2011AHA ASA脑静脉血栓形成指南

ISSN: 1524-4628 Copyright © 2011 American Heart Association. All rights reserved. Print ISSN: 0039-2499. Online Stroke is published by the American Heart Association. 7272 Greenville Avenue, Dallas, TX 72514 DOI: 10.1161/STR.0b013e31820a8364 published online Feb 3, 2011; Stroke on Epidemiology and Prevention Tsai and on behalf of the American Heart Association Stroke Council and the Council Y.Bushnell, Brett Cucchiara, Mary Cushman, Gabrielle deVeber, Jose M. Ferro, Fong Gustavo Saposnik, Fernando Barinagarrementeria, Robert D. Brown, Jr, Cheryl D. Association StrokeHealthcare Professionals From the American Heart Association/American Diagnosis and Management of Cerebral Venous Thrombosis: A Statement for http://stroke.ahajournals.org located on the World Wide Web at: The online version of this article, along with updated information and services, is http://www.lww.com/reprints Reprints: Information about reprints can be found online at journalpermissions@lww.com 410-528-8550. E-mail: Fax:Kluwer Health, 351 West Camden Street, Baltimore, MD 21202-2436. Phone: 410-528-4050. Permissions: Permissions & Rights Desk, Lippincott Williams & Wilkins, a division of Wolters http://stroke.ahajournals.org/subscriptions/ Subscriptions: Information about subscribing to Stroke is online at by on February 7, 2011 stroke.ahajournals.orgDownloaded from AHA Scientific Statement Diagnosis and Management of Cerebral Venous Thrombosis A Statement for Healthcare Professionals From the American Heart Association/American Stroke Association The American Academy of Neurology affirms the value of this statement as an educational tool for neurologists. The American Association of Neurological Surgeons and Congress of Neurological Surgeons have reviewed this document and affirm its educational content. The Ibero-American Stroke Society (Sociedad Iberoamericana de Enfermedad Cerebrovascular) endorses the recommendations contained in this report. Endorsed by the Society of NeuroInterventional Surgery Gustavo Saposnik, MD, MSc, FAHA, Chair; Fernando Barinagarrementeria, MD, FAHA, FAAN; Robert D. Brown, Jr, MD, MPH, FAHA, FAAN; Cheryl D. Bushnell, MD, MHS, FAHA; Brett Cucchiara, MD, FAHA; Mary Cushman, MD, MSc, FAHA; Gabrielle deVeber, MD; Jose M. Ferro, MD, PhD; Fong Y. Tsai, MD; on behalf of the American Heart Association Stroke Council and the Council on Epidemiology and Prevention Background—The purpose of this statement is to provide an overview of cerebral venous sinus thrombosis and to provide recommendations for its diagnosis, management, and treatment. The intended audience is physicians and other healthcare providers who are responsible for the diagnosis and management of patients with cerebral venous sinus thrombosis. Methods and Results—Members of the panel were appointed by the American Heart Association Stroke Council’s Scientific Statement Oversight Committee and represent different areas of expertise. The panel reviewed the relevant literature with an emphasis on reports published since 1966 and used the American Heart Association levels-of-evidence grading algorithm to rate the evidence and to make recommendations. After approval of the statement by the panel, it underwent peer review and approval by the American Heart Association Science Advisory and Coordinating Committee. Conclusions—Evidence-based recommendations are provided for the diagnosis, management, and prevention of recurrence of cerebral venous thrombosis. Recommendations on the evaluation and management of cerebral venous thrombosis during pregnancy and in the pediatric population are provided. Considerations for the management of clinical complications (seizures, hydrocephalus, intracranial hypertension, and neurological deterioration) are also summarized. An algorithm for diagnosis and management of patients with cerebral venous sinus thrombosis is described. (Stroke. 2011;42:00-00.) Key Words: AHA Scientific Statements � venous thrombosis � sinus thrombosis, intracranial � brain infarction, venous � stroke � disease management � prognosis � outcome assessment � anticoagulants � pregnancy � children Author order is alphabetical after the writing group chair. All authors have contributed equally to the present work. The American Heart Association makes every effort to avoid any actual or potential conflicts of interest that may arise as a result of an outside relationship or a personal, professional, or business interest of a member of the writing panel. Specifically, all members of the writing group are required to complete and submit a Disclosure Questionnaire showing all such relationships that might be perceived as real or potential conflicts of interest. This statement was approved by the American Heart Association Science Advisory and Coordinating Committee on October 26, 2010. A copy of the statement is available at http://www.americanheart.org/presenter.jhtml?identifier�3003999 by selecting either the “topic list” link or the “chronological list” link (No. KB-0186). To purchase additional reprints, call 843-216-2533 or e-mail kelle.ramsay@wolterskluwer.com. The American Heart Association requests that this document be cited as follows: Saposnik G, Barinagarrementeria F, Brown RD Jr, Bushnell CD, Cucchiara B, Cushman M, deVeber G, Ferro JM, Tsai FY; on behalf of the American Heart Association Stroke Council and the Council on Epidemiology and Prevention. Diagnosis and management of cerebral venous thrombosis: a statement for healthcare professionals from the American Heart Association/American Stroke Association. Stroke. 2011;42:●●●–●●●. Expert peer review of AHA Scientific Statements is conducted at the AHA National Center. For more on AHA statements and guidelines development, visit http://www.americanheart.org/presenter.jhtml?identifier�3023366. Permissions: Multiple copies, modification, alteration, enhancement, and/or distribution of this document are not permitted without the express permission of the American Heart Association. Instructions for obtaining permission are located at http://www.americanheart.org/presenter.jhtml? identifier�4431. A link to the “Permission Request Form” appears on the right side of the page. © 2011 American Heart Association, Inc. Stroke is available at http://stroke.ahajournals.org DOI: 10.1161/STR.0b013e31820a8364 1 by on February 7, 2011 stroke.ahajournals.orgDownloaded from Thrombosis of the dural sinus and/or cerebral veins (CVT)is an uncommon form of stroke, usually affecting young individuals.1 Despite advances in the recognition of CVT in recent years, diagnosis and management can be difficult because of the diversity of underlying risk factors and the absence of a uniform treatment approach. CVT represents �0.5% to 1% of all strokes.2 Multiple factors have been associated with CVT, but only some of them are reversible. Prior medical conditions (eg, thrombophilias, inflammatory bowel disease), transient situations (eg, pregnancy, dehydra- tion, infection), selected medications (eg, oral contraceptives, substance abuse), and unpredictable events (eg, head trauma) are some predisposing conditions.3,4 Given the diversity of causes and presenting scenarios, CVT may commonly be encountered not only by neurologists and neurosurgeons but also by emergency physicians, inter- nists, oncologists, hematologists, obstetricians, pediatricians, and family practitioners. Our purpose in the present scientific statement is to review the literature on CVT and to provide recommendations for its diagnosis and management. Writing group members were appointed by the American Heart Association (AHA) Stroke Council’s Scientific Statement Oversight Committee and the Council on Epidemiology and Prevention. The panel included members with several differ- ent areas of expertise. The panel reviewed relevant articles on CVT in adults and children using computerized searches of the medical literature through July 2010. These articles were supplemented by other articles known to the authors. The evidence is organized within the context of the AHA frame- work and is classified according to the joint AHA/American College of Cardiology Foundation and supplementary AHA Stroke Council methods of classifying the level of certainty and the class and level of evidence (Tables 1 and 2).5 After review by the panel members, the manuscript was reviewed by expert peer reviewers and members of the Stroke Council Leadership Committee and was subsequently approved by the AHA’s Science Advisory and Coordinating Committee. Although information about the cause and clinical mani- festations of CVT is included for the convenience of readers who may be unfamiliar with these topics, the group’s recom- mendations emphasize issues regarding diagnosis, manage- ment, and treatment. The recommendations are based on the current available evidence and were approved by all members of the writing group. Despite major progress in the evaluation and management of this rare condition in recent years, much of the literature remains descriptive. In some areas, evidence is lacking to guide decision making; however, the writing group made an effort to highlight those areas and provide suggestions, with the understanding that some physicians may need more guidance, particularly in making decisions when extensive evidence is not available. Continued research is essential to better understand issues related to the diagnosis and treatment of CVT. Identification of subgroups at higher risk would allow a more careful selection of patients who may benefit from selective interventions or therapies. Epidemiology and Risk Factors for CVT CVT is an uncommon and frequently unrecognized type of stroke that affects approximately 5 people per million annu- ally and accounts for 0.5% to 1% of all strokes.1 CVT is more commonly seen in young individuals. According to the largest cohort study (the International Study on Cerebral Venous and Dural Sinuses Thrombosis [ISCVT]), 487 (78%) of 624 cases occurred in patients �50 years of age (Figure 1).1,6 Clinical features are diverse, and for this reason, cases should be sought among diverse clinical index conditions. A prior pathological study found a prevalence of CVT of 9.3% among 182 consecutive autopsies.7 No population studies have reported the incidence of CVT. Very few stroke regis- tries included cases with CVT. This may result in an overestimation of risk associated with the various conditions owing to referral and ascertainment biases. In the Registro Nacional Mexicano de Enfermedad Vascular Cerebral (RENAMEVASC), a multihospital prospective Mexican stroke registry, 3% of all stroke cases were CVT.8 A clinic-based registry in Iran reported an annual CVT incidence of 12.3 per million.9 In a series of intracerebral hemorrhage (ICH) cases in young people, CVT explained 5% of all cases.9 Cause and Pathogenesis: Underlying Risk Factors for CVT Predisposing causes of CVT are multiple. The risk factors for venous thrombosis in general are linked classically to the Virchow triad of stasis of the blood, changes in the vessel wall, and changes in the composition of the blood. Risk factors are usually divided into acquired risks (eg, surgery, trauma, preg- nancy, puerperium, antiphospholipid syndrome, cancer, exoge- nous hormones) and genetic risks (inherited thrombophilia). Table 3 summarizes the evidence for a cause-and-effect relationship10,11 between prothrombotic factors and CVT.12–55 Evidence for the strength and consistency of association, bio- logical plausibility, and temporality is summarized. These crite- ria are most closely met for deficiency of antithrombin III, protein C, and protein S; factor V Leiden positivity; use of oral contraceptives; and hyperhomocysteinemia, among others. Prothrombotic Conditions The most widely studied risk factors for CVT include prothrom- botic conditions. The largest study, the ISCVT, is a multina- tional, multicenter, prospective observational study with 624 patients. Thirty-four percent of these patients had an inherited or acquired prothrombotic condition.10 The prevalence of different prothrombotic conditions is summarized in Table 3. Recently, another group in the United States reported that 21% of 182 CVT case subjects in 10 hospitals had a prothrombotic condition.11 Antithrombin III, Protein C, and Protein S Deficiency Two studies have analyzed the role of natural anticoagulant protein deficiencies (antithrombin III, protein C, and protein S) as risk factors for CVT. One study compared 121 patients with a first CVT with 242 healthy control subjects.36 The other study compared 51 patients with CVT with 120 healthy control subjects.12 Only 1 patient (2%) had antithrombin III deficiency. The combined odds ratio (OR) of CVT when these 2 studies were combined was 11.1 for protein C deficiency (95% confi- 2 Stroke April 2011 by on February 7, 2011 stroke.ahajournals.orgDownloaded from dence interval [CI] 1.87 to 66.05; P�0.009) and 12.5 for protein S deficiency (95% CI 1.45 to 107.29; P�0.03). Antiphospholipid and Anticardiolipin Antibodies The first study mentioned above found a higher prevalence of antiphospholipid antibodies in patients with CVT (9 of 121) than in control subjects (0 of 242).36 In another study from India with 31 CVT patients, anticardiolipin antibodies were detected in 22.6% of CVT patients compared with 3.2% of normal control subjects.12 Similar findings (5.9%) were observed in the ISCVT study.10 Factor V Leiden Gene Mutation and Resistance to Activated Protein C Resistance to activated protein C is mainly caused by the presence of the factor V Leiden gene mutation, which is a common inherited thrombophilic disorder. A recent meta-anal- ysis of 13 studies, including 469 CVT cases and 3023 control subjects,28 reported a pooled OR of CVT of 3.38 (95% CI 2.27 to 5.05) for factor V Leiden, which is similar to its association with venous thromboembolism (VTE) in general.28 Prothrombin G20210A Mutation The prothrombin G20210A mutation is present in �2% of whites and causes a slight elevation of prothrombin level.55,56A meta-analysis of 9 studies,38 including 360 CVT patients and 2688 control subjects, reported a pooled OR of CVT of 9.27 (95% CI 5.85 to 14.67) for this mutation,28 which is stronger than its association with VTE in general. Hyperhomocysteinemia Hyperhomocysteinemia is a risk factor for deep vein thrombosis (DVT) and stroke but has not been clearly associated with an increased risk of CVT. Five case-control studies evaluated Table 1. Applying Classification of Recommendations and Level of Evidence *Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as gender, age, history of diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use. A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Even though randomized trials are not available, there may be a very clear clinical consensus that a particular test or therapy is useful or effective. †For recommendations (Class I and IIa; Level of Evidence A and B only) regarding the comparative effectiveness of one treatment with respect to another, these words or phrases may be accompanied by the additional terms “in preference to” or “to choose” to indicate the favored intervention. For example, “Treatment A is recommended in preference to Treatment B for. . . ” or “It is reasonable to choose Treatment A over Treatment B for….” Studies that support the use of comparator verbs should involve direct comparisons of the treatments or strategies being evaluated. Saposnik et al Diagnosis and Management of Cerebral Venous Thrombosis 3 by on February 7, 2011 stroke.ahajournals.orgDownloaded from hyperhomocysteinemia in patients with CVT.13,16,17,29,30 Re- searchers from Milan13 reported on 121 patients with a first CVT and 242 control subjects, finding hyperhomocysteinemia in 33 patients (27%) and 20 control subjects (8%; OR 4.2, 95% CI 2.3 to 7.6). Low levels of serum folate and the 677TT methylene- tetrahydrofolate reductase genotype were not associated with CVT risk, independent of homocysteine level.13 A study of 45 patients with CVT and 90 control subjects in Mexico reported an adjusted OR of CVT of 4.6 (95% CI 1.6 to 12.8) associated with high fasting homocysteine and an OR of 3.5 (95% CI 1.2 to 10.0) associated with low folate.29 A small Italian study of 26 consecutive patients with CVT and 100 healthy control subjects reported that 38.5% of case subjects and 13% of control subjects had hyperhomocysteinemia (OR 4.2, 95% CI 1.6 to 11.2).16 No significant differences were found in the prevalence of prothrombin or methylenetetrahydrofolate reductase mutation. No factor V Leiden mutation was found. Another Italian group17 found a strong and significant associa- tion of the prothrombin G20210A mutation (30% versus 2.5% in patients versus control subjects, respectively, P�0.001; OR 16.2, P�0.002) and hyperhomocysteinemia (43.3% versus 10%, P�0.002; OR 6.9, P�0.002). Pregnancy and Puerperium Pregnancy and the puerperium are common causes of tran- sient prothrombotic states.57 Approximately 2% of pregnancy-associated strokes are attributable to CVT.31 The frequency of CVT in the puerperium is estimated at 12 cases per 100 000 deliveries, only slightly lower than puerperal arterial stroke.58 In a study from Mexico, �50% of CVT occurred during pregnancy or puerperium.32 Most pregnancy-related CVT occurs in the third trimester or puerperium. Seven of 8 CVTs among 50 700 admissions for delivery in Canada occurred postpartum.33 During pregnancy and for 6 to 8 weeks after birth, women are at increased risk of venous thromboembolic events.34 Pregnancy induces several prothrombotic changes in the coagulation system that persist at least during early puerperium. Hypercoagulability worsens after delivery as a result of volume depletion and trauma. During the puerpe- rium, additional risk factors include infection and instrumen- tal delivery or cesarean section. One study reported that the risk of peripartum CVT increased with increasing maternal age, increasing hospital size, and cesarean delivery, as well as in the presence of hypertension, infections, and excessive vomiting in pregnancy.35 Recently, it was reported that in pregnant women, hyperhomocysteinemia was associated with increased risk of puerperal CVT (OR 10.8, 95% CI 4.0 to 29.4) in a study of 60 case subjects and 64 control subjects.30 Oral Contraceptives A 1998 study compared the prevalence of several risk factors, including use of oral contraceptives, among 40 female patients with CVT, 80 female patients with DVT of the lower extremi- ties, and 120 female control subjects.36 Nearly all CVT case subjects were using oral contraceptives (96%), which conferred 22.1-fold increased odds of CVT (95% CI 5.9 to 84.2). The OR for women with the prothrombin G20210A mutation who used oral contraceptives was 149.3 (95% CI 31.0 to 711.0) compared with those with neither characteristic. Stratification for the presence of factor V Leiden or prothrombin mutation and the use 0 20 40 60 80 100 120 140 160 180 16-20 21-30 31-40 41-50 51-60 61-70 71-80 >80 Males Females Total N º c as es Figure 1. Age and sex distribution of cerebral venous and sinus thrombosis (CVT) in adults. Bars represent the number of patients with CVT for the specific age/sex category. Data pro- vided by Dr Jose Ferro from the International Study on Cerebral Venous and Dural Sinuses Thrombosis. Table 2. Definition of Classes and Levels of Evidence Used in AHA Stroke Council Recommendations Class I Conditions for which there is evidence for and/or general agreement that the proced