thromboxane-a2 and Thrombophlebitis

It has been postulated that metabolites of the arachidonic acid pathway exert an important influence on hemostasis and thrombosis. This notion is based on in vitro experiments. We have utilized two experimental models to elucidate the physiologic roles of thromboxane A2 (TxA2) and prostacyclin (PGI2) in the modulation of thrombus formation. The role of TxA2 in promoting thrombus formation was evaluated in a rabbit model where the aorta was deendothelialized by a balloon catheter technique and indium-111-labeled platelets were used as a marker for quantifying platelet deposition. Both 1-benzylimidazole, a thromboxane synthase inhibitor, and 13-azaprostanoic acid, an antagonist of thromboxane/endoperoxide receptors significantly reduced the platelet deposition onto the damaged vessel wall. The data indicate the TxA2 plays an important role in thrombosis and hemostasis. The influence of PGI2 insufficiency due to accelerated PGI2 degradation on microvascular thrombosis was evaluated in a unique clinical disease, i.e. thrombotic thrombocytopenic purpura (TTP). Accelerated PGI2 degradation was observed in several patients with chronic TTP. The degradation abnormalities were corrected by plasma infusion in vivo or serum supplement in vitro. To test the hypothesis that PGI2 must be bound to serum macromolecules to prevent rapid hydrolysis, serum binding capacity for PGI2 was measured by Sephadex G-25 gel filtration. The binding capacity was significantly reduced in the patients and was corrected by serum supplement. Abnormalities of PGI2 binding were also noted in a group of patients with ischemic stroke. Our findings suggest that there exist in the serum certain constituents which bind and stabilize PGI2.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Arachidonic Acid; Arachidonic Acids; Blood Platelets; Chromatography, Gel; Epoprostenol; Humans; Imidazoles; In Vitro Techniques; Prostanoic Acids; Serum Albumin; Thrombophlebitis; Thromboxane A2; Thromboxane-A Synthase

Topics: Animals; Arachidonic Acids; Aspirin; Dipyridamole; Dogs; Epoprostenol; Hemostasis; Humans; Platelet Adhesiveness; Platelet Aggregation; Pulmonary Embolism; Thromboembolism; Thrombophlebitis; Thromboxane A2

The authors should like to contribute to the unsettled problem of the development of varicose venous disease with their own experience. They evaluate parallel the histomorphological observations and certain pathobiochemical changes which can be recognized in exstirpated varicose veins. Fourty five stripped saphenas have been studied. They were divided into two groups: a macroscopically normal and a varicose one. The varicose patients were divided again into two subsamples according to the occurrence or lack of thrombophlebitis in their medical case history. The authors were looking for the appropriate pathobiochemical changes of the vessel walls running parallel to the usual histopathological changes. It seems quite possible that the effect which triggers the development of the disease could be anything which causes hypoxia, alters the energy metabolism of the otherwise bradytrophic vascular tissues. Accumulation of proteoglycans, as well as collagen and elastic fibers in place of the smooth muscle cells may cause a decrease in the elasticity of the veins and may produce favourable conditions to thrombus formation and local inflammation.

Topics: Carbon Dioxide; Collagen; Elastin; Electron Transport Complex IV; Female; Humans; Lactates; Lactic Acid; Male; Middle Aged; Proteoglycans; Saphenous Vein; Thrombophlebitis; Thromboxane A2; Tissue Plasminogen Activator; Varicose Veins

The activities of two structurally unrelated thromboxane/prostaglandin endoperoxide receptor antagonists, SQ 30,741 and BM 13,505, were compared to heparin in a model of venous thrombosis. A combination of blood stasis with osmotic and pressure stress was used to induce thrombus formation in the vena cava of anesthetized rats. Intravenous infusions of SQ 30,741 (500 micrograms/kg/min) and BM 13,505 (50 micrograms/kg/min) produced significant (P less than .01) and equivalent reductions in thrombus mass of 58 and 56%, respectively. Thrombus reduction in response to heparin (50 U/kg) was greater (95%; P less than .001) than in response to the thromboxane antagonists. Either lower doses of SQ 30,741 (50 and 100 micrograms/kg/min) or aspirin (30 and 60 mg/kg) were ineffective in altering thrombus formation. However, a subthreshold dose of SQ 30,741 (100 micrograms/kg/min) increased (P less than .01) the antithrombotic activity obtained with both threshold (0.5 U/kg) and subthreshold (0.3 U/kg) doses of heparin. SQ 30,741 (500 micrograms/kg/min) did not change activated partial thromboplastin times or inhibit platelet loss induced by contact activation in response to kaolin in vivo. This suggests that SQ 30,741 does not interfere with components of the coagulation cascade that are not dependent on platelet factors. The extent of thromboxane antagonism achieved with SQ 30,741 (50 and 500 micrograms/kg/min) and BM 13,505 (50 micrograms/kg/min) was determined from parallel shifts in dose-dependent U-46,619-induced vasoconstriction in vivo (approximately 200- and 1300-fold, respectively, for SQ 30,741 and 200-fold for BM 13,505). These data demonstrate that thromboxane antagonists inhibit venous thrombosis partially, but only at doses producing near complete receptor inhibition.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Bleeding Time; Blood Platelets; Drug Synergism; Heparin; Male; Partial Thromboplastin Time; Phenylacetates; Platelet Aggregation Inhibitors; Rats; Rats, Inbred Strains; Receptors, Prostaglandin; Receptors, Thromboxane; Sulfonamides; Thrombophlebitis; Thromboxane A2; Thromboxanes

The urinary excretion of 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha (the major urinary metabolites of thromboxane B2 and prostacyclin) was measured in ten patients with confirmed deep vein thrombosis, using specific methods based on gas chromatography - mass spectrometry with deuterium-labelled internal standards. Measurements of these major urinary metabolites makes it possible to monitor the in vivo formation of thromboxane A2 and prostacyclin. The results demonstrate an abnormally high and very variable excretion of 2,3-dinor-TxB2 and 2,3-dinor-6-keto-PGF1 alpha in patients with deep vein thrombosis. This indicate that both thromboxane A2 and prostacyclin are involved in the course of events associated with this disease.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aged; Blood Platelets; Epoprostenol; Evaluation Studies as Topic; Female; Humans; Male; Middle Aged; Thrombophlebitis; Thromboxane A2; Thromboxane B2; Thromboxanes; Time Factors

Topics: Arachidonic Acids; Aspirin; Epoprostenol; Humans; Platelet Aggregation; Postoperative Complications; Thrombophlebitis; Thromboxane A2