Authors: Jovana Momic, Laura Allen, Kelly Vogt, Daniele Wiseman, Bradley Moffat
Categories: Research
Source: Canadian Journal of Surgery
Doi: 10.1503/cjs.007124
Authors: Jovana Momic, Laura Allen, Kelly Vogt, Daniele Wiseman, Bradley Moffat
Traditionally, pulmonary thrombi following trauma were believed to occur secondary to embolization from deep vein thrombosis (DVT). However, computed tomography (CT) during initial trauma resuscitation has identified pulmonary thrombi, which raises the possibility of primary pulmonary thrombosis as a distinct clinical entity. This study identifies cases of pulmonary thrombosis identified immediately after trauma and describes associated injury patterns and treatments.
We conducted a retrospective review of the trauma and radiology registries at a Canadian level-1 trauma centre from January 2010 to April 2021. A chart review identified patients with pulmonary thrombi on initial CT. We extracted and analyzed patient demographic characteristics, mechanism of injury, summary of injuries, treatments, and outcomes.
A total of 24 patients (15 male, 9 female; mean age 54, standard deviation [SD] 18.6, yr) met the inclusion criteria. All patients experienced blunt trauma (mean Injury Severity Score 23.5, SD 9.5). Rib fractures (n = 11, 46%), pneumohemothorax (n = 7, 29%), and spinal fractures (n = 8, 33%) were common. Four patients had a concomitant DVT, and 10 patients did not undergo assessment for DVT; 10 patients were identified as having primary pulmonary thrombosis. Treatment was started in 18 patients (75%): 9 patients were treated with dalteparin, 2 with dalteparin and inferior vena cava (IVC) filter, 6 with IVC filter in isolation, and 1 with IVC filter and intravenous heparin. Five patients (21%) died from their injuries.
Early pulmonary thrombosis was associated with chest injuries, often without DVT. These findings challenge the traditionally held view of DVT embolization as the cause of pulmonary thrombosis immediately following trauma and suggest that primary pulmonary thrombosis is a distinct clinical entity.
Severe injury and multisystem trauma can lead to trauma-induced coagulopathy, resulting in increased risks of both bleeding and maladaptive hypercoagulopathy, or clotting.1 Early insights into the incidence and mortality of venous thromboembolism (VTE) after trauma come from autopsy studies conducted in the 1930s–1960s, which showed an incidence of deep vein thrombosis (DVT) of 65% and an incidence of pulmonary thrombosis of 20.3%, resulting in death in 3.8%–15% of studied patients.2,3 Increasing use of computed tomography (CT) cross-sectional imaging has resulted in increased detection of pulmonary thrombosis, with current estimates of incidence ranging from less than 1% to 24%.4–6
Pulmonary thrombosis (the presence of blood clots within the pulmonary vasculature) following trauma, though occurring infrequently, substantially contributes to morbidity and mortality.4,7–9 Pulmonary thrombosis is associated with longer hospital stays; longer intensive care unit (ICU) stays and more ventilator days; higher rates of transfer to other health care or rehabilitation facilities; increased rates of complications, such as pneumonia, osteomyelitis, wound infection, sepsis, and multi-organ failure; and increased mortality.10,11
Trauma patients are at high risk for venous thromboembolism; trauma often causes direct damage to blood vessels, venous stasis as a result of paralysis or prolonged immobilization, and hypercoagulable states following severe trauma.3 Acute inflammation, which occurs in response to trauma or damage to blood vessels and results in the release of pro-inflammatory cytokines and the creation of a pro-coagulant state, is also thought to contribute to thrombosis and the risk of DVT and pulmonary embolism.6 Many trauma patients also sustain injuries known to be associated with increased risks of venous thromboembolism, such as lower-extremity fractures, head injuries, pelvic fractures, spinal cord injury with paralysis, or venous injury, which puts them at high risk for VTE.8
Traditionally, pulmonary thrombosis following trauma was believed to occur several days to weeks after trauma secondary to formation of DVTs in the lower extremities that subsequently embolize to the pulmonary circulation (pulmonary embolism). However, recent data challenge this view, with case reports of pulmonary thrombi detected as early as 2 hours after injury in the absence of DVT,12 and subsequent larger studies identifying patients with pulmonary thrombosis following trauma at the time of admission.9,13–18 Successive studies have called into question whether pulmonary thrombi occur primarily in the lungs in the absence of DVT, thus representing a novel clinical entity distinct from pulmonary embolization (the presence of clots in the pulmonary arteries that originate from clots within the deep veins of the lower extremities and travel to the lungs).13–18
Questions remain about the timing of clot formation; the clinical significance of asymptomatic, potentially incidentally found pulmonary thrombi occurring immediately after injury; screening and treatment for pulmonary thrombosis, especially given risks of anticoagulation in injured patients; and whether traditionally used preventive modalities, such as inferior vena cava (IVC) filters, are useful in combatting this problem.9,13–18 More research is needed to better understand the pathophysiology and clinical impact of early pulmonary thrombosis after trauma to guide patient care. This study is a retrospective cohort study aimed at identifying the role and characteristics of pulmonary thrombosis identified immediately following trauma to provide insights into patient characteristics, injury mechanisms and patterns, treatments, and outcomes for this distinct clinical entity.
We conducted a retrospective review of the prospectively maintained trauma and radiology registries at a Canadian level-1 trauma centre from Jan. 1, 2010, to Apr. 30, 2021. We sought to identify and describe patient characteristics and injury patterns resulting in pulmonary thrombosis immediately following trauma (within 24 hours from injury, detected on the first CT scan performed during trauma workup). See Box 1 for definitions.
We included patients aged 18 years and older who had sustained major trauma and underwent CT of the chest (using a 64-slice CT scanner following intravenous injection of 100 mL of Omnipaque 350) as part of their initial trauma workup, which resulted in a diagnosis of pulmonary embolism or pulmonary thrombosis. Some patients also underwent investigation of possible concomitant DVT via bilateral proximal leg Doppler ultrasonography, at the discretion of the treating physician. Patients younger than 18 years were excluded from the study.
We queried the radiology registry for scans that made reference to pulmonary emboli or thrombi using the following “pulmonary embolism,” “pulmonary embolus,” “pulmonary emboli,” “pulmonary artery embolism,” “pulmonary artery emboli,” “pulmonary thrombus,” “pulmonary artery thrombus,” and “pulmonary artery thrombi.” We cross-referenced studies with the trauma registry to identify trauma patients with a diagnosis of pulmonary thrombosis and to eliminate cases in which the scan was performed more than 24 hours after injury. Manual chart review confirmed CT scans resulting in a diagnosis of pulmonary thrombosis were performed during initial imaging, immediately following trauma. We extracted patient demographic characteristics, mechanism and severity of injury, summary of injuries, treatments, and outcomes from the database.
We conducted a descriptive analysis with IBM SPSS Statistics for Windows (IBM Corp., Version 29.0), reporting data using means with standard deviations (SD), medians with interquartile ranges (IQRs), and frequencies with percentages.
The project was reviewed and approved by the Western University Health Sciences Research Ethics Board (REB # 118646).
We reviewed a total of 7965 trauma cases between Jan. 1, 2010, and April 30, 2021. Twenty-four patients met criteria for diagnosis of early pulmonary thrombosis, 10 of whom were confirmed not to have a concomitant DVT (suggesting primary pulmonary thrombosis), resulting in an incidence of 0.3% for early pulmonary thrombosis and 0.1% for primary pulmonary thrombosis. Of the 24 patients meeting criteria for early pulmonary thrombosis (Table 1 and Box 1), 15 were male and 9 were female, with a mean age of 54.4 (SD 18.6) years. Excluding 4 patients with a concomitant DVT and 10 patients who did not undergo evaluation for DVT, 10 patients were identified as having primary pulmonary thrombosis (diagnosis of pulmonary thrombosis on the initial CT performed in the first 24 hours after trauma, in the absence of lower-limb DVT). Of these 10 patients, 8 were male and 2 were female, and the mean age was 49.4 (SD 15.6) years.
Five patients (21%) had a previously existing medical condition predisposing to clotting (e.g., cancer), clotting disorder, or prior history of clotting (previous DVT or pulmonary embolism, myocardial infarct, or stroke or transient ischemic attack), necessitating antiplatelet or anticoagulation therapy at the time of injury in 3 cases. Three of the 5 patients with a pre-existing disorder increasing the risk of VTE were diagnosed with a DVT, 1 was identified as having a primary pulmonary thrombus (no DVT), and 1 succumbed to their injuries before further evaluation for DVT or initiation of treatment.
All patients had suffered blunt traumatic injuries, most commonly as a result of motor vehicle collisions (n = 14, 58%) or falls (n = 8, 33%), with a mean Injury Severity Score (ISS) of 23.5 (SD 9.5). Chest trauma, such as rib fractures (n = 11, 45.8%), pneumohemothorax (n = 7, 29%), and pulmonary lacerations or contusions (n = 4, 17%), as well as spinal fractures (n = 8, 33%) and pelvic trauma (n = 5, 21%) were associated with early pulmonary thrombosis. Almost half of patients had a concomitant traumatic brain injury or intracranial hemorrhage (n = 10, 42%).
Most clots were located in the segmental arteries (n = 20, 83%), followed by the main pulmonary artery (n = 2, 8%) and subsegmental arteries (n = 2, 8%). In 2 patients (8%), the most proximal clot was in the main pulmonary arteries; in 18 patients (75%), the most proximal clot was in the segmental arteries; and in 4 patients (17%), the location of the clots was not stated. More than half of patients had multiple clots identified (n = 13, 54%), resulting in low to moderate clot burden in most patients. Four patients (17%) with pulmonary thrombosis ultimately had a concomitant diagnosis of DVT (diagnosed after the detection of pulmonary thrombosis by bilateral lower-extremity ultrasonography in response to the detection of pulmonary thrombosis), although only 13 of 24 patients (54%) had lower-extremity Doppler ultrasonography performed to evaluate for the presence of DVT, and 1 patient had a diagnosis of lower-limb DVT on initial CT of the abdomen and pelvis.
Treatment for pulmonary thrombosis was started in 18 patients (75%), with an average time from diagnosis to treatment of 37.8 (SD 27.7) hours. Therapeutic weight-based dalteparin was the most common treatment, with 38% of patients (n = 9) receiving therapeutic dalteparin monotherapy and 2 patients receiving both therapeutic dalteparin and IVC filter. Inferior vena cava filter in isolation was used in 25% of patients (n = 6); IVC filter with IV heparin was used in 1 patient. Three of 9 patients treated with an IVC filter had a diagnosed DVT. Of the patients treated with an IVC filter (with or without additional anticoagulation therapy), 3 patients had a diagnosed DVT before IVC filter insertion, 3 patients had Doppler ultrasonography excluding the presence of DVT before IVC filter insertion, and 3 patients did not undergo Doppler ultrasonography (DVT status unknown). Patients with primary pulmonary thrombosis were most commonly treated with dalteparin (n = 6, 60%). Despite there being evidence that DVT was not present, 3 patients were treated with an IVC filter (1 with IVC filter in isolation, and 2 with IVC filter and dalteparin or heparin, respectively). One patient with primary pulmonary thrombosis did not receive any treatment. The most common reasons for delaying or not starting treatment were severe brain injury and/or death, with 4 patients dying before receiving treatment for pulmonary thrombosis.
The median length of stay was 10.0 (IQR 3.8–21.2) days. Fifteen patients (62%) were admitted to the ICU, with a median length of ICU stay of 6.0 (IQR 1.0–10.0) days. Eleven patients (46%) required surgical treatment for their injuries, with 9 of those patients (82%) undergoing surgery within 48 hours from the time of injury. Five patients (21%) died as a result of their injuries. Of the patients who survived to discharge, 6 (32%) were discharged to another subacute hospital, 3 (16%) to a rehabilitation centre, and 1 (5.3%) to a long-term care home; 9 patients were discharged home (47.4%).
This study is a case series focused on pulmonary thrombosis identified immediately following traumatic injury, as detected on the first CT scan performed during trauma resuscitation and workup, within 24 hours of injury. Over the course of a 10-year study period, 24 patients had pulmonary thrombosis identified during their initial CT scan. Four of these patients were diagnosed with a concomitant DVT, and 10 did not undergo evaluation for DVT, resulting in 10 patients with primary pulmonary thrombosis. The presence of pulmonary thrombosis in the absence of DVT suggests a different pathophysiology than the commonly accepted pathophysiology of embolization of clots originating in the deep veins of the lower extremities within days to weeks after injury. However, the possibility that early pulmonary thrombosis was a result of complete embolization of DVT, with no detectable DVT remaining, cannot be ruled out.
In this study, pulmonary thrombosis occurring immediately after trauma was commonly associated with thoracic trauma, including rib fractures and flail chest, pneumohemothorax, and lung contusions and lacerations. Compared with the accepted incidence of blunt thoracic trauma in the literature, ranging from 10% to 15% of blunt traumatic injuries19 and up to 60% in some studies,20 patients with early and primary pulmonary thrombosis were more likely to experience thoracic trauma. Fifteen of the 24 patients included in this study (62%) and 8 of 10 patients with primary pulmonary thrombosis (80%) were found to have some degree of thoracic trauma, suggesting a possible etiology of inflammation and direct injury to the pulmonary vasculature as a cause for primary pulmonary thrombosis.
Recent studies investigating pulmonary thrombosis after trauma have made similar observations of pulmonary thrombi detectable on the admitting CT scan,15,16 with multiple reports in the literature identifying pulmonary thrombosis after trauma in the absence of DVT.12,14,15 In the Consortium of Leaders in the Study of Traumatic Thromboembolism (CLOTT) study, a large, prospective, multicentre cohort study investigating trauma-associated VTE, 543 patients out of 7880 studied had VTE following trauma, with 117 patients (1.5%) diagnosed with pulmonary thrombosis in the absence of DVT.15 Of these, 28 patients (23.9%) were diagnosed with pulmonary thrombosis on the admitting CT scan, resulting in an incidence of 0.38%.15 The definition of pulmonary thrombosis in the CLOTT study (presence of clots in the pulmonary vasculature in the absence of lower-limb DVT) varies slightly from the defining criteria of primary pulmonary thrombosis in the current study, which defines primary pulmonary thrombosis as the presence of clots within the pulmonary vasculature within 24 hours of injury (detected on the initial CT scan), in the absence of DVT. The incidence of pulmonary thrombosis on the admitting CT scan in the current study was similar to that of the CLOTT study, although the studied populations differed substantially. Further, the CLOTT study identified chest trauma and shock at the time of admission as risk factors independently associated with traumatic pulmonary thrombosis in the absence of DVT, with chest trauma and major venous injury associated with the diagnosis of pulmonary thrombosis on the admitting scan, suggesting a role for direct vascular injury, inflammation, and the hypercoagulable state associated with severe trauma as potential contributing factors for primary clot formation in the pulmonary vasculature.
Many of the patients identified in this study had low clot burdens, and it is possible that incidentally detected pulmonary thrombi may not be causing any symptoms. Currently, there are no established treatment recommendations for small incidentally found pulmonary thrombi occurring immediately following traumatic injury. The CLOTT study authors proposed observation for asymptomatic subsegmental pulmonary thrombi found incidentally in the absence of DVT,15 which is in line with the most recent update of the CHEST guideline21 for nontraumatic pulmonary thrombi. A recent international prospective observational study evaluating the risk of recurrent venous thromboembolism after observational management of subsegmental pulmonary thrombi showed relatively low risks of recurrent VTE (DVT or pulmonary embolism) of 1.1% per month; however, the incidence of concomitant DVT was relatively high, at 9.6%,22 suggesting that screening for DVT may be indicated to guide the need for anticoagulation therapy. It is unclear whether screening all patients who have sustained major trauma and been diagnosed with incidental primary pulmonary thrombi is indicated, or what the optimal management strategy for these patients should be.
Based on the results of this study, however, there is a high association between early pulmonary thrombosis and DVT (4 of 14, or 29%, of patients evaluated for the presence of DVT were found to have lower-extremity clots), suggesting that a diagnosis of pulmonary thrombosis on the initial CT scan should prompt clinicians to evaluate for the presence of lower-extremity DVT in all patients and treat appropriately, if present. Further, while subsegmental pulmonary thrombi may not require treatment, as suggested by the CLOTT study authors and CHEST guideline,15,21 no patients in this study had subsegmental pulmonary thrombi in isolation. Most patients (18 of 24, 75%) had segmental pulmonary thrombi, 2 of 24 patients (8%) had thrombi in the main pulmonary arteries as the most proximally affected arteries, and more than half of patients had multiple clots identified (n = 13, 54%). This indicates that pulmonary thrombosis after severe trauma likely affects larger, more proximal arteries, and therefore requires treatment, although optimal treatment strategies are undefined.
Further questions remain about the pathophysiology of primary pulmonary thrombosis and its associated injuries and risk factors. Potential avenues aimed at definitively proving the development of pulmonary thrombi within the pulmonary vasculature may include screening all trauma patients diagnosed with pulmonary thrombosis on admission with lower-extremity Doppler ultrasonography to determine the incidence of coexisting DVT, or performing basic science and animal studies to induce pulmonary thrombosis in the absence of DVT to better understand the underlying pathophysiology.
This study was an observational descriptive study with a limited sample; as such, no definitive conclusions can be made about the pathophysiology of primary pulmonary thrombosis.
The results of the study suggest that pulmonary thrombosis immediately following trauma is a distinct clinical entity from pulmonary emboli that originate from DVT in the lower extremities. More research is needed to investigate the effects of treatments employed during trauma care, such as transfusion and administration of tranexamic acid, on pulmonary thrombosis development, as well as the effects of primary pulmonary thrombosis on morbidity and mortality, and the most effective preventive and treatment strategies. Further work investigating optimal treatment strategies, treatment duration, re-imaging, and follow-up care are required to better inform management of this distinct clinical entity.