Venous thrombosis is an important
cause of morbidity; incidence is low in young people but increases
with age to 1% per year in the elderly. In a small proportion
of cases, venous thrombosis leads to pulmonary embolism, which can
be fatal. Persons with an initial venous thrombosis are at
increased risk for recurrence; however, long-term use of
anticoagulant prophylaxis can result in major hemorrhagic
complications. This challenging clinical problem has received
new attention since the discovery of certain genetic variants that
increase susceptibility to venous thrombosis.
Under normal conditions, procoagulant
and anticoagulant factors in the blood are in balance. However, persons with inherited alterations in proteins that promote
or prevent coagulation may be predisposed to excessive bleeding (as
in hemophilia) or clotting (thrombophilia). Persons with
thrombophilia are at increased risk of developing clots that
obstruct blood flow locally or that detach and embolize. Environmental factors that cause vascular injury (e.g., surgery),
stasis (e.g., prolonged immobility), or increased coagulability
(e.g., hormone use) interact with genetic susceptibility to increase
the risk for thrombosis.
Mechanisms controlling coagulation
are complex, involving many different proteins. The schematic
below represents a portion of the feedback mechanism that regulates
the conversion of prothrombin to thrombin in the intrinsic pathway.
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