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The effects of ovarian steroids on erythrocytes and coagulation markers in women with sickle cell disease

Yoong, Wai-Cheong; (2003) The effects of ovarian steroids on erythrocytes and coagulation markers in women with sickle cell disease. Doctoral thesis (M.D), UCL (University College London). Green open access

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Abstract

Sickle cell disease (SCD) is an inherited haemoglobin disorder characterised by chronic haemolysis, anaemia and recurrent episodes of occlusion in the microvasculature by poorly deformable erythrocytes. There is experimental and clinical evidence suggesting that ovarian hormones, principally oestradiol and progesterone, modify the process of sickling. As red cells do not appear to express steroid receptors, it has been postulated that ovarian steroids may influence the clinical nature of SCD by modulating the cell membrane of sickle erythrocytes or by adversely affecting haemostatic balance. This is of clinical and therapeutic relevance as the use of hormonal contraception, in particular the combined oral contraceptive pill (COCP), in women with SCD remains the subject of considerable uncertainty and controversy. The use of depot medroxyprogesterone acetate has been shown in two studies to safely reduce the incidence of painful crises, but there is still anxiety that women with SCD who use the COCP may have an additional risk of thromboembolic disease. This thesis examines the in vitro and ex vivo effects of oestradiol and progesterone on the cell membrane of erythrocytes and on molecular markers of coagulation from women with SCD. The menstrual pattern in women with SCD and the influence of the menstrual cycle on painful crises were investigated. Data were also collected on the effects of the menopause in women with SCD. Oestradiol and progesterone associated loosely with the red cells and no specific receptors sites were identified in the sickle erythrocytes. The association was greater with oestradiol than progesterone and for both hormones, this association was significantly diminished in erythrocytes from women with Hb SS compared to Hb SC or Hb AA. Incubation with oestradiol and progesterone did not inhibit sickling or alter the plasma cell membrane thickness or morphology of the erythrocyte as examined by transmission electron microscopy. The deformability and osmotic fragility of sickle erythrocytes was not affected by in vitro incubation with therapeutic concentrations of oestradiol and progesterone. The more acute effect of incubation in vitro may, of course, differ from the effect of longer term exposure to synthetic steroids in vivo. This was therefore further explored in the ex vivo situation, when the use of different types of exogenous contraceptive steroids in women with SCD was also found not to affect red cell deformability. Women with SCD exhibit a degree of hypercoagulability and increased platelet activation even in the quiescent steady state. However, it is reassuring that the haemostatic markers, which measure thrombotic tendency, were not significantly higher in women with SCD who used the COCP compared to those who used non- hormonal forms of contraception. Menstrual clustering of crises was reported by 37% of women with natural menstrual cycles and these were usually of moderate severity, controllable with oral analgesia. The frequency of painful crises decreased following menopause and the commonest post-menopausal complaints were of joint pains and vagina dryness. Post-menopausal women with SCD also appear to have an increased risk of developing osteoporotic fractures. In conclusion, this sequence of studies establishes an ethical basis for a future patient-level interventional study using therapeutic preparations of oestradiol and progestogen relevant to effective contraception for women with SCD.

Type: Thesis (Doctoral)
Qualification: M.D
Title: The effects of ovarian steroids on erythrocytes and coagulation markers in women with sickle cell disease
Open access status: An open access version is available from UCL Discovery
Language: English
Additional information: Thesis digitised by ProQuest.
Keywords: Biological sciences; Health and environmental sciences; Sickle cell disease
URI: https://discovery.ucl.ac.uk/id/eprint/10105673
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