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Spontaneous Spinal Epidural Hematoma in a Patient on Rivaroxaban: Case Report and Literature Review
The Journal of Emergency Medicine, Vol. 53, No. 4, pp. 536–539, 2017 Ó 2017 Elsevier Inc. All rights reserved. 0736-4679/$ - see front matter
http://dx.doi.org/10.1016/j.jemermed.2017.06.005
Selected Topics: Neurological Emergencies
SPONTANEOUS SPINAL EPIDURAL HEMATOMA IN A PATIENT ON RIVAROXABAN: CASE REPORT AND LITERATURE REVIEW Raed Ismail, MD, Elie Zaghrini, MD, and Eveline Hitti, MD American University of Beirut, Beirut, Lebanon Reprint Address: Eveline Hitti, MD, American University of Beirut, Beirut 1107 2020, Lebanon
, Abstract—Background: Spinal hematomas (SHs) are rare yet potentially debilitating causes of acute back pain. Although spontaneous SHs have been described in the setting of anticoagulation with warfarin or enoxaparin, few cases of spontaneous SH on direct oral anticoagulants (DOACs) have been reported. Case Report: We report a case of spontaneous spinal epidural hematoma in a patient on rivaroxaban. A 72-year-old man on rivaroxaban and aspirin presented with a 4-day history of nontraumatic back pain. In the emergency department he developed lower-extremity weakness and numbness, followed by urinary incontinence. Magnetic resonance imaging revealed spinal epidural hematoma at T11–L2. The patient underwent emergent decompression and hematoma evacuation and was discharged home 8 days later with complete resolution of symptoms. Why Should an Emergency Physician Be Aware of This?: Early recognition and surgical intervention for SHs with neurologic compromise is key to favorable outcome. Optimal timing of surgery in patients on DOACs requires an assessment of the risk of intraoperative or postoperative bleeding, an assessment of the patient’s symptom progression, as well as an understanding of the pharmacokinetics of the DOAC used and possible reversal options available. We also review all published cases of spontaneous SHs in patients on DOACs and report on their management and outcomes. Ó 2017 Elsevier Inc. All rights reserved.
INTRODUCTION Spontaneous spinal hematoma (SH) is a rare cause of acute back pain. Symptoms can range from pain alone to complete paralysis. In some cases, spontaneous recovery is possible, while others necessitate urgent management. Although spontaneous SH has been described in the setting of anticoagulation with warfarin or enoxaparin and can also be precipitated by trauma, vascular malformations, or neoplasm, few cases of spontaneous SHs on direct oral anticoagulants (DOACs) have been reported. Here we report a case of spontaneous spinal epidural hematoma in a patient receiving rivaroxaban, and review the literature on management and outcomes of similar cases published in the peer-reviewed literature. CASE REPORT A 72-year-old man with a history of hypertension, coronary artery disease status post coronary artery bypass, and nonvalvular atrial fibrillation on rivaroxaban presented to the emergency department (ED) with severe low back pain and left-sided radiculopathy. The patient reported an episode of heavy lifting 7 days before presentation with no subsequent symptoms until 4 days later, when he started experiencing mild low back pain that intensified 4 h before presentation to the ED. The pain worsened with movement of his lower extremities. He denied any fever, extremity numbness or weakness, and fecal or urinary incontinence or
, Keywords—dabigatran; direct oral anticoagulants; rivaroxaban; spontaneous spinal hematoma
RECEIVED: 12 February 2017; FINAL SUBMISSION RECEIVED: 30 May 2017; ACCEPTED: 3 June 2017 536
Spontaneous Spinal Epidural Hematoma
retention. On presentation he was afebrile with normal blood pressure, heart rate, respiratory rate, and oxygen saturation. He was in extreme distress from 10/10 pain and received an Emergency Severity Index score of 2 at triage, leading to his assignment to the high-acuity section of our ED. He had intact upper-extremity strength and was moving bilateral lower extremities against gravity, had intact reflexes and no saddle paresthesia. There was no focal tenderness and no erythema or ecchymosis overlying the back. Home medications included rivaroxaban 20 mg daily, with last dose 18 h before ED visit, aspirin (acetylsalicylic acid) 81 mg once daily, amiodarone, bisoprolol, diltiazem, and pravastatin. Blood workup revealed a hematocrit of 40%, platelets of 221,000/mm3, international normalized ratio of 2.1, and an activated partial thromboplastin time (aPTT) of 39 s. Creatinine was 1.3 mg/dL with creatinine clearance of 55 mL/min. Plain radiography of the lumbosacral spine revealed mild narrowing of the L5–S1 disk space.
537
On arrival, the patient received tramadol with minimal pain relief requiring subsequent administration of parenteral fentanyl. Approximately 2 h after presentation, his pain score had dropped to 2/10, but he started complaining of lower-extremity weakness. Reexamination revealed a motor power of 4/5 in the lower extremities that progressed 15 min later to 1/5, and moderate saddle anesthesia. He then developed urinary incontinence and digital rectal examination revealed weak anal sphincter tone. Urgent magnetic resonance imaging (MRI) revealed an epidural hematoma measuring 6.7 1.7 1.5 cm extending from T11–L2 causing severe compression of the thecal sac (Figure 1A). In the absence of available prothrombin complex concentrate (PCC) at our institution, the patient received a transfusion of fresh frozen plasma (FFP) and was transferred emergently to the operating room, where he underwent T11–L2 decompressive laminectomy and hematoma evacuation.
Figure 1. Magnetic resonance imaging T1-weighted images of the thoracolumbar spine revealed a 6.7 1.7 1.5 cm epidural hematoma (highlighted with arrow) that is causing severe compression of the thecal sac (A). Significant decrease in the hematoma size post laminectomies from T11 to L2 levels and hematoma drainage (B).
538
Table 1. Summary of Reviewed Cases
First Author, Year
Radiographic Findings
Duration of Anticoagulant Use
Onset of Pain to First Neurologic Symptom
Onset of Neurologic Symptoms to Intervention
DOAC or Antiplatelet
Presenting Symptoms
This case
Rivaroxaban/ aspirin
MRI: T11–L2 posterior epidural hematoma
Laminectomy and hematoma evacuation
FFP
Complete recovery
24 h
2 mo
4d
4h
Jaeger, 2012 (1)
Rivaroxaban
MRI: C2–T8 anterior compressing epidural hematoma
Bed rest
None
Complete recovery
NA
48 h
2h
NA
Dargazanli, 2016 (2)
Rivaroxaban
MRI: subdural hematoma from T6 to T8
Laminectomy and hematoma evacuation
PCC
No motor or sensory improvement 6 mo after follow-up
<48 h
3y
Simultaneous
Within 24 h
Castillo, 2015 (3)
Rivaroxaban
Low back pain, bilateral leg weakness and numbness, urinary incontinence Pain in the thoracic spine, bilateral leg weakness and numbness Interscapular pain, gait impairment, paraplegia, left-leg paresthesia Upper and lower back pain, paraplegia, bowel and bladder dysfunction
MRI: subdural hematoma from T3–L1
Cervical and lumbar evacuation
None
10 d
19 mo
Simultaneous
10 d
Bamps, 2015 (4)
Dabigatran
Acute cervical pain tetraplegia, sensory loss, autonomic instability
CT: C2–C3–C4 epidural hematoma
Cervical laminectomy and hematoma evacuation
PCC
No recovery of bladder, bowel, and neurologic functions 6 mo after follow-up Complete recovery
12 h
Unknown
Simultaneous
Within 24 h
Management
Blood Products
Last Dose of Anticoagulant Before Surgery
Morbidity
CT = computed tomography; DOAC = direct oral anticoagulant; FFP = fresh frozen plasma; MRI = magnetic resonance imaging; NA = not applicable; PCC = prothrombin complex concentrate.
R. Ismail et al.
Spontaneous Spinal Epidural Hematoma
MRI repeated 1 day postoperatively showed a significant decrease in the size of the hematoma and milder compression of the thecal sac (Figure 1B). The patient showed significant improvement post surgery with gradual return of sensory and motor function to baseline by the time he was discharged 8 days post operation. DISCUSSION A PubMed search of spinal epidural hematoma and rivaroxaban, spinal subdural hematoma and rivaroxaban or dabigatran or apixaban or edoxaban, direct oral anticoagulants and epidural hematoma, direct oral anticoagulants and subdural hematoma was conducted without language or year of publication restrictions. References were manually reviewed for additional studies pertaining to our topic. Four additional case reports of spontaneous SH in patients on DOACs were identified and are summarized in Table 1 (1–4). Patients with SH most commonly present with acuteonset back pain and might rapidly develop signs and symptoms of spinal cord compression or cauda equine syndrome. In our review, the average time from onset of pain to progression of neurologic symptoms in patients with spontaneous SH on DOACs was 19.6 h (range 0– 96 h). These occurred anywhere between 2 days to 3 years after starting DOAC use and only 1 of 5 patients was on an additional antiplatelet. The most common location for spinal epidural and subdural hematoma is the cervicothoracic or thoracolumbar area (5). In our review of cases, 80% (n = 4) involved the thoracic spine, 40% (n = 2) involved the cervical spine, and 40% (n = 2) involved the lumbar spine. The majority of cases (80%) were diagnosed by MRI, which is the imaging modality of choice used in diagnosing spinal epidural or subdural hematomas, and one case was diagnosed by computed tomography (5). Treatment of SH associated with neurologic compromise requires emergent surgical hematoma evacuation (6). There is no consensus, however, on the timing of surgery in patients on DOACs. Time of the last dose of DOAC is an important consideration, as the anticoagulation effect is expected to have resolved fully after five half-lives of the drug have elapsed. Although 3 of the 4 patients who underwent surgery had their intervention performed before the five half-lives, there was no significant intraoperative or postoperative bleeding reported. Although prothrombin time and aPTT may rise with direct factor Xa inhibitor use, normal levels do not correlate with resolution of drug effect. Anti factor Xa activity level can be measured for rivaroxaban; this, however, is not always available or reliable. Reversal options
539
include idarucizumab for patients on dabigatran and PCC for factor Xa inhibitors, when available (7). Two of the 5 patients (40%) received PCC, while the patient in our case received FFP. In 80% (n = 4) of the patients, the treatment was surgical with laminectomy and hematoma evacuation or drainage. This resulted in complete resolution of symptoms in 50% (n = 2) of cases, while the other 50% (n = 2) of them had no improvement after 6 months. In the 2 patients with poor outcomes postoperatively, mean time from onset of neurologic symptoms to surgery was 5.5 days compared to 14 h for postoperative patients with good outcomes. In the one case that was treated conservatively, mainly bed rest, the outcome was complete resolution of symptoms. No deaths were reported. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS? We present this case to increase awareness among emergency physicians of SH in patients taking DOACs. Patients on DOACs with severe pain or neurologic compromise should be evaluated emergently for SH, while those with mild pain and no alarm symptoms should be considered for urgent outpatient imaging, given the higher risk of further expansion of missed SH in this population. Early surgical intervention for SH with neurologic compromise is key to favorable outcomes. Optimal timing of surgery in patients on DOACs requires an assessment of the risk of intraoperative or postoperative bleeding, an assessment of the patient’s symptom progression, as well as an understanding of the pharmacokinetic properties of the DOAC used and possible reversal options available. REFERENCES 1. Jaeger M, Jeanneret B, Schaeren S. Spontaneous spinal epidural haematoma during factor Xa inhibitor treatment (rivaroxaban). Eur Spine J 2012;21(suppl 4):S433–5. 2. Dargazanli C, Lonjon N, Gras-Combe G. Nontraumatic spinal subdural hematoma complicating direct factor Xa inhibitor treatment (rivaroxaban): a challenging management. Eur Spine J 2016; 25(suppl 1):100–3. 3. Castillo JM, Afanador HF, Manjarrez E, Morales XA. Non-traumatic spontaneous spinal subdural hematoma in a patient with non-valvular atrial fibrillation during treatment with rivaroxaban. Am J Case Rep 2015;16:377–81. 4. Bamps S, Decramer T, Vandenbussche N, et al. Dabigatran-associated spontaneous acute cervical epidural hematoma. World Neurosurg 2015;83:257–8. 5. Baek BS, Hur JW, Kwon KY, Lee HK. Spontaneous spinal epidural hematoma. J Korean Neurosurg Soc 2008;44:40–2. 6. Groen RJM, van Alphen HAM. Operative treatment of spontaneous spinal epidural hematomas (a study of factors determining postoperative outcome). Neurosurgery 1996;39:494–508. 7. Levi M. Management of bleeding in patients treated with direct oral anticoagulants. Crit Care 2016;20:249.
http://dx.doi.org/10.1016/j.jemermed.2017.06.005
Selected Topics: Neurological Emergencies
SPONTANEOUS SPINAL EPIDURAL HEMATOMA IN A PATIENT ON RIVAROXABAN: CASE REPORT AND LITERATURE REVIEW Raed Ismail, MD, Elie Zaghrini, MD, and Eveline Hitti, MD American University of Beirut, Beirut, Lebanon Reprint Address: Eveline Hitti, MD, American University of Beirut, Beirut 1107 2020, Lebanon
, Abstract—Background: Spinal hematomas (SHs) are rare yet potentially debilitating causes of acute back pain. Although spontaneous SHs have been described in the setting of anticoagulation with warfarin or enoxaparin, few cases of spontaneous SH on direct oral anticoagulants (DOACs) have been reported. Case Report: We report a case of spontaneous spinal epidural hematoma in a patient on rivaroxaban. A 72-year-old man on rivaroxaban and aspirin presented with a 4-day history of nontraumatic back pain. In the emergency department he developed lower-extremity weakness and numbness, followed by urinary incontinence. Magnetic resonance imaging revealed spinal epidural hematoma at T11–L2. The patient underwent emergent decompression and hematoma evacuation and was discharged home 8 days later with complete resolution of symptoms. Why Should an Emergency Physician Be Aware of This?: Early recognition and surgical intervention for SHs with neurologic compromise is key to favorable outcome. Optimal timing of surgery in patients on DOACs requires an assessment of the risk of intraoperative or postoperative bleeding, an assessment of the patient’s symptom progression, as well as an understanding of the pharmacokinetics of the DOAC used and possible reversal options available. We also review all published cases of spontaneous SHs in patients on DOACs and report on their management and outcomes. Ó 2017 Elsevier Inc. All rights reserved.
INTRODUCTION Spontaneous spinal hematoma (SH) is a rare cause of acute back pain. Symptoms can range from pain alone to complete paralysis. In some cases, spontaneous recovery is possible, while others necessitate urgent management. Although spontaneous SH has been described in the setting of anticoagulation with warfarin or enoxaparin and can also be precipitated by trauma, vascular malformations, or neoplasm, few cases of spontaneous SHs on direct oral anticoagulants (DOACs) have been reported. Here we report a case of spontaneous spinal epidural hematoma in a patient receiving rivaroxaban, and review the literature on management and outcomes of similar cases published in the peer-reviewed literature. CASE REPORT A 72-year-old man with a history of hypertension, coronary artery disease status post coronary artery bypass, and nonvalvular atrial fibrillation on rivaroxaban presented to the emergency department (ED) with severe low back pain and left-sided radiculopathy. The patient reported an episode of heavy lifting 7 days before presentation with no subsequent symptoms until 4 days later, when he started experiencing mild low back pain that intensified 4 h before presentation to the ED. The pain worsened with movement of his lower extremities. He denied any fever, extremity numbness or weakness, and fecal or urinary incontinence or
, Keywords—dabigatran; direct oral anticoagulants; rivaroxaban; spontaneous spinal hematoma
RECEIVED: 12 February 2017; FINAL SUBMISSION RECEIVED: 30 May 2017; ACCEPTED: 3 June 2017 536
Spontaneous Spinal Epidural Hematoma
retention. On presentation he was afebrile with normal blood pressure, heart rate, respiratory rate, and oxygen saturation. He was in extreme distress from 10/10 pain and received an Emergency Severity Index score of 2 at triage, leading to his assignment to the high-acuity section of our ED. He had intact upper-extremity strength and was moving bilateral lower extremities against gravity, had intact reflexes and no saddle paresthesia. There was no focal tenderness and no erythema or ecchymosis overlying the back. Home medications included rivaroxaban 20 mg daily, with last dose 18 h before ED visit, aspirin (acetylsalicylic acid) 81 mg once daily, amiodarone, bisoprolol, diltiazem, and pravastatin. Blood workup revealed a hematocrit of 40%, platelets of 221,000/mm3, international normalized ratio of 2.1, and an activated partial thromboplastin time (aPTT) of 39 s. Creatinine was 1.3 mg/dL with creatinine clearance of 55 mL/min. Plain radiography of the lumbosacral spine revealed mild narrowing of the L5–S1 disk space.
537
On arrival, the patient received tramadol with minimal pain relief requiring subsequent administration of parenteral fentanyl. Approximately 2 h after presentation, his pain score had dropped to 2/10, but he started complaining of lower-extremity weakness. Reexamination revealed a motor power of 4/5 in the lower extremities that progressed 15 min later to 1/5, and moderate saddle anesthesia. He then developed urinary incontinence and digital rectal examination revealed weak anal sphincter tone. Urgent magnetic resonance imaging (MRI) revealed an epidural hematoma measuring 6.7 1.7 1.5 cm extending from T11–L2 causing severe compression of the thecal sac (Figure 1A). In the absence of available prothrombin complex concentrate (PCC) at our institution, the patient received a transfusion of fresh frozen plasma (FFP) and was transferred emergently to the operating room, where he underwent T11–L2 decompressive laminectomy and hematoma evacuation.
Figure 1. Magnetic resonance imaging T1-weighted images of the thoracolumbar spine revealed a 6.7 1.7 1.5 cm epidural hematoma (highlighted with arrow) that is causing severe compression of the thecal sac (A). Significant decrease in the hematoma size post laminectomies from T11 to L2 levels and hematoma drainage (B).
538
Table 1. Summary of Reviewed Cases
First Author, Year
Radiographic Findings
Duration of Anticoagulant Use
Onset of Pain to First Neurologic Symptom
Onset of Neurologic Symptoms to Intervention
DOAC or Antiplatelet
Presenting Symptoms
This case
Rivaroxaban/ aspirin
MRI: T11–L2 posterior epidural hematoma
Laminectomy and hematoma evacuation
FFP
Complete recovery
24 h
2 mo
4d
4h
Jaeger, 2012 (1)
Rivaroxaban
MRI: C2–T8 anterior compressing epidural hematoma
Bed rest
None
Complete recovery
NA
48 h
2h
NA
Dargazanli, 2016 (2)
Rivaroxaban
MRI: subdural hematoma from T6 to T8
Laminectomy and hematoma evacuation
PCC
No motor or sensory improvement 6 mo after follow-up
<48 h
3y
Simultaneous
Within 24 h
Castillo, 2015 (3)
Rivaroxaban
Low back pain, bilateral leg weakness and numbness, urinary incontinence Pain in the thoracic spine, bilateral leg weakness and numbness Interscapular pain, gait impairment, paraplegia, left-leg paresthesia Upper and lower back pain, paraplegia, bowel and bladder dysfunction
MRI: subdural hematoma from T3–L1
Cervical and lumbar evacuation
None
10 d
19 mo
Simultaneous
10 d
Bamps, 2015 (4)
Dabigatran
Acute cervical pain tetraplegia, sensory loss, autonomic instability
CT: C2–C3–C4 epidural hematoma
Cervical laminectomy and hematoma evacuation
PCC
No recovery of bladder, bowel, and neurologic functions 6 mo after follow-up Complete recovery
12 h
Unknown
Simultaneous
Within 24 h
Management
Blood Products
Last Dose of Anticoagulant Before Surgery
Morbidity
CT = computed tomography; DOAC = direct oral anticoagulant; FFP = fresh frozen plasma; MRI = magnetic resonance imaging; NA = not applicable; PCC = prothrombin complex concentrate.
R. Ismail et al.
Spontaneous Spinal Epidural Hematoma
MRI repeated 1 day postoperatively showed a significant decrease in the size of the hematoma and milder compression of the thecal sac (Figure 1B). The patient showed significant improvement post surgery with gradual return of sensory and motor function to baseline by the time he was discharged 8 days post operation. DISCUSSION A PubMed search of spinal epidural hematoma and rivaroxaban, spinal subdural hematoma and rivaroxaban or dabigatran or apixaban or edoxaban, direct oral anticoagulants and epidural hematoma, direct oral anticoagulants and subdural hematoma was conducted without language or year of publication restrictions. References were manually reviewed for additional studies pertaining to our topic. Four additional case reports of spontaneous SH in patients on DOACs were identified and are summarized in Table 1 (1–4). Patients with SH most commonly present with acuteonset back pain and might rapidly develop signs and symptoms of spinal cord compression or cauda equine syndrome. In our review, the average time from onset of pain to progression of neurologic symptoms in patients with spontaneous SH on DOACs was 19.6 h (range 0– 96 h). These occurred anywhere between 2 days to 3 years after starting DOAC use and only 1 of 5 patients was on an additional antiplatelet. The most common location for spinal epidural and subdural hematoma is the cervicothoracic or thoracolumbar area (5). In our review of cases, 80% (n = 4) involved the thoracic spine, 40% (n = 2) involved the cervical spine, and 40% (n = 2) involved the lumbar spine. The majority of cases (80%) were diagnosed by MRI, which is the imaging modality of choice used in diagnosing spinal epidural or subdural hematomas, and one case was diagnosed by computed tomography (5). Treatment of SH associated with neurologic compromise requires emergent surgical hematoma evacuation (6). There is no consensus, however, on the timing of surgery in patients on DOACs. Time of the last dose of DOAC is an important consideration, as the anticoagulation effect is expected to have resolved fully after five half-lives of the drug have elapsed. Although 3 of the 4 patients who underwent surgery had their intervention performed before the five half-lives, there was no significant intraoperative or postoperative bleeding reported. Although prothrombin time and aPTT may rise with direct factor Xa inhibitor use, normal levels do not correlate with resolution of drug effect. Anti factor Xa activity level can be measured for rivaroxaban; this, however, is not always available or reliable. Reversal options
539
include idarucizumab for patients on dabigatran and PCC for factor Xa inhibitors, when available (7). Two of the 5 patients (40%) received PCC, while the patient in our case received FFP. In 80% (n = 4) of the patients, the treatment was surgical with laminectomy and hematoma evacuation or drainage. This resulted in complete resolution of symptoms in 50% (n = 2) of cases, while the other 50% (n = 2) of them had no improvement after 6 months. In the 2 patients with poor outcomes postoperatively, mean time from onset of neurologic symptoms to surgery was 5.5 days compared to 14 h for postoperative patients with good outcomes. In the one case that was treated conservatively, mainly bed rest, the outcome was complete resolution of symptoms. No deaths were reported. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS? We present this case to increase awareness among emergency physicians of SH in patients taking DOACs. Patients on DOACs with severe pain or neurologic compromise should be evaluated emergently for SH, while those with mild pain and no alarm symptoms should be considered for urgent outpatient imaging, given the higher risk of further expansion of missed SH in this population. Early surgical intervention for SH with neurologic compromise is key to favorable outcomes. Optimal timing of surgery in patients on DOACs requires an assessment of the risk of intraoperative or postoperative bleeding, an assessment of the patient’s symptom progression, as well as an understanding of the pharmacokinetic properties of the DOAC used and possible reversal options available. REFERENCES 1. Jaeger M, Jeanneret B, Schaeren S. Spontaneous spinal epidural haematoma during factor Xa inhibitor treatment (rivaroxaban). Eur Spine J 2012;21(suppl 4):S433–5. 2. Dargazanli C, Lonjon N, Gras-Combe G. Nontraumatic spinal subdural hematoma complicating direct factor Xa inhibitor treatment (rivaroxaban): a challenging management. Eur Spine J 2016; 25(suppl 1):100–3. 3. Castillo JM, Afanador HF, Manjarrez E, Morales XA. Non-traumatic spontaneous spinal subdural hematoma in a patient with non-valvular atrial fibrillation during treatment with rivaroxaban. Am J Case Rep 2015;16:377–81. 4. Bamps S, Decramer T, Vandenbussche N, et al. Dabigatran-associated spontaneous acute cervical epidural hematoma. World Neurosurg 2015;83:257–8. 5. Baek BS, Hur JW, Kwon KY, Lee HK. Spontaneous spinal epidural hematoma. J Korean Neurosurg Soc 2008;44:40–2. 6. Groen RJM, van Alphen HAM. Operative treatment of spontaneous spinal epidural hematomas (a study of factors determining postoperative outcome). Neurosurgery 1996;39:494–508. 7. Levi M. Management of bleeding in patients treated with direct oral anticoagulants. Crit Care 2016;20:249.