All patients received standard postoperative deep vein thrombosis prophylaxis in the form of warfarin in accordance with existing practice. Warfarin was given once a day starting the night of surgery and was continued until discharge based on daily INR values with an agreed-on target of 2.0. Thigh-high compression stockings and calf sequential compression devices were used in all cases. No patient in either group predonated blood or was given erythropoietin injections before or after surgery. Postoperative allogeneic transfusions were given to patients who were clinically symptomatic or short of breath; patients with hypotension uncorrectable with IV volume supplementation and an Hb level under 9.0 g/dL; and patients with an Hb level under 7.0 g/dL regardless of symptoms. All patients were monitored for postoperative adverse events and complications.
Postoperative blood loss (drain output), Hb levels on postoperative days 1 and 2 (POD-1, POD-2), blood transfusion amounts, and complications were recorded for all patients. Group means were compared with 2-sample t tests for independent samples. Data are reported as group means and SDs. All significance tests were 2-tailed, and statistical significance was set at P < .05.
Results
Fifty patients enrolled in the study: 25 in the control group and 25 in the antifibrinolytic group. Table 1 compares the main characteristics of the 2 groups. No significant differences were found between these groups for any of the characteristics considered.
There was significantly (P < .0001) more postoperative drainage in the control group: Mean drain output was 410.9 mL for the control group and 155.0 mL for the antifibrinolytic group (Table 2). Patients in the antifibrinolytic group did not receive any blood transfusions, whereas 40% of patients in the control group received transfusions (P = .022). On average, the transfused patients received 0.4 unit of packed red blood cells.
Although there was no statistically significant difference in POD-1 or POD-2 Hb levels between the antifibrinolytic and control groups, the antifibrinolytic group trended higher on POD-1 (11.1 g vs 10.7 g; P = .108) and POD-2 (11.5 g vs 10.2 g; P = .117) (Table 3). Mean Hb level was 8.1 g for control patients transfused on POD-1 and 7.9 g for control patients transfused on POD-2. For control patients who were not transfused, mean Hb level was 10.7 g on POD-1 and 10.2 g on POD-2.
There were no adverse events (eg, anaphylaxis, hypersensitivity) in either group, and there was no difference in incision drainage or returns to operating room between the groups.
Discussion
In TKA, a tourniquet is used to minimize intraoperative blood loss; postoperative bleeding, however, is often extensive. Both surgery and tourniquet use are reported to enhance local fibrinolytic activity within the limb.8 The synthetic antifibrinolytic ACA reduces blood loss by clot stabilization rather than by promotion of clot formation.8
In the present study, a single intraoperative dose of IV ACA administered in primary unilateral TKA significantly reduced postoperative wound drainage and eliminated the need for postoperative allogeneic blood transfusions. In addition, patients who received ACA had higher Hb levels on POD-1 and POD-2. These results are similar to those of other clinical trials in which external blood losses were measured.4-7 The postoperative drain output differences (~250 mL) in our study are clinically relevant, as they indicate significant reductions in postoperative blood loss with the implementation of an antifibrinolytic operative protocol.
In a study by Ponnusamy and colleagues,1 blood transfusion after orthopedic surgery accounted for 10% of all packed red blood cell transfusions, but use varied widely. National TKA transfusion rates vary from 4.3% to 63.8% among surgeons and hospitals.9 This evidence calls for standardization and critical review of practices to ensure more efficient use of blood products, effectively protecting patients from unneeded complications and reducing hospital costs. Mounting evidence supporting the efficacy of ACA in reducing perioperative blood loss and lowering postoperative blood transfusion rates points toward including antifibrinolytic therapy in standard TKA protocols. In our study, 40% of control patients and no antifibrinolytic patients required a transfusion—a stark contrast.
Although our antifibrinolytic group’s postoperative Hb levels were not statistically significantly higher, their being elevated illustrates the protective effect of intraoperative use of antifibrinolytics in TKA. This elevation in Hb levels is especially valid given the similarity of the antifibrinolytic and control patients’ preoperative Hb levels (P = .871) (Table 1). Other studies have shown similar upward trends in postoperative Hb levels, many of which were statistically significant.5-8,10
Conclusion
This study showed that a single intraoperative 10-g dose of IV ACA significantly reduced perioperative blood loss and lowered blood transfusion rates in TKA. In addition, postoperative Hb levels were higher in the patients who received ACA than in patients who did not receive an antifibrinolytic. The positive effects of ACA were obtained without adverse events or complications, making use of this antifibrinolytic a relevant addition to TKA protocols.