Published online by Cambridge University Press: 01 February 2010
The pathophysiology of the thrombotic process is multicomponent and involves blood, vascular system, humoral mediators and target sites. Furthermore, the intiating event and the site of thrombogenesis play a key role in the overall pathogenesis. The process of thrombogenesis is depicted in Figure 11.1. Initially, vascular injury results in the localized alterations of the vessels, generation of tissue factor, and subsequent activation of platelets. Activated cells mediate several direct or signal transduction induced processes resulting in the activation of platelets. Cellular activation also results in the release of various mediators which amplify vascular spasm and the coagulation process. Adhesion molecules, cytokines, oxidative stress and flow conditions signficantly contribute to the ischemic and occlusive outcome. Drugs that target various sites of the activation process have been developed to control thrombotic events. Because of the coupled pathophysiology, a drug that targets a single site may not be able to produce the desired therapeutic effects. Furthermore, many of these mediators produce localized actions at cellular and subcellular levels. Feedback amplification processes also play an important role in the pathology of these disorders and interruption of these pathways can be a therapeutic goal. This understanding has led to the concept of polytherapy in the management of thrombotic disorders.
Pregnancy and thrombosis
Pregnancy is associated with a hypercoagulable state that can lead to thrombosis and thromboembolism. The risk of venous thromboembolism (VTE) in pregnancy is approximately six times higher than in non-pregnant women.