1.1 General information
The 8 patients included in this study were male, 25-38 years of age (mean 31.6 years). There were 6 cases of hemophilia A and 2 cases of hemophilia B. They all had a history of hematology diagnosis and treatment and coagulation factor infusion. All patients were routinely tested for 4 coagulation factors, factor VIII and IX inhibitors and 10 immunizations (hepatitis, syphilis and HIV antibody tests were negative). The average activity of factor VIII in the 6 patients with type A hemophilia was 2.1 (± 2.3)%, and that of factor IX in the 2 patients with type B hemophilia was 1.5 (± 1.4)%. Preoperative factor VIII inhibitor test of all patients with type A hemophilia, and factor IX inhibitor test of all patients with type B hemophilia were zero. All patients had different degrees of ipsilateral knee and hip pain and decreased range of motion, as well as different degrees of joint deformity, which seriously affected their quality of life. Conservative treatment was ineffective. Six patients (6 knees) had genu varus deformity (10-25 degrees), and two patients (2 knees) had genu valgus deformity (12-20 degrees).
Inclusion criteria: ① all patients had hemophilic ipsilateral hip and knee arthritis. ② Patients with hemophilia whose hip joint function was clearly impaired and whose knee joint was classified as stage IV or V according to Arnold ⁃ Hilgartner imaging classification and had no factor VIII or factor IX inhibitor before operation. ③ All patients received informed consent to about the treatment plan and their participation was approved by the hospital ethics committee.
Exclusion criteria: ① joint infection; ② hip and knee arthroplasty was performed on the other side or at the same time; ③ osteoarthritis, rheumatoid arthritis, etc.; ④ the detection of factor VIII inhibitor in type A hemophilia was positive, and the detection of factor IX inhibitor in type B hemophilia was positive.
1.2 Perioperative coagulation factor arthroplasty therapy
In the perioperative period of THA and TKA, the monitoring of coagulation factor arthroplasty therapy is mainly performed by measuring activated partial thromboplastin time (aPTT), the activity and concentration of coagulation factors, and the presence of coagulation factor inhibitors . After admission, patient is asked to consult with hematology department and schedule tests. For patients with type A hemophilia: the keyuqi recombinant factor VIII preparation (Bayer AG, Leverkusen, Germany) was used at the supplementary dose of (U) = body weight (kg) × (required factor Ⅷ: C level% -- actual factor Ⅷ: C level%) / 2. The half-life of factor VIII is 8-12 h, so half of the first dose should be supplemented every 8-12 h to maintain the level of factor VIII. Blood coagulation factor Ⅷ was infused at a dose of 25 IU / kg every 8-12 h 1-3 days after operation to keep its activity at 60- 80%. Factor Ⅷ was infused every 8-12 h at a dose of 20 IU / kg 4-7 days after operation, and its activity was maintained at 50 - 60%. At 1-2 weeks after operation, factor Ⅷ was infused intravenously at the dose of 20 IU / kg to maintain the plasma factor Ⅷ: C level of 30 - 50%. Subsequently, according to the bleeding situation and factor Ⅷ: C level, the amount of coagulation factor supplement was reduced until discharge.
For patients with type B hemophilia B: The Pfizer's bFGF IX preparation (Pfizer Inc., New York, NY, USA) was used at the supplementary dose (U) = body weight (kg) ×(required factor IX: C level% -- actual factor IX: C level%). The half-life of factor IX is 12-24 h, so it is given 1-2 times a day. Blood coagulation factor IX was infused at a dose of 25 IU / kg every 12-24 h 1-3 days after operation to keep its activity at 60- 80%. Factor IX was infused every 12-24 h at a dose of 20 IU / kg 4-7 days after operation, and its activity was maintained at 50 - 60%. At 1-2 weeks after operation, factor IX was infused intravenously at the dose of 20 IU / kg to maintain the plasma factor IX: C level of 30 - 50%. Subsequently, according to the bleeding situation and factor IX: C level, the amount of coagulation factor supplement was reduced until discharge.
1.3 Operation method
In this study, after general anesthesia, all patients were first operated on the hip and then the knee.
For THA: ① the patient was positioned in the healthy lateral position, and the surgical field was routinely disinfected and covered with towel. ② The posterolateral incision of the affected hip, about 10-12 cm long, was made to cut the skin and subcutaneous adipose tissue, and the fascia lata surface was properly stripped to form a "moving window" (also conducive to close the incision tightly). The fascia lata (gluteal fascia) was cut along the posterior margin of the trochanter with an electric knife, and then the gluteus maximus fiber bundle was separated using the electric knife to expose the posterior outer fat layer of the joint capsule. After confirming the posterior edge of the gluteus medius and gluteus minimus, the affected limb was slightly rotated, the insertion point of the piriformis was peeled off along the piriformis fossa at the posterior edge of the trochanter, a "U" shape incision was made in the joint capsule to reach the lateral apex of the acetabulum, and expose the femoral neck and head. ③ The affected limb was straightened in the neutral position, and marked with an electric knife at the midpoint of the greater trochanter. A single suture was placed and fixed on the skin of the iliac crest along the long axis of the limb. The operator pulled the suture to the marked position with appropriate tension, cut and retained it, so as to evaluate whether the limb length was balanced after the prosthesis implantation. ④ The hip dislocation was caused by extreme internal rotation and adduction of the femur. The femoral neck osteotomy was protected by an acetabular retractor with 90 ° internal rotation of the affected limb, 45 ° hip flexion and 90 ° knee flexion. According to the preoperative X-ray measurement results, the femoral neck osteotomy was performed with a femoral distance of 1-1.5 cm reserved, and the femoral head was removed with a head extractor. ⑤ The acetabulum was exposed step by step and the labrum was cleaned by using the acetabular retractor of minimally invasive surgery (MIS). The thickened joint capsule, osteophyte and round ligament residue were removed until the bone acetabulum edge was completely exposed. First, the acetabulum file with the size of the femoral head was selected to grind the acetabulum to the bottom of the horseshoe fossa of the acetabulum, and then the grinding file was in turn increased to completely remove the cartilage surface around the acetabulum, resulting in punctate bleeding, especially after the weight-bearing area at the top of the acetabulum. Then, the non-cemented acetabulum was placed under the protection of packaging film (to prevent soft tissue embedding). After confirming the proper position of the prosthesis, the cup was hammered and pressed. The hook needle was used to determine whether the interface between the cup and the bone was tightly pressed through the screw hole, and whether there was soft tissue embedded in the edge of the cup. After the press fit was satisfactory, titanium screws were selected according to the patient's age and bone condition. Some patients with excellent bone and ideal press fit were fixed without screws. For the patients with obvious limitation of hip joint movement before operation, it was necessary to use a MIS hook for a reasonable exposure, making full use of the "mobile window" to gradually release the peri hip, especially the anterior and medial adhesion scar tissue and joint capsule, and gradually increase the range of motion. If there was bone defect, autogenous femoral head or allogeneic cancellous bone graft was used, and acetabular prosthesis was implanted after the preparation of the bone acetabulum was satisfactory. Then, the ceramic liner was implanted along the direction of the prosthesis to avoid soft tissue embedding. ⑥ The knee was bent and the femur was rotated 90 ° so that the leg was perpendicular to the operating table. The proximal femur was lifted with a "Jaw" retractor, and the acetabular retractor was placed in the greater and lesser trochanter of the femur. After determining the anteversion angle of 15-20 °, the box osteotome slotter was used to slot and ream the pulp manually along the direction of the femoral anterior arch (, and the proximal femur was ground with a cone-shaped grinding drill. After reaming to the appropriate model in turn, the femoral stem test mold and test mold head were placed and the hip joint was reset. The range of motion and stability of the hip joint were tested (hip flexion > 100 °, hip extension > 10 ° and internal rotation > 60 °), and the prosthesis was placed after the length of both lower limbs was balanced (the distance between the end of the skin suture and the greater trochanter mark was increased, compared with the preoperative X-ray template measurement value and the comprehensive evaluation of solid measurement). ⑦ A large amount of normal saline was used to thoroughly wash and stop bleeding. After checking the instruments and gauze, a normal pressure drainage tube (open after clamping for 6 h) was placed and sutured layer by layer and bandaged.
Then, after the patient was placed in the supine position, the tourniquet was tied at the root of the affected thigh, and the affected limb was routinely disinfected and covered. The anterior patellar incision made in the affected knee joint was about 12 cm in length. The skin, subcutaneous tissue and fascia were cut in turn, and electrocoagulation was used to stop bleeding. The tibial plateau and femoral condyle of the knee joint were exposed, the patella was turned over to the outside, and the fibrous tissue of the patella was removed with an electric knife. Due to the severe deformity of the femoral condyle and tibial plateau, complete loss of joint space, severe congestion and edema of the synovium, the force line of the lower limb was preliminarily determined using a vertical line rod. The tibial plateau is surrounded by a large number of proliferative synovial tissue and osteophytes. Therefore, the medial and lateral sides of the tibial plateau were separately released. The osteophytes on the femoral condyle and tibial plateau were removed with bone biting forceps to fully expose the tibial plateau. After checking that the knee joint flexion was 90 degrees, a hole in front of the attachment point of the posterior cruciate ligament of the distal femoral intercondylar fossa was drilled, the pulp content was drained, and the anteroposterior femoral dimension measurement guide into the hole.
Methods: the adhesive tissue around the medial and lateral sides of the femoral condyle is released, the hyperplastic osteophyte is removed, proximal tibial osteotomy is performed, the medial and lateral center of the tibia are located, the alignment system of the extramedullary osteotomy guide is installed and safely fixed, the osteotomy plate and extramedullary locator are placed on the tibia, the rod is paralleled with the medial tibial muscle, and the angle of the guide is adjusted, so that the body of the guide is parallel to the anterior tibial shaft. The position of the cutting plate was measured with a tibial osteotomy thickness gauge. The osteotomy plate was nailed to the tibia, and the tibial plateau was cut along the osteotomy device with a pendulum saw. The osteotomy was performed at the back of the femur, the bone defect of the lateral tibia was filled with the osteotomy bone graft, and the suitable tibial pad was placed. The knee joint was straightened to be able to see good flexion and extension. Analgesic drugs (morphine hydrochloride injection 8 mg, morphine hydrochloride injection 8 mg, morphine hydrochloride injection 4 mg, morphine hydrochloride injection 8 mg) were injected into the posterior capsule, quadriceps femoris tendon and around the incision, respectively. Ropivacaine 40 mg, Diprospan 1 mg, mixed with normal saline (60 ml in total) were also given. The femoral and tibial bone cement prostheses were correspondingly installed. A large amount of normal saline was used to thoroughly wash and stop bleeding. After checking the instruments and gauze, a normal pressure drainage tube (open after clamping for 6 h) was placed and sutured layer by layer, and pressure bandaged.
All patients were given tranexamic acid before operation. Tranexamic acid is an antifibrinolytic drug that inhibits the activation of plasminogen. As an antifibrinolytic drug, tranexamic acid can reduce blood loss and transfusion demand in patients with hemophilia. It has good safety and effectiveness, and has no thromboembolic events or other adverse reactions. Cefazolin sodium powder (1.0 g) injection (Shandong Lukang Pharmaceutical Co., Ltd., Jining City, China) was given by intravenous drip 0.5 h before operation.
1.4 Postoperative management
After the operation, according to the supplementary dose requirements for calculating the coagulation factor activity, the recombinant human coagulation factor VIII was infused into hemophilia type A patients, and recombinant human coagulation factor IX powder injection was infused into hemophilia type B patients to maintain the activity of plasma factor VIII. The wound was constantly iced, and the postoperative analgesia pump was generally used for 48 h. The drainage tube was removed after the drainage volume was less than 50 ml the previous day. Foot pump exercise and pressure therapy were used to prevent postoperative deep vein thrombosis (DVT) without anticoagulation. The wound dressings were changed every day for the first 3 days after operation, and then every two days until the stitches were removed 2 weeks after operation. After the operation, the patient returned to the ward and placed in the supine position. The affected limb was abducted in the neutral position. A trapezoidal pillow was placed between the legs. The patient wore t-shoes in the affected foot to prevent external rotation. The affected limb was raised. A soft pillow was placed at the middle and lower 1 / 3 of the leg to make the knee joint fixed and straight. One or two days after the operation, we strengthened the isometric contraction of the quadriceps femoris, ankle flexion and extension, heel sliding, passive knee extension and elevation, and walking aids. Three or four days after the operation, knee extension and flexion exercises were performed along the edge of the bed. After discharge, the patients continued to perform isometric contraction of the quadriceps femoris and active knee flexion and extension exercises. The routine blood tests, including four coagulation items and the concentration of coagulation factors, were monitored, and the input of coagulation factors was timely adjusted. Tranexamic acid (1 g) twice a day was given within 1 week after operation. The patients were followed up at 6 weeks, 3 months, 6 months, 1 year and every year after the surgery. The clinical function and imaging were evaluated at each visit.
1.5 Postoperative observation index
The intraoperative blood loss, the decreasing trend of postoperative hemoglobin and the postoperative drainage of knee joint were examined. The incision was observed early after operation. The anteroposterior and lateral X-ray images of the knee joint at 1.5, 3, 6 and 12 months after operation were used to evaluate the loosening of the prosthesis. The Harris score, American hospital for special surgery (HSS) knee score and American knee society score (KSS) were recorded and compared before and 0.3-1 year after operation. During the follow-up, the X-ray images were examined to detect the signs of implant loosening. If the implant migration or dissolution > 2 mm was detected in the interface, the implant was designated as loosening.
1.6 Data statistics
The SPSS 25.0 software (IBM Corp., Armonk, NY, USA) was used to analyze the data. The measurement data were expressed as the mean ± standard deviation(±s). A paired t-test was used for continuous variables and normal distribution data. A nonparametric test was used to compare continuous variables with non-normal distribution and the χ2 test was used to compare categorical variables. P < 0.05 for the difference was considered statistically significant.