title: The role of the pulmonary circulation in the regulation of coagulation and fibrinolysis in relation to major surgery.
abstract: Cardiac surgery and hip replacement surgery (HRS) are associated with serious cardiorespiratory and vascular complications. Activation of blood coagulation and fibrinolysis in the lung vasculature seem to play a key role in the pathophysiology of this process. This article reviews the results of several experimental and clinical studies within this field. Animal studies have shown that bone traumatization induces a marked 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 slight increase in TAT in femoral vein blood on the unoperated side has also been found and indicates increased activation of coagulation in recirculated blood, which had passed the pulmonary microvasculature. In addition, human studies have shown that bone preparation induced a 200-fold increase in systemic circulating fibrinopeptide-A during surgery and a five-fold increase in TAT (when thromboprophylaxis was stopped 1 week after surgery). Both increases are markers of thrombin generation. Furthermore, cellular studies have shown that thrombin and certain cytotoxic chemicals, such as methylmethacrylate monomer (bone cement), separately and together trigger monocytes to tissue factor (TF) expression and cause endothelial cell shape changes and detachment. This may allow pericellular fibrin formation to occur on monocytes and also transforms the nonthrombogenic endothelial coverage into a highly thrombogenic surface that triggers the conversion of fibrinogen to fibrin and releases fibrinopeptide-A. Finally, sequestration of granulocytes caused release of autodigestive proteases, which may have further strengthened this procoagulant process. Synchronous to the massive intrapulmonary activation of coagulation, an increased fibrinolytic activity was found, as evidenced by a marked drop in arterial blood tPA during surgery. This indicated tPA binding to fibrin deposits in the lung capillaries. However, this clearing process, to obtain adequate blood flow and gas exchange, was shut down several hours after surgery by an antifibrinolytic activity (PAI-1). Thus, these studies indicated that bone surgery induces a substantial intraoperative hemostatic activation in the lung capillaries, which is the primary target organ for venous blood-borne bone-marrow debris. Soft-tissue surgery and vascular surgery seem to induce less systemic activation of coagulation and fibrinolysis.
authors.affiliation: Department of Orthopaedic Surgery, Ullevaal University Hospital, Oslo, Norway.
authors.forename: O E
authors.initials: OE
authors.lastname: Dahl
mesh_terms: D000818:Animals; D000990:Antithrombin III / Q000032:analysis; D001777:Blood Coagulation / Q000502:physiology*; D001843:Bone Cements; D001842:Bone and Bones / Q000601:surgery; D006348:Cardiac Surgical Procedures; D002448:Cell Adhesion; D048429:Cell Size; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D005342:Fibrinolysis / Q000502:physiology*; D005344:Fibrinopeptide A / Q000032:analysis; D006098:Granulocytes / Q000502:physiology; D006801:Humans; D008768:Methylmethacrylates; D008833:Microcirculation; D009000:Monocytes / Q000502:physiology; D010447:Peptide Hydrolases / Q000032:analysis; D011652:Pulmonary Circulation / Q000502:physiology*; D013514:Surgical Procedures, Operative; D013917:Thrombin / Q000096:biosynthesis / Q000502:physiology; D013925:Thromboplastin / Q000502:physiology; D013927:Thrombosis / Q000209:etiology; D010959:Tissue Plasminogen Activator / Q000097:blood
chemical_list: D001843:Bone Cements; D008768:Methylmethacrylates; C046193:antithrombin III-protease complex; D005344:Fibrinopeptide A; D000990:Antithrombin III; D013925:Thromboplastin; D010447:Peptide Hydrolases; D013917:Thrombin; D010959:Tissue Plasminogen Activator