Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.6 (thromboplastin)
13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Beta2-glycoprotein-I (beta2GPI) is a phospholipid-binding plasma protein that consists of five homologous domains. Domain V is distinguished from others by bearing a positively charged lysine cluster and hydrophobic extra C-terminal loop. Beta2GPI has been known as a natural anticoagulant regulator. Beta2GPI exerts anticoagulant activity by inhibition of phospholipid-dependent coagulation reactions such as prothrombinase, tenase, and factor XII activation. It also binds factor XI and inhibits its activation. On the other hand, beta2GPI inhibits anticoagulant activity of activated protein C. According to the data from knockout mice, beta2GPI may contribute to thrombin generation in vivo. Phospholipid-bound beta2GPI is one of the major target antigens for antiphospholipid antibodies present in patients with antiphospholipid syndrome (APS). Binding of pathogenic anti-beta2GPI antibodies increases the affinity of beta2GPI to the cell surface and disrupts the coagulation/fibrinolysis balance on the cell surface. These pathogenic antibodies activate endothelial cells via signal transduction events in the presence of beta2GPI. Impaired fibrinolysis has been reported in patients with APS. Using a newly developed chromogenic assay, we demonstrated lower activity of intrinsic fibrinolysis in euglobulin fractions from APS patients. Addition of monoclonal anti-beta2GPI antibodies with beta2GPI also decreased fibrinolytic activity in this assay system. beta2GPI is proteolytically cleaved by plasmin in domain V (nicked beta2GPI) and becomes unable to bind to phospholipids, reducing antigenicity against antiphospholipid antibodies. This cleavage occurs in patients with increased fibrinolysis turnover. Nicked beta2GPI binds to plasminogen and suppresses plasmin generation in the presence of fibrin, plasminogen, and tissue plasminogen activator (tPA). Thus, nicked beta2GPI plays a role in the extrinsic fibrinolysis via a negative feedback pathway loop.
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PMID:Beta2-glycoprotein I, anti-beta2-glycoprotein I, and fibrinolysis. 1550 79

We report the case of a 41-year-old woman, affected by Vaquez syndrome, admitted to our hospital for a severe pain in the right hypochondrium, suddenly followed by hepatomegaly and ascites. The clinical and laboratory data were suggestive of hepatic insufficiency and abdominal ultrasonography, integrated by color Doppler and computed tomography, revealed an interrupted hepatic venous outflow. In addition a spontaneous prolonged partial thromboplastin time was present and the patient was found to be positive for lupus anticoagulant. A transient clinical improvement, with a partial reperfusion of suprahepatic veins, was achieved with medical treatment by using anticoagulants, diuretics and paracentesis. However, the patient showed a subsequence of suprahepatic venous thrombosis, although two transjugular intrahepatic portosystemic shunts with stent placement and local thrombolysis were performed. The polycythemia vera is a disease mainly associated with Budd-Chiari syndrome but, in our patient, the thrombotic event occurred in spite of normal values of hematocrit and platelet count. Certainly in this case the lupus anticoagulant positivity represents an additional thrombogenic factor. Nowadays the antiphospholipid antibody syndrome is a recognized and not unusual cause of Budd-Chiari syndrome but, to our knowledge, this is the first case characterized by the presence of polycythemia vera and antiphospholipid antibody syndrome to be reported.
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PMID:[Budd-Chiari syndrome with fatal outcome in a patient with polycythemia vera and antiphospholipid antibody syndrome]. 1552 39

The role of humoral autoimmunity in virus-induced vascular thrombosis is still not clear. We encountered a patient who experienced cerebral ischemia in his early course of Japanese encephalitis. At the beginning, an increase of blood immunoglobulin G isotype of anti-beta2-glycoprotein I antibody, a prolonged activated partial thromboplastin time and thrombocytopenia resembling antiphospholipid antibody syndrome were found, and these abnormalities disappeared when the patient recovered later. A molecular mimicry between the T(2688)LRVLE in Japanese encephalitis virus and hexapeptide-TLRVYK may contribute for the patient's anti-beta2-glycoprotein I antibody generation. Therefore, an increase of procoagulative antibody, such as anti-beta2-glycoprotein I antibody, may display a crucial role for cerebral thrombosis associated with infectious pathogens such as Japanese encephalitis virus. The interaction between autoimmunity induction by infectious agents and procoagulation in the occurrence of vascular thrombosis may be more important than has been understood in previous studies.
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PMID:An increase of blood anti-beta2-glycoprotein I antibody in Japanese encephalitis associated with cerebral ischemia. 1565 May 47

A retrospective analysis of clinicohematologic parameters of 25 patients with lupus anticoagulant was carried out. The hematologic tests included dilute Russel viper venom test (dRVVT), kaolin clotting time (KCT), activated partial thromboplastin time, and prothrombin time. The diagnosis of lupus anticoagulants was based on the presence of prolonged KCT/dRVVT, its absence of correction with normal plasma and correction by phospholipids. Specific factor assays and platelet aggregation studies were performed wherever required. Ten patients (40%) had thrombosis, which was venous in 5 (50%) and arterial in 4 (40%). One patient (10%) had both arterial and venous thrombosis and presented with catastrophic antiphospholipid syndrome. Eighteen female patients conceived. Four (22%) of these had recurrent first trimester abortion. Five (20%) patients had bleeding manifestations. One (4%) of these had hypoprothrombinemia and was diagnosed to have hypoprothrombinemia lupus anticoagulant syndrome. However in two of these patients, no cause of bleeding could be identified other than the presence of lupus anticoagulants. It is concluded that patients with lupus anticoagulant have a varied spectrum of hemostatic disorders. Bleeding may sometimes occur in these patients due to associated thrombocytopenia or associated factor inhibitors. Rarely, it may occur due to presence of lupus anticoagulants alone.
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PMID:Clinicohematologic spectrum in patients with lupus anticoagulant. 1582 25

The antiphospholipid antibody syndrome (Lupus anticoagulans syndrome) is a rare form of coagulopathy due to the presence of autoantibodies against phospholipids or phospholipid-binding protein cofactors that can lead to vascular thrombosis. We report the case of a 57-year-old female patient presenting with decompensated duodenal stenosis due to a pancreatic tumor. Perioperative testing of coagulation markers revealed with 26 % a strongly decreased Quick-Test and with 81.4 s a prolonged partial thromboplastin time that persisted despite intravenous application of 80 mg vitamin K (Konakion) and 10 units of fresh frozen plasma. Subsequent screening for common causes of thrombophilia revealed antiphospholipid antibodies. Consequently, low molecular weight heparin (Dalteparin-Natrium) was administered perioperatively while a gastroenterostomy with entero-enterostomy was performed with uneventful postoperative course. With this presentation and an analysis of the contemporary literature we would like to discuss different aspects of Lupus anticoagulans syndrome.
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PMID:[Paraneoplastic lupus anticoagulans syndrome]. 1610 64

The presence of antiphospholipid antibodies is associated with arterial and venous thrombosis. A young female with initial presentation of dyspnea and cough that lasted for days is reported. A computed tomographic scan of her chest and echocardiography showed features of thrombus formation over the right atrium, complicated with pulmonary thromboembolism. Antiphospholipid syndrome was diagnosed according to elevated activated partial thromboplastin time, high serum titers of anticardiolipin antibody, and the presence of intracardiac thrombus with pulmonary embolism. This thrombus was subsequently removed successfully with surgical intervention, and the patient's recovery was uneventful.
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PMID:Antiphospholipid syndrome presenting as intracardiac thrombus with pulmonary embolism. 1619 33

Beta2-glycoprotein I (beta2GPI), a phospholipid-binding protein, is one of the major target antigens for antiphospholipid antibodies (aPL) found in patients with antiphospholipid syndrome (APS). Thrombophilic disorders in APS patients are strongly associated with aPL, and their pathogenic properties depend on the presence of beta2GPI. Procoagulant cell stimulation by aPL, via beta2GPI, is one of the most plausible mechanisms of thrombosis in APS, and p38 mitogen activated protein kinase (MAPK) pathway plays a crucial role in such activation. beta2GPI is proteolytically cleaved in domain V by activated factor X or plasmin, leading to the generation of the nicked form of beta2GPI. Recently, increasing attention is focused on the role of nicked-beta2GPI as a regulator of extrinsic fibrinolysis pathway.
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PMID:Research around beta 2-glycoprotein I: a major target for antiphospholipid antibodies. 1622 53

Diagnosis of antiphospholipid antibody syndrome includes laboratory testing for lupus anticoagulants (LAs). Guidelines for testing have been published, but approaches vary, often incorporating multiple tests. We evaluated the performance of the activated partial thromboplastin time using 2 reagents, a dilute Russell viper venom time, and a hexagonal phospholipid assay for detecting LAs in 105 adults. Of the patients, 26 were taking anticoagulants at the time of testing. Based on findings, an algorithm was derived for optimal detection of LAs using 2 easily performed, automated, integrated test systems. Of 105 patient samples, 30 (28.6%) were positive for LAs, using the algorithm interpretive criteria. Of these 30 positive results, 10 were detected in the 26 patients taking anticoagulants. Analysis by chi2 showed no difference in performance of the integrated tests between samples from patients taking and not taking anticoagulants. The algorithm is offered as a means for standardization of laboratory testing for LAs.
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PMID:A simplified algorithm for the laboratory detection of lupus anticoagulants: utilization of two automated integrated tests. 1641 39

The silica clotting time (SCT) is a phospholipid-dependent coagulation assay used for the laboratory diagnosis of lupus anticoagulant (LA) antibodies. The sensitivity and specificity of a new commercial SCT for identifying LA in patients who meet the clinical criteria for antiphospholipid syndrome (APS), and its association with thrombotic events were evaluated here. Forty-five patients who met the clinical criteria for APS according to the Sapporo International Consensus Statement were examined. Sixty-nine patients who did not meet the clinical criteria for APS, and 20 blood donors were used as controls. Plasma samples from the patients and controls were tested for LA using a new commercial SCT with low and high synthetic phospholipid concentrations. The results were compared with those obtained by diluted Russell's viper venom time (dRVVT) and activated partial thromboplastin time (APTT). SCT's sensitivity for identifying LA in patients who met the clinical criteria of APS was higher compared to APTT and dRVVT (53.3% vs. 31.1% and 31.1%), and the specificities of these assays were 96.6%, 100%, and 98.9%, respectively. When dRVVT was combined with SCT, and dRVVT was combined with APTT their sensitivities were 57.7% and 48.8%, and their specificities were 96.6% and 98.9%, respectively. A stepwise logistic regression analysis indicated that the combination of dRVVT with SCT was associated with total thrombotic events (odds ratio (OR)=11.5, 95% confidence interval (CI)=1.25-106.3, P=0.031) as well as with venous thrombosis (OR=4.09, 95% CI=1.16-14.43, P=0.028). According to our results, SCT is the most sensitive assay for identifying LA in patients who meet the clinical criteria for APS. Moreover, the highest sensitivity was reached with a combination of SCT and dRVVT. The method's association with total thrombotic events and venous thrombosis was in fact significant.
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PMID:Use of a new silica clotting time for diagnosing lupus anticoagulant in patients who meet the clinical criteria for antiphospholipid syndrome. 1647 May 27

Antiphospholipid antibodies (aPA) frequently interfere with the protein C pathway. This manifests as acquired activated protein C (APC) resistance in the absence of factor V Leiden and has been proposed as a putative mechanism for the pathogenesis of the antiphospholipid syndrome (APS). We have developed a Russell's viper venom test, performed with and without activation of endogenous protein C, which is sensitive to aPA-associated APC resistance. Results were reported as the endogenous APC ratio (EAPCr); the ratio of the two clotting times normalized against pooled normal plasma. Forty-four patients with aPA, anticardiolipin and/or lupus anticoagulant, including 34 with a history of thrombosis or pregnancy morbidity; a control group of aPA-negative patients; and 26 healthy normals were studied. EAPCr (mean, SD) was significantly higher in APS patients (1.94, 0.58) than normals (0.98, 0.12) or controls (1.14, 0.19; P < 0.00001). Elevated EAPCr (> 1.22) occurred in 91% of aPA-positive patients, predominantly due to resistance to APC (87%) rather than prolonged basal clotting times alone (15%). Significant correlation was observed between the EAPCr value and dilute Russell's viper venom time (rs = 0.44, P = 0.003), IgG anticardiolipin (rs = 0.54, P = 0.002), protein S (r = -0.46, P = 0.01) and activated partial thromboplastin time-based APC resistance (r = -0.61, P = 0.001). There was no significant relationship between EAPCr and protein C concentration, anti-beta2-glycoprotein-I (anti-beta2GPI) or IgM anticardiolipin. Purified aPA IgG caused a dose-dependent increase in APC resistance when added to normal plasma. We conclude that aPA-associated acquired APC resistance is a common feature of APS and may be independent of anti-beta2GPI.
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PMID:Detection of acquired resistance to activated protein C associated with antiphospholipid antibodies using a novel clotting assay. 1690 52


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