Quality in molecular biology testing for inherited thrombophilia disorders.

Abstract:

:As the understanding of the genetic basis of the inherited thrombophilias has increased over recent years, their routine diagnostic genetic analysis has also matured. This review considers methods used to test for the factor V (F5) Leiden mutation and prothrombin 20210A (F2 c.*97G>A) allele, and analysis of the SERPINC1, PROC, and PROS1 genes in cases of antithrombin, protein C (PC), and protein S (PS) deficiency, respectively. Issues relating to quality are explored, highlighting where analytical and sample handling errors may occur. Detection of the factor V Leiden mutation and the prothrombin c.*97G>A allele are best performed using real-time polymerase chain reaction analysis as this relatively simple technique allows their discrimination from rare variants of neighboring nucleotides; not possible using the more time-consuming restriction digestion assays. With the advent of low-cost and high-throughput sequence analysis, direct sequencing has become the first-line method to provide a definitive diagnosis of inherited, rather than acquired, deficiencies. Large cohort studies have shown that antithrombin and PC mutations are identified in between 61 and 87% of patients, whereas the detection rate in PS deficiency is substantially lower in around 40% of patients. Large gene deletions make up between 7 and 10% of PS and antithrombin mutations and only 1% of PC mutations, but it is suggested that dosage analysis techniques such as multiplex ligation-dependent probe amplification should be used for all three genes as part of routine analysis to ensure mutations are not missed. Best practice guidelines are available from EuroGentest covering a wide variety of the issues raised in this review and all laboratories should participate in appropriate external quality assurance schemes to ensure they continue to offer high quality service.

journal_name

Semin Thromb Hemost

authors

Cooper PC,Goodeve AC,Beauchamp NJ

doi

10.1055/s-0032-1321491

subject

Has Abstract

pub_date

2012-09-01 00:00:00

pages

600-12

issue

6

eissn

0094-6176

issn

1098-9064

journal_volume

38

pub_type

杂志文章,评审
  • Differentiation of low-molecular-weight heparins: impact on the future of the management of thrombosis.

    abstract::Low-molecular-weight heparins (LMWHs) are now universally accepted as drugs of choice for postsurgical prophylaxis and treatment of deep vein thrombosis (DVT). Currently, these agents are also being developed for the treatment of various cardiovascular conditions. Because of manufacturing differences, each of the LMWH...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-2004-823007

    authors: Fareed J,Ma Q,Florian M,Maddineni J,Iqbal O,Hoppensteadt DA,Bick RL

    更新日期:2004-02-01 00:00:00

  • Metabolic modulation of inflammation-induced activation of coagulation.

    abstract::The bidirectional interaction between coagulation and inflammation, which is relevant in various disease states that are dominated by systemic inflammatory responses, such as severe infection or chronic vascular disease, is modulated by metabolic factors. Changes in lipoprotein metabolism affect the inflammation-induc...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-2008-1066020

    authors: Levi M,Nieuwdorp M,van der Poll T,Stroes E

    更新日期:2008-02-01 00:00:00

  • DNA sequence analysis of protein S deficiency--identification of four point mutations in twelve Japanese subjects.

    abstract::The molecular basis for the hereditary type I protein S (PS) deficiency was investigated. DNA sequence analysis of 12 patients with PS deficiency in Japan identified four point mutations and three of them were novel. Nonsense mutations found in two unrelated patients resulted in termination of the PS polypeptide chain...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章

    doi:10.1055/s-2001-14075

    authors: Iwaki T,Mastushita T,Kobayashi T,Yamamoto Y,Nomura Y,Kagami K,Nakayama T,Sugiura I,Kojima T,Takamatsu J,Kanayama N,Saito H

    更新日期:2001-01-01 00:00:00

  • The UK National External Quality Assessment Scheme for heritable bleeding disorders.

    abstract::Molecular genetic analysis of families with hemophilia and other heritable bleeding disorders is a frequently requested laboratory investigation. In the United Kingdom, laboratories undertaking genetic testing must participate in a recognized external quality assessment scheme for formal accreditation. The UK National...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章

    doi:10.1055/s-0034-1365843

    authors: Perry DJ,Cumming T,Goodeve A,Hill M,Jennings I,Kitchen S,Walker I

    更新日期:2014-03-01 00:00:00

  • Fibrinolytic system in atherosclerosis.

    abstract::In this short review I have tried to report the literature findings and describe some of our observations on fibrinolysis and atherosclerosis. Although at this time it is difficult to state that diminished FA plays a pathogenic role in atherosclerosis, it certainly seems to represent a risk factor. ...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章

    doi:10.1055/s-2007-1003541

    authors: Balkuv-Ulutin S

    更新日期:1986-04-01 00:00:00

  • Acute ischemic stroke.

    abstract::While case fatality rates in ischemic stroke tend to decline, the total number of strokes is expected to increase further in the future because of more people reaching a greater age. Acute ischemic stroke, usually caused by chronic arterial hypertension, in most cases is induced either by a sudden loss of perfusion pr...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章

    doi:10.1055/s-2007-998991

    authors: Huber M,Heiss WD

    更新日期:1996-01-01 00:00:00

  • Pulmonary embolism in children.

    abstract::Pulmonary embolism (PE) has long been described in children. Nevertheless, most of the algorithms applied to patients within this age range, from diagnosis to therapy, have been adapted from adult protocols. This article reviews the progresses that occurred to PE in children placing them in historical perspective with...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-0031-1297168

    authors: Brandão LR,Labarque V,Diab Y,Williams S,Manson DE

    更新日期:2011-10-01 00:00:00

  • The multiple organ dysfunction syndrome in cancer patients undergoing hematopoietic stem cell transplantation.

    abstract::In the past two decades, major improvements in antibiotics and other elements of supportive care have decreased the number and severity of complications of hematopoietic stem cell transplantation (HSCT). Despite these improvements, many subpopulations of transplant patients still have a significant morbidity and morta...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-2007-994924

    authors: Haire WD

    更新日期:1999-01-01 00:00:00

  • Alpha-thrombin stimulates expression of macrophage migration inhibitory factor in skin fibroblasts.

    abstract::Macrophage migration inhibitory factor (MIF) is induced by various stimuli such as wounds and infection and regulates inflammatory and immunological responses. To date, we have found increased expression of MIF during the wound healing process in rat skin. Immunohistochemical analysis demonstrated enhanced expression ...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章

    doi:10.1055/s-2007-994967

    authors: Shimizu T,Ohkawara A,Mizue Y,Nishihira J

    更新日期:1999-01-01 00:00:00

  • Platelet CLEC-2: Roles Beyond Hemostasis.

    abstract::C-type lectin-like receptor 2 (CLEC-2) has been identified on the surface of platelets as a receptor for a platelet activating snake venom, rhodocytin/aggretin. CLEC-2 belongs to a C-type lectin superfamily and binds to a sialoglycoprotein, podoplanin, in vivo. Platelets play a crucial role in hemostasis and thrombosi...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-0037-1604090

    authors: Suzuki-Inoue K,Tsukiji N,Shirai T,Osada M,Inoue O,Ozaki Y

    更新日期:2018-03-01 00:00:00

  • Thrombosis in myeloproliferative neoplasms.

    abstract::Thrombotic events are very frequent and represent the main cause of morbidity and mortality in patients with Philadelphia chromosome-negative myeloproliferative neoplasms (MPNs), mainly polycythemia vera and essential thrombocythemia. Pathogenesis of blood clotting activation in these diseases is multifactorial, and i...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-0034-1370794

    authors: Falanga A,Marchetti M

    更新日期:2014-04-01 00:00:00

  • Seminal vesicle protein IV and its derived active peptides: a possible physiological role in seminal clotting.

    abstract::Seminal vesicle protein 4 (SV-IV) is a highly flexible molecule that in aqueous solution behaves as a concentration-dependent self-associating system in which the degree of association (monomer <--> dimer <--> trimer equilibrium) seems to be related to its biological activities. This review reports the functional role...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-2006-958462

    authors: Metafora S,Esposito C,Caputo I,Lepretti M,Cassese D,Dicitore A,Ferranti P,Stiuso P

    更新日期:2007-02-01 00:00:00

  • Stimulation of cell surface plasminogen activation by heparin and related polyionic substances.

    abstract::The functional operation of the cell surface pro-u-PA and plasminogen activating system has previously been shown to depend on the assembly of u-PA receptors, plasminogen binding sites, and their respective ligands at the focal adhesions of cell extensions. We now show that additional factors operate that affect the p...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章

    doi:10.1055/s-2007-1002610

    authors: Stephens RW,Pöllänen J,Tapiovaara H,Woodrow G,Vaheri A

    更新日期:1991-07-01 00:00:00

  • Inhibitor development in hemophiliacs: the roles of genetic versus environmental factors.

    abstract::Approximately 5 to 7% of patients with hemophilia A have inhibitory antibodies to factor (F) VIII, which increases to approximately 13% in patients with severe disease. The strongest determinant of the risk of inhibitor development identified is the type of mutation in the FVIII gene that gives rise to the disease. Ho...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-2006-946909

    authors: Lee CA,Lillicrap D,Astermark J

    更新日期:2006-06-01 00:00:00

  • A possible role for thrombopoietin and its receptor c-mpl in the pathobiology of essential thrombocythemia.

    abstract::Essential thrombocythemia (ET) is a clonal myeloproliferative disorder of unknown origin primarily involving the megakaryocyte/platelet lineage. In an attempt to evaluate the role of the receptor c-mpl and its ligand thrombopoietin (TPO) in ET, various studies have been undertaken, the results of which are discussed h...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-2007-996118

    authors: Griesshammer M,Bangerter M,Schrezenmeier H

    更新日期:1997-01-01 00:00:00

  • Point-of-Care Coagulation Monitoring in Trauma Patients.

    abstract::Trauma remains one of the major causes of death and disability all over the world. Uncontrolled blood loss and trauma-induced coagulopathy represent preventable causes of trauma-related morbidity and mortality. Treatment may consist of allogeneic blood product transfusion at a fixed ratio or in an individualized goal-...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-0037-1598062

    authors: Stein P,Kaserer A,Spahn GH,Spahn DR

    更新日期:2017-06-01 00:00:00

  • Clinical significance of hypertriglyceridemia.

    abstract::Available data suggest that elevated triglyceride levels in plasma, associated with increased VLDL or chylomicron remnants, are associated with premature coronary artery atherosclerosis. Whether this is a direct effect or as a result of the association of hypertriglyceridemia with decreased HDL as well as decreased LD...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-2007-1002768

    authors: Schaefer EJ,McNamara JR,Genest J Jr,Ordovas JM

    更新日期:1988-04-01 00:00:00

  • Intracerebral bleeding in patients on antithrombotic agents.

    abstract::Patients treated with oral anticoagulants (OAC) carry a 7- to 10-fold higher risk of intracerebral hemorrhage (ICH) than patients without OAC. ICH related to oral anticoagulation (OAC-ICH) is a particularly severe form of stroke. The overall incidence of OAC-ICH ranges between 2 and 9 per 100,000 population/year and i...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-0033-1357506

    authors: Veltkamp R,Rizos T,Horstmann S

    更新日期:2013-11-01 00:00:00

  • Plasminogen activator inhibitor-1 in aging.

    abstract::Plasminogen activator inhibitor-1 (PAI-1), a principal inhibitor of fibrinolysis, is induced in thrombotic, fibrotic, and cardiovascular diseases, which in turn primarily afflict the older population. This induction of PAI-1 may play an important role in the pathology of these diseases as PAI-1 can regulate the dissol...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-0034-1384635

    authors: Yamamoto K,Takeshita K,Saito H

    更新日期:2014-09-01 00:00:00

  • Fibrin D-dimer in thrombogenic disorders.

    abstract::Measurement of D-dimer (fibrin degradation product) is important for determining not only the activation of fibrinolysis but also the severity of a hypercoagulable state. However, fibrin degradation products are in variable, and the reactivity to cross-linked fibrin degradation products produced during fibrin degradat...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-2000-9811

    authors: Matsuo T,Kobayashi H,Kario K,Suzuki S

    更新日期:2000-01-01 00:00:00

  • Differences between bone marrow and lung endothelial cells.

    abstract::To elucidate the mechanisms by which hematopoietic progenitor cells selectively lodge in bone marrow, we established endothelial cell lines derived from bone marrow and lung and then examined the transendothelial migration of hematopoietic progenitor cells by using cells was examined by a Transwell migration assay. He...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章

    doi:10.1055/s-2007-995854

    authors: Imai K,Kobayashi M

    更新日期:1998-01-01 00:00:00

  • Controversies surrounding platelet glycoprotein IIb/IIIa inhibitors in percutaneous coronary intervention and acute coronary syndromes.

    abstract::Platelet-dependent thrombosis is an important part of the pathophysiology of both percutaneous coronary interventions (PCI) and acute coronary syndrome (ACS). Data support the use of acute therapies that interfere with platelets to provide clinical benefit to patients presenting with acute cardiovascular disease. The ...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-2004-861506

    authors: Harrington RA

    更新日期:2004-12-01 00:00:00

  • The spectrum of coagulation abnormalities in thyroid disorders.

    abstract::The hemostatic balance is a complex system where the delicate equilibrium is regulated by several factors including hormones. A variety of endocrine disorders have been reported to be associated with coagulation abnormalities, ranging from mild laboratory changes to clinically relevant thrombotic or bleeding manifesta...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-0030-1270065

    authors: Vescovi PP,Favaloro EJ,Lippi G,Garofano M,Montagnana M,Manzato F,Franchini M

    更新日期:2011-02-01 00:00:00

  • Active online assessment of patients using new oral anticoagulants: bleeding risk, compliance, and coagulation analysis.

    abstract::Clinicians prescribing new oral anticoagulants (OACs; dabigatran, rivaroxaban, and apixaban) should be aware of the exclusion criteria related to bleeding risks defined in published clinical studies. At least a quarter of patients currently using warfarin have an exclusion criterion that may prevent easy transition to...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-0031-1300948

    authors: Salmela B,Joutsi-Korhonen L,Armstrong E,Lassila R

    更新日期:2012-02-01 00:00:00

  • Management strategies for optimal control of anticoagulation in patients with atrial fibrillation.

    abstract::Most patients with atrial fibrillation need anticoagulant treatment with vitamin K antagonists for prevention of thromboembolism, in particular ischemic stroke. Many studies show the efficacy of this treatment but also that it is difficult to keep patients who use vitamin K antagonists in the proper treatment range. B...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-0029-1240016

    authors: Levi M,de Peuter OR,Kamphuisen PW

    更新日期:2009-09-01 00:00:00

  • Studies on the antithrombotic effects and pharmacokinetics of heparin fractions and fragments.

    abstract::The pharmacokinetics of heparin differ markedly from those of its fractions both in man and in experimental animal models. The route of administration determines the relative availability of different molecular species that exert the anti-Xa, anti-IIa, fibrinopeptide A generation inhibiting actions and the release of ...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-2007-1004360

    authors: Fareed J,Walenga JM,Williamson K,Emanuele RM,Kumar A,Hoppensteadt DA

    更新日期:1985-01-01 00:00:00

  • Clinical syndromes associated with lupus anticoagulants.

    abstract::Recent evidence suggests that lupus anticoagulants are immunologically distinct from the anticardiolipin antibodies. Nevertheless, the associated clinical complications exhibited by the two groups of antibodies are similar. They have been shown to have a strong association with a history of arterial and venous thrombo...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-2007-1001886

    authors: Kampe CE

    更新日期:1994-01-01 00:00:00

  • Thrombotic microangiopathies and the linkage between von Willebrand factor and the alternative complement pathway.

    abstract::Molecular linkages between von Willebrand factor (VWF) and the alternative complement pathway (AP) have recently been discovered. Endothelial cell (EC)-anchored ultra-large (UL) VWF multimeric strings function as an activating surface for the AP. C3 (in active C3b form) binds to the EC-anchored ULVWF strings, and prom...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-0034-1383547

    authors: Turner N,Nolasco L,Nolasco J,Sartain S,Moake J

    更新日期:2014-07-01 00:00:00

  • The Intriguing Link between the Intestinal Microbiota and Cardiovascular Disease.

    abstract::Human microbiota is a term conventionally used to define the normal flora of microbes living in all of us, most of which are resident in the gastrointestinal tract. Despite it having been known for some time that the vast majority of intestinal bacteria exert a strong influence on human life, recent technologic breakt...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章,评审

    doi:10.1055/s-0036-1597903

    authors: Lippi G,Danese E,Mattiuzzi C,Favaloro EJ

    更新日期:2017-09-01 00:00:00

  • Prothrombin-related antigens in human aortic intima.

    abstract::Most plasma proteins are present in both normal and atherosclerotic intima, and their concentrations in intimal interstitial fluid are directly related to plasma concentration and molecular size. All intimal samples also contain soluble fibrin-fibrinogen-related antigens, consisting of variable mixtures of fibrinogen ...

    journal_title:Seminars in thrombosis and hemostasis

    pub_type: 杂志文章

    doi:10.1055/s-2007-999030

    authors: Smith EB,Crosbie L,Carey S

    更新日期:1996-01-01 00:00:00