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Title: The clinical role of fibrinogen and fibrin in peripheral arterial disease
Author: Reid, Donald B.
Awarding Body: University of Glasgow
Current Institution: University of Glasgow
Date of Award: 1991
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Abstract:
There is a high incidence of peripheral arterial disease in the West of Scotland associated with atherosclerosis. This may manifest itself as intermittent claudication, ischaemic rest pain, gangrene or in the form of abdominal aortic aneurysm. These patients have a greatly increased risk of thrombotic events not only in the limb arteries but also in the coronary, extracranial and cerebral vessels. Recently there has been increasing interest in the contributions of thrombosis and haemorheology to arterial disease. The aim of this thesis is to investigate the role of fibrinogen, fibrin formation and blood rheology in patients with peripheral arterial disease. Fibrinogen has roles in thrombosis and haemorheology: the conversion of fibrinogen to fibrin is the central event of coagulation and fibrinogen is a determinant of whole blood viscosity through its effects on plasma viscosity and red cell aggregation. Fibrin is degraded by plasmin into fibrin degradation products. Fibrin degradation products (FDP's) can now be measured using a specific monoclonal antibody to the D-dimer of cross-linked FDP's. Cross-linked FDP's are therefore markers of in vivo fibrin formation and lysis. Red cell aggregation is the major determinant of low shear blood viscosity and can now be measured photometrically by a new technique. Fibrinogen, cross-linked FDP's and red cell aggregation were measured in 115 patients with peripheral arterial disease together with other blood factors of haemostasis and blood rheology. Multivariate analysis showed that the increase in plasma fibrinogen in patients with peripheral arterial disease can be explained by the effect of smoking. Cross-linked FDP's were also increased in peripheral arterial disease and were associated with the fibrinogen level. This has not previously been reported and suggests that the increased fibrinogen level may promote fibrin formation. Cross-linked FDP's increased with age, but were not related to smoking habit. Cross-linked FDP's correlated with severity of ischaemia and were highest in patients with abdominal aortic aneurysm. Cross-linked FDP's increased following reconstructive vascular surgery suggesting increased fibrin formation, which, if intravascular, could be detrimental to the patency of vascular grafts. Cross-linked FDP's may be prognostic markers for subsequent vascular graft occlusion and this possibility merits further investigation. Red cell aggregation was also increased in peripheral arterial disease (not previously reported by a photometric method). This may also be related to the increased fibrinogen level. Red cell aggregation was higher in ischaemic rest pain than in intermittent claudication, and was highest in patients with abdominal aortic aneurysm. High red cell aggregation was found in ex or non smokers compared to current smokers. The reason for this is not clear. This study also confirmed the increased levels of plasma viscosity, white cell count and triglyceride and decreased HDL cholesterol found in peripheral arterial disease in other studies. Total cholesterol was not increased in this study. There has been recent interest in the rheological properties of white cells. White cell count was related to the severity of ischaemia, being highest in patients with ischaemic rest pain. White cell count and fibrinogen were also increased by cigarette smoking. Fibrinogen and white cell count are two possible mechanisms through which the effects of smoking could lead to progress of peripheral arterial disease. Fibrinogen is an acute phase reactive protein. The cytokine interleukin-6 regulates hepatic synthesis of fibrinogen in the acute phase response. In order to assess whether interleukin-6 regulates the raised fibrinogen level in peripheral arterial disease, interleukin-6 was measured in 30 patients and found to be significantly increased when compared to controls. This has not been previously reported and is in keeping with an inflammatory process in peripheral arterial disease. Interleukin-6 was not related to smoking habit. Some correlation between interleukin-6 and fibrinogen was found in this study. It is therefore possible that the raised interleukin - 6 level may be one inducer of the raised fibrinogen level in peripheral arterial disease.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.796619  DOI: Not available
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