Date of Award


Degree Type


Degree Name

Master of Science (MS)


Medical Sciences (Blood and Cardiovascular)


J. Hirsh


A. A comprehensive and in depth review of the increased permeability of the vascular wall in thrombocytopenia was expedited. As part of this review, the following areas were covered: i. irradiation induced thrombocytopenia and the vascular wall defect; ii. anti-platelet serum induced thrombocytopenia and the vascular wall defect; iii. the endothelium and current theories on the role of platelets in supporting endothelial cell homeostasis; iv. the direct effect of irradiation and of anti-platelet sera on endothelium cell function and vitability; v. current models of explaining the endothelial cell changes and the escape of erythrocytes from the macroscopically intact capillaries and venules in thrombocytopenia; vi. a comparative analysis of the two thrombocytopenia models.

B. Although both qualitative and quantitative studies of the spontaneous extravasation of erythrocytes in irradiation induced thrombocytopenia have been made in the past, only qualitative electron microscopic studies have beeh reported up until now for the anti-platelet serum thrombocytopenic model. In the present work, we established such a quantitative estimate by studying the changes of the cellular content of the thoracic duct lymph in anti-platelet serum rendered thrombocytopenic animals. The level of those changes was lower than the level of corresponding changes reported by others in the irradiation thrombocytopenic model, and for equally severe thrombocytopenia. The possible reasons for this difference were evaluated and discussed.

C. The experimental technique developed here to study the vascular wall thrombocytopenic changes has certain advantages that renders it a useful tool in the study of platelet functions and in the evaluation of drugs claimed to have an anti-purpuric effect. One of the main attractions of this model is that it distinguishes between red blood cells extravasated through direct bleeding during the cannulation operations and spontaneously extravasated red blood cells post-operatively and post-APS. This is simply achieved by infusing the tagged RBC long after any possible bleeding has ceased and using those tagged RBC as a measure of RBC content in lymph. The animals are rendered thrombocytopenia post the infusion of the tagged RBCs. Furthermore, the model has been shown to be reversible and platelets can be transfused and survive into the thrombocytopenic animals shortly after the anti-platelet serum infuslon into the same animals.

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