warfarin and Subarachnoid-Hemorrhage

Spinal subarachnoid hemorrhage is a life-threatening condition often associated with markedly high morbidity and mortality rates. However, diagnosis is difficult because of its atypical symptoms. We herein describe a 52-year-old Chinese man who had been receiving warfarin therapy since having undergone mechanical mitral valve replacement surgery 3 years previously. Two days before admission to our hospital, he suddenly developed low back pain, urinary incontinence, and paraplegia. He was diagnosed with acute myelitis at a local hospital, but he subsequently developed a slight headache and was transferred to our hospital 2 days later. The patient was suspected to have subarachnoid hemorrhage based on his computed tomography (CT) findings. On the third day after admission, a CT scan showed both subarachnoid and cerebral hemorrhage. Blood tests revealed an international normalized ratio ranging from 1.44 to 1.86 and a prothrombin time of 16.5 to 21.3 s. We performed a lumbar puncture and obtained bloody cerebrospinal fluid. The patient also underwent spinal CT and angiography, which confirmed the diagnosis of spontaneous spinal subarachnoid hemorrhage. Because his general condition was poor, he underwent conservative treatment, and his neurologic function slightly improved after discharge.

Topics: Delayed Diagnosis; Humans; Male; Middle Aged; Spinal Puncture; Spine; Subarachnoid Hemorrhage; Warfarin

Spinal subarachnoid hemorrhage (SAH) is rare clinical entity possible owing to the diluting and fibrinolytic effects of cerebrospinal fluid (CSF). When it occurs, it is most commonly encountered in the thoracic segment of the subarachnoid space. We present a case of a 50-year-old man who sustained spinal SAH in the cervical and thoracic segments related to anticoagulant therapy. He progressed to significant neurological deficit since he was inoperable, an observation that supports the need for decompression surgery. We should be aware of potential hematomyelia should a patient on anticoagulant therapy develop neurological symptoms localized to the spinal cord. When available, magnetic resonance (MR) imaging is the modality of choice to diagnose and follow-up spinal SAH.

Topics: Anticoagulants; Humans; Magnetic Resonance Imaging; Male; Middle Aged; Subarachnoid Hemorrhage; Tomography, X-Ray Computed; Warfarin

Elderly patients with nonvalvular atrial fibrillation (NVAF) might have a higher risk of intracerebral hemorrhage. To investigate this, we compared the incidence of intracranial hemorrhage (ICH) and its subtypes, as well as ischemic stroke, in patients taking direct oral anticoagulants (DOACs) compared with warfarin in a real-world setting. We also determined the baseline characteristics associated with both ICH and ischemic stroke.. Patients aged ⩾ 75 years with documented NVAF enrolled in the prospective, multicenter, observational All Nippon Atrial Fibrillation in the Elderly Registry between October 2016 and January 2018 were evaluated. The co-primary endpoints were the incidence of ischemic stroke and ICH. Secondary endpoints included subtypes of ICH.. Of 32,275 patients (13,793 women; median age, 81.0 years) analyzed, 21,585 (66.9%) were taking DOACs and 8233 (25.5%) were taking warfarin. During the median 1.88-year follow-up, 743 patients (1.24/100 person-years) developed ischemic stroke and 453 (0.75/100 person-years) developed ICH (intracerebral hemorrhage, 189; subarachnoid hemorrhage, 72; subdural/epidural hemorrhage, 190; unknown subtype, 2). The incidence of ischemic stroke (adjusted hazard ratio (aHR) 0.82, 95% confidence interval (CI) 0.70-0.97), ICH (aHR 0.68, 95% CI 0.55-0.83), and subdural/epidural hemorrhage (aHR 0.53, 95% CI 0.39-0.72) was lower in DOAC users versus warfarin users. The incidence of fatal ICH and fatal subarachnoid hemorrhage was also lower in DOAC users versus warfarin users. Several baseline characteristics other than anticoagulants were also associated with the incidence of the endpoints. Of these, history of cerebrovascular disease (aHR 2.39, 95% CI 2.05-2.78), persistent NVAF, (aHR 1.90, 95% CI 1.53-2.36), and long-standing persistent/permanent NVAF (aHR 1.92, 95% CI 1.60-2.30) was strongly associated with ischemic stroke; severe hepatic disease (aHR 2.67, 95% CI 1.46-4.88) was strongly associated with overall ICH; and history of fall within 1 year was strongly associated with both overall ICH (aHR 2.29, 95% CI 1.76-2.97) and subdural/epidural hemorrhage (aHR 2.90, 95% CI 1.99-4.23).. Patients aged ⩾ 75 years with NVAF taking DOACs had lower risks of ischemic stroke, ICH, and subdural/epidural hemorrhage than those taking warfarin. Fall was strongly associated with the risks of intracranial and subdural/epidural hemorrhage.. The individual de-identified participant data and study protocol will be shared for up to 36 months after the publication of the article. Access criteria for data sharing (including requests) will be decided on by a committee led by Daiichi Sankyo. To gain access, those requesting data access will need to sign a data access agreement. Requests should be directed to yamt-tky@umin.ac.jp.

Topics: Administration, Oral; Aged; Aged, 80 and over; Anticoagulants; Atrial Fibrillation; Cerebral Hemorrhage; Female; Humans; Intracranial Hemorrhages; Ischemic Stroke; Prospective Studies; Registries; Stroke; Subarachnoid Hemorrhage; Treatment Outcome; Warfarin

An increased risk of recurrent stroke is noted in patients with atrial fibrillation despite direct oral anticoagulant (DOAC) use. We investigated the efficacy and safety of treatment with each of 4 different DOACs or warfarin after DOAC failure.. We retrospectively analyzed patients with atrial fibrillation with ischemic stroke despite DOAC treatment between January 2002 and December 2016. The different outcomes of patients with DOAC failure were compared, including recurrent ischemic stroke, major cardiovascular events, intracranial hemorrhage and subarachnoid hemorrhage, mortality, and net composite outcomes according to switching to different DOACs or vitamin K antagonist after index ischemic stroke. We identified 3759 patients with DOAC failure. A total of 84 patients experienced recurrent ischemic stroke after switching to different oral anticoagulants, with a total follow-up time of 14 years. Using the vitamin K antagonist group as a reference, switching to any of the 4 DOACs was associated with a 69% to 77% reduced risk of major cardiovascular events (adjusted hazard ratio [aHR], 0.25 [95% CI, 0.16-0.39] for apixaban, 0.23 [95% CI, 0.14-0.37] for dabigatran, 0.23 [95% CI, 0.09-0.60] for edoxaban, and 0.31 [95% CI, 0.21-0.45] for rivaroxaban), and a 69% to 83% reduced risk of net composite outcomes (aHR, 0.25 [95% CI, 0.18-0.35] for apixaban, 0.17 [95% CI, 0.11-0.25] for dabigatran, 0.31 [95% CI, 0.17-0.56] for edoxaban, and 0.31 [95% CI, 0.23-0.41] for rivaroxaban).. In Asian patients with DOAC failure, continuing DOACs after index stroke was associated with fewer undesirable outcomes than switching to a vitamin K antagonist. Alternative pharmacologic and nonpharmacologic strategies warrant investigation.

Topics: Administration, Oral; Anticoagulants; Atrial Fibrillation; Dabigatran; Humans; Ischemic Stroke; Retrospective Studies; Rivaroxaban; Stroke; Subarachnoid Hemorrhage; Vitamin K; Warfarin

Patients with mechanical heart valves are at high thrombotic risk and require warfarin. Among those developing intracranial hemorrhage, limited data are available to guide clinicians with antithrombotic reinitiation. This 13-patient case series of warfarin-associated intracranial hemorrhages found the time to reinitiate antithrombotic therapy (17 days, interquartile range 21.5 days), and changes to international normalized ratio targets were variable and neither correlated with the type, location, or etiology of bleed, nor the valve and associated thromboembolic risk. The initial presentation significantly impacted prognosis, and diligent assessment and follow-up may support positive long-term outcomes.

Topics: Aged; Anticoagulants; Antifibrinolytic Agents; Aortic Valve; Aspirin; Blood Coagulation Factors; Cerebral Hemorrhage; Female; Heart Valve Prosthesis; Hematoma, Subdural; Humans; International Normalized Ratio; Intracranial Hemorrhages; Male; Middle Aged; Mitral Valve; Plasma; Platelet Aggregation Inhibitors; Pregnancy; Retrospective Studies; Subarachnoid Hemorrhage; Subarachnoid Hemorrhage, Traumatic; Thromboembolism; Vitamin K; Warfarin

Background and Purpose- The effects of anticoagulation therapy and elevated international normalized ratio (INR) values on the risk of aneurysmal subarachnoid hemorrhage are unknown. We aimed to investigate the association between anticoagulation therapy, elevated INR values, and rupture of intracranial aneurysms. Methods- We conducted a case-control study of 4696 patients with 6403 intracranial aneurysms, including 1198 prospective patients, diagnosed at the Massachusetts General Hospital and the Brigham and Women's Hospital between 1990 and 2016 who were on no anticoagulant therapy or on warfarin for anticoagulation. Patients were divided into ruptured and nonruptured groups. Univariable and multivariable logistic regression analyses were performed to evaluate the association of anticoagulation therapy, INR values, and presentation with a ruptured intracranial aneurysm, taking into account the interaction between anticoagulant use and INR. Inverse probability weighting using propensity scores was used to minimize differences in baseline demographics characteristics. The marginal effects of anticoagulant use on rupture risk stratified by INR values were calculated. Results- In unweighted and weighted multivariable analyses, elevated INR values were significantly associated with rupture status among patients who were not anticoagulated (unweighted odds ratio, 22.78; 95% CI, 10.85-47.81 and weighted odds ratio, 28.16; 95% CI, 12.44-63.77). In anticoagulated patients, warfarin use interacts significantly with INR when INR ≥1.2 by decreasing the effects of INR on rupture risk. Conclusions- INR elevation is associated with intracranial aneurysm rupture, but the effects may be moderated by warfarin. INR values should, therefore, be taken into consideration when counseling patients with intracranial aneurysms.

Topics: Adult; Aged; Aneurysm, Ruptured; Anticoagulants; Case-Control Studies; Female; Humans; International Normalized Ratio; Intracranial Aneurysm; Logistic Models; Male; Middle Aged; Multivariate Analysis; Odds Ratio; Propensity Score; Risk Factors; Rupture, Spontaneous; Subarachnoid Hemorrhage; Warfarin

Previously reported only a few times before, we present a case of extracranial vertebral dissection and spontaneous frontoparietal subarachnoid hemorrhage (SAH) in the puerperium, discussing possible mechanisms and difficulties in management. A 35-year-old woman presented 10 days postcaesarean section with neck pain and vertigo with normal initial investigations. Following recurrent vertigo, headache, and ataxia, imaging revealed a frontoparietal SAH and vertebral artery dissection. The patient was consequently treated with aspirin, and then following a return of symptoms 3 weeks later, warfarin therapy was continued for 6 months. The possible underlying mechanisms for this case are discussed, including reversible cervical vasoconstriction syndrome and posterior reversible encephalopathy syndrome, although neither was identified. The small SAH alongside recurrent posterior circulation symptoms resulted in the initiation of antithrombotic therapy. This report supports studies demonstrating higher incidence of cervicocephalic arterial dissection in the puerperium. Moreover, the heterogeneous presentation and manifestations of such cases require individualized treatment, and warrant studies into underlying mechanisms behind extracranial dissection and nonaneurysmal SAH.

Topics: Adult; Anticoagulants; Aspirin; Female; Humans; Neck Pain; Puerperal Disorders; Subarachnoid Hemorrhage; Treatment Outcome; Vertebral Artery Dissection; Vertigo; Warfarin

Subarachnoid hemorrhage (SAH) associated with anticoagulation is a rare event. About 30% of in-hospital patients with aneurysmal SAH develop delayed cerebral ischemia (DCI); however, the occurrence of vasospasm and DCI in patients with nonaneurysmal SAH is still controversial.. This study is a case report of a patient experiencing an anticoagulation-induced SAH complicated by vasospasm and DCI.. A 38-year-old woman presented to our hospital with a sudden onset of severe headache. Head computed tomography (CT) showed bleeding in the posterior fossa subarachnoid space. There was no aneurysm in the CT angiography. The International Normalized Ratio at hospital admission was 9. Anticoagulation was held, and she was treated with fresh frozen plasma (15 mg/kg) and parenteral vitamin K. The patient remained in the intensive care unit and had daily transcranial Doppler (TCD) monitorization. TCD examination detected increased blood flow velocities in the basilar and vertebral arteries, meeting criteria for definitive vasospasm. CT angiography confirmed the presence of posterior circulation vasospasm. Magnetic resonance (MR) imaging 2 weeks after the bleeding showed a small area of restricted diffusion in the left superior cerebellar artery territory. MR angiography showed resolution of the vasospasm at this time point and TCD velocities normalized.. In conclusion, this case report suggests that vasospasm and consequent DCI is a possible mechanism of secondary lesion after anticoagulation-induced SAH. To our knowledge, this is the first report of vasospasm and DCI due to warfarin-associated SAH.

Topics: Adult; Anticoagulants; Brain Ischemia; Female; Humans; Magnetic Resonance Angiography; Magnetic Resonance Imaging; Subarachnoid Hemorrhage; Ultrasonography, Doppler, Transcranial; Vasospasm, Intracranial; Warfarin

Warfarin-associated intracranial hemorrhage is associated with a high mortality rate. Ongoing coagulopathy increases the likelihood of hematoma expansion and can result in catastrophic hemorrhage if surgery is performed without reversal. The current standard of care for emergency reversal of warfarin is with fresh frozen plasma (FFP). In April 2013, the USA Food and Drug Administration approved a new reversal agent, 4-factor prothrombin complex concentrate (PCC), which has the potential to more rapidly correct coagulopathy. We sought to determine the feasibility and outcomes of using PCC for neurosurgical patients. A prospective, observational study of all patients undergoing coagulopathy reversal for intracranial hemorrhage from April 2013 to December 2013 at a single, tertiary care center was undertaken. Thirty three patients underwent emergent reversal of coagulopathy using either FFP or PCC at the discretion of the treating physician. Intracranial hemorrhage included subdural hematoma, intraparenchymal hematoma, and subarachnoid hemorrhage. FFP was used in 28 patients and PCC was used in five patients. International normalized ratio at presentation was similar between groups (FFP 2.9, PCC 3.1, p=0.89). The time to reversal was significantly shorter in the PCC group (FFP 256 minutes, PCC 65 minutes, p<0.05). When operations were performed, the time delay to perform operations was also significantly shorter in the PCC group (FFP 307 minutes, PCC 159 minutes, p<0.05). In this preliminary experience, PCC appears to provide a rapid reversal of coagulopathy. Normalization of coagulation parameters may prevent further intracranial hematoma expansion and facilitate rapid surgical evacuation, thereby improving neurological outcomes.

Topics: Anticoagulants; Antidotes; Blood Coagulation Factors; Brain Injuries; Hemorrhage; Humans; International Normalized Ratio; Intracranial Hemorrhages; Plasma; Practice Guidelines as Topic; Prospective Studies; Randomized Controlled Trials as Topic; Spinal Diseases; Subarachnoid Hemorrhage; Tertiary Care Centers; Warfarin

A case of thrombus formation occurring within a dilation of the dural venous sinuses following aneurysmal sub-arachnoid haemorrhage is presented. Acute neurological deterioration accompanied propagation of the thrombus. The patient was anticoagulated on day 5 post-SAH with no haemorrhagic complications and made a full recovery. The optimum time to commence anticoagulation is not clear and is discussed.

Topics: Adult; Anticoagulants; Cerebral Angiography; Cranial Sinuses; Female; Humans; Subarachnoid Hemorrhage; Thrombosis; Tomography, X-Ray Computed; Treatment Outcome; Warfarin

We report a rare case of simultaneous cranial subarachnoid and spinal subdural hematoma (SDH) in a 42-year-old man who was on Warfarin therapy after cardiac bypass surgery. Computed tomography at presentation revealed a cranial subarachnoid hemorrhage, and spinal Magnetic Resonance Imaging (MRI) showed a spinal SDH extending from the T6 to L5 segments. He had paraparesis due to spinal cord compression. The patient was managed conservatively due to his poor general condition and was infused with intravenous steroid therapy, but he experienced sudden cardiac arrest 5 hours later after being admitted to the hospital. This case is of interest because of its first presentation of spinal subdural hematoma and cranial subarachnoid hemorrhage simultaneously and it is also the second longest vertebral segmental spread in the literature.

Topics: Adult; Anticoagulants; Coronary Artery Bypass; Death, Sudden, Cardiac; Fatal Outcome; Hematoma, Subdural, Spinal; Humans; Magnetic Resonance Imaging; Male; Spinal Cord Compression; Subarachnoid Hemorrhage; Warfarin

Oral anticoagulant therapy with vitamin K antagonists is associated with an increased risk of bleeding, particularly gastrointestinal bleeding. It remains unclear, however, whether use of these medications is a risk factor for subarachnoid haemorrhage (SAH). We therefore examined the association between oral vitamin K antagonist use and risk of SAH.. We conducted this population-based case-control study using medical databases in Northern Denmark (population 1,150,000). We identified 1188 patients admitted to neurologic or neurosurgical departments with a first-time diagnosis of SAH between 1996 and 2008 and 11,880 population controls. We obtained information on use of vitamin K antagonists, other medication use, and comorbidity. We used logistic regression analysis to compute odds ratios (ORs) comparing oral anticoagulant users and non-users, controlling for potential confounding factors.. 9 cases (0.8%) and 157 controls (1.3%) were current users of vitamin K antagonists (at least one prescription filled within 90 days of the diagnosis/index date). Current use of vitamin K antagonists was not associated with increased SAH risk compared with non-use [adjusted OR=0.80 (95% CI: 0.37-1.74)]. Changing the exposure window from 90 days to 120 days or to 60 days before the diagnosis/index date did not change the estimate substantially.. We found no evidence to support an association between use of vitamin K antagonists and increased SAH risk.

Topics: Adolescent; Adult; Aged; Anticoagulants; Case-Control Studies; Confidence Intervals; Female; Humans; Logistic Models; Male; Middle Aged; Odds Ratio; Phenprocoumon; Risk Factors; Subarachnoid Hemorrhage; Thromboembolism; Vitamin K; Warfarin; Young Adult

Topics: Adult; Anticoagulants; Contraceptives, Oral; Female; Humans; Risk Factors; Smoking; Subarachnoid Hemorrhage; Warfarin

Patients with intracranial vertebrobasilar artery (VBA) atherosclerotic occlusive disease have few therapeutic options. Unfortunately, VBA transient ischemic attacks (TIAs) herald a lethal or devastating event within 5 years in 25 to 30% of patients. The authors report their initial experience with eight patients in whom medically refractory TIAs secondary to intracranial posterior circulation atherosclerotic occlusive lesions were treated with stent-assisted angioplasty.. Eight patients (six men), ranging in age from 43 to 77 years, experienced signs and symptoms of VBA insufficiency despite combination therapy with warfarin and antiplatelet agents. Angiographic studies revealed severe distal vertebral (four patients), proximal basilar (one patient), or proximal and midbasilar stenoses (three patients). Aspirin and clopidogrel were administered for 3 days before primary angioplasty and stent placement, and this regimen was maintained by the patients on discharge. Patients underwent heparinization during the procedure and were given a bolus and 12-hour infusion of abciximab. A neurologist specializing in stroke evaluated all patients before and after the procedure. The VBAs in all patients were successfully revascularized with 7 to 28% residual stenosis. Six patients experienced no neurological complications. One patient died the evening of the procedure due to a massive subarachnoid hemorrhage. Two patients had groin hematomas, one developed congestive heart failure, and one had transient encephalopathy. All surviving patients are asymptomatic up to 8 months postoperatively.. Although primary intracranial VBA angioplasty with stent insertion is technically feasible, complications associated with the procedure can be life threatening. As experience is gained with this procedure, it may be offered routinely as an alternative therapy to patients with medically refractory posterior circulation occlusive disease that may develop into catastrophic VBA insufficiency.

Topics: Abciximab; Adult; Aged; Angiography; Angioplasty; Antibodies, Monoclonal; Anticoagulants; Aspirin; Basilar Artery; Cerebrovascular Circulation; Clopidogrel; Female; Follow-Up Studies; Heparin; Humans; Immunoglobulin Fab Fragments; Intracranial Arteriosclerosis; Ischemic Attack, Transient; Male; Middle Aged; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Premedication; Stents; Stroke; Subarachnoid Hemorrhage; Ticlopidine; Vertebral Artery; Vertebrobasilar Insufficiency; Warfarin

Topics: Adult; Anticoagulants; Female; Humans; Magnetic Resonance Imaging; Phenobarbital; Subarachnoid Hemorrhage; Tomography, X-Ray Computed; Warfarin

The incidence of spontaneous intracranial haemorrhage has increased markedly in line with the increased use of oral anticoagulant agents. Recent guidelines for reversal of this acquired coagulation defect in an emergency have been established, but they are not adhered to in all centres. Our unit is referred between 20 and 60 patients per year (1994-1999) who are anticoagulated and require urgent neurosurgical intervention. In order to investigate this, we performed a prospective study using prothrombin complex concentrate (PCC). PCC was given to the first six patients with intracranial haemorrhage admitted to the neurosurgical unit requiring urgent correction of anticoagulation (Group 1) and compared with patients receiving standard treatment with fresh frozen plasma and vitamin K (Group 2). Mean International Normalised Ratios of Group 1 were 4.86 pretreatment and 1.32 posttreatment, and of Group 2 were 5.32 and 2.30, respectively. Results for complete reversal and reversal time were significant for PCC with p < 0.001. We recommend PCC for rapid and effective reversal of warfarin in life-threatening neurosurgical emergencies.

Topics: Adult; Aged; Anticoagulants; Blood Coagulation Factors; Cerebral Hemorrhage; Emergencies; Female; Hematoma, Subdural; Humans; International Normalized Ratio; Male; Middle Aged; Pilot Projects; Preoperative Care; Prospective Studies; Subarachnoid Hemorrhage; Vitamin K; Warfarin

A 45-year-old woman with prosthetic valves replacement, was admitted with severe headache and vomiting one month after starting danazol treatment at 300 mg per day. She was receiving long-term anticoagulation with warfarin and dipyridamole, taking 3.5 mg and 300 mg per day respectively. The patient's thrombotest value was less than 6% at the time of admission. Cranial CT revealed subarachnoid hemorrhage. Warfarin and danazol treatment ware discontinued with replenishment of vitamin K. Recovery was uneventful. Danazol is 2, 3 isoxazol derivative of 17-alpha-ethinyl testosterone. As such, it shares the property of C 17 alkylated steroids in potentiating the action of coumarin. It is suggested that danazol affects the turnover of vitamin-K-dependent clotting factors, an impairment of synthesis being a likely mechanism. The possible hazard of the potentiating effect of danazol on warfarin should be widely appreciated.

Topics: Aortic Valve Insufficiency; Blood Coagulation; Danazol; Drug Therapy, Combination; Female; Heart Valve Prosthesis; Humans; Middle Aged; Mitral Valve Insufficiency; Subarachnoid Hemorrhage; Warfarin

Topics: Adolescent; Drug Synergism; Female; Humans; Partial Thromboplastin Time; Prothrombin Time; Subarachnoid Hemorrhage; Thyroxine; Warfarin

Topics: Humans; Male; Middle Aged; Neurilemmoma; Spinal Cord Diseases; Spinal Cord Neoplasms; Subarachnoid Hemorrhage; Warfarin

Topics: Autopsy; Cerebral Angiography; Cerebral Arterial Diseases; Cerebral Arteries; Female; Humans; Middle Aged; Pons; Rupture, Spontaneous; Subarachnoid Hemorrhage; Warfarin

Topics: Anticoagulants; Blood Coagulation Tests; Cerebrospinal Fluid; Chiropractic; Female; Hematoma; Humans; Laminectomy; Meninges; Middle Aged; Neurologic Manifestations; Prothrombin Time; Spinal Diseases; Subarachnoid Hemorrhage; Warfarin