Introduction
Hemophilic arthropathy occurs as a result of repeated intra-articular bleeding with recurrent inflammation and subsequent articular destruction.[ 1 ] Total knee arthroplasty (TKA) is effective in reducing severe joint pain and reversing functional disability in end-stage hemophilic arthropathy of the knee.[ 2 ] However, patients with hemophilia (PWH) present with extensive arthrofibrosis, severe deformity, anatomical distortion with epiphyseal overgrowth, widening of the femoral intercondylar notch, and poor bone quality.[ 3 ] TKA for PWH is technically demanding, with a high postoperative complication rate;[ 2 ] common complications include periprosthetic joint infection (PJI) and component loosening.[ 4,5 ]
Several authors have reported that the mid-term to long-term outcomes of TKA for PWH achieved modest functional improvement after an average of 4–18 years of follow-up.[ 4–7 ] However, little has been reported on the long-term outcomes in China. To our knowledge, in literature, the patella is regularly resurfaced during TKA procedure, due to the inflammatory nature of hemophilic arthropathy .[ 5,7 ] However, since the anatomical distortion of the patella and osteoporosis were noted in PWH, and the hemophilic patella was relatively thinner than that observed in regular patella in our country, we performed a "patelloplasty ", which is a non-resurfacing technique, during primary TKA for PWH. Short-term follow-up of TKA with patelloplasty has been reported in a previous study.[ 8 ]
This study aimed to evaluate the outcomes of TKA with the patelloplasty technique for PWH using contemporary prostheses for over ten years, as well as its complications, patient satisfaction , and long-term survivorship.
Methods
Patients and ethical approval Between 2003 and 2020, 154 primary TKAs were performed by a single surgeon in patients with end-stage hemophilic arthropathy at Peking Union Medical College Hospital (PUMCH). The follow-up period ended in December 2020. The patients who accepted simultaneous patelloplasty and with a follow-up period of >10 years were included and were retrospectively reviewed. This study was approved by the institutional review board of PUMCH (s-k737) and written informed consent was obtained from all the participants for their clinical records to be used in this study.
A total of 38 primary TKAs were consecutively performed in 27 patients at PUMCH between 2003 and 2010 and were included in this study. One patient was lost to follow-up, while 26 patients with 36 TKAs were successfully followed up. All medical records were retrospectively reviewed. The average level of serum coagulation factor VIII (FVIII) upon initial admission was 3.4% (range: 0.1–6.2%). The mean age of the patients at the time of surgery was 31.4 ± 11.4 (18.0–54.0) years [Table 1 ]. The mean follow-up period was 12.4 ± 2.1 (10.2–17.3) years. Neither human immunodeficiency virus (HIV) infection nor coagulation factor inhibitors were detected in our participants. Ten patients underwent bilateral TKA.
Table 1 -
Demographic information, baseline characteristics and surgical procedure information of the hemophilia patients who underwent primary TKA in this study.
Items
Values
Number of patients
26
Number of knees
36
Age (years)
31.4 ± 11.4
Diagnosis
Type A
25 (96)
Type B
1 (4)
Body weight (kg)
66.9 ± 12.9
BMI (kg/m2 )
24.2 ± 3.6
HBV/HCV (positive/negative)
13/13
Factor inhibitor
None
Baseline coagulation factor level
<1%
17 (65)
1–5%
8 (31)
>5%
1 (4)
Surgical strategy
Bilateral
10 (38)
Unilateral
16 (62)
Surgical approach
MPPA
34 (94)
V–Y quadricepsplasty
2 (6)
Implant
PS (Genesis-II/NexGen)*
34 (29/5)
CCK
2
Patellar thickness (mm)
17.8 ± 1.6
Distal femur cut (mm)
12.1 ± 3.3
Proximal tibia cut (mm)
9.9 ± 1.9
Follow-up (years)
12.4 ± 2.1 (range: 10–17)
Data are expressed as n , n (%), or mean ± standard deviation. Genesis-II: Smith&Nephew, Memphis, TN, USA; Nexgen: Zimmer, Warsaw, IN, USA. BMI: Body mass index; CCK: Constrained condylar knee; HBV: Hepatitis B virus; HCV: Hepatitis C virus; MPPA: Medial parapatellar approach; PS: Posterior stabilized TKA; TKA: Total knee arthroplasty ; V-Y: V-Y plasty.
Surgical technique All procedures were performed using standard surgical techniques under general anesthesia. In all cases, a tourniquet was used, and a standard midline incision was made, allowing medial parapatellar arthrotomy to be performed. A technique of quadricepts snip was performed for extra surgical field exposure in two PWH cases. Extensive synovium removal was performed. The mean preoperative flexion contracture was 18.1°. An additional distal femur cut was used to better correct the flexion contracture. The average distal femur cut was 12.1 mm. Posterior stabilization (PS) was applied in 34 knees [Table 1 ]. For two knees with valgus deformity, a constrained condylar knee (CCK) prosthesis was used to balance the knee. Hemostasis was performed regularly after deflating the tourniquet. Active knee joint exercises were initiated on postoperative day 1 (POD1), and articular drainage was removed on either POD2 or POD3. Anticoagulation was not conducted in all patients, but mechanical prophylaxis for deep vein thrombosis (DVT), such as a booster pump, was used.
The average thickness of the patella in PWH was 17.8 ± 1.6 mm [Table 1 ]. All patellae were treated by patelloplasty , consisting of articular surface smoothing, osteophyte removal, patellar remodeling with an oscillating saw, and patellar rim denervation [Figure 1 ]. The "no thumb test" was performed to assess the patellofemoral tracking after implant insertion in all cases. The lateral retinaculum was released when necessary.
Figure 1: Intraoperative pictures of patelloplasty during TKA for PWH. (A) Picture of patellar before patelloplasty showed the anatomical distortion, cartilage erosion and hemosiderin deposition in the synovium. (B) Picture of patellar after patelloplasty , which consists of articular surface smoothing, osteophyte removal, and patellar rim denervation. PWH: Patient with hemophilia; TKA: Total knee arthroplasty .
Hematological care The regimen of clotting factor replacement therapy was decided with reference to the guidelines of the World Federation of Hemophilia (WFH).[ 9 ] Plasma-derived FVIII or recombinant FVIII was used for hemophilia type A, and plasma-derived prothrombin complex concentrates (PCC) were used for hemophilia type B, and PCC or recombinant factor VIIa (rFVIIa) was used if a patient tested positive for serum FVIII inhibitors. All factors were administered via intermittent bolus injections. Coagulation factor therapy was maintained until the stitches were removed and during rehabilitation. Sixteen patients received prophylactic coagulation factor injections, and ten patients received on-demand factor treatment after the index operation.
Clinical evaluation The Hospital for Special Surgery (HSS) Knee Score Questionnaire was used to evaluate pain and function of the prosthetic knee before operation and at the last follow-up. Pain scores, both at rest and during movement, were evaluated using a visual analog scale (VAS). The patellar score was evaluated according to Fellar's system.[ 10 ] Flexion contracture, maximum flexion, and range of motion (ROM) were measured using a long-armed goniometer. Patient satisfaction and annual bleeding events in the operated knees were recorded. Patient satisfaction was rated according to four categories: very satisfied, satisfied, neutral, and dissatisfied. The symptoms of anterior knee pain (AKP), instability when climbing stairs, and cause of revision were recorded at the last follow-up. The patients underwent further evaluations at the outpatient clinic.
Radiographs were obtained immediately after the operation, and weight-bearing radiographs in the anteroposterior (AP), laterolateral (LL), and skyline views were evaluated at the final follow-up [Figure 2 ]. The mechanical axis (MA) was defined as the angle between the femoral and tibial mechanical axes. Prosthetic loosening was defined as a progressive radiolucent line >2 mm wide around the knee on any radiograph, visible fracture of the cement around the components, or any changes in the component positions, such as subsidence.[ 11 ]
Figure 2: Radiographs of a 43-year-old man with severe hemophilic arthropathy of bilateral knee who underwent one-stage bilateral TKA. (A) Preoperative AP radiography. (B) Preoperative lateral radiography of the left knee. (C) Preoperative lateral radiography of the right knee. (D) Preoperative skyline radiography. Postoperative AP (E), lateral of left knee (F), lateral of right knee (G), and skyline (H) radiographs made 14 years after primary TKA surgery. AP: Anteroposterior; TKA: Total knee arthroplasty .
Statistical analysis Continuous variables are summarized as mean ± standard deviation, and categorical variables as counts and proportions. For continuous variables, the two-tailed unpaired t -test was used to compare differences; for categorical variables, chi-squared analysis was used. For non-normal distribution data, Mann–Whitney U test was used. The level of statistical significance was set at P <0.05. The Kaplan–Meier method was used for survival analysis. Failure was defined as reoperation of the implant for any reason. All statistical analyses were performed using SPSS 15.0 (SPSS Inc., Chicago, IL, USA).
Results
Clinical outcomes The mean HSS knee score increased from 45.8 before operation to 85.9 [Table 2 ] during the follow-up period. ROM increased from 60.6° before operation to 84.8° at the final follow-up, while flexion contracture decreased from 18.1° to 4.2° at the final follow-up. There was a statistically significant improvement in the VAS score, both at rest and during motion. The annual bleeding events in the operated knee were 2.7 times at the last follow-up. All patients required less coagulation factor treatment for the operated knee than that before surgery. There was no statistically significant difference in the clinical outcomes between unilateral TKA and simultaneous bilateral TKA at the last follow-up, except for ROM [Table 3 ]. The unilateral group had a higher average ROM (90.9°) than the bilateral group (83.8°; P = 0.02).
Table 2 -
Summary of clinical and radiological results of TKA for PWH before operation and at the last follow-up.
Items
Preoperation
Postoperation (%)
t value
P- value
Case number
36
36
–
–
HSS score
45.8 ± 15.9
85.9 ± 13.6
14.24
<0.01
VAS at rest
3.8 ± 1.3
0.6 ± 0.6
–13.84
<0.01
VAS at movement
7.2 ± 1.5
2.7 ± 1.5
–13.25
<0.01
ROM (°)
60.6 ± 24.1
84.8 ± 11.8
5.41
<0.01
Flexion contracture (°)
18.1 ± 11.0
4.2 ± 3.6
–8.14
<0.01
Patellar score
7.8 ± 4.1
24.9 ± 3.1
20.76
<0.01
Anterior knee pain
N/A
7 (19)
–
–
Annual bleeding event (time/years)
N/A
2.7 ± 1.1
–
–
Satisfaction –
–
Very satisfied
10 (28)
Satisfied
25 (69)
Neutral
1 (3)
Dissatisfied
0 (0)
Mechanical axis (°)*
–0.2 ± 9.9
0.9 ± 2.7
6.13
<0.01
Varus knees (°)†
7.1 ± 6.1
2.2 ± 2.4
3.55
<0.01
Valgus knees (°)‡
–8.1 ± 6.9
–0.2 ± 2.5
5.24
<0.01
Data are expressed as n , n (%), or mean ± standard deviation. * n = 36, minus represents valgus; positive number represents varus; † n = 20; ‡ n = 16. AKP: Anterior knee pain; HSS: Hospital of Special Surgery; N/A: Not available; PWH: Patient with hemophilia; ROM: Range of motion; TKA: Total knee arthroplasty ; VAS: Visual analog scale; –: Not available.
Table 3 -
Comparison of clinical results of unilateral and simultaneous bilateral TKA for PWH at the last follow-up.
Items
Unilateral
Bilateral
t value
P- value
Number of patients/knees
16/16
10/20
–
–
Follow-up (years)
13.2 ± 2.2
12.2 ± 1.7
1.43
0.16
HSS score
86.6 ± 14.0
85.3 ± 12.7
0.38
0.70
VAS at rest
0.8 ± 0.5
2.6 ± 1.1
0.29
0.78
VAS at movement
3.0 ± 1.2
4.8 ± 2.0
0.19
0.84
ROM (°)
90.9 ± 13.8
83.8 ± 7.3
2.47
0.02
Flexion contracture (°)*
0 (5)
0 (5)
-0.475†
0.64
Patellar score
24.9 ± 3.6
25.0 ± 2.9
0.43
0.67
Anterior knee pain
3 (19)
4 (20)
–
–
Satisfaction 0.93‡
0.63
Very satisfied
5 (31)
5 (25)
Satisfied
11 (69)
14 (70)
Neutral
0 (0)
1 (5)
Dissatisfied
0 (0)
0 (0)
Data are expressed as n , n (%), or mean ± standard deviation. * Non-normal distribution data are expressed as median (interquartile range). † Z value for Mann–Whitney U test. ‡ χ 2 value. AKP: Anterior knee pain; HSS: Hospital of Special Surgery; PWH: Patient with hemophilia; ROM: Range of motion; TKA: Total knee arthroplasty ; VAS: Visual analog scale; –: Not available.
The patellar score of all patients increased from 7.8 before operation to 24.9 at last follow-up [Table 2 ]. None of the patients were diagnosed with patellar erosion or fracture. Mild AKP while climbing the stairs was reported in seven knees (19%), and a patellar crepitus in six knees (17%). However, all patellar-related symptoms were stable.
The vast majority of patients (97%) was satisfied with the operation [Tables 2 and 3 ], 10 of whom were "very satisfied". Only one patient who underwent revision with skin flap repair reported a neutral satisfaction .
Complication and revision surgery As for revision surgeries, one patient was diagnosed with infection one-and-a-half years after primary TKA and underwent one-stage revision surgery. Overall, four knees in two patients underwent one-stage revision surgery for aseptic loosening at averagely 11.3 years after the primary TKA (range: 9 to 13 years). For aseptic loosening cases, revision with CCK was used for three cases, and one case was revised with a hinge. The average preoperation (Pre-OP) flexion contracture of the four cases was 21.3° (range: 20–25°). The mean Pre-OP ROM was 40.3° (range: 25–56°). There were statistically significant differences in Pre-OP flexion contracture (21.2° vs 10.7°, P =0.029) and ROM (40.3° vs. 67.9°, P =0.037) between the four aseptic loosening cases and the rest of the hemophilic knees in our study. Revision with CCK for flexion contracture and stiffness was carried out for two knees in the 14th postoperative year. The revision rates in the unilateral and bilateral groups were 6% (1/16) and 30% (6/20), respectively, which showed a statistically significant difference between them (P <0.001). The 10-year prosthesis survival rate was 85.8% in the present study, and the 15-year survival rate was 75.7% [Figure 3 ]. A positive factor VIII inhibitor was developed in one patient on POD7 and was treated with PCC. No similar scenarios were observed in the other patients during follow-up.
Figure 3: Kaplan–Meier survival analysis of TKA for PWH with revision of the implants for any reason as the endpoint. PWH: Patient with hemophilia; TKA: Total knee arthroplasty .
Radiographic outcome The average MA was 7.1° of varus before operation and 2.2° of varus after operation; for those with valgus deformity, the MA was -8.1° of valgus and -0.2° of valgus pre- and postoperatively [Table 2 ]. Except for cases with aseptic loosening and infection, thin, incomplete, and non-progressive radiolucent lines were noted around seven (23%, 7/31) tibial components and around one (3%, 1/31) femoral component [Figure 2 ] and were thought to have no clinical significance.[ 7 ]
Discussion
TKA is an effective treatment for pain relief, re-alignment, bleeding control, and functional recovery in end-stage hemophilic arthropathy . However, the results of TKA for PWH are expected to be inferior to those without bleeding disorders.[ 12 ] Goddard et al [ 13 ] retrospectively reviewed 60 TKAs performed for PWH. After a mean follow-up of 9.2 years, the average ROM was 79°. A recent meta-analysis evaluated the outcomes of TKA in PWH.[ 2 ] Ten studies comprising 336 cases with a mean follow-up duration of 6.3 years were included. The revision rate was 10.5% at follow-up. They found statistically significant clinical and functional improvements as well as improved ROM, with an average of 9.72° improvement in flexion contractures and an average increase of 15.69° in flexion ROM compared with the presurgical values, with an average maximum flexion of 82.6°. The knee scores also showed statistically significant improvements. The reason for the less clinical improvement observed in hemophilic knees than in uncomplicated knees may be related to marked muscular atrophy, fibrosis, and accompanied knee flexion deformity due to numerous spontaneous intra-articular hemorrhages prior to the operation.[ 14 ]
Although the patients' mechanical function was not as favorable as that of those without hemophilia, PWH reported low pain scores and high satisfaction rates with respect to pain and functional outcomes.[ 7,15,16 ] Wang et al [ 12 ] further reported the outcomes of TKA in 28 PWH patients with a mean follow-up of 10.7 years, concluding that arthroplasty was effective in reducing pain and improving patient satisfaction , despite high complication rates and modest functional outcomes.
The long-term outcomes of TKA for PWH reported in the literature are summarized in Table 4 . Our study reported one of the longest follow-up outcomes of studies in the literature. Our findings are similar to those reported in the literature. Although the HSS score, ROM, flexion contracture, and patellar score were lower in PWH than that in our previously reported results of patients with osteoarthritis (OA) after TKA, patients have relatively high satisfaction rate.[ 17,18 ] In the present study, there was significantly less pain for PWH after the TKA procedure compared with preoperation, and the overall satisfaction rate was 97% for PWH. Satisfaction was mostly due to the decreased pain subset, improved flexion contracture, and reduced activity requirements.[ 6 ] Furthermore, according to this study, patients experienced a lower incidence of annual bleeding in the operated knee after TKA, which is clinically significant in PWH.
Table 4 -
Summary of the
long-term outcome , complication, and survivorship of TKA for PWH in the literature.
Author (publication year)
Case number (initial/follow-up)
Age (years)
Patellar strategy (resurfacing/
non-resurfacing)
Follow-up
(years)
Clinical outcome
Complication
Survivorship
Goddardet al
[13 ] (2010)
70/60
43 (25–70)
N/A
9.2 (2–23)
ROM increased from preoperative 68° to 79° at follow-up. HSS score was 82 at follow-up.
Seven knees experienced complication. One had deep infection. Six were removed for aseptic loosening.
The 5- and 10-year survival rates of those with infection and aseptic loosening were 98% and 89%, respectively.
Zingget al
[22 ] (2012)
43/34
44 (23–68)
N/A
9.6 (2–20)
KSS knee score was 73.3 at follow-up. Flexion contracture reduced from 18.1° to 8.4°.
Hemarthrosis (11 cases), infection (3 cases), aseptic loosening (1 case), arthrofibrosis (3 cases).
10-years prosthetic survival from component replacement was 86%.
Songet al
[5 ] (2018)
131
41 (25–73)
110/21
6.8 (1–10)
Knee score increased from 34.4 to 80.9. WOMAC improved from 66 to 24.
Total complication rate was 13%. Three cases had deep infection. Four cases had periprosthetic fracture.
The 5- and 10-year survival rates were 98.5% and 97.7%, respectively.
Ernstbrunner et al
[4 ] (2017)
43/21
58
N/A
18
KSS knee score increased from 36 to 73. KSS function score improved from 62 to 78. Flexion contracture reduced from 18° to 6°.
30% was revised for infection. 19% was revised for aseptic loosening.
The 15- and 20-year survival rates were 78%, and 59%, respectively.
Andersonet al
[7 ] (2018)
39/24
49.3 (21–75)
39
9.33 (1.7–19.3)
KSS knee score was 85.92, and functional score was 75.26, and the overall satisfaction rate was 69.2%.
Two patients required revision for aseptic loosening, four patients for re-operation, one for infection, one for stiffness, and one for periprosthetic fracture.
N/A
Santos Silva et al
[14 ] (2019)
18/15
39
N/A
11.3 (5.4–25.2)
KOOS score was 85.7 at follow-up. Average ROM was 88°.
Total complication rate was 27.8%, with two for infection and two for stiffness.
The 10-year survival rate was 94.3%.
HSS: Hospital of Special Surgery; KOOS: Knee Injury and Osteoarthritis Outcome Score; N/A: Not available; PWH: Patient with hemophilia; ROM: range of motion; TKA: Total knee arthroplasty ; WOMAC: Western Ontario MacMaster osteoarthritis score.
The patellar strategy during TKA for PWH has rarely been discussed. Given the inflammatory nature of hemophilia, as reported in the literature, patellar resurfacing is routinely performed for PWH during TKA. Mortazavi et al [ 6 ] reported 103 knees with an average of 45.1 months follow-up. The patella of all patients was replaced, except for five knees with a very thin patella. Song et al [ 5 ] reported 131 consecutive primary TKAs in PWH with 6.8 years of follow-up and reported that ten knees underwent patellar resurfacing. Anderson et al [ 7 ] reported that the patella was routinely resurfaced in standardized surgical techniques for PWH. However, the outcomes related to patellar resurfacing have not yet been discussed. Song et al [ 5 ] reported a patient who developed a patellar fracture after patellar resurfacing and healed with conservative treatment. In Moore's[ 2 ] meta-analysis, three patellar complications were reported in a total of 336 TKAs, including one chronic lateral patellar subluxation, one patellar clunk syndrome, and one persistent femoropatellar pain.
The bone quality of patella in hemophilic patients is generally relatively osteoporotic, with a low bone mass density, complicated by anatomical distortion owing to numerous intra-articular hemorrhages. In our study, the average patellar thickness was 17.8 mm. We chose to perform patelloplasty to render the patella in our institute. After >10 years of follow-up, we observed a statistically significant increase in the patellar score, and no patellar-related revision was needed. The results of our study showed that the incidence of postoperative AKP in PWH was similar to that in OA patients after TKA in the literature.[ 19,20 ] PWH have relatively limited activity and low body weight, which are both predisposing factors for less patello-femoral complication.[ 21 ] Even with some AKP, none of the patients required revision for the tolerable AKP. As mentioned earlier, the decreased pain subset, improvement of flexion contracture, and decreased incidence of joint space hemorrhage contributed to the high rate of postoperative satisfaction .
The prosthetic survival after TKA for hemophilic arthropathy is relatively lower than that in non-hemophilic patients [Table 4 ].[ 4,22 ] The 10-year prosthetic survival rate ranges from 86% to 97% in the literature. Infection and aseptic loosening are the most common reasons for revision TKA,[ 2 ] which differ from those in non-hemophilic patients.[ 23 ] The reported incidence of aseptic loosening in PWH ranges from 2.3% to 19% after median- to long-term follow-up.[ 4,7,24 ] Ernstbrunner et al [ 4 ] reported the 18-year follow-up results of TKA in 30 patients (43 knees) with hemophilic arthropathy , with 21 knees successfully followed up, and reported that the 15-year and 20-year survival rates were 78% and 59%, respectively. Revision surgery was performed in eight knees (19%) due to aseptic loosening and five (12%) due to infection. In our present study, seven knees required re-operation, and four knees experienced aseptic loosening 11.3 years after the primary TKA on average. We concluded that the probability of aseptic loosening in our study was related to the severity of the preoperative deformity and bone mass density. All four knees experienced preoperative flexion contracture and stiffness; therefore, additional bone cutting was performed, which resulted in a lower bone reserve for fixation, even though no stem was used in any of the four cases. The stem is recommended for primary TKA when facing severe flexion contracture, in which the knee cannot be properly balanced.[ 25 ] Based on the lessons learned from our revision cases and the findings from the literature, we recommend using stems during primary TKA for PWH with severe deformity to improve the longevity of the implants.
The present study has several limitations. The major limitations are the retrospective nature of the study and its relatively small sample size, which was unavoidable due to the low incidence of hemophilic disorders. We tried to control for confounding variables by evaluating a cohort whose surgeries were performed by a single surgeon at one institution, and all cases accepted replacement with modern prostheses. Second, there are limited studies on the use of stems in primary TKA for PWH. Although four cases were revised for aseptic loosening in our study, this was insufficient to provide more information on the optimal management. We recommend the use of stems, based mainly on the literature and the lesson from this study. Third, this study was a non-randomized case series, and no patients underwent patellar resurfacing. We therefore could not compare the outcomes of TKA with and without patellar resurfacing. Future studies with randomized controlled designs are required to assess it. Despite the aforementioned limitations, the highlight of the present study was its presentation of patella-related outcomes after patelloplasty for PWH. Furthermore, all the patients in this study were followed up for >10 years, which is a longer follow-up time than most studies in the literature [Table 4 ]. This study thus adds to the available knowledge base for this procedure in PWH.
In conclusion, TKA with the patelloplasty is an effective procedure for hemophilic patients with end-stage hemophilic arthropathy , allowing pain relief, improvement of knee functions, decreased flexion contracture, and a high rate of satisfaction based on the statistics of a follow-up for >10 years.
Acknowledgement The authors are grateful to Dr. Xueqing Wang for the data collection in the study.
Funding This study was supported by CAMS Innovation Fund for Medical Sciences(CIFMS; No.2022-I2M-C&T-B-031), and the National High Level Hospital Clinical Research Funding (No. 2022-PUMCH-A-124)
Conflicts of interest None.
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