APROTININ AND EPSILON AMINOCAPROIC ACID ARE EQUALLY EFFECTIVE IN REDUCING BLOOD LOSS AFTER PRIMARY TOTAL HIP ARTHROPLASTY – A PROSPECTIVE RANDOMISED DOUBLE BLIND PLACEBO CONTROLLED STUDY

Abstract

Introduction and Aims: Decreasing blood loss during total hip replacement (THR) remains a challenge for the orthopaedic surgeon. This study investigated the effects of the antifibrinolytics aprotinin and epsilon aminocaproic acid (EACA) against placebo on blood loss during primary total hip replacement. Their safety and mechanism of action was also investigated.

Method: Forty-five patients undergoing primary unilateral total hip arthroplasty were randomised to receive an infusion of either aprotinin, EACA, or placebo. Intra- and post-operative blood loss was measured, as was the rate of blood transfusion and changes in haemoglobin concentration. Clinical examination and duplex ultrasound was used in all patients to detect thrombotic events. All patients were assessed clinically six weeks post-op to detect adverse events. Platelet function was assessed using P-selectin, Platelet-monocyte aggregates (PMA) and factor V/Va levels. D-dimer activity was recorded as an indicator of fibrinolysis. Non-parametric statistical analysis was employed in the interpretation of results.

Results: There was no difference in demographics or pre-operative platelet function between the groups with the exception of the EACA group which had a lower pre-operative haemoglobin concentration. Intra-operative blood loss was significantly lower in the aprotinin group compared to placebo (p=0.01), similarly there was also a reduction in intra-operative blood loss in the EACA group but this did not reach statistical significance. Post-operative bleeding from closed suction drains was markedly reduced for both aprotinin (60%, p=< 0.01) and EACA (53%, p=< 0.001) compared to placebo. Markedly less haemoglobin was lost in drains in both antifibrinolytic groups, with aprotinin showing a 77% (p=< 0.0001) and EACA a 73% reduction (p=< 0.001) in post-operative haemoglobin loss. Despite this, no difference in the rate of blood transfusion was observed between groups. Total hip arthroplasty surgery led to the activation of platelets as evidenced by P-selectin, PMA and factor V/Va levels. However, platelet function was not affected by either aprotinin or EACA. Both antifibrinolytics showed a similar increase in D-dimer levels indicating a similar efficacy in inhibiting fibrinbolysis. There were no DVTs, PEs or infections recorded in the study, and no increase in adverse events was seen with the use of antifibrinolytics.

Conclusion: Infusion of either aprotinin or EACA reduces blood loss after primary THA. Both agents are equally effective and have a favourable safety profile. The two drugs inhibit fibrinolysis in a similar fashion, and this action appears to be independent of platelets.