This study demonstrates the differences in number of VTE events and the associated complications with thromboprophylaxis between two level I trauma populations with different treatment protocols in two different countries. Although the number of patients who received thromboprophylaxis within 48 h after admission was significantly higher at UMCU, no significant difference was demonstrated in either the number of VTEs or hemorrhagic complications between the two populations. However, a noticeable trend with greater than twofold odds ratio was present with more delayed initiation of treatment.
There are still many uncertainties regarding the use of thromboprophylaxis in trauma patients, especially in severe trauma patients. On the one hand, therapy is indicated because it is demonstrated to decrease the risk of VTE, but on the other hand, it is contraindicated because of the potential hemorrhagic risks in these patients . No clear indications exist concerning dosage, timing, frequency, and duration of prophylaxis. This allows variation in the thromboprophylaxis treatment protocols across similar leveled trauma centers, especially in patients who are frequently debated, those with TBI.
Several authors have argued caution in the use of thromboprophylaxis in trauma patients, because the bleeding risk might outweigh the risk of VTE, even more so in patients with TBI [11, 19]. Yet, other studies in addition to ours have demonstrated that the use of LMWH is safe in the majority of trauma patients, including patients with TBI after primary hemostasis has been accomplished or a delayed scan demonstrates a status quo antum . Although in our study, significantly less patients with isolated TBI were treated with chemical prophylaxis, the bleeding rate was not significantly higher in patients with isolated TBI while under chemical thromboprophylaxis (Table 2). This suggests that the treatment is safe in the majority of these patients. Furthermore, in UMCU, the majority of the patients (75%) with a VTE also had isolated TBI. This differs from HMC, where only 8% of the patients with VTE had isolated TBI. We have no clear explanation for this; it could be related to the rare incidence of the events in both populations. However, these results suggest that patients with TBI might be more likely to develop VTEs, which is in line with the previous literature [3, 23,24,25] and might, therefore, benefit from early initiation of VTE prophylaxis.
Previous studies showed that the time of initiation of the chemical prophylaxis in patients is essential [26, 27]; a delay of > 4 days causes a threefold greater risk of VTE in major trauma patients . In our study, while significantly more patients received prophylaxis within 48 h after admission at UMCU, the VTE rate did not significantly differ from the HMC population. This supports that the initiation time in the early stages is not a significant factor in the development of VTEs in these trauma populations or our study was underpowered to detect the difference. On the other hand, in accordance with other recent studies [28, 29], it appears safe to start chemical prophylaxis even at this early stage, even in patients with TBI [30, 31]. Furthermore, the timing of the initiation in the patients with VTE was significantly longer at UMCU. We should be careful to draw firm conclusions from this because the number of events, especially in UMCU, is very low and one outlier influences the mean drastically.
Interestingly, the vast majority of the patients who developed a VTE were adequately treated with chemical prophylaxis, 75% in UMCU and 81% in HMC. This suggests that patients developing a VTE are at such a high risk that even treatment with chemical prophylaxis is not sufficient or unable to be started early enough post-injury to demonstrate an effect.
Although this study demonstrates a low incidence of VTE in both level 1 centers with a well-established VTE prophylaxis protocol, these data question the validity of using VTE as a quality indicator, as proposed in the current literature [32,33,34], as most patients who developed a VTE were on adequate prophylaxis.
It is stated in the literature that trauma patients are at a high risk for the development of VTEs, in particular for DVTs. The incidence of DVT in the literature varies greatly between 11.8 and 65% [3, 35,36,37]. The incidence of PE is estimated between 1.5 and 20% [37,38,39,40]. A major cause of differences between these percentages and the percentages in our two populations in this study is thought to be due to differences in the manner of detection. In our study, no DVT screening was performed. The listed studies used pulmonary angiography, venography, and plethysmography in all patients [3, 35], while the outcome in our study was based on clinically detected and relevant VTEs. This has become a more commonly accepted approach. Our incidence rate corresponds with the German trauma population, which showed an incidence of 1.8% clinically relevant VTEs after severe trauma .
None of the patients in UMCU were treated with a VCF, compared to 117 (12%) patients in HMC. This is likely a consequence of the difference in treatment protocols. HMC maintains a protocol with more contraindications for chemical prophylaxis treatment and is, therefore, more likely to start with a different therapy in patients with a high risk of VTE. Still, 9 patients with a VCF developed a VTE compared to 108 patients with a VCF who did not develop a VTE. The high percentage of patients with a VCF and VTE development from the total number of patients with VTE (24%) could be due to the very high risk of VTE that already exists in these patients. Alternatively, it has been suggested that DVT and PE are two different entities in the trauma population as PE can develop without the presence of a DVT in the same patient [29, 41]. This is in contrast to the normal sequence seen in other patients where the PE is frequently associated with a standing DVT. The present study supports this as four patients developed a PE in the presence of a VCF. Therefore, the usefulness of a VCF becomes more debatable in trauma patients.
The results of this study might be limited for several reasons. One of the main reasons is the retrospective design of the study. The number of the events in our study was very low and could make it difficult to show a significant difference in the outcome in these populations. Furthermore, because of its retrospective design, the low incidence of VTE cannot directly be attributed to prophylaxis given. This study mainly focuses on chemical prophylaxis; still a fair number of patients were also treated with mechanical prophylaxis, such as compression devices. Unfortunately, these data were not sufficiently recorded and could not be included in this study. Furthermore, the potential impact of various different anticoagulants was not taken into account in this study.
According to the literature, multiple injuries increase the risk of VTE up to 60%. The results in the present study demonstrate that with a VTE prevention protocol in place, the incidence is reduced below 4%. No significant difference was demonstrated in the development of VTEs between two trauma populations treated in a similar level trauma center with different thromboprophylaxis treatment protocols with regard to the timing of initiation. Early initiation therapy appears safe, with respect to ongoing bleeding even in patients with TBI. Moreover, in concordance with recent reports, most VTEs developed under adequate prophylaxis, making VTEs not an adequate indicator for quality control measurements.