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Despite pharmacological prophylaxis, 50% of the surgical patients whose Caprini score is >10 develop VTE in the postoperative period suggesting that anticoagulation alone may not be sufficient especially in these high-risk patients. Clinical studies demonstrate that the clot nidus starts to form during the time of operation. Thus, in the postoperative period when pharmacological prophylaxis is initiated, high-risk patients may have already developed a blood clot for which prophylactic doses of anticoagulants would be suboptimal to treat. Therefore, VTE prophylaxis should start at the time of anesthesia induction. Due to bleeding risks associated with pharmacological agents, mechanical modalities, i.e. intermittent pneumatic compression (IPC) devices, with their proven effectiveness in reducing VTE in trauma and high bleeding-risk patients are invaluable tools that should be utilized during surgery frequently. They should be started in the beginning of the operation and then continued together with pharmacological prophylaxis in the postoperative period until full ambulation. Furthermore, there is strong evidence that application of IPCs to any limb, including foot and arm, is sufficient for their prophylactic effect making them suitable for almost any type of surgery. In conclusion, combined pharmacological and mechanical prophylaxis should be utilized more frequently in surgical patients who have high risk for VTE.