Annals of the Royal College of Surgeons of England (1979) vol 6i

Factors affecting the fibrinolytic

response

to surgery N J Griffiths FRCS Department of Surgery, Hope Hospital, Salf ord*

Summary ation, and in the dissemination of malignant cells in the postoperative period. and operation surgical The stress of injury It was not until I9374 that it was recognised results in an initial increase in the spontaneous fibrinolytic activity of the blood which is fol- that changes in the spontaneous fibrinolytic lowed by a period of reduced activity in the activity of the blood accompanied surgical postin jury or postoperative period. This 'fibri- operation. Initially there is an increase in this nolytic shutdown' is particularly marked in activity during operation5'6 which is followed patients with malignant disease and occurs by a period of reduced activity ('fibrinolytic irrespective of whether or not they develop a shutdown')7. deep venous thrombosis. It also occurs in Recently Browse and his co-workers8 have patients with benign disease and in these suggested that the fibrinolytic shutdown does patients is greater, though only on the first not occur in every patient but is particularly postoperative day, in those who develop deep prominent in patients with malignant disease, venotus thrombosis. Venous occlusion studies in whom it might reflect the disease process suggest that this reduction in spontaneous and not necessarily the effects of the operation. fibrinolytic activity may be the result of a re- They have further suggested that the reducduction in the fibrinolytic capacity of the tion in postoperative fibrinolytic activity of the vascular endothelium resulting either from a blood is not associated with postoperative deep deficiency of the enzyme plasminogen activator venous thrombosis. However, in patients with or an inability to release the enzyme from the idiopathic venous thrombosis a correlation can endothelium. Changes in antiplasmins, the be demonstrated between the incidence of inhibitors of the fibrinolytic system, also occur thrombosis and a reduced level of fibrinolytic as a result of the stress of operation. Plasma activity in the blood and also a reduction in levels of a2-macroglobulin fall while those the amount of plasminogen activator in the of a,-antitrypsin rise. These changes occur ir- venous endothelium9"'. Furthermore, these respective of the presence of malignant or patients have been helped by anabolic steroids benign disease and do not appear to influence and oral hypoglycaemic agents, which increase the development of deep venous thrombosis. the tissue level of plasminogen activator and restore the fibrinolytic activity in the blood to normal levels, thereby reducing the incidence Introduction Since the initial recognition that the fluidity of of recurrent thrombosis". To the gastrointestinal surgeon the relationthe blood changes as a result of injury 1,2 and between local gastric fibrinolysis and ship the subsequent introduction of the word haematemesis is of particular interest. It has amount a fibrinolysis by Dastre in i8933 great of research has been undertaken into fibrino- been suggested that certain causes of haemalysis, increasing our knowledge about the temesis might be associated with an increase response of this system to the stress of injury. in local gastric fibrinolytic activity'2'13 and It has been demonstrated that alterations in that the administration of antifibrinolytic drugs fibrinolytic activity are of significance in the such as tranexamic acid results in a reduction aetiology of venous thrombosis and venous in the amount of bleeding14. Finally, it has recently been suggested that ulceration, in erosive gastritis and peptic ulcerthere is an association between the fibrinolytic *Present address: St Bartholomew's Hospital, system and the dissemination of malignant cells in the early postoperative period. Patients with London, ECi Arris and Gale Lecture delivered on 24th February 1977

Factors affecting the fibrinolytic response to surgery

malignant disease have a greater fibrinolytic shutdown in the postoperative period than those with benign disease15. This might reflect a reduction in tissue fibrinolytic activity which could result in an increase in the dissemination of malignant cells by adhesion to venous or capillary endothelium. As further evidence it has been shown that those patients who have circulating malignant cells in the early postoperative period following surgery for colorectal cancer have better 5- and io-year survival rates than those with no circulating malignant cells16, perhaps indicating that these cells do not become adherent to the vascular endothelium.

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It can be seen that knowledge of the fibrinolytic system is of value to the gencral surgeon in the management of several surgical problems. Our studies were designed to increase knowledge of the changes that occur in the fibrinolytic system, particularly during the preoperative and early postoperative periods, to determine the relationship between these changes and the development of deep venous thrombosis, and to ascertain the role of the vascular endothelium in the fibrinolytic shutdown that occurs after operation. In addition, we attempted to explain the association between changes in the fibrinolytic inhibitors accompanying surgical operation and the fibrinolytic shutdown and the development of deep venous thrombosis.

Alteration in spontaneous fibrinolytic activity of the blood accompanying surgical operation The changes that occur in the fibrinolytic system in patients undergoing both major and minor surgery have been studied. Spontaneous fibrinolytic activity of the blood was determined by measuring the euglobulin clot lysis time (ECLT) using an automatic clot lysis time recorder17. All patients undergoing major surgery were given '25I-fibrinogen to detect deep venous thrombosis"6.

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Ind

Day before operation

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FIG. I Changes in ECLT during and immediately after operation in 26 patients (mean

± SEM).

fibrinolytic activity. This increase began immediately after the induction of anaesthesia and reached a maximum about an hour after the start of the operation. By the end of the operation the ECLT had returned towards the postinduction value and if the operation was prolonged it rose above that level, possibly indicating that the patient was going into the period of fibrinolytic shutdown even before the end of the operation. The response during surgery was similar in all patients having major surgery irrespective of the disease process and of whether or not they subsequently developed deep venous thrombosis.

Postoperatively there was a prolongation of the ECLT in all patients, indicating a period The main emphasis in this study was on of reduced fibrinolytic activity of the blood the preoperative and early postoperative period. (fibrinolytic shutdown). This shutdown was It can be seen from Figure i that during major greater in patients with malignant disease but surgery there was a fall in the ECLT in all occurred irrespective of whether or not they patients, indicating an increase in spontaneous developed deep venous thrombosis (Fig. 2).

14

N J Griffiths 800-

Euglobulin Clot Lysis Time 700(Minutes) 600-

o --- O Benign + DVT

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0-0 Malignant+ DVT

(n =6) x---x Benign - DVT (n =25) x_xMalignant - DVT / (n =7)

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FIG. 2 Changes in mean ECLT during and immediately after operation in 43 patients subdivided into those with malignant and benign disease and those with and without deep venous thrombosis (DVT).

Patients with benign disease also showed a period of fibrinolytic shutdown, but only on the first postoperative day was the shutdown greater in those with than in those without deep venous thrombosis.

maintained by a constant diffusion of plasminogen activator from the endothelium into the blood. There are a variety of methods of assessing the fibrinolytic activity of the vascular endothelium, one of which is by measuring the response to forearm venous occlusion2". This technique, which has been shown to be reproducible and reliable, involves occluding the forearm by a sphygmomanometer bag placed around the arm and inflated to a pressure midway between systolic and diastolic pressures for a period of 20 min. This results in the transfer of plasminogen activator from the endothelium into the occluded venous blood, the consequent increase in the fibrinolytic activity of the blood being called the 'fibrinolytic capacity'21. This method was used to study Io patients uindergoing major surgery, comparing the response on the day before operation with that on the first postoperative day. Following the preoperative occlusion there was a fall in the ECLT indicating fibrinolytic enhancement. This fall was significantly less (P

Factors affecting the fibrinolytic response to surgery.

Annals of the Royal College of Surgeons of England (1979) vol 6i Factors affecting the fibrinolytic response to surgery N J Griffiths FRCS Departme...
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