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      Rivaroxaban-Induced Nontraumatic Spinal Subdural Hematoma: An Uncommon Yet Life-Threatening Complication

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          Abstract

          In the last decade, the desire for safer oral anticoagulants (OACs) led to the emergence of newer drugs. Available clinical trials demonstrated a lower risk of OACs-associated life-threatening bleeding events, including intracranial hemorrhage, compared to warfarin. Nontraumatic spinal hematoma is an uncommon yet life-threatening neurosurgical emergency that can be associated with the use of these agents. Rivaroxaban, one of the newly approved OACs, is a direct factor Xa inhibitor. To the best of our knowledge, to date, only two published cases report the incidence of rivaroxaban-induced nontraumatic spinal subdural hematoma (SSDH). Our case is the third one described and the first one to involve the cervicothoracic spine.

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          Reversal of rivaroxaban and dabigatran by prothrombin complex concentrate: a randomized, placebo-controlled, crossover study in healthy subjects.

          Rivaroxaban and dabigatran are new oral anticoagulants that specifically inhibit factor Xa and thrombin, respectively. Clinical studies on the prevention and treatment of venous and arterial thromboembolism show promising results. A major disadvantage of these anticoagulants is the absence of an antidote in case of serious bleeding or when an emergency intervention needs immediate correction of coagulation. This study evaluated the potential of prothrombin complex concentrate (PCC) to reverse the anticoagulant effect of these drugs. In a randomized, double-blind, placebo-controlled study, 12 healthy male volunteers received rivaroxaban 20 mg twice daily (n=6) or dabigatran 150 mg twice daily (n=6) for 2½ days, followed by either a single bolus of 50 IU/kg PCC (Cofact) or a similar volume of saline. After a washout period, this procedure was repeated with the other anticoagulant treatment. Rivaroxaban induced a significant prolongation of the prothrombin time (15.8±1.3 versus 12.3±0.7 seconds at baseline; P<0.001) that was immediately and completely reversed by PCC (12.8±1.0; P<0.001). The endogenous thrombin potential was inhibited by rivaroxaban (51±22%; baseline, 92±22%; P=0.002) and normalized with PCC (114±26%; P<0.001), whereas saline had no effect. Dabigatran increased the activated partial thromboplastin time, ecarin clotting time (ECT), and thrombin time. Administration of PCC did not restore these coagulation tests. Prothrombin complex concentrate immediately and completely reverses the anticoagulant effect of rivaroxaban in healthy subjects but has no influence on the anticoagulant action of dabigatran at the PCC dose used in this study. Clinical Trial Registration- URL: http://www.trialregister.nl. Unique identifier: NTR2272.
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            Spinal hematoma: a literature survey with meta-analysis of 613 patients.

            Spinal hematoma has been described in autopsies since 1682 and as a clinical diagnosis since 1867. It is a rare and usually severe neurological disorder that, without adequate treatment, often leads to death or permanent neurological deficit. Epidural as well as subdural and subarachnoid hematomas have been investigated. Some cases of subarachnoid spinal hematoma may present with symptoms similar to those of cerebral hemorrhage. The literature offers no reliable estimates of the incidence of spinal hematoma, perhaps due to the rarity of this disorder. In the present work, 613 case studies published between 1826 and 1996 have been evaluated, which represents the largest review on this topic to date. Most cases of spinal hematoma have a multifactorial etiology whose individual components are not all understood in detail. In up to a third of cases (29.7%) of spinal hematoma, no etiological factor can be identified as the cause of the bleeding. Following idiopathic spinal hematoma, cases related to anticoagulant therapy and vascular malformations represent the second and third most common categories. Spinal and epidural anesthetic procedures in combination with anticoagulant therapy represent the fifth most common etiological group and spinal and epidural anesthetic procedures alone represent the tenth most common cause of spinal hematoma. Anticoagulant therapy alone probably does not trigger spinal hemorrhage. It is likely that there must additionally be a "locus minoris resistentiae" together with increased pressure in the interior vertebral venous plexus in order to cause spinal hemorrhage. The latter two factors are thought to be sufficient to cause spontaneous spinal hematoma. Physicians should require strict indications for the use of spinal anesthetic procedures in patients receiving anticoagulant therapy, even if the incidence of spinal hematoma following this combination is low. If spinal anesthetic procedures are performed before, during, or after anticoagulant treatment, close monitoring of the neurological status of the patient is warranted. Time limits regarding the use of anticoagulant therapy before or after spinal anesthetic procedures have been proposed and are thought to be safe for patients. Investigation of the coagulation status alone does not necessarily provide an accurate estimate of the risk of hemorrhage. The most important measure for recognizing patients at high risk is a thorough clinical history. Most spinal hematomas are localized dorsally to the spinal cord at the level of the cervicothoracic and thoracolumbar regions. Subarachnoid hematomas can extend along the entire length of the subarachnoid space. Epidural and subdural spinal hematoma present with intense, knife-like pain at the location of the hemorrhage ("coup de poignard") that may be followed in some cases by a pain-free interval of minutes to days, after which there is progressive paralysis below the affected spinal level. Subarachnoid hematoma can be associated with meningitis symptoms, disturbances of consciousness, and epileptic seizures and is often misdiagnosed as cerebral hemorrhage based on these symptoms. Most patients are between 55 and 70 years old. Of all patients with spinal hemorrhage, 63.9% are men. The examination of first choice is magnetic resonance imaging. The treatment of choice is surgical decompression. Of the patients investigated in the present work, 39.6% experienced complete recovery. The less severe the preoperative symptoms are and the more quickly surgical decompression can be performed, the better are the chances for complete recovery. It is therefore essential to recognize the relatively typical clinical presentation of spinal hematoma in a timely manner to allow correct diagnostic and therapeutic measures to be taken to maximize the patient's chance of complete recovery.
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              Nontraumatic acute spinal subdural hematoma: report of five cases and review of the literature.

              Acute subdural spinal hematoma occurs rarely; however, when it does occur, it may have disastrous consequences. The authors assessed the outcome of surgery for this lesion in relation to causative factors and diagnostic imaging (computerized tomography [CT], CT myelography), as well as eventual preservation of the subarachnoid space. The authors reviewed 106 cases of nontraumatic acute subdural spinal hematoma (101 published cases and five of their own) in terms of cause, diagnosis, treatment, and long-term outcome. Fifty-one patients (49%) were men and 55 (51%) were women. In 70% of patients the spinal segment involved was in the lumbar or thoracolumbar spine. In 57 cases (54%) there was a defect in the hemostatic mechanism. Spinal puncture was performed in 50 patients (47%). Late surgical treatment was performed in 59 cases (56%): outcome was good in 25 cases (42%) (in 20 of these patients preoperative neurological evaluation had shown mild deficits or paraparesis, and three patients had presented with subarachnoid hemorrhage [SAH]). The outcome was poor in 34 cases (58%; 23 patients with paraplegia and 11 with SAH). The formation of nontraumatic acute spinal subdural hematomas may result from coagulation abnormalities and iatrogenic causes such as spinal puncture. Their effect on the spinal cord and/or nerve roots may be limited to a mere compressive mechanism when the subarachnoid space is preserved and the hematoma is confined between the dura and the arachnoid. It seems likely that the theory regarding the opening of the dural compartment, verified at the cerebral level, is applicable to the spinal level too. Early surgical treatment is always indicated when the patient's neurological status progressively deteriorates. The best results can be obtained in patients who do not experience SAH. In a few selected patients in whom neurological impairment is minimal, conservative treatment is possible.
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                Author and article information

                Journal
                Case Rep Hematol
                Case Rep Hematol
                CRIHEM
                Case Reports in Hematology
                Hindawi Publishing Corporation
                2090-6560
                2090-6579
                2015
                12 October 2015
                : 2015
                : 275380
                Affiliations
                1Department of Medicine, Staten Island University Hospital, North Shore-LIJ Health System, Staten Island, NY 10305, USA
                2Department of Medicine, Division of Hematology and Oncology, Staten Island University Hospital, North Shore-LIJ Health System, Staten Island, NY 10305, USA
                Author notes

                Academic Editor: Gergely Feher

                Article
                10.1155/2015/275380
                4620391
                26543654
                1427f90a-a41f-4c70-a070-d7f8c3e35cc1
                Copyright © 2015 Mazen Zaarour et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 12 July 2015
                : 14 September 2015
                : 21 September 2015
                Categories
                Case Report

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