Abstract:
:Platelets possess three P2 receptors: two (P2Y (1) and P2Y (12)) are receptors for adenosine diphosphate (ADP), and one (P2X1) is a receptor for adenosine triphosphate (ATP). The P2Y (1) receptor, which is coupled to Gq and phospholipase C-beta, is responsible for mobilization of ionized calcium from internal stores and mediates the ADP-induced platelet shape change and initial wave of rapidly reversible aggregation. The other ADP receptor, P2Y (12), is negatively coupled to adenylyl cyclase through Gi and mediates a progressive and sustained ADP-induced aggregation not preceded by shape change. In addition, this receptor plays an important role in the potentiation of platelet secretion induced by several platelet agonists. The combined action of P2Y (1) and P2Y (12) is necessary for the full platelet aggregation response to ADP. Four patients with severe deficiency of P2Y (12) have been described so far. Sequence analysis of the P2Y (12) locus of three of these patients revealed homozygous mutations that produced a frame shift mutation and premature truncation of the protein. The fourth patient had an allele with a frame shift mutation and a normal allele, which could be silenced by an additional, as yet unknown, mutation. More recently, we described a patient with a congenital bleeding disorder and a dysfunctional P2Y (12). The patient is a compound heterozygote, in whom one allele contained a G to A transition resulting in an Arg (256) to Gln codon substitution (R256Q) and the other allele contained a C to T transition resulting in an Arg (265) to Trp codon substitution (R265W). The two substitutions are located in TM6 and EL3 of the receptor. Stable Chinese hamster ovaries (CHO) cell lines were established expressing either wild-type P2Y (12) and P2Y (12)(R256Q) or P2Y (12)(R265W). Neither mutation blocked the ability of the P2Y (12) receptor to translocate to the CHO cell surface. ADP at all tested concentrations (0.1 to 10 muM) greatly inhibited the forskolin-induced increase of cyclic adenosine monophosphate (cAMP) in CHO cells transfected with wild-type P2Y (12), whereas CHO cells transfected with either mutant protein were only partially inhibited by ADP. Thus, the molecular basis for the patient's dysfunctional platelet phenotype is explained by missense mutations and the expression of a dysfunctional P2Y (12) receptor. The localization of both mutations in TM6 and EL3 identifies this region of P2Y (12) as a structurally and functionally critical region of the receptor.
journal_name
Semin Thromb Hemostjournal_title
Seminars in thrombosis and hemostasisauthors
Cattaneo Mdoi
10.1055/s-2005-869522subject
Has Abstractpub_date
2005-04-01 00:00:00pages
168-73issue
2eissn
0094-6176issn
1098-9064journal_volume
31pub_type
杂志文章,评审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::CD34 (+) progenitor cells are a promising source of regeneration in atherosclerosis or ischemic heart disease. However, as recently published, CD34(+) progenitor cells have the potential to differentiate not only into endothelial cells but also into foam cells upon interaction with platelets. The mechanism of platelet...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-0030-1251499
更新日期:2010-03-01 00:00:00
abstract::Patients receiving oral anticoagulant treatment have abnormally low levels of functional vitamin K-dependent coagulation proteins and consequently a clear risk of hemorrhagic complications. The incidence of hemorrhages has been reported to be around 0.6-0.7% per month at a therapeutic International Normalized Ratio (I...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2000-8464
更新日期:2000-01-01 00:00:00
abstract::Most acute coronary syndromes result from a platelet-rich occlusion of the coronary arteries. Antiplatelet drugs are of proven efficacy in preventing myocardial infarction, unstable angina, and stroke. However, not all patients on aspirin (ASA) benefit. We studied the phenomenon of aspirin resistance with a simple and...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2005-916677
更新日期:2005-01-01 00:00:00
abstract::We investigated the protective effects of DX-9065a, an orally active, newly synthesized, and specific inhibitor of factor Xa, against experimental disseminated intravascular coagulation (DIC) in rats. Experimental DIC was induced by a 4 hour sustained infusion of thromboplastin at a dose of 2.5 mg/kg. The rats were or...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2007-999016
更新日期:1996-01-01 00:00:00
abstract::Immunoblotting techniques for the qualitative and quantitative analysis of FXII, PK, and HMWK in whole plasma are presented. Sensitive, specific, and quantitative immunodetection of FXII and PK can be achieved by developing the blots with polyclonal antiserum followed by radiolabeled FXII or PK, respectively. This app...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2007-1003480
更新日期:1987-01-01 00:00:00
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
更新日期:1996-01-01 00:00:00
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
更新日期:2012-02-01 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::Systolic heart failure is a common syndrome whose incidence is expected to increase. Several treatment modalities, such as beta-blockers and angiotensin-converting enzyme inhibitors, improve survival. Whether antithrombotic treatment is effective remains to be elucidated, although observations suggest a prothrombotic ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0029-1234145
更新日期:2009-07-01 00:00:00
abstract::Schizophrenia, a disabling mental disorder, is characterized by brain atrophy, especially in the superior temporal gyrus and the medial temporal lobe, which includes the hippocampus and the amygdala. The model that better explains brain atrophy includes a trigger and a predisposing condition. The trigger is exemplifie...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0033-1357505
更新日期:2013-11-01 00:00:00
abstract::Factor VIII inhibitory antibodies occur following treatment in more than 30% of subjects with severe factor VIII deficiency. Almost all inhibitor formation occurs in subjects with little if any circulating factor VIII. In the absence of in utero exposure to endogenous or maternal factor VIII, these subjects probably r...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2000-9820
更新日期:2000-01-01 00:00:00
abstract::It has been demonstrated that the surface of large VLDL Sf 100-400 can bind both prothrombin and Factor X(Xa) and that on VLDL Factor Xa can convert prothrombin to thrombin, which degrades apo B and apo E. It has been reported also that the VLDL kinetically supports the conversion of prothrombin to thrombin. The bindi...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-1002786
更新日期:1988-07-01 00:00:00
abstract::Morbidity and mortality for cardiovascular disease are likely to be lower in patients with hemophilia than in the general male population. However, their clinical impact is increasing in parallel with the increase of life expectancy due to modern safe replacement treatments and the improvement of comprehensive care of...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0030-1248728
更新日期:2010-02-01 00:00:00
abstract::Recently it was reported that chorionic villous hemorrhage (CVH) had a significant association with retroplacental hemorrhage (RPH). In this study, to determine whether CVH has a correlation with RPH or intervillous thrombosis (IVT), placentas associated with CVH were clinico-histopathologically investigated and compa...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2007-996046
更新日期:1998-01-01 00:00:00
abstract::A simple RIA method for B beta 15-42 RPs has been evaluated in our laboratory to investigate experimental and clinical fibrinolytic states. The assay utilizes bentonite precipitation to remove cross-reacting fibrinogen. Due to the heterogeneity in molecular weights of the B beta RPs, the results are expressed as nanog...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-2007-1004430
更新日期:1984-10-01 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::Natural inhibitors of coagulation, in other words, antithrombin (AT), the protein C system, and tissue factor pathway inhibitor (TFPI), play an important role in controlling the activation of coagulation during disseminated intravascular coagulation (DIC). Furthermore, they may not only influence coagulation but also ...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2001-18871
更新日期:2001-12-01 00:00:00
abstract::It is generally accepted that the initial event in coagulation and intravascular thrombus formation is the exposure of the flowing blood to cell-surface protein, such as tissue factor (TF). Vascular injury and/or atherosclerotic plaque complication is responsible for this exposure, leading to clinical manifestations s...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0035-1564045
更新日期:2015-10-01 00:00:00
abstract::Protamine sulfate has been used for many years to reverse the effects of unfractionated heparin, but it can cause hemodynamic changes and other serious side effects. Platelet factor 4 (PF4) is a naturally occurring protein synthesized in megakaryocytes and eventually stored in the alpha granules of platelets for later...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 临床试验,杂志文章,随机对照试验,评审
doi:10.1055/s-2004-831050
更新日期:2004-06-01 00:00:00
abstract::Acquired von Willebrand syndrome (AVWS) is a rare bleeding disorder with laboratory findings similar to those for congenital von Willebrand disease (VWD). Unlike VWD, AVWS usually occurs in individuals with no personal or family history of bleeding. The prevalence of AVWS in the general population is unknown because d...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0030-1270069
更新日期:2011-02-01 00:00:00
abstract::Thrombosis is characterized by the formation of in vivo blood clots that are localized within arterial or venous blood vessels. These thrombi form beyond the need for physiologically healthy hemostatic responses and can lead to significant medical issues for affected individuals. Unfortunately, the existing standard-o...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-0039-1697946
更新日期:2020-07-01 00:00:00
abstract::This study aimed to determine the impact of major hemorrhage (MH) protocol (MHP) activation on blood administration and patient outcome at a UK major cardiothoracic center. MH was defined in patients (> 16 years) as those who received > 5 units of red blood cells (RBCs) in < 4 hours, or > 10 units in 24 hours. Data we...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章
doi:10.1055/s-0040-1718869
更新日期:2021-02-01 00:00:00
abstract::Patients undergoing surgery for malignancy are at increased risk of initial and recurrent venous thromboembolism (VTE). Several factors have been found to increase the risk of deep vein thrombosis (DVT) in cancer patients both during the first days after the operation and after discharge from hospital. Although, in ge...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2002-36701
更新日期:2002-12-01 00:00:00
abstract::There is ample evidence of an increased risk of venous thromboembolism (VTE) in inflammatory bowel disease (IBD). Recent large studies have quantified this risk showing that IBD patients run a 1.5 to 3.6 higher risk of developing VTE than healthy controls. The development of VTE in IBD seems to be multifactorial, resu...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-0033-1343886
更新日期:2013-07-01 00:00:00
abstract::Until recently, thrombocytoses in childhood were considered to be rare. The literature on this subject is scarce and contradictory. When thrombocytosis is defined as a platelet count of more than 500 x 10(9)/L (500 000/mm3 or 500 000/microL), the occurrence in routine examinations at pediatric hospitals can be estimat...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2007-1000654
更新日期:1995-01-01 00:00:00
abstract::von Willebrand disease (vWD) is the commonest bleeding disorder in women. More than 70% of women with vWD suffer from menorrhagia and half of them suffer from dysmenorrhea. There is also the risk of hemorrhage with ovulation and mid-cycle pain. These have a significant effect on all aspects of quality of life. vWD als...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 杂志文章,评审
doi:10.1055/s-2006-949665
更新日期:2006-09-01 00:00:00
abstract::The increase of circulating tissue factor pathway inhibitor (TFPI) in plasma by heparins is thought to contribute to their overall antithrombotic activity. In a clinical study in healthy volunteers, we recently found that the specific potency of a heparin to mobilize TFPI from the vessel wall increases with its molecu...
journal_title:Seminars in thrombosis and hemostasis
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1055/s-2001-17952
更新日期:2001-10-01 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::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
更新日期:2006-06-01 00:00:00