Delayed prophylaxis with unfractionated heparin increases the risk of venous thromboembolic events in patients with moderate to severe traumatic brain injury: a retrospective analysis

Abstract

Background Venous thromboembolism (VTE) is a recognized complication in patients with traumatic brain injury (TBI) and is associated with increased morbidity and mortality. Currently, no standard exists for optimal timing or a pharmacological agent for VTE prophylaxis (pharmacological thromboprophylaxis – PTP) in patients with TBI. PTP is often delayed out of fear of causing extension of intracranial hemorrhage (ICH). The purpose of this study was to report the frequency of VTE and ICH progression after initiation of PTP with a continuous infusion of unfractionated heparin in patients with moderate to severe TBI, and to identify risk factors associated with development of VTE. Methods In this single-center retrospective study, patients with moderate to severe TBI admitted to the ICU of a Swiss Level I Trauma Center over a three-year period were analyzed. Results In 23 (13%) of the 177 patients included in the study a VTE episode occurred during the hospital stay. ICH progression after initiation of PTP occurred in 7 (4%) patients. In a multivariable logistic regression model, only the timing of initiation of PTP was identified as an independent predictor of VTE. Conclusions In this study population, the risk of developing VTE increased with the delay of initiation of a pharmacological VTE prophylaxis, while ICH progression after initiation of PTP was a rare event.

Recommendations from the ICM-VTE: Trauma

“…Timing of the initiation of anticoagulant thromboprophylaxis: In major trauma patients, the transition to a hypercoagulable state usually occurs early and is often seen at the time of admission 45-47 . Furthermore, numerous studies have shown that early initiation of anticoagulant thromboprophylaxis is associated with decreased risk of VTE in mixed trauma groups 27,28,37,43,44 and in subgroups, including pelvic trauma 45-48 , spine fractures 49-52 , solid abdominal organ injuries 53-56 , and head injuries 33,57,58 . At the same time, bleeding complications were not shown to be increased with early anticoagulant prophylaxis in most studies 33,37,43-46,48-55 .…”

“…Traumatic brain injury patients : The main barrier to early anticoagulant thromboprophylaxis in patients with orthopaedic trauma is the presence of traumatic brain injury (TBI) 33,58,62 . Although patients with TBI have an increased risk of VTE 63,64 , anticoagulant thromboprophylaxis is often delayed because of concerns about progression of intracranial bleeding (ICB).…”

Management and Challenges of Severe Traumatic Brain Injury

“…114 However, many of these large systematic reviews and meta-analyses are based on nonrandomized and often retrospective evidence, and there is a need for high-quality randomized evidence to address this common clinical question. Overall, the rates of intracranial hemorrhage progression after initiation of chemoprophylaxis for VTE remain low and are consistently around 3 to 4% across several retrospective studies and systematic reviews, [116][117][118][119] with some as high as 12 to 15%. 120 More recent investigations with TEG have demonstrated that critically ill trauma patients typically resolve their coagulopathy within 24 hours, after which time they transition into a hypercoaguable or prothrombotic state.…”

“…117,122 Internationally, some centers use a continuous infusion of unfractionated heparin intravenously for the ability of rapid reversal as needed. 116 The choice between these agents is largely institutionally based. There may be some bias toward UH, as LMWH are newer products and UH is theoretically reversible with protamine, although this is rarely required, especially with subcutaneous prophylactic doses.…”

Relationship between anti-Xa level achieved with prophylactic low-molecular weight heparin and venous thromboembolism in trauma patients: A systematic review and meta-analysis

“…With appropriate pharmacologic VTE prophylaxis (VTEp), VTE may be preventable. Robust evidence supports the safety and efficacy of VTEp, 1,2 even in scenarios, such as spinal cord injury, [3][4][5][6][7][8] pelvic fracture, 9,10 neurosurgery, 11,12 traumatic brain injury, [13][14][15] and solid organ injury. 16,17 However, despite current VTEp regimens "breakthrough" VTE continues to occur and has been observed in 3.2% of injured patients when length of stay is greater than 2 days, 18 and in up to 18% of critically injured patients.…”