Hemorrhage Within the Spinal Cord After Acute Traumatic Injury: The Relationship to Hemodynamic Management and Thromboembolic Prophylaxis

The paralysis that occurs after suffering a traumatic spinal cord injury (SCI) results from the initial mechanical impact causing the 'primary damage,' and then the initiation of a complex series of biologic and physiologic responses around the injury site causing 'secondary damage.' While the primary damage is not treatable per se, early neuroprotective interventions to limit the secondary damage may spare vulnerable tissue at the injury site and ultimately maximize neurologic recovery. Such treatments are inspired by the well-accepted notion that sparing even modest amounts of neural tissue at the SCI site could result in improved neurologic function.

There are many complex responses that mediate secondary damage after SCI. We are interested in a response that may seem simple but has potentially significant effects on the cord: bleeding. Not surprisingly, the spinal cord bleeds when it is subjected to a significant impact. This bleeding can be visualized on a magnetic resonance imaging (MRI) scan, and when it is present, it is assumed that the initial mechanical impact to the cord was extremely severe and caused significant tissue disruption (and bleeding), ultimately resulting in a poor prognosis for neurologic recovery. While this may be true, it is also evident from more recent data that the blood itself and its breakdown products can be deleterious to the spinal cord, causing further secondary injury. It has also been observed that the initial bleeding within the injured spinal cord can worsen over time – a term that some scientists have called 'progressive hemorrhagic necrosis.' For this reason, scientists have explored various treatments to prevent the expansion of the bleeding or to neutralize the effects of the blood breakdown products in the cord.

We propose to evaluate the role that two routine clinical practices may play in inadvertently exacerbating bleeding within the injured spinal cord: (1) the use of drugs called 'vasopressors' to increase the blood pressure in an attempt to increase blood flow to the injured spinal cord, and (2) the use of drugs called 'anticoagulants' or 'blood thinners' to prevent blood clots from developing. The injured spinal cord certainly experiences a disruption of its blood supply, and so it is recommended that clinicians elevate the blood pressure for the first 7 days in order to improve the blood supply to the cord. This increased pressure, however, can cause increased bleeding within the spinal cord, and this is a cause for concern that has not been addressed in acute SCI. Furthermore, because acute SCI patients are also given blood thinners to prevent blood clots from forming, the bleeding within the spinal cord may be further worsened. In some respects, the combination of blood thinners (thus reducing the body's ability to clot) and increased blood pressure may synergistically increase the risk of bleeding within the spinal cord. Interestingly, in patients who have a traumatic brain injury or a stroke with bleeding within the brain, clinicians will consider the risk of worsened bleeding in the management of blood pressure and administration of blood thinners. In contrast, these issues are not considered in acute SCI.

Our study will therefore examine the potential that increasing the blood pressure (to increase blood flow to the spinal cord) and administering blood thinners (to prevent blood clots) inadvertently worsens bleeding inside the injured spinal cord. We will do this in two ways. In an experimental study, we will use our large animal (pig) model of SCI to test whether increased blood pressure alone, blood thinners alone, or the combination exacerbates bleeding within the cord. We will perform ultrasound, MRI, and histology on the spinal cord to measure hemorrhage. We will also conduct a clinical study in which acute SCI patients will have multiple MRI scans within the first 2 weeks of injury to measure how hemorrhage changes within the spinal cord. We will correlate these changes in hemorrhage to increases in blood pressure with vasopressors and the initiation of blood thinning medications to determine if these practices seem to worsen bleeding within the spinal cord in human patients.

In both the experimental and clinical settings, we will evaluate spinal cord bleeding in relation to vasopressors to increase blood pressure and anticoagulants to prevent blood clots. Ultimately, our goal is to inform clinical approaches around blood pressure control and the prevention of blood clotting for acute SCI patients by determining if these routine practices exacerbate bleeding within the injured spinal cord. This translational study will provide guidance around how clinical practices could be tailored to reduce the risk of exacerbating hemorrhage within the injured spinal cord, thereby improving the potential for recovery after acute SCI. For example, when there is obvious bleeding in the cord on the baseline MRI, perhaps clinicians should wait an additional 24 to 48 hours before starting blood thinners, or use other non-pharmacologic measures to prevent blood clots from forming. Or maybe for the first week, clinicians should simply consider targeting lower blood pressure goals or obtaining additional imaging studies to confirm that the bleeding is 'stable' before starting blood thinners or vasopressors. Providing scientific and clinical data to inform these treatment decisions will help clinicians to provide the optimal care for acute SCI patients and maximize their chances of recovery.