Background: The efficacy of tranexamic (TXA) in reducing the blood loss and requirement of transfusion in bilateral TKAs has been described previously through either intravenous (IV) alone, intra-articular (IA) alone or a combination of these. However, it is still unclear whether combined TXA administration offer any additional benefits over IA use alone in bilateral TKA.
 Purposes: (1) Whether the combined IV and IA administration of TXA further reduces the blood loss and requirement of blood transfusion than IA use alone, 2) Whether the incidence of adverse thromboembolic events is similar with both these routes of administration in bilateral TKA.
Methods: A total of 630 patients undergoing bilateral TKA between April 2015 and May 2017 were randomized to four groups: simultaneous IA only (n= 157), simultaneous combined (n= 153), staged IA only (n= 156) and staged combined (n= 155). The primary outcome variables include total blood loss and requirement of blood transfusion, whereas, the secondary outcome variables were incidence of anemia, thromboembolic events, wound complications and periprosthetic joint infection. 
Results: The total blood loss with IA alone TXA administration in simultaneous (1062.9 ± 303.4 ml vs. 1004 ± 287.4 ml, p=0.082) and staged (908.9 ± 282.6 ml vs. 844.8 ± 277.7 ml, p=0.046) bilateral TKA patients was similar to the combined regimen in terms of clinically significant difference. The requirement of blood transfusion was also similar with both the routes of TXA administration. Furthermore, incidence of symptomatic thromboembolic events, wound complications and periprosthetic joint infection were none or extremely low without any difference between groups. 
Conclusion: The combined IV and IA administration of TXA doesn’t offer additional benefit in reduction of total blood loss or requirement of blood transfusion than IA route only in both simultaneous and staged bilateral TKA. Furthermore, both these regimens are safe in terms thromboembolic complications after TKA.
Level of evidence:  Level I

Treatment

A total of 630 patients undergoing bilateral TKA between April 2015 and May 2017 were randomized to four groups: simultaneous IA only (n= 157), simultaneous combined (n= 153), staged IA only (n= 156) and staged combined (n= 155).

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Target Number of Participant

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Arm Description

In addition a slow IV administration of TXA 10 mg/kg with 100ml normal saline was given 10 min before tourniquet inflation and the same dose was repeated 3 hours after the last dose.

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Target Number of Participant

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patients are given 2 g of TXA in 30 ml of normal saline injection into the joint after the closure of the capsule, retinaculum and quadriceps tendon but prior to the subcutaneous closure.

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Description

patients with a diagnosis of primary osteoarthritis (OA) scheduled for bilateral simultaneous or staged primary TKA

exclusion criteria were patients with a diagnosis other than primary OA, severe ischemic heart disease, coagulation disorders, pre-existing hepatic or renal dysfunction, a history of thromboembolic disease and those on anticoagulation therapy

total blood loss and blood transfusion rate after surgery

5 days

blood loss via the drain, postoperative hemoglobin drop, the proportion of patients with hemoglobin lower than 7.0, 8.0, and 9.0 g/dL, and the incidence of deep vein thrombosis (DVT), pulmonary embolism (PE) and wound complications including deep periprosthetic joint infection

1 year

The total blood loss with IA alone TXA administration in simultaneous (1062.9 ± 303.4 ml vs. 1004 ± 287.4 ml, p=0.082) and staged (908.9 ± 282.6 ml vs. 844.8 ± 277.7 ml, p=0.046) bilateral TKA patients was similar to the combined regimen in terms of clinically significant difference. The requirement of blood transfusion was also similar with both the routes of TXA administration. Furthermore, incidence of symptomatic thromboembolic events, wound complications and periprosthetic joint infection were none or extremely low without any difference between groups.