The significant blood loss and risk for blood transfusion are important features that must be considered in TKA. Complications after allogeneic blood transfusions have been well reported in the previous literature . Several methods have been reported to reduce blood loss and blood transfusion after TKA [2–29]. However, the best method remains unknown. Either drain clamping [11–18] or tranexamic acid administration [19–29] is the simple method that we interested. The combined effect of these two methods was still unknown. We therefore aimed to study the efficacy of drain clamping alone, tranexamic acid alone and the combination of these two modalities in the control of bleeding following TKA.
Because most of the blood loss in TKA occurs during the first postoperative day (71.1 and 84% in the first 6 and 12 hour after operation, respectively) [41, 42], it seems reasonable to clamp the drain in the early postoperative period to create a tamponade effect and to control blood loss. Although various protocols for drain clamping have been reported in the literature [11–18], we have established a new interval clamping protocol for reducing blood loss in TKA. Kiely et al.  concluded that 2 hours of drain clamping has no benefit in routine TKA. Thus, a longer period of drain clamping may be required. However, hematoma and wound complications must be taken into consideration for long-period clamping protocols. To balance between creating a tamponade effect and reducing wound complications, an interval clamping protocol using a 3-hour interval pattern that routinely used in our institute was selected for this study. From the results of this study, our drain clamping technique alone could reduce more blood loss and keep higher 12-hour Hb level than the non-clamping group. Nevertheless, the use of this protocol did not affect the reduction of transfusion requirement, either amount or rate.
Fron non-pharmacological to pharmacological method, there are four routes for administrating tranexamic acid in order to reduce blood loss in TKA: oral, intramuscular, intravenous, and intra-articular . The time taken for maximum plasma levels of tranexamic acid to be reached has been reported to be 2 hours for oral, 30 minutes for intramuscular and 5–15 minutes for intravenous administration [43, 44]. Many clinical studies reported tranexamic acid reduced blood loss or transfusion requirements when given on deflation of the tourniquet with a repeated dose postoperatively [19, 20, 22–29, 45]. Tanaka et al.  concluded that the hemostatic effect was best when tranexamic acid was given once 10 minutes before surgery and once upon deflation of the tourniquet. The administration before the operation gave more hemostatic effect than administration upon deflation of the tourniquet. Pharmacokinetic studies [43, 44, 46, 47] indicated that a dose of 20 mg/kg of tranexamic acid is suitable for TKA since therapeutic levels could be maintained for approximately 8 hours after the operation, which covered the period of hyperfibrinolysis in cases of increased blood loss. Thus, we also used a dose of 20 mg/kg of intravenous tranexamic acid that divided into two parts: 10 mg/kg at 10 minutes before tourniquet inflation and another 10 mg/kg at 3 hours postoperatively. Then, an oral form of tranexamic acid was given for 5 days in order to control bleeding during rehabilitative training.
With using our tranexamic acid regimen, we found that it significantly reduced about 40% of blood loss, compared to those in control group. This result was in the same way of previous studies that reported on 30-50% of blood loss reduction [19–24, 27]. Furthermore, our protocol also showed the superior efficacy in reducing amount and rate of blood transfusion, and maintaining the Hb level, over the control group.
The hemostatic effects of the tranexamic acid alone were significantly better than the drain clamping alone with regards to the level of decreasing Hb, amount of blood transfusion and number of patients requiring blood transfusion, despite the volume of drained blood between these two methods was not significantly different. These findings confirmed that some blood might remain around the knee joint, leak through the wound, or diffuse into the soft tissue, especially when the drain was clamped [13, 48].
Importantly, this study also verified the efficacy of the administration of tranexamic acid combined with the drain clamping, which had never been studied before. Compared to the control group, the use of this combination could reduce the volume of drained blood up to 55% that significantly more than using the tranexamic acid alone (40% of reducing blood loss) or the drain clamping alone (30% of reducing blood loss). Furthermore, this combined method provided the lowest amount of transfusion unit. For the efficacy in maintaining the Hb level and reducing the rate of transfusion requirement, the use of our tranxenamic acid protocol combined with the 3-hour interval drain clamping was proved to give more benefit than using drain clamping alone. Nevertheless, it was not significantly different from using tranexamic acid alone. The superior effect of tranexamic acid over clamping of the drain might explain this phenomenon. After calculating the relative risks, the number of patients required blood transfusion in control group was 4.4-fold, in drain clamping alone was 3.0-fold and in tranexamic acid alone was 1.4-fold when compared to the combined method.
There are some limitations in this study. First, the female to male ratio was high because most patients undergoing TKA in our country are females. Female patients may have less preoperative hemoglobin than male, which may affect the rate of blood transfusion. Nevertheless, after randomization, the female-to-male ratios and preoperative hemoglobin levels were not different among the four groups. Second, we used only clinical evaluations to evaluate the thromboembolic complications that could not detect asymptomatic deep vein thrombosis and pulmonary embolism. The correlation of using tranexamic acid and venous thromboembolism remains unknown. Third, although we proposed a 5-day regimen of oral formed tranexamic acid might assist to control blood loss during rehabilitation, there were no measurement tools to assess this hypothesis. Finally, we focused only on the efficacy in controlling blood loss. This report did not include functional scoring systems or patient satisfaction.