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)

The development of effective approaches to the management of the unstable coronary syndromes has resulted from an improved understanding of interactions between the vascular wall, platelets, and coagulation factors, and of their response to pharmacologic and mechanical interventions. Furthermore, the occurrence of frequent adverse events after discharge in patients with unstable coronary artery disease (CAD) treated with these therapies alone would argue that, for many of these patients, such stabilization is not the end of the therapeutic pathway; rather, these therapies are for many a preparation for ultimate revascularization, to preserve myocardium and minimize periprocedural complications. The low-molecular-weight heparins with their unique pharmacology offer a new option in the therapy of patients with unstable CAD. There is now extensive experience in the use of several of the low-molecular-weight heparins, particularly dalteparin and enoxaparin, in the management of patients with unstable angina. Several trials have investigated the questions raised by these observations, taking advantage of the unique pharmacologic properties of the low-molecular-weight heparins for both acute inpatient use and prolonged outpatient administration. Although differences in study design preclude direct comparison between the available low-molecular-weight heparins, in these trials low-molecular-weight heparins have been shown to be effective alternatives to conventional heparin for the management of patients with unstable angina and non-Q-wave infarction. These include several small-scale trials and the larger FRagmin during InStability in Coronary artery disease (FRISC), Fragmin in Unstable Coronary Artery Disease (FRIC), Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events (ESSENCE), FRISC II, and Thrombolysis in Myocardial Infarction (TIMI)-11B trials. Thus, the low-molecular-weight heparins appear to be a superior alternative to traditionally administered intravenous unfractionated heparin. They are more predictable in action, do not require frequent activated partial thromboplastin time (aPTT) measurements and dosage adjustments, are easier to administer, and are potentially more efficacious. With their proven efficacy, predictability of action, and convenience of administration and dosing, there are very good reasons for selecting them as first-line therapies for patients presenting with unstable angina and non-Q-wave myocardial infarction.
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PMID:Role of low-molecular-weight heparins in the management of patients with unstable angina pectoris and non-Q-wave acute myocardial infarction. 1079 74

A 70-year-old patient with a history of hypertension and hypercholesterolemia was referred for evaluation of necrotic toes. The patient had a history of several cerebrovascular accidents during the previous month. Initially, she developed sudden-onset left upper extremity weakness which, over the ensuing 4 days, progressed to complete left-sided weakness. This was followed by the development of acute dysarthria. A transesophageal echocardiogram revealed moderate left ventricular hypertrophy, several vegetations on her tri-leaflet aortic valve associated with moderate aortic regurgitation, and a large right atrial thrombus with a mobile component. Bubble studies failed to reveal any septal defects. The patient's electrocardiogram was nonspecific. As serial blood cultures were negative despite fevers of up to 39.8 degrees C, the patient was treated with a 6-week course of intravenous ceftriaxone, ampicillin, gentamicin, and ciprofloxacin for a presumed diagnosis of culture-negative endocarditis. Fungal cultures of the blood were negative. The patient, however, progressed and developed several necrotic toes. Physical examination was significant for ischemic changes of the left first, second, third, and fifth toes, as well as the right first and second toes. Diffuse subungual splinter hemorrhages in the toenails, numerous 2-4-mm palpable purpuric papules on the lower extremities, and nontender hemorrhagic lesions of the soles were also noted. Peripheral and carotid pulses were intact and no carotid bruits were heard. Cardiopulmonary and abdominal examinations were unremarkable. Neurologic examination revealed a disoriented, dysarthric patient with left central facial nerve paralysis, as well as spasticity, hyperactive reflexes, and diminished strength and sensation in the left upper and lower extremities. A left visual field defect and left hemineglect were also present. The patient's last brain computerized tomogram revealed areas of low attenuation consistent with cerebral infarctions in three distinct areas of the brain. These included the left occipitotemporal area, the right parieto-occipital area, and the right posterior frontal region. The regions affected were in the distribution of both the anterior and posterior circulation. No evidence of hemorrhage was noted. The patient subsequently complained of abdominal discomfort. A computerized tomogram of the abdomen with oral and intravenous contrast revealed a 4-cm x 3-cm irregular mass in the tail of the pancreas with several low-attenuation lesions throughout the liver which were consistent with infarctions or metastases. Several splenic infarctions were also present. A biopsy of the tumor revealed pancreatic adenocarcinoma. The patient's carcinoembryonic antigen level was 18. 4 ng/mL (0-3) and the CA 19-9 antigen level was 207,000 U/mL (0-36). The alpha-fetoprotein level was normal. Other significant laboratory findings included a prothrombin time of 16.7 (international normalized ratio, 1.4), an activated partial thromboplastin time of 32 (ratio, 1.3), and a platelet count of 85,000/mm3. The Russell viper venom time, sedimentation rate, and C3 levels were normal, and the patient was negative for antinuclear antibodies, anticardiolipin antibodies, and antibodies to extractable nuclear antigens. Of note, the patient was not receiving any anticoagulation. Blood cultures for mycobacteria and fungi, human immunodeficiency virus serology, and urinalysis and culture were negative. The patient subsequently developed an inferior wall myocardial infarction and was transferred to the coronary care unit. In line with the family's request, aggressive care was ceased and the patient expired. The patient's family refused an autopsy.
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PMID:Cutaneous manifestations of marantic endocarditis. 1080 80

Traditionally, unfractionated heparin has played an important role in the treatment of acute coronary syndromes. Low molecular weight heparin (LMWH), is a promising new type of heparin, which is fractionated to include only heparin molecules of lower molecular weight. LMWHs are administered subcutaneously and do not require monitoring of the activated partial thromboplastin time, making them much easier to use. LMWHs are combined inhibitors of both thrombin and Factor Xa inhibitors. Several recent large trials in unstable angina and non-Q wave myocardial infarction have shown that LMWH is effective, and one agent has been shown to be superior to unfractionated heparin in reducing death, myocardial infarction, or recurrent angina. They also are very low cost (approximately $50 per day) and appear to be very cost effective in the treatment of unstable angina. Thus, LMWHs appear to be the new anticoagulant agent in acute coronary syndromes.
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PMID:Low molecular weight heparin in acute coronary syndromes. 1098 Aug 43

The primary antiphospholipid syndrome is a disorder which is characterized by: arterial and/or venous thrombosis, thrombocytopenia, recurrent fetal loss and high plasma levels of antiphospholipid antibodies. Valvular involvement is associated with arterial thrombosis and the most frequent manifestation is regurgitation. We report the case of a young male with primary antiphospholipid syndrome and previous cerebrovascular thrombosis hospitalized for subacute myocardial infarction. Coronary angiography revealed right and left anterior descendent coronary artery stenosis, the latter being successfully recanalized by direct percutaneous transluminal coronary angioplasty. Transthoracic echocardiography demonstrated aortic valve involvement with predominant regurgitation and transesophageal echocardiography detected valve excrescences on the aortic leaflets. Laboratory study demonstrated thrombocytopenia, prolonged activated partial thromboplastin time and high titers of anticardiolipin antibodies. Oral anticoagulation therapy was started. Thrombotic events have not recurred after three months of follow-up.
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PMID:[Antiphospholipid syndrome with myocardial infarction and aortic valve involvement]. 1108 11

Thrombolytic agents activate plasminogen and induce a systemic fibrinolytic and anticoagulant state. Interaction of fibrinolysis with coagulation and platelet aggregation might be important for synergistic interactions with other antiplatelet or anticoagulant drugs. Thrombolytic agents are most often used in patients with coexisting cardiovascular medication, including various antihypertensives, beta-blocking agents, nitrates and aspirin (acetylsalicylic acid). In acute coronary syndromes, anticoagulants and antiplatelet compounds such as clopidogrel or glycoprotein IIb/IIIa receptor antagonists might be given. Inducers or inhibitors of the cytochrome P450 system are not reported to affect the pharmacokinetics of any thrombolytic agent. Since the elimination of the recombinant plasminogen activators saruplase and alteplase is dependent on liver blood flow, drugs affecting hepatic blood flow could theoretically affect the hepatic clearance of these agents. In fact, a reduction in thrombolytic activity has only been demonstrated for alteplase with nitroglycerin (glyceryl trinitrate). Pharmacodynamic interactions occur more often. The additive and beneficial effect of aspirin as concomitant therapy to thrombolysis has been demonstrated without excessive bleeding rates. No data are available on the interaction between ticlopidine or clopidogrel and thrombolytic agents in humans. Anticoagulation by heparin concomitantly with thrombolysis improves the patency rate of the occluded coronary vessel, but bleeding complications are seen more frequently. Although there has been no controlled study on the interaction between oral anticoagulants and thrombolytic agents, patients with myocardial infarction who were taking an oral anticoagulant before admission seem to be at higher risk for intracranial haemorrhage during thrombolytic therapy. Currently, no recommendations can be given for possible dose adjustment of thrombolytic therapy in patients receiving antiplatelet comedication. For comedication with heparin, it has been advised to monitor activated partial thromboplastin time frequently and to avoid values >2.5-fold normal. Patients receiving thrombolytic treatment should be monitored frequently for bleeding and the physician should be aware of any comedication exerting antiplatelet (e.g. aspirin, clopidogrel and ticlopidine) or anticoagulant (e.g. warfarin) effects.
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PMID:Thrombolytics: drug interactions of clinical significance. 1108 46

Enoxaparin, a low-molecular-weight heparin, and tirofiban, an intravenous platelet glycoprotein IIb/IIIa receptor antagonist, have each been shown to be effective in reducing cardiac ischemic events compared to unfractionated heparin alone in separate trials of patients with unstable angina and non-Q wave myocardial infarction. The combination of these agents may offer further therapeutic benefit. In a pilot study (ACUTE I), fifty-five patients with non-Q wave myocardial infarction were randomized to receive double-blind treatment with tirofiban (0.1 microg/kg/min intravenously) for 48/108 hours co-administered with either enoxaparin (1 mg/kg sc q 12 hours) (n = 26) or unfractionated heparin (intravenous, adjusted to activated partial thromboplastin time) (n = 27). Co-administration of tirofiban and enoxaparin was generally well tolerated. Plasma clearance of tirofiban was similar for enoxaparin and unfractionated heparin-treated patients. When combined with tirofiban, enoxaparin, relative to unfractionated heparin, resulted in less variability and a trend toward greater inhibition of platelet aggregation using 5 microM adenosine phosphate agonist. More patients achieved target inhibition of platelet aggregation (> 70%) in the tirofiban and enoxaparin group (84% versus 65%; p = 0.19). Median bleeding time was 21 minutes for tirofiban and enoxaparin versus 30 minutes for tirofiban and unfractionated heparin (p = non-significant). For a given level of inhibition of platelet aggregation, bleeding time was less prolonged with tirofiban and enoxaparin than tirofiban and unfractionated heparin (adjusted mean bleeding time 19.6 versus 24.9 minutes, respectively; p = 0.02). There were no major or minor bleeding events in either group by the TIMI criteria. The more consistent inhibition of platelet aggregation and lower adjusted bleeding time of tirofiban and enoxaparin versus tirofiban and unfractionated heparin support the therapeutic potential of combining these two agents. These observations have now been extended to more than 500 patients.
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PMID:Initial experience with the low-molecular-weight heparin, enoxaparin, in combination with the platelet glycoprotein IIb/IIIa blocker, tirofiban, in patients with non-ST segment elevation acute coronary syndromes. 1115 22

It is known that a low-molecular-weight heparin (LMWH) is more effective than unfractionated heparin in unstable angina/non-Q-wave myocardial infarction (UA/NQMI) and the platelet GPIIb/IIIa receptors play an important role in acute myocardial infarction (AMI). Therefore, enoxaparin might have a similar advantage over heparin when used with a GPIIb/IIIa antagonist (RPR109891) in coronary thrombolysis. After induction of coronary thrombosis in anesthetized dogs, infusion of saline, enoxaparin, heparin, RPR109891, enoxaparin+RPR109891, or heparin+RPR109891 was initiated followed 15 min later by recombinant tissue plasminogen activator (rt-PA). The incidence of reperfusion in the enoxaparin+RPR109891- and the heparin+RPR109891-treated groups was similar, but time to reperfusion tended to be shorter for enoxaparin versus heparin. Only 43% of the vessels reoccluded in the enoxaparin+RPR109891 group, compared to 100% vessels in the heparin+RPR109891 group. Enoxaparin+RPR109891 maintained flow for a significantly longer time compared to saline, enoxaparin, heparin, and heparin+RPR109891. Enoxaparin+RPR109891 and heparin+RPR109891 increased the template bleeding time by 2- and 3-fold and activated partial thromboplastin time (APTT) by 1.3- and 3-fold, respectively. These data suggest that enoxaparin is more effective and potentially safer than heparin when combined with a GPIIb/IIIa receptor antagonist during rt-PA-induced coronary thrombolysis.
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PMID:Superiority of enoxaparin over heparin in combination with a GPIIb/IIIa receptor antagonist during coronary thrombolysis in dogs. 1136 20

Despite major innovations in antithrombotic and antiplatelet therapy, unfractionated intravenous heparin is widely used to treat acute coronary syndromes. Recommendations for unfractionated heparin dosing in acute myocardial infarction and unstable angina have been issued in two recent American College of Cardiology/American Heart Association guidelines. An initial heparin bolus of 60 U/kg (maximum, 4000 U) followed by a 12-U/kg/h infusion (maximum 1000 U/h) is recommended with alteplase for ST-elevation myocardial infarction. When intravenous heparin is administered for myocardial infarction with non-ST elevation and unstable angina, an initial bolus of 60 to 70 U/kg (maximum, 5000 U) followed by a 12- to 15-U/kg/h infusion is recommended. The goal is to achieve an activated partial thromboplastin time of 50 to 70 seconds. Here, we review these new dosing regimens and explain the rationale for their use. We also review the risk of bleeding with heparin, especially when administered concurrently with aspirin, thrombolytic agents, and glycoprotein IIb/IIIa antagonists, and the relationship between activated partial thromboplastin time and cardiac events.
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PMID:New heparin dosing recommendations for patients with acute coronary syndromes. 1138 73

Acute coronary syndromes account for tens of thousands of emergency room visits and cost the United States healthcare system billions of dollars each year. Dalteparin is a low molecular weight heparin (LMWH) recently approved for treatment of unstable angina and non-Q wave myocardial infarction (NQWMI). The LMWHs possess distinct advantages over unfractionated heparin (UFH). Some of these advantages include administration by subcutaneous injection with no intravenous access required; laboratory monitoring of activated partial thromboplastin time (aPTT) is not required; improved side effect profile; and more predictable and consistent anticoagulant response. In conjunction with aspirin, dalteparin was evaluated for the treatment of unstable angina and NQWMI in three large clinical trials. The FRISC study established the value of short-term dalteparin in patients with unstable coronary artery disease, but suggested that treatment with 120 IU/kg subcutaneously twice daily may be required for more than 6 days. The FRIC trial determined there was no difference between dalteparin and UFH in the acute setting for prevention of death or myocardial infarction (MI). Similar to the FRISC trial, the FRIC trial failed to demonstrate a benefit of dalteparin beyond the acute phase. The FRISC II study demonstrated a significant decrease in the composite endpoint of death or MI in the dalteparin group at 30 days, but not at 3 or 6 months. The early protective effects of dalteparin could be used to lower the risk of events in patients waiting for invasive procedures.
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PMID:Dalteparin for acute coronary syndromes. 1172 Jun 39

Antiphospholipid antibodies are a heterogeneous family of immunoglobulins that includes lupus anticoagulant and anticardiolipin antibodies. They are strongly associated with a clinical syndrome characterized by venous and arterial thrombosis and spontaneous fetal losses. This syndrome may be primary or else secondary to autoimmune or neoplastic diseases. The cardiovascular system is frequently involved with mitral or aortic insufficiency, juvenile myocardial infarction, and primitive pulmonary hypertension. However, the occurrence of intracardiac thrombi is rare. We describe a case of an intracardiac right atrial thrombus in a 19-year-old asymptomatic woman who was admitted in December 1998 to the Thrombosis Center owing to the finding, during routine work-up, of a prolonged activated partial thromboplastin time (71 s) and thrombocytopenia (71 x 1000/mm3), a positive antinuclear antibody test (1/320), positivity for lupus anticoagulant, and increased IgG (92 GPL-U/ml) and IgM (27 MPL-U/ml) anticardiolipin antibodies. Six months later, the patient presented with headache, edema and cyanosis of the face and jugular swelling. Transthoracic and transesophageal echocardiography revealed a right atrial mass which was clearly distinguishable from the tricuspid valve and extended to the superior vena cava. The patient was successfully submitted to surgical excision of the thrombus. Histology revealed that the mass was adherent to an abnormal septum consisting of mesenchymal tissue. Although the American Rheumatology Association criteria for the diagnosis of systemic lupus erythematosus were not fulfilled, the positivity of antinuclear antibody test is in favor of a lupus-like syndrome. The decision to opt for surgical excision of the thrombus was determined by the unclear nature of the atrial mass. It may be necessary that such patients be submitted to anticoagulant therapy for the rest of their lives or temporarily (6-12 months). This underscores the importance of the anatomical abnormality as a promoting factor. Transthoracic echocardiography (as well as transesophageal echocardiography in selected cases) must be considered as an essential component of the initial diagnostic work-up in patients presenting with antiphospholipid antibodies.
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PMID:[Left atrial thrombosis in patients with antiphospholipid antibody syndrome and mesenchymal abnormal septum]. 1172 15


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