Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0042373 (vascular disease)
 17,070 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

All agree on altered platelet function in vitro (and increasingly in vivo) in diabetics of substantial duration and/or with clinical evidence of angiopathy. However, a platelet abnormality earlier in the disease remains uncertain. Three sets of data from Oxford will be reviewed: (1) Observations of Honour on platelet aggregation at sites of minimal injury within blood vessels of anesthetized rabbits, with greater sensitivity to superfused ADP when hyperglycemia has followed alloxan only days previously. This increased aggregatability (not hyperglycemia determined) is reversed by a few days of insulin treatment or by dipyrimadole (alone or with synergistic acetyl salicylic acid): (2) Beta-thromboglobulin is released from platelets and is increased in venesected blood from diabetics after a standardized procedure (no prostaglandin E1 in anticoagulant) with final radioimmunoassay. Results in diabetics after surgery, etc., will also be presented, and (3) in a prospective study of newly-diagnosed, mostly maturity-onset type diabetics, an increase in plasma fibrinogen (thrombin coagulation of plasma, controlled against normals) was observed during the first 3 yr, largely due to males treated with sulfonylureas; decreases in platelet count and in prothrombin concentration were also statistically significant.
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PMID:Direct animal and indirect human evidence of altered platelet function in diabetics. 16 73

There is considerable evidence that the quantity or quality of plasma lipids influences platelet function tests, and clofibrate reduces high plasma lipids and alters some platelet tests. Clofibrate was accordingly given to patients with vascular disease who were at risk of thrombosis. The heparin thrombin clotting time (HTCT), initially short and thus possibly reflecting increased activation, was regularly returned to normal after about a month's delay. The fibrinogen was also normalized but the initially abnormal anti-thrombic activity became more abnormal. ICI 55,897, an analogue of clofibrate, also normalized the HTCT and the fibrinogen and had no adverse effect on the anti-thrombin levels. This compound has no effect on plasma lipids. If it can be shown that the correction of abnormal tests conveys clinical benefit these findings suggest that ICI 55,897 might clinically be more beneficial than clofibrate. However, direct comparison of clofibrate and ICI 55,897 suggests that clofibrate is more effective in normalizing the HTCT. The mechanism underlying these drug-induced changes are unknown but they cannot be directly related to lipid changes.
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PMID:The effect of ICI 55,897 and clofibrate on platelet function and other tests abnormal in atherosclerosis. 36 63

The thrombogenic mechanism of arterial grafts has been studied by determining the relative utilization of platelets, fibrinogen and plasminogen by human arterial prostheses, and by direct examination of arterial grafts in a baboon model. Forty-one survival and turnover measurements of (51)Crplatelets, (131)I-fibrinogen and (125)I-plasminogen in ten patients with aortofemoral knitted Dacron prostheses demonstrated platelet consumption after graft placement (platelet survival 4.2 days +/- 0.5 and turnover 68,000 plat/ul/day +/-10,000 compared with 8.2 days +/- 0.3 and 35,000 plat/ul/day +/- 5,000 respectively for control subjects with stable vascular disease, p < 0.01). In vitro platelet function test results were normal. Platelet consumption was interrupted by dipyridamole or a combination of dipyridamole and acetylsalicylic acid, and platelet survival normalized spontaneously during nine months postoperatively. No significantly increased consumption of fibrinogen or plasminogen was found in these patients with arterial grafts. Placement of impervious knitted Dacron velour aortic grafts in baboons reproduced platelet consumption that progressively normalized over six weeks postoperatively. Platelet survival measurements correlated directly with endothelial cell coverage of the graft luminal surface in these animals implying that endothelialization of the graft surface was also occurring postoperatively in patients.
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PMID:Platelet consumption by arterial prostheses: the effects of endothelialization and pharmacologic inhibition of platelet function. 41 28

Haemostatic factors in 33 Black and 32 White maturity-onset diabetics were analysed and compared with those in 19 normal Black and 19 White subjects. The Black-White diabetic group comparisons revealed depressed antithrombin (AT) III functional activity, a raised factor VII level and a raised factor V level in females in the White diabetic group. On comparing the White diabetics with their respective controls a rise in factor VIII and fibrinogen activity was demonstrated. These changes are suggestive of a hypercoagulable state in the White maturity-onset diabetic. In contrast, Black diabetics have higher functional AT III levels than their respective controls. This may indicate a protective reaction which would explain in part the reported lower incidence of occlusive vascular disease in this group. Platelet hyperactivity was not demonstrated in the majority of White and Black diabetics. Black diabetics and controls demonstrated higher factor VIII levels than the corresponding White groups, confirming previous observations of raised factor VIII levels among Blacks and suggesting that this feature is a racial characteristic.
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PMID:Haemostatic factors in Black and White diabetics. 44 93

Studies of platelet and fibrinogen kinetics in 27 patients with hyperlipoproteinemia and 28 control subjects demonstrated shortened platelet survival and increased platelet turnover in seven patients with type III and 10 patients with type IV-V hyperlipoproteinemia (p less than 0.01). There was no correlation between platelet survival time and specific lipid levels, vascular disease, sex or age. Platelet kinetics were not significantly altered from control values in eight patients with familial hypercholesterolemia. Platelet aggregation studies and fibrinogen kinetic measurements did not differ in any of the hyperlipoproteinemic groups of patients from those in control subjects. Despite significant changes in plasma lipids induced by clofibrate, platelet survival was significantly extended only in patients with type IV-V hyperlipoproteinemia (p less than 0.05). These results are consistent with the hypothesis that atherogenesis in patients with types III--V hyperlipoproteinemia may be associated with a process of endothelial desquamation, and type IIa hyperlipoproteinemia may involve nondesquamating endothelial injury.
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PMID:Platelet kinetic studies in patients with hyperlipoproteinemia: effects of clofibrate therapy. 45 11

To study the possible role of an "increased thrombotic tendency" in the vascular complications of diabetes several tests of haemostatic function were carried out on 91 men and 63 women with diabetes aged 35-54 years and the results compared with findings in 686 men and 393 women of the same age in the Northwick Park Heart Study. Mean values for factors VII and X, fibrinogen, and platelet adhesiveness were higher in the diabetics, but mean fibrinolytic activity and whole blood platelet counts were lower. Antithrombin III values were also higher in the diabetics, which may have constituted a protective response to other changes favouring the onset of vascular disease. Diabetics with retinopathy had higher factor VII and antithrombin III values, and those with proteinuria had higher values for factor VII, fibrinogen, and platelet adhesiveness than those without these complications. These findings suggest a potentially important association between a thrombogenic tendency and vascular disease in diabetes. Nevertheless, prospective data are needed to clarify whether the haemostatic abnormalities precede the onset of clinically manifest vascular complications or are a consequence of them.
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PMID:Haemostatic variables associated with diabetes and its complications. 50 77

In a double-blind control of xanthinol nicotinate ('Complamin'; 'Complamex') in patients with severe progressive obliterative vascular disease, 25 of 33 patients who completed the trial were helped significantly by the drug, as shown by both clinical and laboratory findings. Placebo helped in 4 of 33 patients. The difference is significant (p less than 0-001). These are the results for the trial period only. The results of follow-up for 6 to 30 months are available in 18 patients: 14 of these still had appreciable help from the drug, which was continued in maintenance doses. It should be noted that 3 of 6 diabetics were no longer helped after 6 months, and that only 3 of a total of 7 patients under the age of 50 were helped; however 3 of the 4 not helped were diabetics under the age of 50. Special caution was indicated in the use of the drug in patients who have ischaemic heart disease in addition to their peripheral arterial disease. Side-effects were common, particularly a severe prolonged flush shortly after taking a dose of the drug; many patients helped by it accepted this side-effect if it occurred. Xanthinol nicotinate reduced whole-blood viscosity and cholesterol and fibrinogen in about half of the patients helped. This is a useful drug for about half the patients in whom surgery is not indicated or is contraindicated.
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PMID:Xanthinol nicotinate in peripheral vascular disease. 77 53

Electrophoresis in 3.5% polyacrylamide gel was used to determine the patterns of fibrinogen heterogeneity in healthy subjects, in postoperative patients and in patients with cancer or occlusive vascular disease. Two major and one minor fibrinogen fractions, differing in molecular weight, were identified, and their concentrations in blood determined. The high-molecular-weight (HWM) fraction was found in greatest concentration after operation, during the period of hyperfibrinogenemia, whereas no simultaneous increase of lower-molecular-weight (LMW and LMW') fractions occurred, suggesting that these were derivatives of HMW ("native") fibrinogen. No correlation between the concentrations of the LMW and LMW' fractions and fibrinolytic activity was found, suggesting that direct degradation of HMW fibrinogen by plasmin was unlikely. The high fibrinogen level in cancer patients was related to increased concentrations of HMW and LMW fractions, whereas in the vascular-disease patients it was due exclusively to increased concentrations of LMW and LMW' fibrinogen. Serial observations indicated little fluctuation in the concentration of these fractions, indicating a persistently accelerated rate of conversion of HMW to LMW and LMW' fibrinogen in occlusive vascular disease. Possible pathogenic implications are discussed.
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PMID:Fibrinogen heterogeneity in cancer, in occlusive vascular disease, and after surgical procedures. 99 69

Alternations in the coagulation mechanism were looked for in a population of eclamptic women, most of when were young, nulliparous, and without evidence of chronic vascular disease, and all of whom survived. Thrombocytopenia was identified in 29% of these women. A prolonged plasma thrombin time was demonstrated in 51% yet elevated fibrinogen-fibrin degradation products in serum were uncommon, as was fibrin monomer in plasma. Overt microangiopathic hemolysis was rare. It is concluded that disseminated intravascular coagulation, when it does occur in eclampsia, is the consequence of the disease rather than the cause. Moreover, endothelial damage, rather contents, probably initiates the thrombocytopenia and other coagulation changes.
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PMID:Does coagulation have a causative role in eclampsia? 100 57

29 cadaveric renal transplant recipients were assessed clinically for evidence of occlusive arterial disease prior to undergoing blood viscosity studies. Nineteen patients had manifest arterial disease (myocardial infarction, cerebral thrombosis, angina, intermittent claudication, absent peripheral pulses), while ten were free from vascular complications. Patients with arterial disease showed significant elevations of plasma viscosity (p less than 0.005), aggregation of red cells measured both at 37 and 20 degrees C (p less than 0.05), fibrinogen (p less than 0.005), serum triglyceride (p less than 0.01), serum cholesterol (p less than 0.01), erythrocyte sedimentation rate (p less than 0.02), and a significant reduction in the albumin/fibrinogen ratio (p less than 0.005) when compared with those free of disease. Two patients with no apparent vascular disease when investigated were found to have distinctly abnormal blood viscosity factors, and one subsequently developed retinal arterial thrombosis while the other suffered serious damage of the graft within 3 months of viscosity study. When all patients were considered together, significant correlations were found between viscosity of artificial thrombi or aggregation of red cells and fibrinogen level (both p less than 0.05), and serum triglyceride level (both p less than 0.05); and between rigidity of red cells and the parathyroid hormone level (p less than 0.01).
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PMID:Blood viscosity factors and occlusive arterial disease in renal transplant recipients. 110 19


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