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)

We report the diagnosis and management of a 32-year-old Hungarian male, whose only known risk factor for coronary artery disease was smoking, who presented with an acute thrombotic anterolateral wall myocardial infarction requiring percutaneous transluminal coronary angioplasty (PTCA) stenting of his proximal left anterior descending coronary artery. He arrived to the emergency room with an abnormally prolonged partial thromboplastin time (PTT) that subsequently did not correct by mixing with normal plasma. This was suggestive of an underlying coagulopathy. An extensive coagulopathy work up found him to have the antiphospholipid antibody syndrome with antibodies positive for anticardiolipin, lupus anticoagulant and false-positive VDRL. Genetic typing found him to be homozygous for a mutation in the methylenetetrahydrofolate reductase (MTHFR A1298C) gene, which, in the presence of additional thrombophilic factors, may have increased his risk of myocardial infarction. He was discharged on high dose coumadin.
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PMID:Case report: Acute myocardial infarction in a 32-year-old white male found to have antiphospholipid antibody syndrome and MTHFR mutation homozygosity. 1289 Nov 67

A child presented with excessive bruising and prolonged activated partial thromboplastin time. Mixing studies in plasma were positive for phospholipid dependence of the anticoagulant, confirming a diagnosis of lupus anticoagulant. Factor II level was reduced. Laboratory findings normalised after three months, with spontaneous resolution of bruising. This case demonstrates a transient antiphospholipid antibody syndrome as a rare presentation of bleeding diathesis in a previously healthy child, and should be considered in children with new onset bruising and prolonged activated partial thromboplastin time.
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PMID:Transient lupus anticoagulant: an unusual cause of bruising in children. 1295 11

A patient with antiphospholipid antibody syndrome (APS) and a history of heparin-induced thrombocytopenia required lepirudin therapy. The patient had an abnormal baseline activated partial thromboplastin time (aPTT), complicating management of his therapy. We investigated whether an alternative monitoring system, using a dry reagent technology [Thrombolytic Assessment System (TAS)], could be used to monitor the patient's whole blood ecarin clot time (ECT) and aPTT. Baseline values for the ECT and aPTT were normal with this system. During a continuous infusion of lepirudin, the patient's whole blood ECT was maintained between a desired range of 150-200 s for 73% of the time. Similarly, his whole blood aPTT was maintained between 60 and 80 s for 80% of the time. In contrast, the patient's plasma-based aPTT by standard methods was consistently > 150 s. The patient underwent surgical procedures without complications. To further investigate the finding that the patient's antibody did not affect the aPTT with this system, we performed the ECT and the aPTT assays on the TAS Analyzer with plasma samples from 10 patients with APS and abnormal aPTTs. All 10 samples had plasma ECT values within the normal range. Four patients had normalization of the aPTT, suggesting that a subset of patients with APS may benefit from the TAS aPTT assay when monitoring heparin or other anticoagulation therapy.
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PMID:Management of lepirudin therapy for a patient with antiphospholipid antibody syndrome using the whole blood ecarin clot time and activated partial thromboplastin time. 1296 Jun 16

The comparatively high rate of complications, both to the mother and foetus, of warfarin and unfractionated heparin have led to an increased use of low molecular weight heparins (LMWH) in pregnant women at risk of thrombosis. However, despite reliable pharmacokinetics of LMWH, current practice is that anti-activated factor X levels are monitored in this group of patients. We report the use of unmonitored dalteparin in 27 pregnancies of 25 women who had previous thrombotic events. All women had normal renal function and weighed less than 85 kg prior to conceiving. The regimen consisted of 5000 IU dalteparin once daily started at the time of a positive pregnancy test, and increased to twice daily at 16-20 weeks gestation. In this cohort of patients there was a low complication rate. None of the women developed recurrent venous thromboses during these pregnancies but two women with known cerebral antiphospholipid syndrome developed recurrent cerebral ischaemia, which responded to an increase in dose. In our small group of patients, we have found that the use of intermediate-dose LMWH in pregnant women does not need to be monitored, and that it is safe and probably effective in preventing recurrent venous but not arterial thromboembolic events in high-risk pregnancies.
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PMID:Thromboprophylaxis with unmonitored intermediate-dose low molecular weight heparin in pregnancies with a previous arterial or venous thrombotic event. 1461 52

New synthetic direct and indirect factor Xa or factor IIa inhibitors are increasingly used for the prevention and treatment of thrombotic disorders, including patients suffering from antiphospholipid syndrome. In this study, the effects of the synthetic direct factor Xa inhibitor DX-9065a, the indirect synthetic heparinomimetic pentasaccharide, and the direct factor IIa inhibitor Argatroban were studied. These two widely used assays for the detection of lupus anticoagulant, namely the tissue thromboplastin inhibition (TTIT) and the dilute Russell viper venom tests (DRWT) proved useful. The drugs were added to a normal human plasma pool ranging in concentration from 0.04 to 10 microg/mL. Using the two tests named above, DX-9065a and Argatroban showed a dose-related prolongation of TTIT and DRWT in the concentration range from 0.04 to 5 micromol/mL, but the pentasaccharide only slightly prolonged the clotting times of these assays even at high concentrations. Argatroban had the more pronounced effect on both tests when compared with DX-9065a (p < 0.001). The most responsive assay for DX-9065a up to a concentration of 2.5 micromol/mL was the DRWT. For Argatroban both TTIT and DRWT were equally responsive. Patients whose plasma was tested for suspected lupus anticoagulant and who have been given DX-9065a or Argatroban may have false-positive results with the TTIT tests and DRWT. This effect should be considered during patient management. These results indicate that these assays could be used for the effective quantitation of the direct factor Xa or factor IIa inhibitors when suitable controls are used.
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PMID:Differential effects of DX-9065a, argatroban, and synthetic pentasaccharide on tissue thromboplastin inhibition test and dilute Russell's viper venom test. 1465 41

We report a 27-year-old primigravida with systemic lupus erythematosus, erythema multiforme-like lesions and a peculiar immunological pattern consisting of antinuclear antibody (speckled pattern) and rheumatoid factor, an association known as Rowell's syndrome. She also had a probable antiphospholipid syndrome as evidenced by the presence of a prolonged activated partial thromboplastin time, kaolin clotting time and thrombocytopenia.
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PMID:Rowell's syndrome and associated antiphospholipid syndrome. 1472 13

Protein Z (PZ) is a vitamin K dependent factor identified in human plasma in 1984 whose physiological function was poorly understood. It was recently shown that protein Z is implicated in the down-regulation of coagulation by forming a complex with a plasma proteinase inhibitor called protein Z-dependent protease inhibitor (ZPI) which inhibits activated factor Xa on phospholipid surfaces. In the absence of an additional challenge, the disruption of PZ gene in mice is asymptomatic, but the association with the factor VLeiden mutation leads to a near complete mortality during the neonatal period with microvascular thrombosis. Unexpectedly, in humans, a relationship between protein Z deficiency and ischemic strokes, was firstly evidenced, but not confirmed by all the epidemiological study. Additional studies suggest that protein Z deficiency could be also a risk factor for acute coronary syndromes, early fetal losses, and increased the arterial risk in antiphospholipid syndrome. This review analyzes the different studies so far published and discusses the different results obtained in order to understand whether or not protein Z deficiency could be considered as an arterial ischemic risk factor.
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PMID:[Protein Z: a new regulator of coagulation in arterial vessels?]. 1531 79

The antiphospholipid syndrome is characterized by the presence of antiphospholipid antibodies in plasma of patients with thromboembolic complications. A major problem in defining the syndrome is that serologic assays to detect antiphospholipid antibodies have a low specificity. We recently published a method that specifically detects lupus anticoagulant (LAC) caused by anti-beta(2)-glycoprotein I antibodies. Here, we studied the clinical relevance of detecting beta(2)-glycoprotein I-dependent LAC. Plasma samples were collected from 198 patients with autoimmune diseases. In those samples with a positive partial thromboplastin time-lupus anticoagulant (PTT-LA), a modified activated partial thromboplastin time (aPTT)-based LAC test was performed with cardiolipin as confirming agent. Twenty-five of 58 patients with an aPTT-based LAC were dependent on the presence of anti-beta(2)-glycoprotein I antibodies. Presence of beta(2)-glycoprotein I-dependent LAC was almost completely associated with a history of thromboembolic complications (odds ratio, 42.3; 95% confidence interval, 194.3-9.9). An increased frequency of thrombosis was not found in 33 patients with LAC independent of anti-beta(2)-glycoprotein I antibodies (odds ratio, 1.6; 95% confidence interval, 3.9-0.8). The use of an LAC assay with cardiolipin as confirming agent strongly improves the detection of patients at risk of thrombosis. Our findings suggest that anti-beta(2)-glycoprotein I antibodies with LAC activity are antibodies that are responsible for the thromboembolic complications in the antiphospholipid syndrome.
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PMID:beta2-glycoprotein I-dependent lupus anticoagulant highly correlates with thrombosis in the antiphospholipid syndrome. 1531 75

Autoimmune factors are involved in some of the cases of reproductive failure. These factors entail several autoantibodies, especially in patients having systemic lupus erythematosus (SLE) or the antiphospholipid syndrome (APS). These autoantibodies include mainly antibodies directed to phospholipid such as cardiolipin, phosphatidylserine, phosphatidylethanolamine or phospholipids binding glycoproteins such as beta2glycoprotein-I, annexin V, prothrombin and protein-Z. There are also some other autoantibodies directed to laminin-I, thromboplastin, mitochondrial antibodies of the M5 type, corpus luteum, prolactin, poly (ADP-ribose), thyroglobulin and more, which were also found in SLE or APS patients with reproductive failure. Moreover, the presence of additional autoantibodies directed to actin, enolase, cubilin and others, needs further investigation to support a firm association to reproductive failure in women. Future studies are likely to help to determine and expand the number of autoantibodies screened in these patients, as well as by the use of proteomics technology, to determine peptides resembling the epitope specificities associated with the specific clinical manifestations.
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PMID:Autoantibodies associated with reproductive failure. 1548 94

Some cases of reproductive failure with autoimmune background are characterized by the involvement of autoantibodies. This occurs mainly in patients having systemic lupus erythematosus or antiphospholipid syndrome. The autoantibodies associated with reproductive failure include: a) antibodies which directly bind phospholipid (e.g., cardiolipin, phosphatidylserine, phosphatidylethanolamine); b) antiphospholipid Abs which bind the phospholipid via phospholipid-binding glycoproteins such as beta2glycoprotein-I, annexin V and prothrombin; c) autoantibodies directed to laminin-I, actin, thromboplastin, the corpus luteum, prolactin, poly (ADP-ribose), thyroglobulin and mitochondrial antibodies of the M5 type. This paper will focus on the association of antiphosphatidylserine autoantibodies and reproductive failure. Future studies are likely to help to identify peptides resembling the epitope specificities associated with the specific clinical manifestations.
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PMID:Antiphosphatidylserine antibodies and reproductive failure. 1548 98


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