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Biomedical subjects

Y Stirling

Publications and source records attributed to Y Stirling.

At least 55 records · Page 3Linked to original sources

Fibrinopeptide A and sudden coronary death.

Fibrinopeptide A (FPA) concentrations were measured in blood taken by direct cardiac puncture from 31 patients who had died suddenly of ischaemic heart disease (IHD) and from 8 patients who had died suddenly of other causes. Mean FPA concentration in the IHD group was five times higher than that in the non-IHD group. This difference was almost entirely due to the high FPA level in the IHD subjects with a history of the disease. The FPA difference between the IHD and non-IHD groups is unlikely to have been due to differences in methods of resuscitation. A possible interpretation of the findings is that thrombin production causes or aggravates the course of events leading to sudden IHD death, particularly in subjects with a past history of IHD.

Aged↗

Management of planned pregnancy in a patient with congenital antithrombin III deficiency.

Long-term warfarin therapy was changed to subcutaneous heparin to cover a planned pregnancy in a patient with congenital antithrombin III (AT III) deficiency. Satisfactory anticoagulation was easily maintained in spite of low levels of biologically active AT III. Delivery and the puerperium were covered by a reduced dose of heparin and alternate day infusions of AT III concentrate. A mean dose of 0.77 U/kg of AT III concentrate produced a rise of 1% in AT III and the half-life was of the order of 24 h, with no evidence of increased consumption during labour and delivery. Pregnancy and labour were uncomplicated and resulted in delivery of a healthy female infant. The importance of early and adequate anticoagulation during pregnancy is emphasized.

Adult↗

Haemostatic variables and the outcome of myocardial infarction.

In a study of 272 patients with myocardial infarction (MI) the 68 who died within 1 year had significantly higher levels of factor VIIIR:Ag, factor VIII:C, fibrinogen, alpha 1 antitrypsin and alpha 2 macroglobulin than those who survived. The mean white cell count (WCC) and peak creatine kinase (CK) were also significantly higher in those who died compared with the survivors. There was considerable intercorrelation between many of the haemostatic variables, WCC and CK as well as between many of the clinical predictors of outcome and the laboratory variables. The differences in haemostatic variables between those who died and those who survived may merely reflect the size of the infarct; alternatively, the haemostatic system may influence prognosis following an MI.

Antigens↗

Haemostatic changes following surgery.

Changes in factors V, VII and VIII and in fibrinogen were studied in 32 patients undergoing major abdominal surgery. Mean levels of factors V and VII were similar to population-based values preoperatively. Factor V fell following elective surgery and then rose above the mean pre-operative level before returning to it by the tenth post-operative day. Factor VII fell following both elective and emergency surgery and tended to remain depressed throughout the post-operative period. Pre-operative values of factor VIII and fibrinogen were higher than population-based values and higher in the emergency than in waiting-list patients. Both factor VIII and fibrinogen rose following elective surgery but no statistically significant change was seen following emergency surgery. The uncomplicated conditions leading to elective surgery, the acute complications leading to emergency surgery, and surgery itself may each have contributed to increases in factor VIII and fibrinogen levels, whereas the fall in factors V and VII was largely related to surgery itself. The findings may help in the interpretation of associations between clotting factors and thrombotic disease, particularly in the case of factor VII.

Aged↗

Hypertriglyceridaemia and hypercoagulability.

18 patients with severe hypertriglyceridaemia (mean fasting plasma triglyceride 5.7 mmol/l) had significantly higher concentrations of plasma fibrinogen and clotting factor Xc than did a normolipidaemic comparison group. Fibrinolytic activity was significantly lower in the hyperlipidaemic patients. Six months of treatment (diet or diet and clofibrate) lowered the patients mean plasma triglyceride to 3.1 mmol/l and caused a fall of clotting factors VIIc and Xc and a significant rise in fibrinolytic activity. None of these variables changed in the comparison group. Raised fibrinogen and factor VIIc concentrations are risk factors for cardiovascular mortality, and raised factor Xc and lowered fibrinolytic activity have both been found in groups at high risk of ischaemic heart-disease. Despite the fact that in population studies triglycerides do not consistently appear to be an independent risk factor for ischaemic heart disease, these data suggest that a pronounced increase in triglycerides warrants energetic therapy because it may be associated with a "hypercoagulable state".

Adult↗

Menopausal status and haemostatic variables.

The incidence of ischaemic heart disease (IHD) is higher in postmenopausal women than in premenopausal women of the same age. The difference may be partly explicable in terms of differences between premenopausal and postmenopausal women in haemostatic function. This possibility has been studied in 833 White women in the Northwick Park Heart Study (NPHS). Mean levels of factor VIIC, fibrinogen, and cholesterol were between 6% and 10% higher in postmenopausal women than in premenopausal women of the same age. When allowances were made for associations between these variables, the difference between the two groups in cholesterol was no longer evident. By analogy with NPHS data on men, the differences in factor VIIC, fibrinogen, and cholesterol would increase the risk of fatal IHD in postmenopausal women by about 40% compared with the risk in premenopausal women of the same age.

Age Factors↗

Common units for clotting factors assayed against different standards.

There are no generally accepted units for clotting factors except factor VIII. Results are usually expressed as percentages of the standards used in the assays and standards vary in their potency. Over a six year period, factors V, VII and VIII were measured in over 3000 participants in the Northwick Park Heart Study. Six different standards had to be used. For comparative purposes, all results were expressed in terms of the first standard (71/11). This paper describes how appropriate conversion values were derived. Three different methods were compared. One consisted of the assay of each standard against its replacement. Another was based on the use of a reference plasma spanning the use of two successive standards. The third was a population-based, or epidemiological method using the data from all the participants in the study. This method is based on the assumption that results would be the same in comparable groups of study participants. In order to ensure comparability, personal characteristics which affect clotting factor levels, such as age and degree of obesity, were taken into account. The three methods gave similar results but the population method was, in general, the most satisfactory for factor VIII as well as factors V and VII, and has been adopted for routine use.

Adolescent↗

Variation between batches in clotting factor assays.

Differences in factor V, VII and VIII potency between the standards used in the Northwick Park Heart Study (NPHS) are described in the previous paper. This paper discusses the variation from batch to batch within each standard. In every case there was significant variation between batches, the standard deviation of batch means being between a third and a half of that within batches. Some of this variation could be attributed to drifts over time, but most of the "batch effect" was not easily accounted for. It is relatively simple to correct for steady drift, but there is no satisfactory way of allowing for unexplained batch variation.

Adolescent↗

Comparison of the bioavailabilities and anticoagulant activities of two warfarin formulations.

Changes in the British Pharmacopoeia dissolution time requirements have necessitated reformulation of warfarin sodium ('Marevan'). The old and new formulations were compared with each other in eight healthy volunteers given a single 15 mg dose of each in a cross-over study and also in 19 patients receiving warfarin therapy. In the volunteer study, a significant but small increase in bioavailability was observed for the new formulation. However, the effects of the two formulations on the prothrombin ratio and on clotting factors II, VII, IX and X were not significantly different. Irrespective of formulation, the greatest changes in factors II, VII and X were observed after the first dose of warfarin. With factor IX, the greatest response was observed after the second dose. The clinical study in patients confirmed that the old and new formulations of Marevan are interchangeable on a dose for dose basis. A sensitive semi-automated warfarin assay technique is described.

Adolescent↗

Effect of treatment of hyperlipidaemia on haemostatic variables.

The haemostatic function of 11 men with hyperlipidaemia was measured before and after they were treated with a carbohydrate-reduced, fat-modified diet. After treatment, which significantly reduced serum triglyceride and cholesterol concentrations, they showed a significant fall in mean levels of clotting factors VII, VIII, and X and a rise in fibrinolytic activity. These findings suggest that haemostatic function may be important in the pathogenesis of ischaemic heart disease.

Adult↗

Haemostatic function and cardiovascular death: early results of a prospective study.

Components of the haemostatic system which may be involved in the pathogenesis of ischaemic heart disease (IHD) were measured in the Northwick Park Heart Study. Of 1510 white men aged 40-64 at recruitment, 49 have since died. 27 died from cardiovascular disease (IHD in all but 3), 18 from cancer, and 4 from other causes. The mean recruitment levels of factor VIIc, factor VIIIc, and fibrinogen were significantly higher in those who died of cardiovascular disease than in those who survived. The independent associations of factor VIIc and fibrinogen with cardiovascular death were at least as strong as the association of blood cholesterol with cardiovascular death. A clustering of two or three high clotting-factor values (factor VIIc, factor VIIIc, and fibrinogen) was present at recruitment in 63% of those who died of cardiovascular disease, compared with 23% of those who survived. The clotting-factor results appeared to be specific for cardiovascular disease: there was no evidence that high levels of factor VIIc, factor VIIIc, and fibrinogen were associated with death from cancer. The general epidemiology of factor VIIc, factor VIIIc, and fibrinogen is consistent with their having a role in the pathogenesis of IHD.

Adult↗

Haemostatic variables associated with diabetes and its complications.

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.

Adult↗

Characteristics affecting fibrinolytic activity and plasma fibrinogen concentrations.

As part of a study to determine the extent to which the haemostatic system is implicated in the onset of clinically manifest ischaemic heart disease, characteristics influencing fibrinolytic activity (FA) and plasma fibrinogen concentrations were examined in 1601 men aged 18-64 and 707 women aged 18-59 in several occupational groups in North-west London. In men FA noticeably decreased till the age of about 58, when there was a small rise. In women a small increase in FA between 18 and about 40 was followed by a slightly larger fall between 40 and 59. There was a pronounced negative association of FA with obesity. FA was significantly less in smokers than non-smokers, though the effect was not large. FA increased with alcohol consumption. FA in men appeared to be greatest in the lower social classes, and men on night shift had poorer FA than those on day work. FA was greater in women using oral contraceptives than in those not using these preparations. In both sexes FA increased with exercise, but there were no associations between any of the characteristics studied and the increase. Plasma fibrinogen concentrations increase with age and obesity, are higher in smokers than non-smokers, and fall with alcohol consumption. In women the concentrations are higher in those using oral contraceptives. The general epidemiology of FA and plasma fibrinogen concentrations suggests that they may well be implicated in the pathogenesis of ischaemic heart disease.

Adolescent↗

Relationship of air temperature to various chemical, haematological, and haemostatic variables.

Results for biochemical and haematological variables have been correlated with data on atmospheric temperature in order to identify possible mechanisms through which low environmental temperature may increase mortality from myocardial infarction and cerebrovascular disease. With the exception of cholesterol, there were no associations in the case of several clinical chemistry variables, or of haemoglobin and related indices. With varying degrees of consistency among the sex and age groups studied, temperature was positively correlated with factor VII, antithrombin III, and cholesterol, and negatively correlated with fibrinolytic activity. The correlations were all low but may offer some clues to mechanisms whereby air temperature influences ischaemic heart and cerebrovascular disease mortality.

Adolescent↗