Risk factors for DVT in patients after acute stroke varied in different clinical researches. The typical factors included older age, medical history of DVT, increased body mass index(BMI), malignant tumor, pulmonary infection, increased level of some laboratory variables(9–13). In our study, pulmonary infection and increased muscle tone were identified as independent factors associated with in-hospital incidence of DVT in patients after acute stroke.
In our multiple logistic regression model, patients with pulmonary infection experienced an increased risk of DVT. A higher risky relevance of pulmonary infection with DVT was also demonstrated in other researches(14, 15). A research on the psychiatric inpatients revealed that the average in-hospital incidence of DVT was up to 10%, while the DVT risk in the group with pulmonary infection was significantly increased(16). In addition, a clinical case review showed that patients died secondary to staphylococcal community-acquired pneumonia had higher risk of DVT(14). Research clarified that some pathogens, especially bacteria had surface proteins and exotoxins leading to damaging endothelial cells, activating coagulation pathway and forming micro-thrombosis and DVT(17).
Immobility was a major risk factor for DVT in neurological diseases(4, 18).An observational research analyzed 542 stroke patients with DVT and found that DVT occurred in 73% of patients with weaker muscle strength while only 11% of patients with stronger were diagnosed with DVT(19). Our study showed that there was no difference in muscle strength between DVT-group and non-DVT group. The difference could be partly explained by the different samples and subtypes of the patients. In our study, ischemic stroke accounted for 77.2%,while others were hemorrhagic stroke patients. Some researches on different subtypes of stroke clarified that patients with hemorrhagic stroke had significantly higher risk of DVT due to lower rate of antithrombotic management and more severe neurological disability in patients with hemorrhagic stroke compared with patients with ischemic stroke(20).
Although muscle strength was not linked with DVT in our study, muscle tone was identified as a negative relevant factor with the incidence of DVT and patients with increased muscle tone were less likely to developing DVT. Among patients with stroke, increased muscle tone and muscle spasms of lower extremities usually develop gradually within several months(21),which theoretically resulted in emptying of veins in lower extremities by enhancing the capability of the calf muscle pump. Previous studies observed some vascular changes with a generalized atrophy of the arteries and decreased blood flow in the paralyzed lower extremities, which could adjust the lower oxygen supply to match the decreased activity of the paralyzed muscles(22). With blood stasis reduced in extremities, the risk of DVT was decreased. Moreover, clinical observations suggested that increased muscle tone was a protective factor against DVT in neurological disorders(19, 23). Increased muscle tone in stroke patients at the initial stage indicated the gradual emergence of active exercise, which could lead to increase the cerebral blood flow in the injured site and promote the recovery of motor function and intelligence, resulting in blood flow velocity of hemiplegic extremities increased and the occurrence of DVT decreased(24, 25).
Interestingly, we compared the laboratory variables in different times and found that the level of D-dimer was significantly higher when DVT detected than that on admission, which suggested that dynamically testing D-dimer could be a predictive method for DVT. D-dimer as a sensitive marker for thrombus formation ,was an indicator for predicting DVT in different disorders(12, 15, 26). In the current studies, D-dimer demonstrated a sensitivity of 85%-95% and a specificity of 25%-50% for DVT(27, 28). Baseline levels of D-dimer varied in different age due to variability in the inflammatory and immune response dependent on age(29)and the elders were more likely to suffering from stroke, which could explain why the specificity of a standard D-dimer cut-off at 500ug/L for DVT prediction in elderly patients with stroke was comparatively low. A systemic review indicated that utility of an age-adjusted D-dimer cut-off (patient’s age*10)ug/L) for elderly patients for ruling out DVT was recommended(30). The average levels of D-dimer when DVT detected were about 4-fold as the levels of that on admission in our study, which suggested that the gradually increased level of d-dimer was associated with DVT.
The strength of this study is that it concludes that pulmonary infection as a risk factor and increased muscle tone as a protector factor for DVT, which enables physicians to take early managements to reduce the incidence of DVT such as paying more attention to the patients with pulmonary infection and taking more effective therapies to improve muscle tone of patients. In addition, the significant change in level of D-dimer could be a warning for DVT occurrence so that dynamically monitoring the level of D-dimer is of importance in patients after stroke.
There were some limitations. First, due to relatively small samples, we didn’t divide the cohort into several subtypes groups such as ischemic stroke, hemorrhagic stroke and traumatic brain injury. Further study with larger samples and more subtypes needs to be explored. Second, because it was a retrospective research, the time when DVT detected by CDUS might be delayed compared to the actual time when DVT developed. Further prospective research should be performed to validate our conclusions. Moreover, bias couldn’t be avoided. Caution should be needed while our findings is interpreted in other multiple-center cohort studies. Third, although venography was the gold standard for diagnosing DVT, serial compression ultrasonography as the reference test was applied in our study for detecting DVT owing to its non-invasiveness. It might be not as perfectly accurate as venography.