk effectively.
Our study found that among the patients included in this research, the DVT group exhibited higher WBC levels compared to the non-DVT group, which is consistent with the findings of many other studies. In Hou et al.'s brief review, it is demonstrated that the contribution of biomarkers, including WBC, to the diagnosis and guidance of therapy for DVT is significant[27]. Additionally, Passamonti et al. conducted an evaluation of the impact of the increase in WBC over time on the risk of thrombosis. Their study revealed that patients who experienced an increase in WBC within the first two years after diagnosis had a higher risk of thrombosis compared to patients with stable WBC[28]. Furthermore, in Chen et al.'s prospective cross-sectional study, higher WBC and LDH levels may be associated with thrombosis, as they were significantly elevated in the VTE group compared to the non-VTE group[29]. Stimulation by various agents can activate blood leukocytes, leading to the development of potent procoagulant activity that can trigger the extrinsic pathway of blood clot formation. Furthermore, it has been established that early events in the initiation of DVT involve leukocyte adhesion and transmigration[30-31]. It's important to note that an elevated WBC level is a non-specific indicator and cannot be used for the direct diagnosis of DVT. Further research is needed to confirm the impact of WBC on the formation of DVT.
While this study presents several innovative findings, it is essential to acknowledge certain limitations. Firstly, it was conducted at a single center, indicating the need for a multicenter clinical study with a larger sample size. Secondly, given its retrospective nature, this study had limited access to certain potential variables associated with DVT risks, such as prior surgical history. Additionally, like any multivariate analysis, we could not account for all confounding factors, leaving residual confounding as a potential issue. Lastly, Our study involved multiple variables to assess DVT risk, using binary logistic regression. However, we did not specifically adjust for the multiplicity of over 40 covariates, which could raise the chance of finding significant results by chance. Future research should consider methods to control for this issue to ensure more reliable conclusions.
In conclusion, our study identified age, D-dimer, and WBC levels as independent predictors of DVT through logistic regression analysis. We determined the optimal cutoff values for these variables to be 73 years for age, 9.5 x 10^9/μL for WBC, and 3.3 ng/mL for D-dimer. These findings offer a personalized assessment of DVT risk in elderly patients with concurrent hip fractures and CKD, enabling early targeted interventions.