Extrinsic Pathway Inhibitor in Elective Surgery: A Comparison with other Coagulation Inhibitors

Summary

Extrinsic coagulation pathway inhibitor may be an important regulator of haemostasis to prevent thrombosis after tissue damage. The functional activity of this inhibitor was determined using a chromogenic substrate assay, and compared to the activities of anti thrombin, heparin cofactor II and protein C during the perioperative period of elective hip replacement (n = 28), cholecystectomy (n = 11), and vascular surgery (n = 5). Peroperatively, all the inhibitors decreased rather similarly and to the same degree as the decrease in albumin concentration. The decreases during hip surgery were about 2-fold the decreases observed during cholecystectomy. A significant peroperative increase in extrinsic pathway inhibitor activity was observed in vascular surgery, probably due to a bolus injection of heparin. Antithrombin, heparin cofactor II and protein C levels normalized on days 3-5 postoperatively in all three patient groups. Sustained low levels of extrinsic pathway inhibitor were observed on postoperative days 1 to 7 in hip surgery patients. Apparently, extrinsic pathway inhibitor is not an acute phase reactant. In uncomplicated surgery, the decreases of the coagulation inhibitor levels are mainly due to hemodilution.

Keywords

Hip surgery - Coagulation inhibitors - Tissue thromboplastin - Extrinsic pathway inhibitor

• References

• 1 Sanders NL, Bajaj SP, Zivelin A, Rapaport SI. Inhibition of tissue factor/factor Vila activity in plasma requires factor X and an additional plasma component. Blood 1985; 66: 204-212
• 2 Hubbard AR, Jennings CA. Inhibition of tissue thromboplastin-mediated blood coagulation. Thromb Res 1986; 42: 489-498
• 3 Broze GJ, Miletich JP. Characterization of the inhibitor of tissue factor in serum. Blood 1987; 69: 150-155
• 4 Sandset PM, Abildgaard U, Pettersen M. A sensitive assay of extrinsic coagulation pathway inhibitor (EPI) in plasma and plasma fractions. Thromb Res 1987; 47: 389-400
• 5 Wun T-C, Kretzmer KK, Girard TJ, Miletich JP, Broze GJ. Cloning and characterization of a cDNA coding for the lipoprotein-associated coagulation inhibitor shows that it consists of three tandem Kunitz-type inhibitory domains. J Biol Chem 1988; 263: 6001-6004
• 6 Giercksky K-E, Bjprklid E, Prydz H, Renck H. Circulating tissue thromboplastin during hip surgery. Eur Surg Res 1979; 11: 296-300
• 7 Nillius AS, Nylander G. Deep vein thrombosis after total hip replacement: A clinical and phlebographic study. Br J Surg 1979; 66: 324-326
• 8 Sue-Ling HM, Johnston D, McMahon MJ, Philips PR, Davies JA. Pre-operative identification of patients at high risk of deep venous thrombosis after elective major abdominal surgery. Lancet 1986; I: 1173-1176
• 9 Gitel SN, Salvati EA, Wessler S, Robinson HJ, Worth MH. The effect of total hip replacement and general surgery on antithrombin III in relation to venous thrombosis. J Bone Joint Surg 1979; 61: 653-656
• 10 Schipper HG, Roos J, Meulen Fdv, ten Cate JW. Antithrombin deficiency in surgical intensive care patients. Thromb Res 1981; 21: 73-80
• 11 Mannucci PM, Vigano S. Deficiencies of protein C, an inhibitor of blood coagulation. Lancet 1982; II: 463-466
• 12 Harbourne T, Nicolaides AN. The effect of operation and subcutaneous heparin on plasma levels of antithrombin-III. Thromb Res 1986; 43: 657-662
• 13 Andersson TR, Berner NS, Larsen ML, Ødegaard OR, Abildgaard U. Plasma heparin cofactor II, protein C and antithrombin in elective surgery. Acta Chir Scand 1987; 153: 291-296
• 14 Hjort PF. Intermediate reactions in the coagulation of blood with tissue thromboplastin. Scand J Clin Lab Invest 1957; 9 (suppl27): 001-183
• 15 Sandset PM, Abildgaard U, Larsen ML. Heparin induces release of extrinsic coagulation pathway inhibitor (EPI). Thromb Res 1988; 50: 803-813
• 16 Handeland GF, Abildgaard U, Aasen AO. Simplified assay for antithrombin III activity using chromogenic peptide substrate. Scand J Haematol 1983; 31: 427-437
• 17 Ødegaard OR, Try K, Andersson TR. Protein C: An automated activity assay. Haemostasis 1987; 17: 109-113
• 18 Abildgaard U, Larsen ML. Assay of dermatan sulfate cofactor (heparin cofactor II) activity in human plasma. Thromb Res 1984; 35: 257-266
• 19 Pinell AE, Northam BE. New automated dye-binding method for serum albumin determination with bromcresyl purple. Clin Chem 1978; 24: 80-86
• 20 Hoye RC, Paulson DF, Ketcham AS. Total circulating albumin deficits occurring with extensive surgical procedures. Surg Gynecol Obstet 1970; 131: 943-952
• 21 Sandset PM, Andersson TR. Coagulation inhibitor levels in pneumonia and stroke: Changes due to consumption and acute phase reaction. J Internal Med (formerly Acta Med Scand) 1989; 225: 311-316
• 22 Swart CA M, Nijmeyer B, Andersson LO, Holmer E, Sixma JJ, Bouma BN. Elimination of intravenously administered radiolabelled antithrombin III and heparin in humans. Thromb Haemostas 1984; 52: 66-70
• 23 Sie P, Dupouy D, Pichon J, Boneu B. Turnover study of heparin cofactor II in healthy man. Thromb Haemostas 1985; 54: 635-638
• 24 Sandset PM, Røise O, Aasen AO, Abildgaard U. Extrinsic pathway inhibitor in postoperative/posttraumatic septicemia: Increased levels in fatal cases. Haemostasis 1989; 19: 189-195
• 25 Lindahl AK, Sandset PM, Abildgaard U, Andersson TR, Harbitz TB. High plasma levels of extrinsic pathway inhibitor and low levels of other coagulation inhibitors in advanced cancer. Acta Chir Scand 1989. in press.