Oral factor Xa inhibitors and risk of subdural hematoma: COMPASS trial results and meta-analysis.

OBJECTIVE: Subdural hematomas (SDHs) are an uncommon, but important, complication of anticoagulation therapy. We hypothesized that the risks of SDH would be similar during treatment with oral factor Xa inhibitors compared with aspirin. METHODS: We assessed the frequency and the effects of antithrombotic treatments on SDHs in the recent international Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) randomized trial comparing aspirin 100 mg daily, rivaroxaban 5 mg twice daily, and rivaroxaban 2.5 mg twice daily plus aspirin. A systematic review/meta-analysis of randomized trials comparing oral factor Xa inhibitors vs aspirin on SDH risk was undertaken. RESULTS: Among 27,395 COMPASS participants, 28 patients with SDHs were identified (mean age 72 years). SDH-associated mortality was 7%. Incidence was 0.06 per 100 patient-years (11 SDH/17,492 years observation) during the mean 23-month follow-up among aspirin-assigned patients and did not differ significantly between treatments. Three additional randomized controlled trials including 16,177 participants reported a total of 14 SDHs with an incidence ranging from 0.06 to 0.1 per 100 patient-years. Factor Xa inhibitor use was not associated with an increased risk of SDH compared to aspirin (odds ratio, 0.97; 95% confidence interval, 0.52-1.81; I2 = 0%). CONCLUSION: The frequency of SDH was similar in all 3 treatment arms of the COMPASS trial. The COMPASS trial results markedly increase the available evidence from randomized comparisons of oral factor Xa inhibitors with aspirin regarding SDH. From available, albeit limited, evidence from 4 randomized trials, therapeutic dosages of factor Xa inhibitors do not appear to increase the risk of SDH compared with aspirin. CLINICAL TRIAL IDENTIFIER NUMBER: NCT01776424.

Acute Intracranial and Spinal Subdural Hematoma Associated with Vardenafil.

A 28-year-old healthy man was admitted to our hospital because of right-sided headache, vomiting, and lower back pain after the administration of vardenafil. Computed tomography and magnetic resonance imaging of the brain showed a small, right-sided, subdural hematoma. A lumbar magnetic resonance imaging showed a longitudinally extended subdural hematoma. He had no history of trauma. We speculated that vardenafil might have had an association with the bleeding. Several reports have suggested a relationship between phosphodiesterase-5 inhibitors and intracerebral or subarachnoid hemorrhage. Our case suggested that there may also be risks of bleeding into the subdural space. Although headache and nausea are common side effects of vardenafil, hemorrhagic diseases should also be considered when symptoms are severe or prolonged.

A case report of parenchymal hematoma after intravenous thrombolysis in a rivaroxaban-treated patient: Is it a true rivaroxaban hemorrhagic complication?

RATIONALE: To date, the only treatment approved for acute ischemic strokes is thrombolysis. Whether intravenous thrombolysis may be safe in patients taking direct oral anticoagulants (DOACs) is currently a matter of debate. PATIENT CONCERNS: A 74-year-old woman, who was on rivaroxaban 20 mg/d for nonvalvular atrial fibrillation, was admitted to our stroke unit with left-sided hemiparesis and aphasia. The onset of neurologic deficits had occurred 5 hours after the last rivaroxaban dose. DIAGNOSIS: An acute ischemic stroke was diagnosed. INTERVENTIONS: The patient was administered thrombolytic treatment with intravenous recombinant tissue plasminogen activator (r-TPA) 3 hours and 20 minutes after symptoms onset. Seven hours post-r-TPA treatment, the neurological deficit had worsened, and a type I intraparenchymal hematoma was detected on a computed tomography brain scan. OUTCOMES: The clinical/neuroradiological picture improved significantly in the following days. The patient was discharged to a rehabilitation facility after 3 weeks. LESSONS: In this case, factor ten activated (Xa) inhibitor, rivaroxaban might have increased the risk of hemorrhagic transformation of the ischemic stroke. However, this risk was overweighed by the benefit of thrombolysis, as the patient's clinical condition had improved significantly in the following weeks. The current guidelines discourage the use of thrombolytic treatment in patients with DOACs administered within the last 24(48) hours. However, the case reported herein and other world experiences, even though limited, suggest that an ongoing DOAC medication could no longer be considered a barrier to r-TPA treatment which may be a reasonable and valuable option, at least in selected acute stroke patients taking factor Xa inhibitors.

Intracranial subdural hematomas with elevated rivaroxaban concentration and subsequently detected spinal subdural hematoma: A case report.

A 79-year-old lean man with a height of 157cm and weight of 42kg (body mass index, 17.2kg/m(2)) receiving rivaroxaban developed an intracranial subdural hematoma and was treated conservatively. Because he had a reduced creatinine clearance of 44mL/min, his dosage of rivaroxaban was reduced from 15 to 10mg daily according to official Japanese prescribing information. However, he developed bilateral intracranial subdural hematomas 2weeks later. Plasma rivaroxaban concentration on anti-factor Xa chromogenic assay was elevated at 301ng/mL, suggesting excessive accumulation. He underwent burr hole drainage and resumed anticoagulation with warfarin. Subsequently, he developed a lumbosacral hematoma. He was treated conservatively and discharged without neurological sequelae. The main cause of the increased concentration of rivaroxaban was believed to be his older age and low body weight. The etiology of the spinal hematoma was suspected to be the migration of intracranial hematoma to the spinal subdural space.

Subdural hematoma in a patient taking imatinib for GIST: a case report and discussion of risk with other chemotherapeutics.

Although anticancer drugs have existed for over 50 years, targeted drugs have only recently been marketed, and their side effects may not be completely understood. The patient is a 56-year-old woman with a gastrointestinal stromal tumor who presented with headache, nausea, and vomiting lasting 2 weeks. An MRI to rule out brain metastasis found a large right-hemispheric subdural hematoma without metastases. She denied trauma, seizures, or alcohol abuse. Laboratory test results were normal. Eight months prior, she had begun a dose escalation of imatinib, which became the suspected cause of her hemorrhage. The literature was reviewed for reports of intracranial hemorrhage with targeted chemotherapeutics excluding metastases, anticoagulation, and trauma. Multiple events have been documented but only one for imatinib with gastrointestinal stromal tumor. Imatinib is believed to cause platelet dysfunction (missed by standard testing), leading to intracranial hemorrhage. Intracranial hemorrhage risk may be under-reported and neurosurgical consultation for immediate treatment and oncology for reinitiation of chemotherapy are recommended.

Spinal subdural hematoma associated with traumatic intracranial interhemispheric subdural hematoma.

A 78-year-old female fell and hit the back of her head on the floor. Head computed tomography (CT) showed right acute interhemispheric subdural hematoma (ISDH). Her left hemiparesis worsened, so partial removal of ISDH was performed. The hemiparesis was improved, but leg monoparesis persisted. Lumbar magnetic resonance imaging showed spinal subdural hematoma (SSDH) at the S1-2 level. Nerve conduction velocity measurements at the knee joint to lower limb showed disappearance of the left peroneal nerve conduction wave, indicating that one of the causes of drop foot was common peroneal nerve palsy. With conservative therapy, her drop foot was gradually improved, then she recovered to walk with a stick and moved to a rehabilitation hospital. Lumbar MR imaging should be performed to rule out SSDH in a patient with posterior fossa subdural hematoma on initial head CT who develops leg palsy.