Adequate evidences have shown the risk of DVT is increased immediately after trauma, and is particularly high in elderly patients with hip fracture due to their poor immune status, prevalent underlying disease and stress response to trauma [15, 16]. In this study, we found that the incidence of preoperative DVT following femoral neck fracture was 6.8%, with 1.7% for proximal and 5.1% for distal DVT. Chronic renal insufficiency, current smoking status, time from injury to DUS and PLT > 220*109/L were identified as independent factors associated with DVT.
Previous studies reported the greatly varied incidence rates of DVT following hip fracture, ranging from 2.6–35.0% [8, 11, 16–19], mainly dependent on the different settings (pre- or postoperation), participating subjects, definition of DVT, methods used to diagnose the DVT, and particularly whether or not use of thromboembolic agents. Shin et al [17] reported the incidence of preoperative DVT of 5.8% in patients with a hip fracture, with a comparable time from injury to diagnose DVT (7.6 verse 6.0 days) using CT scan. In a South Korean prospective study, Cho et al [8] reported the lowest incidence rate of DVT of 2.6% in 152 geriatric patients who were examined by ultrasonography or CT scan, and they attributed this to the earlier admission to hospitalization (90.1% within 3 days after injury). We found the prevalence of DVT following femoral neck fracture in the elderly patients was 6.8%, which was lower than most previous reports but higher than that reported by Shin et al [17] and Cho et al [8]. This figure should be cautiously treated under our pre-setting conditions. First, we only focused on femoral neck fracture, with onset age 5–10 years younger than that of intertrochanteric fracture. Second, we only included the DVTs that occurred before prophylactic or therapeutic thromboembolic agents were prescribed. Third, patients who had well-established risk factors, such as history of VTE, past peripheral vascular disease or use of lower extremity compressive devices after injury, were excluded from this study. Fourth, we excluded isolated thrombi in intramuscular veins (e.g. soleal or gastrocnemius vein), which were estimated to take a certain proportion (40%-77.2%) [16, 19], because of its relatively clinical significance, at least regarding the relationship with preoperative use of therapeutic anticoagulation [19].
Theoretically, admission to hospitalization and performance of operation as early as possible had more advantages in reducing perioperative complications and improving the prognosis. However, in China and some eastern countries, it seems unpractical to carry out that. In this study, the time from injury to admission was 1.4 days and to the definite operation was 5.4 days, both of which potentially increase the risk of preoperative DVT. Compared to patients who had no DVTs, those with DVTs had a significantly longer preoperative stay (7.3 vs 5.0 days) or delay to DUS (6.0 vs 4.1 days). In the multivariate analysis, we re-confirm this finding that each-day delay to DUS detection was associated with 21% increased risk of DVT. Review of the literature showed the similar conclusion [8, 15, 17]. These findings highlighted the importance of early detection of DVTs in patients with delay to admission or operation, and future study is necessitated to focus on determining the optimal cut-off point for delay to detection, above which the risk of DVT is significantly increased. We suggest that, consistent with our policy, patients admitted 3 days later after injury should be treated as a high-risk group, and DUS scan is priorly performed.
Although all of the DVTs were asymptomatic, the risk of proximal migration of thrombi even to form PE should not be neglected; and such asymptomatic DVTs should be paid more attention, because they cannot provide suggestive significance [20]. We also found a relatively high proportion of DVTs in the uninjured extremity that was 23.9%, which included 9.0% in the bilateral and 14.9% in the non-fractured extremity. This finding was conflicting with a previous report that DVTs were located solely in the injured extremity [17], but was lower than that of another report that 38.9% of DVTs were located in bilateral or only uninjured extremity. Weiss et al [21] reviewed 6674 trauma patients and found 14% of the DVTs were located in the uninjured extremity. The authors believed it was not adequate in screening the patients for DUS, especially for those with external fixation devices. The detailed mechanism for DVT occurring in uninjured extremity remains unclear, but at least partly related to reduced systemic hemodynamics or blood hypercoagulable state in the elderly patients [22]. For patients with hip fracture, particularly those carrying one or multiple risk factors, more emphasis should be placed for thrombus detection in the uninjured extremity.
In the present study, we identified four independent risk factors for preoperative DVT in elderly hip fracture patients: the aforementioned delay to DUS detection, chronic renal insufficiency, current smoking status and the platelet count > 220*109/L. Conversely, age, gender, BMI or chronic comorbidities except for renal insufficiency were not significant factors, differing from those in previous reports [7, 8, 15–17]. The possible explanation might be that we excluded the well-established risk factors, such as past VTE episode, peripheral vascular disease, recent anticoagulant therapy for other reasons and use of lower extremity compressive devices, which were demonstrated to be major risk factors and highly related to DVT occurrence. Therefore, supposed that any of them is included, the statistical result is predictably altered. Additionally, higher level of AST or ALT was tested to be significant factors for DVT in the univariate analysis, but not in the multivariate analysis after adjustment for multiple variables. AST or ALT was important biomarkers indexes, most often indicating the degree of damage of hepatocyte; but in this study, they are more likely reflecting the severity of skeletal muscle cell around the fracture site. Therefore, it is possible that, relative to systemic disease (renal insufficiency), bone trauma or related hypercoagulability, damage of skeletal muscle after low-energy-impact femoral neck fracture exerts inadequate effect on development of DVT.
Current smoking status maybe a modifiable factor, but it could provide little effect in prevention of preoperative DVT, because the response to trauma and especially the blood coagulation remain at the dynamic peak during the preoperative waiting timeframe (3-7days of injury) [22]. Chronic renal insufficiency itself, its related complications or the treatment agents (hormonal medications, immunosuppressive agents) all might exhibit the adverse effect on DVT occurrence [23]. Furthermore, in patients with renal insufficiency the pharmacokinetics and pharmacodynamics were affected [24]. Future study is necessary to elucidate exactly which mechanism acts or their effect magnitude in DVT formation. The increased platelet count might be the result of innate immune responses, together with activated coagulation and complement system, which resulted in a stemming hemorrhage and protected against bacteria invasion [22], and imbalanced innate immune response likely causes complementopathy or coagulopathy, resulting in DVT formation. Although most not modifiable, these identified risk factors should be kept in mind when assessing the risk of DVT and thereby the stratifying the patients.
Despite a large sample and multivariate potential factors included for adjustment, this study suffered from several limitations. First, the inherent limitation of the this study was the retrospective design, which may affect the accuracy and precision in data collection and introduce the unavoidable selection bias. Second, as with every other multivariate analysis, we were unable to include all confounding factors, therefore the residual confounding remained. Some potential factors, such as the duration of immobolization of injured extremity and the use of glucocorticoids, were not captured. Third, the relationship between variables and DVT identified in this study was correlative rather than causative, which was decided by the cross-sectional nature of this study. Therefore, these results should be interpreted with caution. Fourth, this is a two-center study, and both participating hospitals are teritiary referral hospitals, which might limit the ablity to generalize these findings to elsewhere.
In conclusion, this study demonstrated that the incidence of preoperative DVT in elderly femoral neck fracture patients was 6.8%. In patients with DVT, 23.9% had thrombi in the uninjured extremity, highlighting the necessity of adequate screening for DVT. Chronic renal insufficiency, current smoking status, delay to DUS and PLT > 220*109/L were identified as independent factors associated with DVT. These data are helpful to understand the epidemiologic characteristics of DVT following hip fracture, and should be kept in mind when in individualized risk of DVT and accordingly the risk stratification.