Application of thromboelastography to evaluate the effect of different routes administration of tranexamic acid on coagulation function in total hip arthroplasty

Patients were diagnosed with osteoarthritis, and those who underwent unilateral primary cementless THA were prospectively enrolled in this trial between October 2016 and July 2018. The exclusion criteria included (1) if they had a history of hemorrhagic blood diseases; (2) pre-operative anticoagulant treatment within 7 days of the surgery; (3) allergy to TXA, renal, or hepatic impairment; (4) patients with a known of the thrombotic disorder. All the included patients underwent 6 months follow-up postoperatively.

Computerized block randomization was performed by an independent research assistant who was not involved in the study. Opaque sealed envelopes containing a number were opened after the patients arrived in the operating room. The numbers in the envelopes were created using a computer-generated randomization list. One of our researchers, who was not involved in the operation, was responsible for opening the envelopes and preparing the appropriate medication. Then, patients were allocated into three groups: (1) 2 g TXA in 50 ml normal saline topical injection of TXA into articular cavity of hip after the uncemented prosthesis was installed and joint capsule closed (topical-TXA group); (2) 20 mg/kg TXA in 100 ml normal saline delivered by intravenous injection 5 min prior to skin incision (IV-TXA group); (3) and the control group. For all the groups, the same amounts of saline solution were applied at the same time points (if not IV injection or topical administration of TXA).

All the surgeries were performed under continuous lumbar epidural anesthesia. All surgeries were performed by the same surgeon and all the operations were completed using the posterolateral hip approach. The prosthesis was a cementless acetabular cup (Trilogy IT Acetabular System, Shell with Cluster Holes Porous, Zimmer, USA) and a cementless femoral stem (VerSys Hip System, Fiber Metal Taper, Zimmer, USA). A drain was placed in all groups and clamped for 2 h. The drainage was removed 48 h after the operation. All the patients, surgeons, and outcome assessors were blinded to the randomization. All patients started passive and active function training after anesthesia resolution. An inflatable lower-extremity venous pump was applied on the first day after surgery until hospital discharge. Ten milligrams of rivaroxaban was given orally once daily for 35 days for venous thromboembolism prophylaxis.

Patients received blood transfusions based on the following criteria: (1)patients with Hb levels less than 70 g/l; (2)patients with Hb levels more than 70 g/l but with a poor mental state or other signs of distress such as pallor, polypnea, hypotension, palpitation, or dizziness.

Demographic data were collected before the operation including age, gender, height, and weight. Body mass index(BMI) is the weight(kg) divided by the square of height (m²). Hematocrit (Hct), fibrinogen (FIB), prothrombin time (PT), and activated partial thromboplastin time (APPT) were measured before and after the operation. The primary outcomes were TEG parameters, the rates of deep vein thrombosis(DVT), and pulmonary embolism (PE). Blood samples of 2 ml were extracted from all patients who met the criteria before the operation and first, fourth, and seventh days after the operation, respectively. Blood was then examined by TEG (CFMS LEPU-8800, LEPU TECHNOLOGY, China), which produced five parameters including reaction time (R value), coagulation time (K value), alpha angle (α angle), maximum amplitude (MA), and coagulation index (CI). R is the time elapsed until the first evidence of a clot. K is the time from the end of R until the clot reaches 20 mm and represents the speed of clot formation. α angle is the angle of the curve made as K is reached and offers information like that from K. The maximum amplitude (MA)is an indication of the maximum strength of the clot. A mathematical formula can be used to determine a coagulation index (CI) (or overall assessment of coagulability) that takes of these parameters into account [17].In TEG, hypercoagulability can be defined as CI > + 3. All patients underwent a routine ultrasound examination to screen for DVT on the fourth and seventh days after the operation. If the patients were suspected of pulmonary embolism(PE) based on clinic signs such as acute dyspnea or unexplained hypoxemia,a CT pulmonary angiography was performed to confirm the diagnosis. Signs of symptomatic DVT and pulmonary embolism (PE) were continuously monitored for 6 months by follow-up examinations.

The secondary outcomes were total volume of drainage, intraoperative blood loss, total blood loss, and other perioperative complications (including wound infection, wound hematoma, and dislocation). The staff who evaluated the results was blinded to the allocation. The blood volume of each patient was calculated according to the formula of Nadler et al. [18]. Total blood loss was calculated according to the formula of Gross [19].

A total of 256 patients were screened for eligibility from October 2016 to July 2018. Thirty-four patients were excluded on the basis of our exclusion criteria, and 15 patients declined to participate. Two hundred seven patients were analyzed at last. Seventy-two patients were randomized to topical-TXA group, 68 patients were randomized to IV-TXA group, and 67 patients were randomized to the control group. The duration of postoperative follow-up in this study was 6 months. The demographic and pre-and postoperative characteristics of the patients are shown in Table 1. There were no statistically significant differences among the groups. This included no differences in baseline age, gender, body mass index, preoperative laboratory indices, or postoperative complications (deep vein thrombosis, pulmonary embolism, wound infection, and wound hematoma or dislocation).

The mean total blood loss in the topical-TXA, IV-TXA, and control groups were 832.7 ± 279.8, 834.8 ± 322.9, and 1093.3 ± 379.7 ml, respectively (Table 2 and Fig. 1). The topical-TXA group and IV-TXA group had significantly lower amounts of total blood loss than the control group (p < 0.05). There were no significant differences between topical-TXA and IV-TXA groups in total blood loss (p value = 0.970). The postoperative total volume of drainage was significantly lower in the topical-TXA group than in the other two groups (p value < 0.05 for both) (Table 2). The mean amount of intraoperative blood loss was 166.7 ± 42.5 ml in the topical-TXA group, 168.0 ± 47.4 ml in the IV-TXA group and 176.7 ± 46.2 ml in the control group, with no significant intergroup differences. Six patients in the topical-TXA group, 7 patients in the IV-TXA group, and 18 patients in the control group required transfusions. These differences were statistically significant (p value = 0.004) (Table 2 and Fig. 2).

There were no significant differences in R, K, α angle, MA, or CI among groups preoperatively (Table 3,Fig. 3, and Fig. 4). K and R have reached a nadir from preoperative levels to the fourth day postoperatively and then began to increase.

α angle and CI peaked from preoperative levels to the fourth day postoperatively and then began to decline. IV-TXA group enhanced coagulation peak values (P < 0.05), but it did not obviously change the coagulation tendency in general. MA increased steadily from preoperative levels to the seventh day postoperatively.IV-TXA significantly (p < 0.05) promoted coagulation levels in the early postoperative period (Table 3, Fig. 3, and Fig. 4). Almost no significant differences were observed between topical-TXA and control groups (except for the R on the first day postoperatively).