Antithrombin deficiency: issues in laboratory diagnosis

OBJECTIVE: To review the current understanding of the pathophysiology of antithrombin deficiency and its role in congenital thrombophilia. Recommendations for diagnostic testing of antithrombin function and concentration, derived from the medical literature and consensus opinions of recognized experts in the field, are included. These recommendations specify whom, how, and when to test. DATA SOURCES: Review of the published medical literature. DATA EXTRACTION AND SYNTHESIS: A summary of the medical literature and proposed testing recommendations were prepared and presented at the College of American Pathologists Conference XXXVI: Diagnostic Issues in Thrombophilia. After discussion at the conference, consensus recommendations presented in this article were accepted after a two-thirds majority vote by the participants. CONCLUSIONS: Antithrombin deficiency is an infrequent genetic abnormality that may be a significant contributing cause of thrombophilia. Antithrombin deficiency also may be observed in conjunction with other genetic or acquired risk factors. Assay of antithrombin plasma levels is appropriate in the laboratory evaluation of individuals with thrombophilia, preferably using a functional, amidolytic antithrombin assay. The diagnosis of antithrombin deficiency should be established only after other acquired causes of antithrombin deficiency, such as liver disease, consumptive coagulopathy, or heparin therapy, are excluded. A low antithrombin level should be confirmed with a subsequent assay on a fresh specimen, and family studies may be helpful to establish the diagnosis. Antigenic antithrombin assays may be of benefit in subclassification of the type of antithrombin deficiency and to confirm the decreased antithrombin level in patients with type I deficiency.     

Clinical utility of factor V leiden (R506Q) testing for the diagnosis and management of thromboembolic disorders

OBJECTIVE: To review the current state of the art regarding the role of the clinical laboratory in diagnostic testing for the factor V Leiden (FVL) thrombophilic mutation (and other protein C resistance disorders), and to generate, through literature reviews and opinions of recognized thought-leaders, expert consensus recommendations on methodology and diagnostic, prognostic, and management issues pertaining to clinical FVL testing. DATA SOURCES, EXTRACTION, AND SYNTHESIS: An initial thorough review of the medical literature and of current best clinical practices by a panel of 4 experts followed by a consensus conference review, editing, and ultimate approval by the majority of a panel of 28 additional coagulation laboratory experts. CONCLUSIONS: Consensus recommendations were generated for topics of direct clinical relevance, including (1) defining those patients (and family members) who should (and should not) be tested for FVL; (2) defining the preferred FVL laboratory testing methods; and (3) defining the therapeutic, prophylactic, and management ramifications of FVL testing in affected individuals and their family members. As FVL is currently the most common recognized familial thrombophilia, it is hoped that these recommendations will assist laboratorians and clinicians caring for patients (and families) with this common mutation.     

Genetic polymorphisms associated with venous and arterial thrombosis: an overview

OBJECTIVE: To provide an overview of genetic polymorphisms associated with thrombotic cardiovascular disease. DATA SOURCES: A literature search using the National Library of Medicine database. STUDY SELECTION: The literature on genetic polymorphisms associated with venous and arterial thrombosis was reviewed. DATA EXTRACTION: Based on the literature review, the clinical significance of polymorphisms in various coagulation proteins was assessed and a summary was developed. CONCLUSIONS: Thrombosis is a multifactorial disorder, with both congenital and acquired risk factors. It is now clear that there are many genetic abnormalities that impart an increased risk for thrombophilia, and the presence of more than 1 abnormality results in a further increased risk of thrombosis. In hemostasis, there is a balance between procoagulant factors and natural anticoagulant proteins. The first genetic thrombotic disorders described were deficiencies of the natural anticoagulants, such as antithrombin, protein C, and protein S, but these abnormalities are rare and are caused by many different mutations. More recently, single polymorphisms that are relatively common in the general population have been described in procoagulant factors, such as factor V and prothrombin, which impart an increased risk for venous thrombosis. As more scrutiny is placed on the hemostatic system, further polymorphisms have come to light. The current challenge is to elucidate the relationship between these new polymorphisms and either venous or arterial thrombotic cardiovascular disease.     

Summary statement: appropriate medical care for the secondary school-aged athlete

OBJECTIVE: To present the recommendations made by the Appropriate Medical Care for Secondary School-Aged Athletes Task Force and to summarize the subsequent monograph developed around 11 consensus points. DATA SOURCES: The MEDLINE, CINAHL, and SportDiscus databases were searched for relevant literature regarding secondary school-aged athletes; health care administration; preparticipation physical examination; facilities; athletic equipment; emergency action planning; environmental conditions; recognition, evaluation, and treatment of injuries; rehabilitation and reconditioning; psychosocial consultation; nutrition; and prevention strategies. CONCLUSIONS AND RECOMMENDATIONS: Organizations that sponsor athletic programs for secondary school-aged athletes should establish an athletic health care team to ensure that appropriate medical care is provided to all participants. The 11 consensus points provide a framework-one that is supported by the medical literature and case law-for the development of an athletic health care team and for assigning responsibilities to the team, administrators, and staff members of institutions sponsoring secondary school and club-level athletic programs.     

Consensus minimum standards for use in a trainer''s report for summative assessment in general practice.

BACKGROUND: Summative assessment of general practitioner registrars is to be introduced in September 1996, one component of which will be a report by the trainer. Standards must be set and guidance provided as to the most appropriate ways of obtaining evidence for the trainer's assessment. AIM: The first aim of this study was to set consensus minimum standards for 30 items that are likely to form the content of a trainer's report; the second aim was to provide a consensus view on the most appropriate methods of assessment to be used by trainers. METHOD: A consensus conference was held in March 1995 during which the 30 items were discussed by a group of 30 general practitioners, of whom 27 were experienced trainers. This resulted in a draft document that was circulated to the conference attenders and other experts for consultation. RESULTS: Draft minimum standards were produced for all 30 items after the consensus conference with a mean of 2.5 standards for each item. Of those involved in the consultation exercise, 82% replied. Most of the revisions suggested at this stage were of a minor nature; the only major revision was to divide one item into two, resulting in a final total of 31 items. All but one of the 80 standards could be assessed by direct observation; 41 (51%) could be assessed by tutorial-based discussion and 61 (76%) by methods specific to that standard. Trainers or their practice partners were viewed as acceptable sources of evidence for all items and hospital consultants and primary health care team members were viewed as acceptable for just over half of the items. CONCLUSION: Standards for use by trainers when providing a general practitioner report for the summative assessment of registrars have been developed by consensus conference and have been subjected to review by consultation. Acceptable methods by which registrars could be assessed against these standards, and suitable personnel who could provide evidence, have also been suggested.     

鼻出血的止血材料学研究

背景：鼻腔栓塞是治疗鼻出血和鼻窦术后粘连或再狭窄的主要方法,目前应用的鼻腔栓塞材料很多,哪种材料更适合鼻腔栓塞,根据患者病情如何选择栓塞材料,如何有效止血并减轻对鼻腔造成的不利影响,加快伤口愈合,是鼻腔止血材料研究需要解决的难题。 目的：利用CNKI数据库文献检索和深度分析功能,对鼻出血的止血材料学研究的文献资料趋势进行多层次探讨分析。 设计：文献计量学分析。 资料提取：以电子检索方式对CNKI数据库2002-01/2011-12有关鼻出血的止血材料学研究的文献进行分析,采用检索词为“止血材料(hemostatic materials);鼻出血(epistaxis)”,对检索的相关文献运用数据库中自带的分析功能和Excel软件绘制图表的功能进行分析,通过文字和图表的形式将统计和计量数据分析,描述其分布特征。 入选标准：纳入标准：①与止血材料相关的基础研究论文。②与止血材料临床应用相关的论文。③与鼻出血相关的基础和临床研究论文。排除标准：①与文章目的无关的文献。②重复研究的文献。③刊社信息。④未发表的文章。⑤需电话追踪和手工检索逐一分析的文章。⑥年鉴。⑦护理内容的文献。 主要数据判定指标：以CNKI数据库学术期刊文献出版时间、文献数量、学科类别、来源期刊、出版机构、文献被引频次、文献下载频次、关联文献和主要关键词进行相关分析。并对CNKI数据库中优秀硕士学位论文、重要会议论文进行分析,鼻出血止血材料学研究文献的病例进行分析。 结果：在CNKI数据库学术期刊收录2002/2011的文献中,共检索到88篇与鼻出血的止血材料学研究相关文献。文献数量产出趋于平稳上升趋势,最多的时间在2008年共13篇;《中国耳鼻咽喉头颈外科》杂志发表文献量较多为7篇,占全部文献的8.0%;鼻出血止血材料学研究主要关键词为鼻腔填塞、鼻出血、止血材料,从止血材料的应用看,与鼻内镜相关研究的使用最多,从止血材料的选择看,以藻酸钙敷料和高膨胀止血材料的研究为主。 结论：通过文献计量学方法对CNKI数据库学术期刊关于鼻出血的止血材料文献进行分析,结果可见鼻腔填塞止血材料各具特点,应该根据患者鼻腔病情选择不同生物学特性的止血材料,为从事鼻腔填塞止血材料学基础研究和临床应用的医务工作者提供参考。     

College of American Pathologists Conference XXXV: solid tumor prognostic factors-which, how and so what? Summary document and recommendations for implementation. Cancer Committee and Conference Participants

The College of American Pathologists convened a prognostic factor conference in June 1999 to consider prognostic and predictive factors in breast, colon, and prostate cancer, and to stratify these factors into categories reflecting the strength of published evidence. Because so little progress in prognostic factor clinical utility has been made in the last 5 years, the conference participants focused their attention on decreasing variation in methods, interpretation, and reporting of these factors so that greater clarity of value could be achieved. The conference was organized to promote discussion, broad input, and future planning. An initial plenary session provided an overview of the status of tumor marker research, the impact of variation in medicine and pathology, and statistical issues related to prognostic factor research. In working group sessions for each cancer type, participants interactively evaluated and refined the documents created by the expert panels. A second plenary session dealt with issues common to all 3 groups, including the problem of micrometastases in lymph nodes in these sites; statistical issues that arose during the breakout discussions; and issues of variation in methods, interpretation, and reporting of immunohistochemical assays. A faculty session brainstormed strategies that could be used to implement the changes recommended. This session included invited representatives of the Food and Drug Administration, Health Care Financing Administration, Centers for Disease Control and Prevention, National Cancer Institute, American Joint Committee on Cancer, and International Union Against Cancer. Cancer site and general recommendations were presented and discussed during a final session to achieve consensus of the conference participants and to address feasibility of implementation of these recommendations. A final discussion focused on future initiatives that might lead to implementation of the changes proposed in the conference by the various organizations represented. This report summarizes the general conference recommendations, cancer working group recommendations, and plans for implementation of the recommendations.     

The role of cytotoxic therapy with hematopoietic stem cell transplantation in the therapy of acute lymphoblastic leukemia in adults: an evidence-based review.

Evidence supporting the role of hematopoietic stem cell transplantation (SCT) in the therapy of acute lymphoblastic leukemia in adults (> or =15 years) is presented and critically evaluated in this systematic evidence-based review. Specific criteria were used for searching the published medical literature and for grading the quality and strength of the evidence, and the strength of the treatment recommendations. Treatment recommendations based on the evidence are presented and were reached unanimously by a panel of acute lymphoblastic leukemia experts. The priority areas of needed future research for adult acute lymphoblastic leukemia are: definition of patients at high risk in first complete remission, beyond Philadelphia chromosome positive; outcomes of SCT in older (>50 years) adults; determination if reduced intensity versus myeloablative conditioning regimens yield an equivalent graft-versus-leukemia effect with reduced toxicity; monitoring of minimal residual disease to achieve disease control before SCT; and the use of cord blood and other alternative sources of stem cells for use in adult SCT recipients.     

New guidelines and recommendations on the detection, evaluation, and treatment of patients with undesirable cholesterol levels

To help reduce the prevalence of elevated blood cholesterol levels in adult Americans, the National Heart, Lung, and Blood Institute (NHLBI) of the National Institutes of Health (NIH) launched the National Cholesterol Education Program (NCEP) in 1985. The program aims to raise awareness and understanding about high blood cholesterol levels as a risk for coronary artery disease (CAD) and the benefits of lowering cholesterol levels as a means of preventing CAD. This national awareness program is aimed at three target groups: (1) health professions, (2) the public and patient, and (3) the community. This article summarizes the highlights of the NHLBI NCEP Laboratory Standardization Panel's (LSP) report and the Adult Treatment Panel's (ATP) report. The LSP report emphasized the need for accurate and precise cholesterol measurements and evaluated the current state of reliability of these measurements. It also described the degree to which accurate and precise cholesterol measurements are possible based on currently available instrumentation, reagents, and methods. The LSP report made a series of broad recommendations designed to improve laboratory performance that are discussed in this article. The ATP's report established criteria that define candidates with high blood cholesterol levels who should receive medical intervention and provided guidelines on how to detect, set goals, treat, and monitor these patients over time. For the first time in medical history there is a consensus by leading experts in the field on the measurement, detection, and treatment of patients with hypercholesterolemia. The detailed recommendations of the LSP and ATP should have a major impact on 40 million adults in the United States and may save approximately 300,000 lives annually.     

Initial Clinical Guidelines for Co-Occurring Autism Spectrum Disorder and Gender Dysphoria or Incongruence in Adolescents

Evidence indicates an overrepresentation of youth with co-occurring autism spectrum disorders (ASD) and gender dysphoria (GD). The clinical assessment and treatment of adolescents with this co-occurrence is often complex, related to the developmental aspects of ASD. There are no guidelines for clinical care when ASD and GD co-occur; however, there are clinicians and researchers experienced in this co-occurrence. This study develops initial clinical consensus guidelines for the assessment and care of adolescents with co-occurring ASD and GD, from the best clinical practices of current experts in the field. Expert participants were identified through a comprehensive international search process and invited to participate in a two-stage Delphi procedure to form clinical consensus statements. The Delphi Method is a well-studied research methodology for obtaining consensus among experts to define appropriate clinical care. Of 30 potential experts identified, 22 met criteria as expert in co-occurring ASD and GD youth and participated. Textual data divided into the following data nodes: guidelines for assessment; guidelines for treatment; six primary clinical/psychosocial challenges: social functioning, medical treatments and medical safety, risk of victimization/safety, school, and transition to adulthood issues (i.e., employment and romantic relationships). With a cutoff of 75% consensus for inclusion, identified experts produced a set of initial guidelines for clinical care. Primary themes include the importance of assessment for GD in ASD, and vice versa, as well as an extended diagnostic period, often with overlap/blurring of treatment and assessment.