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Genetics and pulmonary medicine • 4
Pulmonary embolism
    1. Michael Laffan
    1. Department of Haematology, Imperial College School of Medicine, Hammersmith Hospital, London W12 ONN, UK
    1. Dr M Laffan.

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    Pulmonary embolism (PE) and deep venous thrombosis (DVT) are often regarded as two aspects of the same disease. Indeed, 50–70% of patients with DVT have evidence of silent PE and DVT is present in 70–90% of patients presenting with PE.1-5 This analysis may therefore be largely true, but there may also be important reasons—some of them genetic—why some patients present with DVT, some with PE, and others with signs of both. This problem will be discussed at the end of this review. In any event, most studies investigating possible genetic predispositions to venous thrombosis have either concentrated on DVT—for example, the Leiden thrombophilia study6—or have not made any distinction between DVT and PE.7-9 We therefore have to rely on these data to indicate the role of genetic variation in pulmonary embolism.

    A genetic tendency to thromboembolism is also referred to as inherited thrombophilia and, although traditionally regarded as monogenic, it is undoubtedly a polygenic abnormality.10 ,11 The basis of our understanding of the thrombophilic state is that it arises from an imbalance between the procoagulant and anticoagulant components of the coagulation system, resulting in an increased tendency to thrombosis. This tendency usually becomes manifest as thrombosis as a result of its interaction with numerous environmental and acquired factors.

    The coagulation cascade and classical thrombophilia

    The coagulation system is activated at the site of injury by the exposure of tissue factor which is ubiquitously expressed in extravascular tissues. Tissue factor binds factor VIIa and triggers a network of serine proteinases and their cofactors resulting in the cleavage of fibrinogen by thrombin to form fibrin, the basis of the blood clot. Regulatory (or inhibitory) systems have evolved in parallel to inhibit this network and prevent inappropriate propagation of this activity (fig 1). The principal inhibitor of the coagulation proteinases—and, in particular, of …

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