THE ROLE OF THE PULMONARY CIRCULATION IN THE REGULATION OF COAGULATION AND FIBRINOLYSIS IN RELATION TO MAJOR SURGERY

Cardiac surgery and hip replacement surgery (HSS) are associated with serious cardiorespiratory and vascular complications. Activation of bl ood coagulation and fibrinolysis in the lung vasculature seem to play a key role in the pathophysiology of this process. This article review s the results of several experimental and clinical studies within this field. Animal studies have shown that bone traumatization induces a m arked local activation of coagulation and fibrinolysis in femoral vein blood draining from the surgical area as shown by a 2.5-fold increase in plasma levels of thrombin-antithrombin complexes (TAT) and a seven -fold increase in tissue plasminogen activator (tPA) activity. A sligh t increase in TAT in femoral vein blood on the unoperated side has als o been found and indicates increased activation of coagulation in reci rculated blood, which had passed the pulmonary microvasculature. In ad dition, human studies have Shown that bone preparation induced a 200-f old increase in systemic circulating fibrinopeptide-A during surgery a nd a fivefold increase in TAT (when thromboprophylaxis was stopped 1 w eek after surgery). Both increases are markers of thrombin generation. Furthermore, cellular studies have shown that thrombin and certain cy totoxic chemicals, such as methylmethacrylate monomer (bone cement), s eparately and together trigger monocytes to tissue factor (TF) express ion and cause endothelial cell shape changes and detachment. This may allow pericellular fibrin formation to occur on monocytes and also tra nsforms the nonthrombogenic endothelial coverage into a highly thrombo genic surface that triggers the conversion of fibrinogen to fibrin and releases fibrinopeptide-A. Finally, sequestration of granulocytes cau sed release of autodigestive proteases, which may have further strengt hened this procoagulant process. Synchronous to the massive intrapulmo nary activation of coagulation, an increased fibrinolytic activity was found, as evidenced by a marked drop in arterial blood tPA during sur gery. This indicated tPA binding to fibrin deposits in the lung capill aries. However, this clearing process, to obtain adequate blood flow a nd gas exchange. was shut down several hours after surgery by an antif ibrinolytic activity (PAI-1). Thus, these studies indicated that bone surgery induces a substantial intraoperative hemostatic activation ih the lung capillaries, which is the primary target organ for venous blo od-borne bone-marrow debris. Soft-tissue surgery and vascular surgery seem to induce less systemic activation of coagulation and fibrinolysi s. Copyright (C) 1997 by W.B. Saunders Company.