Faculty of Health Sciences
School of Medicine
Department of Surgery
Selected Highlights from Research Findings
A comparative analysis was designed to explore the ultrastructural morphology of fibrin networks derived from three different sources of platelets and fibrinogen ie. lyophilized platelet rich plasma, fresh platelet rich plasma and fresh human platelet concentrate. The results showed that there was a remarkable ultrastructural similarity between the three fibrin clots and it would seem that lyophilized platelet rich plasma can be used successfully in fibrin platelet ultrastructural morphology studies. The study of activated platelet fibrin networks may also provide valuable insights into the applicability of a topical platelet concentrate clotted with thrombin in the treatment of recalcitrant ulceration of the skin. Of particular interest was the finding that irrespective of their source all the fibrin clots showed thick fibrin fibres as well as a well defined fine fibrin network which appeared to be superimposed after the major fibrin network was established. An intensive literature search indicates that this phenomenon has never been documented.
Contact person: Prof JHR Becker.
The Department of Surgery recently completed Phase I of this project and is currently working on Phase II. The project was launched to account for the observed hypercoagulability or the prothrombotic state in HIV infected patients. These include a decline in anticoagulant factors such as protein C – and S, antithrombin III and heparin cofactor II the presence of antiphospholipid antibodies, and an increase in the procoagulant products of endothelial cell activation. Endothelial cell activation does not only lead to enhanced expression of procoagulant proteins, but is also related to altered functions of various other haemostatic factors like Von Wilelbrand factor, PAI and endothelium derived thrombomodulin. It has also been postulated that AIDS itself could be a mulfifactorial thrombophilic condition caused by the dysfunction of platelets and endothelial cells that may be unmasked by protease inhibitor (PI) therapy. Of particular interest were the findings of Majluf-Cruz et al of Mexico City who showed that whereas the rate of thrombosis in 600 patients during a 42 month study period was 1.52%, the thrombosis rate before the advent of protease inhibitor therapy was only 0.33% (P<0,001). Their data therefore strongly suggested that PI therapy could be a major risk factor for inducing venous thrombosis. These findings are strongly supported by several other groups. Due to the high incidence of thrombotic recurrences and haemorrhagic complications while using oral anticoagulants, aspirin was institued as a standard measure in AIDS patients with VTE. No thrombotic episodes were recorded in patients with recurrent thrombosis after antithrombotic monotherapy with acetyl salicylic acid was started. In their patients experiencing only one thrombotic episode no recurrent thrombotic episodes were recorded while their patients were on aspirin. Researchers at the Karolinska Institude in Stockholm found that patients receiving protease inhibitor therapy showed decreased fibrinolysis and increased coagulability which may represent additional risk factors in this patient group – an observation which is reinforced by several other leaders in the field. Furthermore, the well documented post-operative decline in plasma fibrinolytic activity or “fibrinolytic shutdown” has also been shown to be a significant contributory factor in the pathogenesis of post-operative venous thrombo-embolic disease. Our own findings have also shown that raised alpha-1-antitrypsin levels were not only found to be potent inhibitors of plasma and neutrophil protease (plasmin and also non-plasmin) fibrinolytic activity, but also appeared to be a prominent thrombophilic factor in a cohort of patients with “idiopathic” venous thrombo-embolism. Based on an extensive literature search, it is evident that thrombelastography in the evaluation of hypercoagulability in patients with AIDS has not been explored before. It would be easy, more cost-effective and clinically reliable to use the TEG to determine the thrombelastographic characteristics of coagulation in HIV patients with stage IV desease. A further objective is to investigate which parameter of the TEG correlates with the hypercoagulable state. If the TEG can be use to provide evidence of a hypercoagulable state, certain guidelines can be established regarding thromboprophylaxis in stage IV disease.
Contact person: Prof JHR Becker.
In this study researchers investigated the morphology of platelet aggregates in platelet rich plasma clotted with thrombin. The aim of the study was to compare the morphology of the platelet aggregates in platelet rich plasma clots prepared from HIV patients with those of controls without HIV. The results showed that shrivelled platelet aggregates with the bleb-like protrusion possibly resulting from cytoplasm and organelles bulging through a disrupted membrane are reminiscent of the characteristic Apoptotic changes. Changes in platelet aggregate morphology may be related to ultrastructural damage by the virus or antibody-induced destruction by entering through the open canalicular system channels. The shrunken Apoptotic appearance of the fibrin-bound platelet aggregates seems to provide further evidence of the devastating cyto destructive effects of HIV.
Contact person: Prof JHR Becker.
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