Leisner, Raina Joan; (1999) The control of thrombin generation in haemoglobinopathies and other haemolytic red cell disorders in children. Doctoral thesis (Ph.D.), University College London (United Kingdom).

Text The_control_of_thrombin_genera.pdf Download (4MB)

Abstract

Vascular occlusion is a complex process that has a central role in the pathophysiology of sickle cell disease (SCD) and it is known that thrombosis contributes to large vessel and possibly also to small vessel occlusion. In childhood the most serious complication of SCD is stroke secondary to cerebrovascular disease (CVD) which is symptomatic in 7-10% of children and a further 14% have asymptomatic disease on imaging. The role of haemostatic abnormalities in the development of vascular occlusion in children with SCD, in particular those with CVD, has not been comprehensively studied before. The principle objectives of this thesis were to perform a prothrombotic profile, including coagulation inhibitors and markers of thrombin generation, in children with SCD and to compare results between different groups; untransfused and transfused; those with CVD and those without; those with haemoglobin SS (HbSS) and those with haemoglobin SC (HbSC), thalassaemia major, other haemolytic red cell disorders and normal controls. I have found significant reductions in the majority of the natural anticoagulants in children with HbSS compared to sibling controls and also substantial elevation in markers of thrombin generation in the steady-state and evidence of acquired activated protein C resistance. These findings were only partially reversed by transfusion and were not as marked in the group with HbSC though thalassaemics also had reduced levels of most inhibitors. There was no evidence that antiphospholipid antibodies were involved in any group. In the groups with or without CVD there were no differences for any of the parameters measured except for lower haemoglobin levels and higher white cell counts in those with asymptomatic CVD so the abnormalities found in the HbSS children do not appear to play a primary role in the development of CVD.

Download activity - last month

Export as XMLJSONCSV

Download activity - last 12 months

Export as CSVXMLJSON

Downloads by country - last 12 months

Export as JSONXMLCSV

Archive Staff Only

View Item