Abstract:
:The identification of the JAK2 V617F mutation in patients with myeloproliferative disorders (MPDs) represents a major breakthrough in our understanding of the pathogenesis of these diseases. One year after its discovery, an impressive number of publications appeared. These articles confirmed most of the initial results and tried to focus on the main issues arising from this discovery. JAK2 V617F came as recognition of the work of many investigators, starting with William Dameshek, who demonstrated that classical MPDs shared phenotypical mimicry and a general pattern of clinical evolution. We now know that this mutation is the common mark of a molecular clinical entity of MPD shared by 90% of polycythemia vera (PV) and approximately 50% of essential thrombocythemia and idiopathic myelofibrosis patients. However, many questions arise from this discovery. This review, in view of the recent literature, tries to address crucial questions regarding the mechanism of action and the clinical relevance of the JAK2 V617F mutation. The first question is how a unique mutation may explain the clinical diversity of JAK2 V617F-positive MPDs. We now know that acquisition of this mutation is only one step, and that gain of the JAK2 V617F locus, as gain in constitutive Janus kinase 2 (JAK2) activity, may represent another step in disease progression. It is still not known if and how this event or other unknown events may favor disease diversity and possibly disease onset. The second question is how the identification of the JAK2 V617F mutation will change our approach to patients. If detection of JAK2 V617F drastically simplifies the diagnosis of MPDs, and especially PV, prospective clinical trials will be necessary to determine if the therapeutic attitude and disease prognosis will depend on the presence of JAK2 V617F. The third question is how this discovery will benefit the patients. The immediate benefits are still difficult to evaluate, but this discovery, as a major advance in our understanding of the pathogenesis of MPDs, surely has opened perspectives for possible targeted therapies and raises new hopes for patients and clinicians.
journal_name
Semin Thromb Hemostjournal_title
Seminars in thrombosis and hemostasisauthors
Villeval JL,James C,Pisani DF,Casadevall N,Vainchenker Wdoi
10.1055/s-2006-942755subject
Has Abstractpub_date
2006-06-01 00:00:00pages
341-51issue
4 Pt 2eissn
0094-6176issn
1098-9064journal_volume
32pub_type
杂志文章,评审abstract::Impaired placental development is a well-known pathogenesis in preeclampsia. The present study was undertaken to elucidate the involvement of fibrinolytic factors in amniotic fluid in midtrimester with development of severe early-onset preeclampsia. Amniotic fluid was obtained by amniocentesis at 15 to 18 weeks of ges...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2007-994948
更新日期:1999-01-01 00:00:00
abstract::The three-dimensional structures of several forms of the factor XIII A subunit have been determined using single crystal x-ray diffraction methods. Our crystallographic studies have provided the first detailed structural view of the factor XIII A subunit and information that is useful for understanding transglutaminas...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2007-999035
更新日期:1996-01-01 00:00:00
abstract::Congenital factor XIII (FXIII) deficiency is a rare, autosomal recessive bleeding disorder with potentially life-threatening consequences. FXIII is composed of two subunits (A and B), and a deficiency or dysfunction of either can result in FXIII deficiency. Traditionally, FXIII deficiency has been managed by infusing ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-0036-1585076
更新日期:2017-02-01 00:00:00
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
更新日期:2014-07-01 00:00:00
abstract::Numerous studies have shown that early radiation injury is characterized by vascular damage and that the initial site of damage appears to be the EC lining of the vessel wall. Chronic irreversible tissue reactions to radiation include thrombotic occlusion of capillaries, enhanced atherosclerosis in larger vessels, inf...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2007-1002708
更新日期:1989-04-01 00:00:00
abstract::Pregnancy is associated with a significant procoagulant shift in the hemostatic system balance as well as other metabolic changes. Pregnancy can thereby provoke manifestation of otherwise dormant disorders of hemostasis (e.g., thrombophilia), or even cause new, pregnancy-specific disorders (e.g., HELLP syndrome). Appl...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0036-1592303
更新日期:2016-10-01 00:00:00
abstract::Anti-factor Xa methods have been generally accepted for the monitoring of heparin treatment mainly due to their sensitivity to LMWH and excellent performance on automated equipment. When such equipment is not available, as in small laboratories or on the night shift, there is a need for a simple manual method. In the ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:
更新日期:1993-01-01 00:00:00
abstract::Cancer often leads to the activation of coagulation, manifesting as disseminated intravascular coagulation (DIC) in its most extreme form. DIC is characterized by systemic intravascular coagulation activation (leading to deposition of intravascular platelets and fibrin) and simultaneous consumption of coagulation prot...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0039-1687890
更新日期:2019-06-01 00:00:00
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
更新日期:2018-03-01 00:00:00
abstract::Agonists of the estrogen receptor include estrogens and selective estrogen receptor modulators (SERMs). Both types of compounds increase the risk for thrombosis in the arterial and the venous tree. The magnitude of the effect is influenced by potency, which depends on the type of compound and the dose. The particulars...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0032-1328883
更新日期:2012-11-01 00:00:00
abstract::Currently, in Germany, there is a successful program where patients monitor their own coagulation status through self-testing. The advent of a new generation of coagulometers has allowed more and more patients to use self-testing to monitor their coagulation status. The development of a structured training program by ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-996423
更新日期:1999-01-01 00:00:00
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
更新日期:2017-06-01 00:00:00
abstract::Rapid and accurate risk stratification is critical in determining the optimal treatment strategy for patients with acute pulmonary embolism (PE). Early identification of patients with normal blood pressure and a favorable prognosis (low-risk PE) might select a subset of patients for outpatient treatment, which is asso...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0036-1597287
更新日期:2017-07-01 00:00:00
abstract::Coagulation management requires the balancing of different components that contribute to clot formation. These components include the interactions between platelets, procoagulant, anticoagulant, and fibrinolytic factors. The cause of bleeding or thrombotic events is often multifactorial; however, the tests clinicians ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0030-1265286
更新日期:2010-10-01 00:00:00
abstract::Of all the coagulation factor deficiencies, only deficiency of factor XIII (FXIII) and fibrinogen are associated with pregnancy loss. FXIII deficiency and a complete or partial deficiency of fibrinogen are associated with bleeding since childhood, impaired wound repair, and recurrent spontaneous abortions. Both FXIII ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2003-38832
更新日期:2003-04-01 00:00:00
abstract::Neonatal hemostasis differs qualitatively, but in particular quantitatively, from hemostasis in older children and adults. Nevertheless, hemostasis in healthy neonates is functionally stable with no tendency to bleeding or thrombotic complications. In sick neonates, however, risk factors may disrupt this equilibrium a...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-0036-1592299
更新日期:2016-10-01 00:00:00
abstract::Neutrophils have long been known as innate immune cells that phagocytose and kill pathogens and mount inflammatory responses protecting the host from infection. In the past decades, new aspects of neutrophils have emerged unmasking their importance not only in inflammation but also in many pathological conditions incl...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0034-1370765
更新日期:2014-04-01 00:00:00
abstract::Platelets have classically been considered crucial effector cells in hemostasis, but now are increasingly recognized as players during inflammatory responses in innate and adaptive immunity. Platelets can recognize and kill invading pathogens, and, upon stimulation, also release a wide array of mediators that modify i...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0037-1607432
更新日期:2018-03-01 00:00:00
abstract:: ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 社论,历史文章
doi:10.1055/s-0038-1677460
更新日期:2019-02-01 00:00:00
abstract::Thrombophilia includes multiple inherited and acquired risk factors that determine a shift in the balance of procoagulant and anticoagulant factors promoting hypercoagulability, which is associated with an increased risk of venous thromboembolism (VTE). VTE is characterized by more common clinical manifestations, such...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-985754
更新日期:2007-09-01 00:00:00
abstract::The mechanism of thrombosis in patients with antiphospholipid syndrome is not clear. To investigate it, we examined the effect of monoclonal anticardiolipin (aCL) antibodies and beta2-glycoprotein I (beta2-GPI), which is required for formation of the aCL epitopes, on activated protein C (APC) and on fibrinolytic activ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-994958
更新日期:1999-01-01 00:00:00
abstract::Eradication of factor VIII (FVIII) specific neutralizing antibodies (also known as inhibitors) by the traditional method of immune tolerance induction (ITI) is costly and unsuccessful in one out of three patients. Furthermore, effective inhibitor prevention strategies are presently lacking. An overview is given in thi...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0038-1666823
更新日期:2018-09-01 00:00:00
abstract::These results show that heparin and dextran sulfate protect endothelial cells from oxygen-free radicals. Heparan sulfate and dermatan sulfate showed mild protection when measuring cell viability but none when examining the presence of LDH in media. These GAGs are obviously not as effective as heparin and dextran sulfa...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:
更新日期:1991-01-01 00:00:00
abstract::There are several genetic and acquired risk factors for venous thromboembolism. Exposure to high altitude (HA), either during air travel, ascension of mountains, or while engaging in sports activities, has been observed to result in a hypercoagulable state, thus predisposing to thromboembolic events. Although several ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0032-1301413
更新日期:2012-03-01 00:00:00
abstract::Hip replacement surgery carries a high risk of thromboembolic complications, and pharmacological prophylaxis is routinely adopted in clinical practice. Meta-analyses have indicated that low molecular weight heparins (LMWHs) are clinically superior to conventional prophylaxis with unfractionated heparin. These analyses...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:
更新日期:1999-01-01 00:00:00
abstract::This article explores the application of viscoelastic tests (VETs) in trauma-induced coagulopathy and trauma resuscitation. We describe the advantages of VETs over conventional coagulation tests in the trauma setting and refer to previous disciplines in which VET use has reduced blood product utilization, guided prohe...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0040-1702171
更新日期:2020-03-01 00:00:00
abstract::Hemophilia A (HA) and hemophilia B (HB) are rare congenital severe bleeding disorders, that may be controlled by proper administration of adequate prophylaxis with factor VIII (FVIII), and factor IX (FIX) concentrates, respectively, to prevent joint damage due to recurrent bleeding. However, approximately 30% of patie...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0037-1612626
更新日期:2018-09-01 00:00:00
abstract::Heparin is a familiar anticoagulant drug with properties that may impede tumor growth; it modifies properties of cells that contribute to malignant dissemination such as angiogenesis, growth factor and protease activity, immune function, proliferation, and gene expression. Heparin has antitumor effects in animal model...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2000-9499
更新日期:2000-01-01 00:00:00
abstract::Severe factor XI (FXI) deficiency is an injury-related bleeding disorder common in Ashkenazi Jews and rare worldwide. In the past two decades, more than 180 mutations in the FXI gene have been reported in patients with FXI deficiency, five of which show a founder effect (Cys38Arg, Gln88Stop, Cys128Stop, Glu117stop, an...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0029-1225764
更新日期:2009-06-01 00:00:00
abstract::Thromboembolic complications are leading causes of both maternal and fetal morbidity and mortality. To reduce the incidence of venous thromboembolism (VTE) in pregnancy and improve outcomes, a wider understanding of the risk factors involved and better identification of women at risk of thrombosis are required. Optima...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2002-34072
更新日期:2002-08-01 00:00:00