Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of dipyridamole (Persantine) on the thrombocyte count and bleeding tendency in connection with open-heart surgery and perfusion was studied in 22 patients. A control series of 21 patients undergoing open-heart surgery was available. The treatment group received dipyridamole, 0.5 mg. per kilogram of body weight, in the beginning of cardiopulmonary bypass into the heart-lung machine and thereafter 10 mg. intravenously three times daily for 2 days. From the third day dipyridamole was administered by mouth, 75 mg. three times a day, until the patient was discharged from hospital. We found that dipyridamole had the effect of maintaining the thrombocyte count during cardiopulmonary bypass and the first and second postoperative days. Thereafter no significant difference was seen between the dipyridamole and control groups. The use of dipyridamole did not increase the postoperative hemorrhagic tendency. There were no significant differences in per- and postoperative blood loss and in bleeding and activated partial thromboplastin times between the groups.
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PMID:The effect of dipyridamole on the thrombocyte count and bleeding tendency in open-heart surgery. 88 83

Fifty-four adult mongrel dogs receiving a lipid-supplemented diet were used to determine the effects of aspirin and dipyridamole on vein graft intimal hyperplasia. Twenty-one animals received the diet alone, 17 animals received a combination of dipyridamole and aspirin, while a further 16 animals received dipyridamole. Segments of undistended external jugular vein were anastomosed to bilaterally-divided femoral arteries. The vein grafts were harvested at six weeks and intimal thickness was measured with a Zeiss computerized microscope. Serum cholesterol, prothrombin time, partial thromboplastin time and clotting time was measured before the diet and at two, four and six weeks after operation. Plasma thromboxane B2 (TXB2) and the metabolite of prostacyclin I2 (6-keto PGF1 alpha) were determined by radioimmunoassay before and four weeks following operation. A similar and significant increase in serum cholesterol was observed in all animals receiving lipid supplementation. Platelet counts were significantly decreased in those animals receiving a combination of aspirin and dipyridamole while all other hematological parameters remained unchanged. Plasma TXB2 and 6-keto PGF1 alpha were unaffected by dipyridamole but were significantly decreased in those animals receiving the combined drug regimen. Intimal thickness measured 59 +/- 6 micron at six weeks in the controls. Dipyridamole reduced intimal thickness to 26 +/- 2 micron while aspirin and dipyridamole decreased intimal thickness to 28 +/- 2 micron. The data indicate that dipyridamole was as effective in reducing smooth muscle cell proliferation as the combination of aspirin and dipyridamole. Furthermore, the data suggest that antiplatelet drug regimens may reduce intimal thickening in autologous vein grafts by a mechanism other than affecting the thromboxane:prostacyclin ratio.
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PMID:Correlation between the effects of aspirin and dipyridamole on platelet function and prevention of intimal hyperplasia in autologous vein grafts. 335 54

Dipyridamole, an inhibitor of platelet aggregation, has been shown to have beneficial effects in disorders characterized by extravascular fibrin deposition. Mononuclear phagocytes are present in extravascular sites and are capable of expressing both plasminogen activator and procoagulant activities, which suggests these cells play a central role in extravascular fibrin turnover. We therefore sought to determine whether dipyridamole affects the expression of plasminogen activator and procoagulant activities by rabbit alveolar macrophages cultured in vitro. We found that dipyridamole (10 to 100 mumol/L) caused increases in both cell-associated and released plasminogen activator activity, which reached levels of 240% (P less than .05) and 543% (P less than .01) of controls, respectively. In contrast, dipyridamole decreased the cell-associated procoagulant activity of alveolar macrophages to as little as 21.3% of controls (P less than .01). Similar effects were seen in cells cotreated with lymphokines. The procoagulant activity expressed by these cells functioned as a tissue thromboplastin. The plasminogen activator of control and treated cells was a urokinase as determined by molecular weight characteristics (50 kilodaltons) and by antibody neutralization profiles using polyclonal antibodies against human urokinase and tissue plasminogen activator. These effects of dipyridamole could not be duplicated by structurally dissimilar agents sharing some of the pharmacological actions of dipyridamole; however, two pyrimidopyrimidine compounds structurally similar to dipyridamole effectively mimicked the effects on both procoagulant and plasminogen activator activities. We conclude that dipyridamole may have antithrombotic effects by directly modulating the role of mononuclear phagocytes in fibrin turnover. Thus, dipyridamole may be useful in situations where extravascular fibrin deposition is important to the pathogenesis of tissue injury and repair.
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PMID:Dipyridamole stimulates urokinase production and suppresses procoagulant activity of rabbit alveolar macrophages: a possible mechanism of antithrombotic action. 380 75

Anticoagulation in infants and children on a ventricular assist device presents particular challenges. Unfractionated heparin has poor bioavailability; it can be difficult to achieve a stable anticoagulant effect; and, in the long-term, there is a risk of osteopenia. Long-term warfarin can be difficult to manage in infants on formula milk with vitamin K supplementation. We review our recent experience with subcutaneous low molecular weight heparin. Two patients received a left ventricular assist device (Excor, Berlin Heart AG) as a bridge to transplantation. Initial anticoagulation consisted of unfractionated heparin infusion beginning 6 hours after implantation to maintain an activated partial thromboplastin time of 70 seconds, checked every 4 to 6 hours. Platelet count (aim >80,000/microl) and thromboelastography were assessed daily. Antithrombin required substitution to maintain levels >70 IU/dl. To optimize anticoagulation, both infants were switched to subcutaneous low molecular weight heparin twice daily aiming for an anti-Xa activity between 0.5 and 1.0 IU/ml. Aspirin was added on day 4, checking platelet aggregation every 2 to 4 days, aiming at arachidonic acid stimulated aggregation 10% to 30% of baseline, collagen 100% of baseline. Dipyridamole was added once stability was reached if platelets count exceeded 150,000/microl. There were no clinical thromboembolic or bleeding events. Both patients had successful transplantation.
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PMID:Subcutaneous low molecular weight heparin for management of anticoagulation in infants on excor ventricular assist device. 1711 62

Peripheral arterial disease (PAD) is a major medical/surgical problem associated with high risk for coronary heart disease (CHD). Anticoagulation plays a significant role in the management of the PAD patient. However, evidence-based medicine supports only select anticoagulants, mainly antiplatelet agents. The available anticoagulant classes, their individual medications, and the mechanisms of action are described. Dextran 40, platelet glycoprotein (GP) IIb/IIIa receptor antagonists, direct thrombin (factor IIa, FIIa) inhibitors, and factor Xa (FXa) inhibitors do not, at this juncture, appear to have a significant role to play in the PAD patient. Aspirin has been used in PAD patients for a few decades, as has warfarin, but the role of warfarin is very limited. An attempt has been made to place each medication and its function in context all the way to the present with oral direct thrombin (FIIa) and FXa inhibitors described. These inhibitors may ultimately play an, as yet, undefined role in PAD. Specific use of anticoagulants in PAD patients is described and aspirin still stands out as a fundamental therapy. The thienopyridines, especially clopidogrel, have their established place and there is some evidence for benefit from the use of clopidogrel in dual therapy with aspirin. Dipyridamole, especially with aspirin as dual therapy, and cilostazol also have their evidence-based niches. The main role played by warfarin is for the patient with a vein graft in the arterial circulation. Heparin retains significant procedural importance. For now, Class I, Level of Evidence A center around aspirin for the PAD patient with clopidogrel, an alternative agent.
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PMID:A review of the role of anticoagulation in the treatment of peripheral arterial disease. 2429 75