The Effect Of The Natural Proteinase Inhibitor Aprotinin On The Activation Of Platelet Function During Total Hip Replacement

Abstract

Postoperative thromboembolism is a well known problem after total hip replacement. Besides the intravasation of bone marrow and thromboplastic material it is discussed that it is caused by activated platelets. Therefore, we focussed our interest on platelet function during total hip replacement.In 12 male and female patients (age:52-84 years) with total hip replacement blood samples were taken at the following time intervals: 1.induction of anesthesia, 2.arthrotomy, 3.preparation of the acetabulum, 4. polymerization of the bone cement in the acetabulum, 5. preparation of the bone marrow in the femur shaft, 6. implantation of the prosthesis shaft, 7.2 hours postoperatively. A second group of 14 patients (age:55-81 years) was treated with 20 000 KIU/ kg BW aprotinin (TrasylolR) immediately after induction of anesthesia. Following tests were carried out: 1. platelet morphology according to KRZYWANEK, 2. platelet adhesiveness according to MORRIS, 3. collagen-induced platelet aggregation according to BORN, 4. spontaneous platelet aggregation according to BREDDIN.The number of shape-changed platelets is increasing with the duration of the operation and the maximum is to be seen when the femur shaft is prepared for the prosthesis. In contrast to these findings only a slight increase of shape- changed platelets occurs after application of aprotinin. Concerning the adhesiveness of platelets corresponding results were found. Platelet aggregation induced by collagen was also increased during the operation time. The increase of the aggregability characterized by the maximal amplitude was not seen in the aprotinin-group. The spontaneous platelet aggregation was enhanced in the non-treated group (angle α 2↑ maximal amplitude↑) whereas this phenomenon was not observed after application of aprotinin. The total hip replacement is closely related with a stimulation of platelet function. This could be the origin of postoperative thromboembolism.

Thoughts on the Mechanism of Action of Aprotinin

“…28 In contrast to these data, the role of aprotinin in preservation of the initial adhesion of platelets as the mechanism of action is questioned. Firstly, in hip surgery the normally observed increase in platelet adhesion to glass beads was inhibited in patients given aprotinin, [8][9][10] and secondly platelet attachment to thrombin-stimulated endothelium was also inhibited by aprotinin at clinically relevant concentrations. 11 The precise mechanism of this action has not been established but these studies suggested the mechanism was not by way of a nitricoxide-dependent pathway.…”

“…There is a considerable literature to show the aggregation of platelets to known agonists such as adenosine diphosphate (ADP), collagen and ristocetin is inhibited not only by aprotinin, 9,10,28,46 but also the lysine analog antifibrinolytics 47 and certain antiplatelet agents such as prostacyclin and its derivatives. These actions may play some part to protect the platelet from certain of the damages induced during a period of extracorporeal circulation or reperfusion injury in the liver.…”

“…The concentration of D-dimer was reported not to be associated with postoperative bleeding after major orthopedic surgery 7 and increased rather than depressed platelet activity is usually reported in association with joint replacement. [8][9][10] It would seem logical that the hemostatic action(s) of aprotinin is in some way related to the plasma concentration of the drug. However, thus far there is no data showing a robust relationship between the plasma concentration and an index of bleeding.…”

Pharmacological approaches to reducing allogeneic blood exposure

“…During hip replacement, low doses of aprotinin inhibit platelet function without a reduction in transfusions [25][26][27]. Two reports from randomized placebo-controlled studies of a higher dose of aprotinin [28,29] (equivalent to the high-dose regimen used during cardiac surgery) showed a significant reduction in the need for allogeneic transfusion.…”

Pharmacological Interventions to Prevent the Need for Blood and Blood Component Therapies:

“…Early studies demonstrated the effect of low-dose aprotinin therapy on such variables as platelet function but without any consistent benefit for reducing transfusion requirements. [37][38][39][40] There are two reports from randomized placebo-controlled studies on patients who underwent primary hip surgery. 41,42 The first, from Belgium, showed a significant reduction in drain loss and need for donor blood and blood products with aprotinin doses equivalent to the highdose regimen used during cardiac surgery.…”