Multisystem trauma patients have a significant risk of developing deep venous thrombosis (DVT). Without prophylaxis, the rates of DVT may exceed 50 % in high-risk patients. After major trauma the risk of pulmonary embolism ranges from 0.4 to 50 % [46]. In trauma patients there is level I evidence supporting DVT prophylaxis with LMWH or LDUH as soon as resuscitation is complete and the bleeding risk acceptable [47]. The challenge in clinical decision making centers around the timing of initiation of prophylaxis based on assessment of bleeding risk. Reasonable concern exists regarding the appropriate time to begin prophylaxis, specifically in patients suffering from high-risk injuries including intracranial hemorrhage (ICH), blunt solid organ injury, and spinal cord injury. Mechanical prophylaxis, in the form of intermittent compression pumps, is recommended instead of or as an adjunct to pharmacologic prophylaxis, depending on the bleeding risk and the VTE risk for the given patient [48].

Few studies exist which evaluate the failure of nonoperative management (NOM) of blunt solid organ injuries in patients treated with LMWH. Alejandro et al. found no change in the failure of NOM and no increase in blood transfusion requirements for patients with blunt splenic trauma who received early (≤48 h) and late (>48 h) prophylaxis [49]. Eberle et al. studied failure of NOM in patients with splenic, liver, and kidney injuries treated with early and late administration of LMWH. They found no differences in the failure rates or PE/DVT rates between early (≤3 days) and late (>3 days) administration of LMWH. A smaller study of 22 patients with solid organ injury receiving LMWH within the first 24 h found that 0 of 10 patients with liver injures, and 2 of 12 patients with splenic injuries receiving LMWH failed NOM [50]. Limitations of this study, and others assessing the management of blunt trauma, include failure to document specific risks for failure of NOM including contrast extravasation, pseudoaneurysm, or large hemoperitoneum. Further studies are necessary to assess organ-specific failure rates. Studies are ongoing, though seem to indicate that prophylactic LMWH is safely administered between 48 and 72 h, in patients who have demonstrated cessation of acute bleeding.

Perhaps more worrisome than solid organ bleeding is that of worsening intracranial hemorrhage in patients with traumatic brain injury. Patients with brain injury are especially at risk for venous thromboembolism (VTE) compared to the general trauma population [51]. Reported rates of progression of hemorrhage after LMWH range from 1.46 to 14.5 %, depending on exclusion criteria [52]. Although Kwiatt et al. present a higher progression rate than other studies secondary to broad inclusion criteria, they also concluded that the timing for initiation of LMWH did not alter the rebleed rate, when comparing LMWH administered at ≤48 h, >48 h, and after 7 days [52]. Although not standardized, the majority of studies assessing the timing of initiation of VTE prophylaxis in patients with intracranial hemorrhage suggest documentation of stable head CT, which are monitored every 24 h after admission until stability is documented. These decisions are often made in conjunction with neurosurgical specialists and tend to start 24 h after documentation of stable CT head findings [53]. Following a similar protocol Dudley et al. demonstrated a low incidence of VTE (7.3 %), and 0.4 % symptomatic rebleed rate, when LMWH was started 48–72 h after initial trauma, provided stability of intracranial hemorrhage was documented [54]. Further studies are needed to evaluate the rates of progression, as well as rates of VTE in this population to better determine the safety and efficacy.

Determining the appropriate timing for initiation of chemoprophylaxis for VTE often requires a multidisciplinary evaluation in the polytrauma patient. Clinicians should take into consideration the patients’ clinical risk factors relative to specific organ injured and presence of risk factors for bleeding. This should be weighed against the known relative increase in VTE in the trauma population and associated morbidity and mortality.

Cardiovascular disease, including acute coronary syndrome, remains the leading cause of death in industrialized countries, despite evolving therapeutic targets [55]. Platelets serve as a major therapeutic target, as the use of antiplatelet therapy allows for the inhibition of platelet aggregation [56]. Research is ongoing into the effect of such irreversible platelet inhibitors, without adequate reversal agents in the trauma population. Within the first 24 h after injury, posttraumatic intracranial hemorrhage increased in more than half of patients with traumatic brain injuries. Exacerbation secondary to inhibition of platelet activity is most likely to occur during this time period, and withdrawal of antiplatelet agents must be considered [57]. However, cessation of medication will not have an immediate impact on bleeding as the effect of the antiplatelet agents is not rapidly reversed. Cessation of antiplatelet therapy is also not without risk. After coronary stent placement, the risk of thrombosis is increased 30-fold if clopidogrel is discontinued within the first 30 days [58]. Stopping clopidogrel within the first 6 months of stent placement is an independent determinant of stent thrombosis [59]. At the same time, it is recognized that there is an increased risk of bleeding in patients on antiplatelet therapy. The risk of stent thrombosis must be carefully weighed against the risk of worsening intracranial hemorrhage. Bridging therapy with heparin was shown to be ineffective in reducing cardiac events after cessation of antiplatelet therapy [60]. In a review of 1,236 patients hospitalized for acute coronary syndrome, 4.1 % of cases were secondary to withdrawal of antiplatelet therapy, with a mean delay of 10 ± 1.9 days [61]. The rate of delayed intracranial hemorrhage is found in approximately 1–1.4 % of patients on antiplatelet therapy [62].

Wong et al. performed a retrospective case-controlled study comparing patients with traumatic brain injury who were receiving clopidogrel, aspirin, or warfarin compared to a control group. The results demonstrated a 14.7-fold increase in mortality in patients on clopidogrel [63]. Although the studies assessing morbidity and mortality are limited, primarily related to small sample size and retrospective nature, concern exists that patients on antiplatelet therapy are at a higher risk of mortality and morbidity following traumatic brain injury. Subsequent studies may also benefit from measurement of platelet function, rather than absolute presence of absence of medication as it related to bleeding risk. Nonetheless, extreme caution and liberal use of CT imaging should be employed in patients treated with antiplatelet therapy. No evidence exists at this time regarding the timing for resuming antiplatelet therapy in patients with multisystem trauma. Care should be taken in patients with closed-space injuries, where delay in recognition of delayed bleed can be catastrophic. This risk of surgical or traumatic bleeding must closely be balanced with the risk of stent thrombosis. Patient history, including timing of stent placement, type of stent, and reason for initiation of antiplatelet therapy, although often unavailable in the acute traumatic setting, is of significant value in this decision-making process. Further studies are ongoing in this evolving arena.