thromboxane-a2 and Thrombophilia

Diet is one of the environmental factors that influences thrombosis and hemostasis. Macronutrients, micronutrients, and other bioactive food components alter the predisposition to thrombosis. The type and amount of dietary fat has been shown to alter thromboxane A2 production and platelet aggregation, bleeding time, factor VII, fibrinogen, tissue plasminogen activator (t-PA) and plasminogen activator inhibitor 1 (PAI-1). Both epidemiological studies and clinical trials indicate that the very long chain n-3 fatty acids lower thrombotic tendency and risk of heart disease. Other polyunsaturated fats and monounsaturated fat appear to have antithrombotic properties, but further studies are indicated. Hypercaloric diets and those with high glycemic loads are associated with elevations of PAI-1. Moderate consumption of alcohol is associated with decreased platelet aggregation. Low intakes of folate, vitamin B12, and vitamin B6 predispose to hyperhomocysteinemia, and the benefits of supplementation in decreasing vascular disease are under investigation. In a limited number of clinical and laboratory studies, vitamin E has been shown to decrease platelet aggregation and the concentration of PAI-1. Flavonoids and isoflavones appear to inhibit platelet aggregation at pharmacologic concentrations only. Nutritional status frequently declines with aging and may exacerbate the already increased risk for thrombosis. Diet presents an interesting area for research into thrombophilia, but additional work is indicated before specific recommendations are made.

Topics: Aging; Alcohols; Bleeding Time; Carbohydrate Metabolism; Diet; Dietary Fats; Factor VII; Fatty Acids; Fatty Acids, Unsaturated; Fibrinogen; Hemostasis; Humans; Isoflavones; Niacin; Nutritional Physiological Phenomena; Plasminogen Activator Inhibitor 1; Platelet Aggregation; Risk; Thrombophilia; Thrombosis; Thromboxane A2; Tissue Plasminogen Activator

Topics: Arterial Occlusive Diseases; Blood Coagulation Factors; Blood Platelets; Comorbidity; Endothelium, Vascular; Fibrinolysis; Free Radicals; Genetic Predisposition to Disease; Homocysteine; Homocystinuria; Humans; Hyperhomocysteinemia; Nitric Oxide; Oxidative Stress; Thrombin; Thrombomodulin; Thrombophilia; Thromboxane A2

Aspirin has a well established role in the prevention of arterial thrombosis. Discussion on the efficacy and safety of aspirin in the treatment and prophylaxis of thrombosis in essential thrombocythemia (ET) has become an important issue. The rationale for its use in ET comes from the observation that arterial thrombosis and platelet-mediated microcirculatory disturbances are the major causes of morbidity and mortality in ET. Experimental data have shown persistently elevated levels of thromboxane A2 (TXA2) in ET patients probably reflecting an enhanced in vivo platelet activation. Increased TXA2 biosynthesis and platelet activation in vivo in ET are selectively suppressed by repeated low doses of aspirin. ET-related symptoms such as erythromelalgia, transient neurologic and ocular disturbances are sensitive to aspirin. However, the benefit of low-dose aspirin is still uncertain in the primary prevention of thrombosis in ET. Furthermore, aspirin may unmask a latent bleeding diathesis frequently present in ET which may result in severe hemorrhagic complications. Thus, aspirin is contraindicated in ET patients with a bleeding history or a very high platelet count (> 1500 x 10(9)/L) leading to the acquisition of von Willebrand factor deficiency. If indicated, aspirin is presently used in the widely accepted low-dose regimen of 100 mg daily. However, an optimal effective dose has not yet been established. To further evaluate the efficacy and safety of aspirin in ET, prospective clinical trials are needed.

Topics: Abortion, Habitual; Aspirin; Cerebrovascular Disorders; Cohort Studies; Contraindications; Erythromelalgia; Female; Fibrinolytic Agents; Forecasting; Hemorrhage; Humans; Incidence; Middle Aged; Myeloproliferative Disorders; Pilot Projects; Platelet Activation; Platelet Aggregation Inhibitors; Pregnancy; Pregnancy Complications, Hematologic; Retrospective Studies; Safety; Thrombocythemia, Essential; Thrombophilia; Thrombosis; Thromboxane A2; Vision Disorders; von Willebrand Diseases

Topics: Administration, Oral; Animals; Anti-Inflammatory Agents, Non-Steroidal; Arachidonic Acid; Arteriosclerosis; Arteriosclerosis Obliterans; Aspirin; Cell Division; Cells, Cultured; Clinical Trials as Topic; Eicosanoids; Eicosapentaenoic Acid; Epoprostenol; Fibrinolytic Agents; Growth Inhibitors; Hemostasis; Humans; Hypolipidemic Agents; Muscle, Smooth, Vascular; Platelet Aggregation; Platelet Aggregation Inhibitors; Rats; Signal Transduction; Thrombophilia; Thrombosis; Thromboxane A2

Recurrent miscarriage is a major women's health problem. Aspirin and heparin have been shown to have potentially beneficial effects on trophoblast implantation. However, few published data on this issue are available from developing countries.. An open clinical trial was conducted at the Department of Obstetrics and Gynecology at Misurata Teaching Hospital in Libya from January 2009 to December 2010 to investigate the effects of treatment with low dose aspirin (LDA) versus treatment with low-molecular-weight-heparin (LMWH) in combination with LDA on patients with a history of recurrent miscarriages. A total of 150 women were enrolled in the study. Women were eligible for the study if they had a history of three or more consecutive miscarriages. Participants were randomly assigned to receive either LDA (75 mg daily) alone or a combination of LDA and LMWH (75 women per treatment group). The primary outcomes were the rate of miscarriages and live births for each group.. Compared with the group who received LDA alone, the combination group had a significantly lower number of miscarriages (22/75 [29%] vs. 43/75 [47%], P < 0.001) and had a significantly higher number of live births (53/75 [71%] vs. 32/75 [42%], P < 0.001). Two preterm infants in the LDA group and three in the combination group were admitted to the neonatal intensive care unit. There were no significant differences in the mean (SD) birth weights of neonates born in either group (2955.4 ± 560 vs. 3050 ± 540 g for the LDA and combination groups, respectively, P = 0.444). There were no congenital abnormalities detected in either group.. The combination of LDA and LMWH is better than LDA alone for the maintenance of pregnancy in patients with recurrent first trimester miscarriage.. NCT01917799.

Topics: Abortion, Habitual; Adult; Aspirin; Birth Weight; Embryo Implantation; Enoxaparin; Female; Fibrinolytic Agents; Humans; Infant, Newborn; Libya; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Pregnancy Outcome; Prostaglandins I; Thrombophilia; Thromboxane A2; Trophoblasts; Vasodilation; Young Adult

There is substantial evidence of increased platelet reactivity in vivo and in vitro during pregnancy, with the risk of developing pre-eclampsia. In this study, platelet function was studied during 28-40 weeks of gestation in a group of women who remained normotensive and in a group of nonpregnant female controls. Platelet aggregation stimulated by thrombin and adenosine diphosphate was markedly enhanced in washed platelets from pregnant subjects. Thrombin (0.04 U/ml)-evoked increases in intracellular Ca+2 mobilization of Fura 2-AM-loaded platelets were also enhanced in pregnant subjects. The binding of fluorescein isothiocyanate (FITC)-triflavin (2 microg/ml) to the glycoprotein IIb/IIIa complex in thrombin-activated platelets did not differ significantly between the nonpregnant and pregnant groups. Thromboxane A2 (TXA2) formation in both resting and thrombin-activated platelets from pregnant subjects was significantly greater than from nonpregnant subjects. Levels of cyclic adenosine monophosphate (cAMP) in both resting and prostaglandin E1-treated platelets (10 micromol/l) from pregnant subjects were significantly lower than those from nonpregnant subjects. There were no significant differences between nonpregnant and pregnant subjects in platelet cAMP levels in the presence of imidazole (600 micromol/l) and indomethacin (500 micromol/l). Intracellular pH values in platelets were measured spectrofluorometrically using the fluorescent probe, BCECF-AM. The increase in intracellular pH stimulated by thrombin (0.04 U/ml) in pregnant subjects was markedly greater than that in observed nonpregnant subjects. We conclude that the agonist-induced hyperaggregability of platelets in normal pregnancy may be due, at least partly, to stimulation of the Na+/H+ exchanger and subsequently to elevated intracellular Ca+2 mobilization, and then to increased TXA2 formation and a lowered level of cAMP, which leads to further increases in intracellular Ca+2 mobilization, and finally to enhanced platelet aggregation.

Topics: Adult; Alprostadil; Calcium Signaling; Cyclic AMP; Disease Susceptibility; Female; Humans; Hydrogen-Ion Concentration; Imidazoles; Indomethacin; Intracellular Fluid; Peptides; Platelet Aggregation; Pre-Eclampsia; Pregnancy; Pregnancy Complications, Hematologic; Second Messenger Systems; Sodium-Hydrogen Exchangers; Thrombin; Thrombophilia; Thromboxane A2