Soluble fibrinogen-fibrin complexes in pre-eclampsia and other clinical conditions which may be associated with intravascular coagulation

McKillop, Caroline Annis (1977) Soluble fibrinogen-fibrin complexes in pre-eclampsia and other clinical conditions which may be associated with intravascular coagulation. PhD thesis, University of Glasgow.

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This thesis is concerned with the identification of soluble fibrinogen-fibrin complexes by plasma fibrinogen chromatography. These soluble complexes are thought to reflect intravascular coagulation in vivo. The studies, which will be described, were undertaken to investigate further the proposed association between pre-eclampsia and disseminated intravascular coagulation by searching for soluble fibrinogen-fibrin complexes in plasma samples from pre-eclamptic patients. Pre-eclampsia remains an important obstetrical syndrome of unknown primary aetiology. There is, nevertheless, considerable evidence based on animal experimental work and on both histological and haematological studies in patients to suggest that low-grade disseminated intravascular coagulation may be associated with pre-eclampsia (Chapter V. 2). Such an association might be of importance not only in the pathogenesis and clinical management of pre-eclampsia, but might also contribute to a greater understanding of disseminated intravascular coagulation itself. In Chapter I the biochemistry of fibrinogen, fibrinogen-fibrin degradation products and soluble fibrinogen-fibrin complexes is discussed in detail. The methods currently available for the identification of soluble complexes (and soluble fibrin) in plasma samples and the results obtained in various clinical conditions are then described (Chapter 1.6). In Chapter II the development of the technique of plasma fibrinogen chromatography is traced and details are given of the methods used for the studies to be described in the thesis. It was confirmed in a series of in vitro experiments (Chapter III) that soluble complexes could be produced by the action of coagulant enzymes (thrombin and ancrod) and that these complexes could be partially separated from fibrinogen by the plasma fibrinogen chromatography technique. Patients were then studied during the initial stages of intravenous infusion with the coagulant enzyme, ancrod (Chapter IV). Increased plasma soluble complex levels were found 6 hours after starting treatment, thus confirming that soluble complexes can be produced in vivo by a coagulant enzyme and identified using the plasma fibrinogen chromatography technique. Following these preliminary studies plasma samples from pregnant patients were examined (Chapters V-VII). In order to assess the results in pre-eclampsia several other obstetrical groups were studied. Small, but statistically significant increases in plasma soluble complex concentration were found to occur in normal pregnancy (Chapter V and VII). In patients with intrauterine growth retardation a further small but significant increase in soluble complex levels was noted (Chapter VII), while a more marked increase was found in association with pre-eclampsia (Chapter V and VI). This did not appear to be simply related to the combination of hypertension and pregnancy, as pregnant patients with essential hypertension were found to have soluble complex levels similar to those found in normal pregnancy (Chapter VII). In addition, plasma soluble complex levels were found to be slightly increased in women taking oestrogen-containing oral contraceptive drugs (Chapter VIII), a state which in some ways resembles early pregnancy. Although soluble fibrinogen-fibrin complexes probably reflect activation of the coagulation pathway in vivo and therefore in this sense intravascular coagulation, it is not possible to distinguish between the different forms of intravascular coagulation (see the definitions in the Preface) by this technique or, indeed, to make any firm conclusions regarding insoluble fibrin deposition from the results. Insoluble fibrin deposition occurs in local thrombosis and in local and disseminated intravascular coagulation. In each of these states increased plasma soluble fibrinogen-fibrin complex levels might be found, but it is also possible that a pure hyper-coagulable state can exist in which soluble complexes are formed without insoluble fibrin deposition. The results described in this thesis are, however, compatible with hypercoagulability in women taking oestrogen-containing drugs and in normal pregnancy, with in addition a degree of local intravascular coagulation within the maternal placental vasculature in normal pregnancy, a tendency which is increased in intrauterine growth retardation, and with disseminated intravascular coagulation in pre-eclampsia. The soluble complex levels were most markedly increased in pre-eclampsia and during ancrod therapy. Fibrinogenolysis/fibrinolysis, however, was much more marked in the ancrod-treated patients. It may be that fibrin microclots are lysed very rapidly, perhaps even as they form, in ancrod therapy; while in pre-eclampsia they persist within the placenta, kidney, liver and other organs leading to the development of some of the clinical features of the syndrome. The theory that disseminated intravascular coagulation is an integral part of the pathology of the pre-eclamptic syndrome is therefore strongly supported by the work described in this thesis.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Additional Information: Adviser: E M McGirr
Keywords: Biochemistry, Physiology
Date of Award: 1977
Depositing User: Enlighten Team
Unique ID: glathesis:1977-73956
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 14 Jun 2019 08:56
Last Modified: 14 Jun 2019 08:56

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