The Influence of DDAVP Infusion on the Coagulation and Fibrinolytic Response to Surgery

Summary

The response of components of the coagulation and fibrinolysis systems to infusion of DDAVP has been examined in patients undergoing elective surgery. In the DDAVP treated group there was a significant increase, compared to control, in plasminogen activator (by fibrin plates p <0.005, ECLT p <0.0125, by Student’s t test) before operation. No difference between groups was seen by either methods in the activator levels in samples 24 h postoperation, whereas a significant drop (p <0.002) in protein C concentration was observed at this stage in the treated group. Levels of factor VIII components were significantly higher (p <0.005) than control at all stages of operation and a significant shortening (5 sec p <0.05) of the APTT was seen at all stages (apart from 24 h samples). DDAVP infusion therefore may exacerbate the hypercoagulable state observed in surgical patients without preventing the (post-operatively) fibrinolytic shutdown. Instead, infusion tends to produce fibrinolytic depletion at the key mid-operative stage.

Key words

Plasminogen activator - Factor VIII components - Protein C - Haemostasis - DDAVP

• References

• 1 Ygge J. Changes in blood coagulation and fibrinolysis during the postoperative period. Am J Surg 1970; 119: 225-232
• 2 Mansfield AO. Alteration in fibrinolysis associated with surgery and venous thrombosis. Br J Surg 1972; 59: 754-757
• 3 Gordon-Smith IC, Hickman JA, Le Quesne LP. Postoperative fibrinolytic activity and deep vein thrombosis. Br J Surg 1974; 61: 213-218
• 4 Rem J, Feddersen C, Brandt MR, Kehlet H. Postoperative changes in coagulation and fibrinolysis independent from neurogenic stimuli and adrenal hormones. Br J Surg 1981; 68: 229-233
• 5 Mannucci PM, Vigano S. Deficiencies of protein C, an inhibitor of blood coagulation. Lancet 1982; 2: 463-466
• 6 Hirsh J. Hypercoagulability. Semin Haematol 1977; 14: 409-425
• 7 Nilsson JM, Vilhardt H, Holberg L, Astedt B. Association between factor VIII related antigen and plasminogen activator. Acta Med Scand 1982; 211: 105-112
• 8 Holmberg L, Nilsson IM, Wallen P, Astedt B. Studies of the blood plasminogen activator induced by 1-desamino-8-D-arginine vasopressin with observations in von Willebrand’s disease. Proc Soc Exp Biol Med 1982; 170: 126-132
• 9 Bloom AL. The biosynthesis of factor VIII. Clin Haematol 1979; 8: 53-77
• 10 Kitaguchi H, Hirata M, Fynahara U, Tada K, Okamoto S. Effect of vasoactive agents on factor VIII release from perfused isolated dog leg. Thromb Res 1979; 16: 159-173
• 11 Collen D. On the regulation and control of fibrinolysis. Edward Kowalski Memorial Lecture. Thromb Haemostas 1980; 43: 77-89
• 12 Marsh NA. Fibrinolysis J. Wiley and Sons Ltd; New York: 1981
• 13 Hardisty RM, MacPherson JC, Ingram GI C. A one stage factor VIII (antihaemophilic globulin) assay and its use on venous and capillary plasma. Thrombos Diathes Haemorrh 1962; 7: 215-229
• 14 Evans RJ, Austen DE G. Assay of ristocetin cofactor using fixed platelets and platelet counting technique. Br J Haematol 1977; 37289-37294
• 15 Laurell CB. Quantitative estimation of proteins by electrophoresis gel containing antibodies. Anal Biochem 1966; 15: 45-52
• 16 Blombäck B, Blombäck M. Purification of human and bovine fibrinogen. Arkiv Kemi 1956; 10: 415-447
• 17 Friberger P, Knos M, Gustavsson S, Aurell L, Claeson G. Methods for the determination of plasmin, antiplasmin and plasminogen by means of the substrate S-2251. Haemostasis 1978; 7: 138-145
• 18 Scully MF, Kakkar VV. Methods for semimicro or automated determination of thrombin, antithrombin and heparin cofactor using the substrate H-D-Phe-Pip-Arg-p-nitroanilide 2HC1. Clin Chim Acta 1977; 79: 595-602
• 19 Teger-Nilsson AC, Friberger P, Gyzander E. Determination of a new rapid plasmin inhibitor in human blood by means of a plasmin specific tripeptide substrate. Scand J Clin Lab Invest 1977; 37: 403-409
• 20 Melissari E, Scully MF, Paes T, Kakkar VV. The influence of LMW heparin on the coagulation and fibrinolytic response to surgery. Thromb Res 1985; 37: 115-126
• 21 Allenby F, Jeyasingh K, Calnan J. Ethyloestrenol and postoperative venous thrombosis. Lancet 1973; 2: 38-39
• 22 Fossard DP, Friend JR, Field ES, Corrigan TP, Kakkar VV, Flute PT. Fibrinolytic activity and postoperative deep vein thrombosis. Lancet 1974; 1: 9-11
• 23 Blarney SL, McArdle BM, Burns P, Lowe GD O, Forbes CD, Carter DC, Prentice CRM. Prevention of fibrinolytic shutdown after major surgery by intramuscular stanozolol. Thromb Res 1983; 31: 451-459
• 24 Gader GM A, da Costa J, Cash JD. A new vasopressin analogue and fibrinolysis. Lancet 1973; 2: 1417-1418
• 25 Mannucci PM, Aberg M, Nilsson IM, Robertson B. Mechanism of plasminogen activator and factor VIII increase after vasoactive drugs. Br J Haematol 1975; 30: 81-93
• 26 Aberg M, Nilsson IM, Vilhardt H. The release of fibrinolytic activator and factor VIII after injection of DDAVP. In Progress in Chemical Fibrinolysis and Thrombolysis Davidson JF. (Ed) Vol 4 92-97 Churchill Livingstone; Edinburg: 1979
• 27 Mannucci PM, Rota L. Plasminogen activator response after DDAVP. A clinico-pharmacological study. Thromb Res 1980; 20: 69-76
• 28 MacGregor IR, Prowse CV. Tissue plasminogen activator in human plasma measured by radioimmunoassay. Thromb Res 1983; 31: 461-474
• 29 Rossi EC, Green D, Rosen TS, Spies SM, Jao ST. Sequential changes in factor VIII and platelets preceding deep vein thrombosis in patients with spinal cord injury. Br J Haematol 1980; 45: 143-151
• 30 Gallus AS, Hirsh J, Gent M. Relevance of preoperative and postoperative blood tests to postoperative leg-vein thrombosis. Lancet 1973; 2: 805-809
• 31 Esmon CT. Protein C, Biochemistry, physiology and clinical implications. Blood 1983; 62: 1155-1158