thromboxane-b2 and Thromboembolism

We evaluated the short-term safety and efficacy of aspirin-plus-clopidogrel as antithrombotic therapy in nonvalvular atrial fibrillation (AF).. Thirty patients (11 women, 45 to 75 years of age) with non-high-risk permanent (n = 12) or persistent AF awaiting cardioversion (n = 18) underwent transesophageal echocardiography to exclude left heart thrombi and were then randomly assigned to receive warfarin (international normalized ratio, 2 to 3 for 3 weeks) or aspirin (100 mg/d alone for 1 week)-plus-clopidogrel (75 mg/d added to aspirin for 3 weeks). Bleeding time and serum thromboxane B2 were measured at entry and at 3 weeks. Bleeding time, not affected by warfarin, was prolonged by 71% by aspirin (P <.05) and further, by 144%, by adding clopidogrel (P <.01 vs aspirin alone; +319%, P <.01, vs baseline). Thromboxane B2, not affected by warfarin, was reduced by aspirin (-98%, P <.01) but not further by clopidogrel. No thrombi or dense spontaneous echo-contrast were found at the 3-week transesophageal echocardiography. Seven of 9 patients receiving warfarin and 7 of 9 patients receiving aspirin-plus-clopidogrel, undergoing electrical cardioversion, achieved sinus rhythm. No thromboembolic or hemorrhagic events occurred in both arms throughout the 3-week treatment and a further 3-month follow-up.. Aspirin-plus-clopidogrel and warfarin were equally safe and effective in preventing thromboembolism in this small group of patients with non-high-risk AF.

Topics: Aged; Anticoagulants; Aspirin; Atrial Fibrillation; Bleeding Time; Clopidogrel; Drug Therapy, Combination; Echocardiography, Transesophageal; Electric Countershock; Female; Humans; International Normalized Ratio; Male; Middle Aged; Pilot Projects; Platelet Aggregation Inhibitors; Thromboembolism; Thromboxane B2; Ticlopidine; Warfarin

Aspirin has been shown to be beneficial in the prophylaxis of arterial thromboembolic disease. The rationale for its use as an antithrombotic drug lies in its inhibition of thromboxane A2-dependent platelet function. However, the effect of aspirin on coagulation and fibrinolysis during chronic therapy has not been studied. We have measured a range of haemostatic and platelet functions in 49 patients with transient ischaemic attacks randomly allocated to aspirin 300 mg a day, aspirin 1,200 mg a day or placebo. All had been taking their allocated treatment for between 9 months and 4 years prior to investigation. Bleeding time was prolonged, serum thromboxane diminished and platelet aggregation to arachidonic acid but not ADP was abolished by both 300 mg and 1,200 mg aspirin, in a non-dose dependent fashion. Serum salicylate increased with the dose of aspirin ingested. No effect was seen with either dose of aspirin on urinary thromboxane and 6-keto-PGF1 alpha excretion, or on coagulation. Patients taking 1,200 mg aspirin a day had a lower haemoglobin and packed cell volume, lower resting fibrinopeptide A concentration and lower basal plasminogen activator activity than those on placebo. Response to venous occlusion was normal in all groups. The results suggest 300 mg and 1,200 mg aspirin have an equivalent platelet inhibitory effect but 1,200 mg aspirin causes greater gastro-intestinal blood loss.

Topics: Aged; Aged, 80 and over; Aspirin; Bleeding Time; Blood Coagulation; Dose-Response Relationship, Drug; Female; Fibrinolysis; Fibrinopeptide A; Humans; Male; Middle Aged; Placebos; Plasminogen Activators; Platelet Aggregation; Platelet Aggregation Inhibitors; Salicylates; Thromboembolism; Thromboxane B2; Time Factors

The effect of acetylsalicylic acid (ASA) on plasma thromboxane A2 (TXA2) and platelet aggregation was studied in 12 healthy, non-smoking, male students, in a double-blind, cross-over study, after single doses and 14-days on ASA 50, 100, 250 and 1000 mg/day. Platelet production of TXA2 was assessed by measuring the thromboxane B2 (TXB2) content of clotted venous blood by RIA. Platelet aggregation induced by ADP and adrenaline was studied by the method of Born. All doses of ASA completely suppressed the production of TXB2 within 3 h, with the exception of the 50 mg dose, which effected only 61% suppression (p less than 0.001). After administration for 14 days the suppression was complete, even including the lowest dose. At that time ASA had blocked the secondary phase of adrenaline- and ADP-induced platelet aggregation. It is concluded that the maximal antithromboxane and antiaggregatory effects, which last for at least 24 h, can be achieved by continuous daily administration of ASA 50 mg.

Topics: Adult; Aspirin; Dose-Response Relationship, Drug; Humans; Male; Platelet Aggregation; Thromboembolism; Thromboxane B2; Thromboxanes

In 19 patients with unstable angina pectoris at rest, plasma levels of the platelet-derived proteins beta-thromboglobulin and platelet factor 4 were significantly elevated in blood samples obtained during or within 4 hours after episodes of angina, but were usually normal during quiescent intervals. Plasma levels of the arachidonic acid metabolite thromboxane B2 were less clearly related to angina, and there was no association of angina with levels of the coagulation product fibrinopeptide A. This demonstration of an association of platelet activation and secretion with unstable angina pectoris by radioimmunoassay of circulating platelet constituents offers a new approach to assessment of therapy in ischemic heart disease and suggests that agents that alter platelet function should be evaluated in patients with unstable angina.

Topics: Adult; Aged; Angina Pectoris; beta-Thromboglobulin; Blood Platelets; Electrocardiography; Female; Fibrinopeptide A; Heparin; Humans; Male; Middle Aged; Myocardial Infarction; Platelet Factor 4; Thromboembolism; Thromboxane B2

Aspirin is now recommended for splenectomized thalassemia patients with high platelet counts. However, aspirin resistance defined by arachinodic acid (ACA) induced platelet aggregation ≥20%, has never been reported in this group of patients. In this study, twenty-four splenectomized thalassemia patients (15.7±4.1years), with platelet counts ≥800x10(9)/L, and 21 non-splenectomized severe thalassemia patients (14.3±3.2years), were enrolled. After taking aspirin (2mg/kg/day), seven patients (29.2%) displayed aspirin resistance. Serum thromboxane B2 (TXB2) levels in the aspirin responsive group decreased significantly [52.6(8.8-174.6) vs 4.0(1.6-7.3) mcg/mL, p<0.001], while no change was demonstrated in the aspirin resistant group. Having increased aspirin to 4mg/kg/day, three of the seven aspirin resistant patients responded, while one developed upper GI bleeding from esophageal varices and was withdrawn from the study. For the three remaining patients, their doses were increased to the maximum of 300mg/day, and two of the three responded. Thrombin antithrombin complex and D-dimer levels were significantly decreased after taking aspirin (2mg/kg/day), although D-dimer level was still significantly higher than that in non-splenectomized group. Therefore, aspirin dosage can be adjusted individually to reach maximum effect of platelet inhibition. In addition, aspirin can reduce the levels of coagulation markers.

Topics: Adolescent; Aspirin; Blood Coagulation; Child; Child, Preschool; Drug Resistance; Female; Fibrin Fibrinogen Degradation Products; Humans; Male; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Count; Platelet Function Tests; Splenectomy; Thalassemia; Thromboembolism; Thromboxane B2; Young Adult

Previous studies suggest that cyclooxygenase-2 (COX-2) might influence megakaryocyte (MK) maturation and platelet production in vitro. Using a gene deletion model, we analysed the effect of COX-2 deficiency on megakaryopoiesis and platelet function. COX-2-/- mice (10-12 weeks old) have hyper-responsive platelets as suggested by their enhanced aggregation, TXA2 biosynthesis, CD62P and CD41/CD61 expression, platelet-fibrinogen binding, and increased thromboembolic death after collagen/epinephrine injection compared to wild-type (WT). Moreover, increased platelet COX-1 expression and reticulated platelet fraction were observed in COX-2-/- mice while platelet count was similar to WT. MKs were significantly reduced in COX-2-/- bone marrows (BMs), with high nuclear/cytoplasmic ratios, low ploidy and poor expression of lineage markers of maturation (CD42d, CD49b). However, MKs were significantly increased in COX-2-/- spleens, with features of MK maturation markers which were not observed in MKs of WT spleens. Interestingly, the expression of COX-1, prostacyclin and PGE2 synthases and prostanoid pattern were modified in BMs and spleens of COX-2-/- mice. Moreover, COX-2 ablation reduced the percentage of CD49b+ cells, the platelet formation and the haematopoietic stem cells in bone marrow and increased their accumulation in the spleen. Splenectomy decreased peripheral platelet number, reverted their hyper-responsive phenotype and protected COX-2-/- mice from thromboembolism. Interestingly, fibrosis was observed in spleens of old COX-2-/- mice (28 weeks old). In conclusion, COX-2 deletion delays BM megakaryopoiesis promoting a compensatory splenic MK hyperplasia, with a release of hyper-responsive platelets and increased thrombogenicity in vivo. COX-2 seems to contribute to physiological MK maturation and pro-platelet formation.

Topics: Animals; Antigens, CD; Antigens, Differentiation; Blood Platelets; Bone Marrow; Crosses, Genetic; Cyclooxygenase 1; Cyclooxygenase 2; Hematopoietic Stem Cells; Hyperplasia; Megakaryocytes; Membrane Proteins; Mice; Mice, Inbred C57BL; Mice, Knockout; Platelet Count; Ploidies; Purpura, Thrombocytopenic, Idiopathic; Receptors, Thromboxane A2, Prostaglandin H2; Spleen; Splenectomy; Thromboembolism; Thrombophilia; Thrombopoiesis; Thromboxane B2

Aspirin is used to prevent thromboembolism in children with heart disease without evidence supporting its efficacy. Studies in adults report a 5%-51% prevalence of aspirin resistance, yet the mechanisms involved are poorly understood. Our aims were to determine its prevalence in these children and to explore its possible mechanisms. One hundred twenty-three cardiac patients routinely receiving aspirin were prospectively enrolled. Platelet function was measured by Platelet Function Analyzer (PFA)-100 using epinephrine and adenosine diphosphate (ADP) agonists. Aspirin resistance was defined as failure to prolong the epinephrine closure time following aspirin administration. Urine levels of 11-dehydro-thromboxane B(2) (11-dTXB(2)) were measured to determine inhibition of the cyclo-oxygenase pathway. The prevalence of aspirin resistance was 26%. Median ADP closure time was shorter for aspirin-resistant (79.60-115 s) than for aspirin-sensitive (100.60-240 s) patients (p < 0.01). 11-dTXB(2) levels did not correlate with aspirin resistance. Aspirin-resistant patients had higher 11-dTXB(2) levels before (7297 vs. 4160 pg/mg creatinine; p < 0.01) and after (2153 vs. 1412 pg/mg; p = 0.03) aspirin, with a similar percentage decrease in thromboxane (70.5% vs. 66.1%; p = 0.43). Our findings suggest that resistance is not entirely due to lack of inhibition of platelet thromboxane production. Alternative sources of thromboxane and thromboxane-independent mechanisms, such as ADP-induced platelet activation, may contribute to aspirin resistance.

Topics: Adolescent; Aspirin; Blood Platelets; Child; Child, Preschool; Dose-Response Relationship, Drug; Drug Resistance; Female; Follow-Up Studies; Heart Defects, Congenital; Humans; Infant; Male; Platelet Aggregation Inhibitors; Prevalence; Prognosis; Retrospective Studies; Risk Factors; Texas; Thromboembolism; Thromboxane B2

Aspirin (ASA) failure to inhibit in vitro platelet function had been termed ASA resistance. The prevalence of this phenomenon as measured with different platelet function tests varies widely among studies.. In this study, we propose to determine the prevalence of ASA non-responsiveness in stable coronary artery patients using three different tests.. One hundred ninety-one patients with a stable coronary artery disease and receiving secondary ASA prophylaxis (250 mg/day) were tested. For each patient the ASA-induced platelet inhibition was determined using three different tests: Ivy Bleeding time (BT), collagen/epinephrine closure time (CEPI-CT; PFA-100, Dade-Behring) and urinary 11-dehydrothromboxane B2 (uTxB2) excretion level. The agreement between these tests was evaluated by kappa statistics test.. The prevalence of biological ASA resistance was 15.7% (n=30), 20.4% (n=39) and 24.6% (n=47) by BT, PFA-100 and UTxB2, respectively. Only fourteen patients (7.3%) were non-responders for two tests: 6 (3.1%) BT/ PFA-100; 1 (0.5%) BT/UTxB2; 7 (3.7%) PFA-100/UTxB2). A poor agreement was found between these three methods and only 3 patients were resistant with all the tests (1.6%).. The lack of agreement supposed that different types of aspirin resistance exist. Thus, combination of two tests or more could be a primary solution for a better identification of ASA resistant patients. This hypothesis must be confirmed by a large-scale randomized study with clinically well-defined endpoints.

Topics: Adult; Aged; Aged, 80 and over; Aspirin; Bleeding Time; Blood Platelets; Coronary Artery Disease; Drug Evaluation, Preclinical; Drug Resistance; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Platelet Function Tests; Thromboembolism; Thromboxane B2

We have used the EaHy926 endothelial cell line, able to secrete both pro and anti-aggregant platelet agents, as a model for thrombo-embolic diseases. We experimentally established, by comparing these two secretions with or without a Faraday cage, that the environmental electromagnetic field significantly increases the thrombo-embolic risks in this endothelial cell line.

Topics: 6-Ketoprostaglandin F1 alpha; Cell Line; Electromagnetic Fields; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Epoprostenol; Humans; Risk Factors; Thromboembolism; Thromboxane A2; Thromboxane B2

To observe the changes of thromboxane B(2) (TXB(2)), 6-keto-prostaglandin F1alpha (6-K-PGF1alpha) and anticardiolipin antibody (ACA) in patients with obstructive sleep apnea-hypopnea syndrome (OSAHS) before and after institution of nasal continuous positive airway pressure (nCPAP).. Sixty cases of OSAHS confirmed by polysomnography (PSG) were selected as the trial group, and 20 normal donors without OSAHS were recruited as the control group. Nineteen patients with severe OSAHS were treated by nCPAP. Plasma levels of TXB(2), 6-K-PGF1alpha were detected by enzyme-linked immunosorbent assay (ELISA).. Plasma (serum) level of TXB(2) (ACA) was significantly higher in patients with moderate to severe OSAHS than that in control group (P < 0.01), and nCPAP therapy decreased its level significantly (P < 0.01). Plasma level of 6-K-PGF1alpha was significantly lower than that in the control group (P < 0.01), and nCPAP therapy increased its level significantly (P < 0.01). TXB(2) and ACA were correlated positively with AHI, and negatively with minimal oxygen saturation (P < 0.01). 6-K-PGF1alpha was correlated negatively with AHI, and positively with minimal oxygen saturation (P < 0.01).. The results indicate that patients with OSAHS are susceptible to thromboembolism disease. TXB(2), 6-K-PGF1alpha, ACA may be associated with the high prevalence of thromboembolism in patients with OSAHS. nCPAP therapy is effective in correcting TXB(2), 6-K-PGF1alpha, ACA.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Antibodies, Anticardiolipin; Continuous Positive Airway Pressure; Female; Humans; Male; Middle Aged; Sleep Apnea, Obstructive; Thromboembolism; Thromboxane B2

To evaluate the effects of lupus anticoagulant (LA) on pulmonary thromboembolism (PTE).. Thirty-eight patients with PTE (17 massive and 21 submassive) and 30 healthy adults were studied. Russell's viper venom time (RVVT) was used to examine the ratio of LA (LAR), and a colorimetric method was used to detect the activity of plasma protein C (PC:A) and radioimmunoassay (RIA) was employed to measure the level of plasma thromboxane B(2) (TXB(2)) and 6-keto-prostaglandin F1alpha (6-keto-PGF1alpha).. Compared with the normal group, LAR, TXB(2) and TXB(2)/6-keto-PGF1alpha showed significant increase in the massive PTE and the submassive PTE groups (P < 0.01), and the levels were higher in the massive group than in the submassive group (P < 0.01). Both groups showed significant decrease in PC:A and 6-keto-PGF1alpha compared with the normal group (P < 0.01).. LA can increase TXB(2)/6-keto-PGF1alpha and decrease PC:A in patients with PTE. It is suggested that there may be an association between the increase of LAR and the presence of PTE.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; C-Reactive Protein; Female; Humans; Lupus Coagulation Inhibitor; Male; Middle Aged; Prostaglandins; Pulmonary Embolism; Radioimmunoassay; Thromboembolism; Thromboxane B2

Metallothionein (MT) is a low-molecular-weight, cysteine-rich protein that contains heavy metals such as cadmium and zinc. The biological function of MT in platelets is not yet understood. Therefore, the aim of this study was to systematically examine the inhibitory mechanisms of metallothionein in platelet aggregation. In this study, metallothionein concentration-dependently (1-8 microM) inhibited platelet aggregation in human platelets stimulated by agonists. Metallothionein (4 and 8 microM) inhibited phosphoinositide breakdown in [3H]-inositol-labeled platelets, intracellular Ca+2 mobilization in Fura-2 AM-loaded platelets, and thromboxane A2 formation stimulated by collagen. In addition, metallothionein (4 and 8 microM) significantly increased the formation of cyclic GMP but not cyclic AMP in human platelets. Rapid phosphorylation of a protein of Mr 47,000 (P47), a marker of protein kinase C activation, was triggered by PDBu (100 nM). This phosphorylation was markedly inhibited by metallothionein (4 and 8 microM) in phosphorus-32-labeled platelets. In an in vivo thrombotic study, platelet thrombus formation was induced by irradiation of mesenteric venules in mice pretreated with fluorescein sodium. Metallothionein (6 microg/g) significantly prolonged the latency period for inducing platelet plug formation in mesenteric venules. These results indicate that the antiplatelet activity of metallothionein may involve the following pathways: (1) metallothionein may inhibit the activation of phospholipase C, followed by inhibition of phosphoinositide breakdown and thromboxane A2 formation, thereby leading to inhibition of intracellular Ca+2 mobilization; (ii) Metallothionein also activated the formation of cyclic GMP in human platelets, resulting in inhibition of platelet aggregation. The results strongly indicate that metallothionein provides protection against thromboembolism.

Topics: Animals; Blood Platelets; Collagen; Cyclic AMP; Cyclic GMP; Humans; In Vitro Techniques; Metallothionein; Mice; Models, Biological; Phorbol 12,13-Dibutyrate; Phosphatidylinositols; Platelet Aggregation; Platelet Aggregation Inhibitors; Platelet Glycoprotein GPIIb-IIIa Complex; Protein Conformation; Signal Transduction; Thromboembolism; Thromboxane B2

Among several different types of phospholipase A(2) (PLA(2)), cytosolic PLA(2) (cPLA(2))alpha and group IIA (IIA) secretory PLA(2) (sPLA(2)) have been studied intensively. To determine the discrete roles of cPLA(2)alpha in platelets, we generated two sets of genetically engineered mice (cPLA(2)alpha(-/-)/sPLA(2)-IIA(-/-) and cPLA(2)alpha(-/-)/sPLA(2)-IIA(+/+)) and compared their platelet function with their respective wild-type C57BL/6J mice (cPLA(2)alpha(+/+)/sPLA(2)-IIA(-/-)) and C3H/HeN (cPLA(2)alpha(+/+)/sPLA(2)-IIA(+/+)). We found that cPLA(2)alpha is needed for the production of the vast majority of thromboxane (TX)A(2) with collagen stimulation of platelets. In cPLA(2)alpha-deficient mice, however, platelet aggregation in vitro is only fractionally decreased because small amounts of TX produced by redundant phospholipase enzymes sufficiently preserve aggregation. In comparison, adenosine triphosphate activation of platelets appears wholly independent of cPLA(2)alpha and sPLA(2)-IIA for aggregation or the production of TX, indicating that these phospholipases are specifically linked to collagen receptors. However, the lack of high levels of TX limiting vasoconstriction explains the in vivo effects seen: increased bleeding times and protection from thromboembolism. Thus, cPLA(2)alpha plays a discrete role in the collagen-stimulated production of TX and its inhibition has a therapeutic potential against thromboembolism, with potentially limited bleeding expected.

Topics: 12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; Animals; Bleeding Time; Blood Platelets; Bridged Bicyclo Compounds, Heterocyclic; Collagen; Cytosol; Fatty Acids, Unsaturated; Group IV Phospholipases A2; Hydrazines; Mice; Mice, Inbred C3H; Mice, Inbred C57BL; Mice, Knockout; Phospholipases A; Platelet Aggregation; Thromboembolism; Thromboxane B2

A series of 1H-imidazol-1-yl- and 3-pyridyl-substituted 3,4-dihydroquinolin-2(1H)-ones was designed and synthesized as combined inhibitors of thromboxane (TXA2) synthase and cAMP phosphodiesterase (PDE) in human blood platelets. A number of structures, e.g. 4b, 7a, 7e, 13a, and 21-25, were superior to dazoxiben 26 as inhibitors of TXA2 synthase in in vitro ADP-induced aggregation experiments with human blood platelets. The TXA2 synthase inhibitory activity was confirmed by measurement of the prostanoid metabolites derived from 14C-labeled arachidonic acid. Three compounds (7a, 7e, and 25) demonstrated in vitro inhibition of human platelet cAMP PDE at micromolar concentrations in conjunction with their TXA2 synthase inhibitory activity. Synergistic enhancement of antiaggregatory and antithrombotic actions was expected when simultaneous stimulation of adenylate cyclase (through increased PGI2 production) and inhibition of platelet cAMP PDE were possible from the same compound. Ex vivo and in vivo experiments were conducted in rats and mice, respectively, to evaluate the effects of compounds 7e and 23 on platelet aggregation and thrombotic events within these animals. Compound 7e, which has a comparable level of TXA2 synthase (IC50 1.2 microM) and human platelet cAMP PDE (IC50 6.4 microM) inhibitory activities, was found to be orally bioavailable with a long duration of action and offered effective protection against mortality in a collagen-epinephrine-induced pulmonary thromboembolism model in mice. Significant blood pressure and heart rate effects were observed for several compounds, e.g. 7e, 9e, 13a, 13d, 18, 20, 21, and 23, when dosed orally in conscious spontaneously hypertensive rats.

Topics: 3',5'-Cyclic-AMP Phosphodiesterases; 6-Ketoprostaglandin F1 alpha; Adenosine Diphosphate; Animals; Aorta; Blood Platelets; Fibrinolytic Agents; Humans; Hypertension; Male; Microsomes; Platelet Aggregation; Platelet Aggregation Inhibitors; Quinolones; Rats; Rats, Inbred SHR; Rats, Inbred Strains; Swine; Thromboembolism; Thromboxane B2; Thromboxane-A Synthase

Thromboxane++ (TX), prostacyclin (PC) and platelet factor IV (PF) were assayed using radioimmune kits in 46 patients with cardiac fibrillation secondary to coronary heart disease and rheumatic fever. The study established elevated TX beta 2 levels, low concentrations of 6-ketoPGF1 alpha, enhanced activity of PF. Restoration of the sinus rhythm by electroimpulse treatment (EIT) brought about augmentation of the Tx-Pc-PF unbalance on day 2-3. This may give rise to "normalization" thromboembolism. On days 5-7 after EIT the intensity of platelet aggregation and PF secretion diminish. It is concluded that patients with sudden cardiac fibrillation in need of sinus rhythm correction will benefit from disaggregation and anti-coagulant therapy.

Topics: 6-Ketoprostaglandin F1 alpha; Atrial Fibrillation; Electric Countershock; Humans; Platelet Factor 4; Thromboembolism; Thromboxane B2; Time Factors

A ninhydrin positive compound (L2) now identified as 2-amino-5-(N-ethylcarboxyamido)-pentanoic acid, from unprocessed tea leaves was a potent inhibitor of thrombin-stimulated thromboxane formation in rabbit whole blood (Ali and Afzal; Prostaglandins, Leukotrienes and Medicine, 27: 9, 1987). In the present study, processed and unprocessed tea leaf extracts were given to rats to consume for a period of eight weeks. Cholesterol and thromboxane levels were measured in the serum obtained from clotting the blood at 37 degrees C. A significant reduction in thromboxane levels was observed in rats taking unprocessed tea extract. This reduction was equally distributed in adult as well as in juvenile rats. However no appreciable changes in the levels of thromboxane were noticed in the serum of rats taking processed tea extracts. This might be due to the presence of a labile component which is destroyed during the processing of green tea leaves. A decreased level of cholesterol was observed in rats consuming unprocessed tea extract. This decrease could be linked to the decrease in thromboxane levels as observed. Processed tea refers to commercially available tea of different brands while unprocessed tea refers to dried green tea leaves.

Topics: Amino Acids; Animals; Cholesterol; Female; Food Handling; Rats; Rats, Inbred Strains; Tea; Thromboembolism; Thromboxane B2

An animal model suitable for study of the origin and method of prevention of thromboembolic complications of arterial prostheses has been developed in the rabbit. In phase I of the experiments 42 New Zealand white rabbits underwent insertion of polytetrafluoroethylene (PTFE) aortic grafts, 10 mm in length and of 2 mm internal diameter (I.D.) (n = 17) and 3 mm I.D. (n = 25). The patency rate at 3 months was 24% and 82%, respectively. Unexpected ischemic hind limb ulcers occurred in nine (38%) of the long-term survivors. Arteriograms in these animals showed a typical embolic occlusion of a distal artery, suggesting that the ulcers were due to embolization of loose mural thrombus, which was present in 50% of the grafts when removed. In phase II experiments 54 rabbits were randomly allocated to receive aspirin (ASA) 10 mg/kg/day and dipyridamole (DPM) 10 mg/kg/day (n = 25) or placebo (n = 29). Both regimens began 3 days before insertion of PTFE aortic grafts (10 mm long and 3 mm I.D.). Serum thromboxane B2 concentrations in the control group averaged 300.4 +/- 147.4 ng/ml and 43.2 +/- 58.6 ng/ml in the ASA/DPM group (p less than 0.0005). With the use of autologous indium 111 oxine-labeled platelets, a graft platelet accumulation index (GPAI) was calculated as the graft: reference ratio of emissions. ASA/DPM significantly reduced the mean GPAI calculated from grafts and reference aorta removed 48 hours after graft insertion from 69.3 +/- 4.0 on placebo (n = 4) to 34.3 +/- 2.9 (n = 4) (p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Aspirin; Blood Vessel Prosthesis; Dipyridamole; Graft Occlusion, Vascular; Male; Platelet Aggregation; Polytetrafluoroethylene; Postoperative Complications; Rabbits; Thromboembolism; Thromboxane B2; Vascular Patency

We have previously demonstrated that platelets obtained from patients with anorexia nervosa or severe peripheral vascular disease are hyperaggregable. Since conventional heparins are known to activate platelets in vitro and occasionally induce thrombosis and consumptive thrombocytopenia in vivo, we have investigated the direct effect of a conventional heparin on platelets obtained from patients with anorexia nervosa or severe peripheral vascular disease. Heparin at therapeutic concentrations was found to induce platelet aggregation of such platelets in vitro. In contrast, a recently developed low molecular weight heparinoid (Org 10172), at therapeutic concentrations, had no effect on these hyperaggregable platelets. We conclude that: heparin may be potentially harmful to patients with hyperaggregable platelets; thrombocytopenia and thrombosis associated with heparin therapy may be mediated through a direct effect of heparin on platelets; it is unlikely that heparin induced thrombocytopenia is always mediated by classical immunological mechanisms, especially in patients with hyperaggregable platelets; and low molecular weight heparinoids may be safer anticoagulants in patients with platelet hyperaggregability.

Topics: Adolescent; Adult; Aged; Anorexia Nervosa; Blood Platelets; Chondroitin Sulfates; Collagen; Dermatan Sulfate; Epinephrine; Female; Glycosaminoglycans; Heparin; Heparitin Sulfate; Humans; Immunoglobulin G; In Vitro Techniques; Male; Middle Aged; Platelet Aggregation; Thrombocytopenia; Thromboembolism; Thromboxane B2; Vascular Diseases

Topics: Arachidonic Acids; Blood Platelets; Humans; Hypercholesterolemia; Platelet Aggregation; Thromboembolism; Thromboxane B2; Thromboxanes