A single-centre experience of 29 total ankle replacement in haemophiliac patients: Therapeutic management, factor consumption and cost.

INTRODUCTION: In patients with haemophilia, repeated bleeding in large joints leads to chronic haemophilic arthropathy, a rare disease that can be managed surgically with ankle arthrodesis or with total ankle replacement (TAR). TAR has been reported to provide good surgical results in the medium/long-term and allow preservation of joint mobility but the medical therapeutic management of the patients has not been described. AIM: To describe the medical therapeutic management of TAR. METHODS: All patients with haemophilia A/B, with haemophilic ankle arthropathy, and who underwent TAR between April 2006 and October 2019 were retrospectively included. Factor consumption, perioperative and early complications, volume of blood lost, and orthopaedic data were collected. RESULTS: A total of 25 patients underwent 29 TAR (mean age was 44.7 years [range: 26-65]). In the 17 patients with HA without history of anti-FVIII inhibitor, the mean ± SD consumption the day of surgery was 116 ± 16 UI/kg when clotting factors were administered by continuous infusion, 106 ± 13 UI/kg when SHL factors were administered by bolus infusion, and 75 ± 22 UI/kg when EHL factors were administered by bolus infusion. During hospitalisation, the mean factor cost was €38,073 (83.7% of the total cost of surgery). Mean blood loss was significantly lower in patients treated with tranexamic acid (164 mL, range: 40-300) than in those not (300 mL, range: 70-800; p = .01). Six patients had haematoma. The 10-year survival free of any prosthesis removal/arthrodesis was estimated to be 92.2% (95% CI [83; 100]). CONCLUSION: The medical therapeutic management of TAR is complex, carried out by a multidisciplinary team but effective in avoiding the occurrence of complications.

Successful living donor liver transplantation in a patient with hemophilia A and factor VIII inhibitor: A case report with perioperative recommendations.

Liver transplantation in patients with end-stage liver disease and coexisting hemophilia A has been described. Controversy exists over perioperative management of patients with factor VIII inhibitor predisposing patients to hemorrhage. We describe the case of a 58-year-old man with a history of hemophilia A and factor VIII inhibitor, eradicated with rituximab prior to living donor liver transplantation without recurrence of inhibitor. We also provide perioperative management recommendations from our successful multidisciplinary approach.

Mid-to long-term postoperative outcomes of ankle joint fusion in patients with haemophilia: A systematic review.

INTRODUCTION AND AIM: The ankle joint is the most common site for haemophilic arthropathy. The aim of this study was to review the outcomes of ankle joint fusion in patients with haemophilia A or B. The primary outcome measures were union rates, time to union, perioperative blood loss/transfusion, postoperative complications and length of hospital stay (LOS). Secondary outcome measures were hind foot functional outcome scores and the visual analogue pain scale (VAS). MATERIALS AND METHODS: A search of PubMed, Medline, Embase, Journals@Ovid and the Cochrane register was performed conforming to the PRISMA guidelines. Only human studies with a minimum follow-up of 1-year were included. The MINORS and ROBINS-1 tools were used for quality appraisal. RESULTS: A total of 952 articles were identified and only 17 studies met the eligibility criteria after the screening. The mean age of the patients was 37.6 (SD 10.2). A total of 271 ankle fusions were performed with the open crossed-screw fixation being the most common technique. Union rates were 71.5%-100% at 2-6 months. The pooled postoperative complication and revision rates were 13.7% and 6.5%, respectively. The range of LOS was 1.8-10.6 days. The mean preoperative American orthopedic foot and ankle society (AOFAS) ankle-hindfoot score was 35 (SD 13.1) whereas the mean postoperative AOFAS score was 79.4 (SD 5.3). The mean preoperative VAS was 6.3 (SD 1.6) while the mean postoperative VAS score was .9 (SD .4) across 38 ankle fusions. CONCLUSION: Ankle arthrodesis offers improved pain and function in haemophilic ankle arthropathy with lower revision and complication rates than that reported in the literature for total ankle replacement.

Simoctocog alfa (Nuwiq®) in previously untreated patients with severe haemophilia A-Final efficacy and safety results from the NuProtect study.

INTRODUCTION: Simoctocog alfa (Nuwiq®) is a 4th generation recombinant FVIII with proven efficacy for the prevention and treatment of bleeding episodes (BEs) in previously treated patients with severe haemophilia A. The NuProtect study assessed the immunogenicity, efficacy and safety of simoctocog alfa in 108 previously untreated patients (PUPs). The incidence of high-titre inhibitors was 16.2% and no patients with non-null F8 mutations developed inhibitors. AIM: To report the efficacy and safety results from the NuProtect study. METHODS: PUPs received simoctocog alfa for prophylaxis, treatment of BEs, or as surgical prophylaxis. The efficacy of prophylaxis (during inhibitor-free periods) was assessed using annualised bleeding rates (ABRs). The efficacy in treating BEs and in surgical prophylaxis was assessed using a 4-point scale. Adverse events were recorded throughout the study. RESULTS: Of 108 PUPs treated with simoctocog alfa, 103 received at least one prophylactic dose and 50 received continuous prophylaxis for at least 24 weeks. In patients on continuous prophylaxis, the median ABR was 0 (mean 0.5) for spontaneous BEs and 2.5 (mean 3.6) for all BEs. In 85 patients who had BEs, efficacy of BE treatment was excellent or good for 92.9% (747/804) of rated BEs; 92.3% of BEs were treated with 1 or 2 infusions. The efficacy of surgical prophylaxis was excellent or good for 94.7% (18/19) of rated procedures. There were no safety concerns and no thromboembolic events. CONCLUSION: Simoctocog alfa was efficacious and well tolerated as prophylaxis, surgical prophylaxis and for the treatment of BEs in PUPs with severe haemophilia A.

Perioperative continuous infusions of factor VIII versus factor IX for patients with hemophilia A or B undergoing major surgery.

Continuous factor VIII (FVIII) or factor IX (FIX) infusions are commonly used for patients with hemophilia A (HA) or B (HB) undergoing surgery to secure perioperative hemostasis. To describe differences between the initial recovery and subsequent FIX and FVIII levels, and describe clinical outcomes among HB and HA patients receiving perioperative continuous infusion (CI) of recombinant FVIII and FIX concentrates. Retrospective chart review was conducted on 8 consecutive patients with HB and 7 consecutive patients with HA who underwent major surgery between 2014 and 2018 and received continuous infusions of standard half-life factor concentrate. Median initial bolus dose per kilogram was higher for HB compared to HA patients [90.8 (IQR 78.0-98.7) vs. 52.1 (IQR 48.6-55.6) IU/kg], while initial CI dose-rates were similar [4.3 (IQR 3.8-4.6) vs. 4.2 (IQR 3.8-4.4) IU/kg/h]. Median post-bolus recovery was higher for FVIII compared to FIX [1.70 (IQR 1.23-1.75) vs. 0.88 (IQR 0.75-1.00) IU/mL]. Median factor levels also were higher for FVIII on post-operative days 1 to 3. HB patients had greater mean intraoperative estimated blood loss [285.7 (range 0-1000) vs. 142.8 (range 0-400) mL] and longer median length of hospital stay [9 (IQR 8-12) vs. 5 (IQR 4-6.5) days]. Our initial evidence suggests greater in vivo yield of rFVIII compared to rFIX in the perioperative setting. We identified poorer clinical outcomes in this small cohort of perioperative HB patients indicating that they may benefit from a higher CI rate for adequate surgical hemostatic coverage.

Total hip and knee arthroplasty in HIV- and HCV-positive hemophilia patients: short term follow-up of 14 patients.

BACKGROUND: Haemophilic arthropathy (HA) is a common comorbidity of haemophilia. Some people with haemophilia (PWH) were human immunodeficiency virus (HIV)-positive. Arthroplasty is an effective treatment for end-stage HA. This study was carried out to report the effectiveness and satisfaction following total hip arthroplasty (THA) or total knee arthroplasty (TKA) in PWH with HIV. PATIENTS AND METHODS: All patients with haemophilia and HIV undergoing THA or TKA in our centre from January 2015 to June 2020 were reviewed. All patients were followed for at least twenty-four months. The improvements in postoperative indicators were evaluated at the latest follow-up, including the Visual Analogue Scale (VAS) score, range of motion (ROM), and validated joint scores such as Knee Society Score (KSS; clinical and functional) and Harris Hip Score (HHS). The complications and satisfaction were analysed likewise. Those were utilized to weigh the risks and benefits of the procedure in the population. RESULTS: Fourteen patients (7 hips and 14 knees) were included in the study. The follow-up of the THA cohort was 53.3 months (range, 27-82) and the TKA cohort was 50.1 months (range, 25-85), respectively. The average VAS score was ameliorated from 7.3 to 3.0 and 6.6 to 2.8 in the two groups (P < .001, respectively). Similarly, two cohorts (THA and TKA) showed statistically significant changes in the extension and flexion ROM between the preoperative and the latest follow-up (P < .05, P < .001, respectively). Besides, statistically significant differences between the preoperative and final follow-up values of HHS (from 41.6 to 82.3), clinical KSS (from 34.8 to 72.8), and functional KSS (from 42.9 to 73.2) were observed (P < .001, respectively). Notably, there were 4 complications noted among 21 arthroplasties performed, giving a 19.0% complication rate. Based on the satisfaction score, the majority of patients were optimistic about the arthroplasty. CONCLUSION: Given these findings, THA or TKA of the PWH with HIV is a worthwhile procedure and can be performed by an experienced and collaborative multidisciplinary team in a tertiary centre with a good haemophilia care system.

Extension contracture stiff knee in haemophilia: Surgical timing and procedure for total knee arthroplasty.

INTRODUCTION: Total knee arthroplasty (TKA) for a stiff knee of patients with haemophilia (PWH) represents a challenge for orthopaedic surgeons for the difficulties of exposing the knee and high complication rate compared to a flexible knee. AIM: To optimize the surgical exposure in primary TKA for PWH and to propose a threshold angle of extension contracture in treating haemophilic knee joints, retrospectively. METHODS: Sixty-seven primary TKAs for PWH (mean age, 48 years) were performed, and incisional approaches to joint were standard (58 cases) and V-Y quadricepsplasty (V-Y) (9 cases). The decision of surgical approach was decided intraoperatively by two surgeons. Pre- and post-knee angles were evaluated in each group. Variables in the V-Y group were evaluated using univariate logistic regression analysis and receiver operating characteristic curve analysis. RESULTS: Univariate logistic regression analysis demonstrated that the preoperative range of motion (ROM) and flexion were significantly associated with V-Y. Threshold values of preoperative flexion and ROM resulting in V-Y using receiver operating characteristic analysis were 45° and 35°, respectively. CONCLUSIONS: Primary TKA for PWH using a standard approach may be performed before the stage preoperative flexion <45° and ROM <35°.

[Profuse Hemorage During Open Heart Surgery in a Patient Late After Liver Transplantation and Remission Stage Acquired Hemophilia].

A 72-year-old male presented with severe mitral regurgitation, moderate tricuspid regurgitation, and chronic atrial fibrillation. One month prior, he encountered difficulties with dialysis and was subsequently referred to our department for cardiac surgery. The patient's medical history includes living-donor liver transplantation for type C cirrhosis associated with acquired hemophilia A. The preoperative liver function was categorized as Child-Pugh grade B, with a model for end-stage liver disease( MELD) score of 23. His factor Ⅷ activity was close to the lower limit of the normal range. The patient underwent mitral valve replacement, tricuspid valve repair, and left atrial appendage closure. Initially, he experienced intractable bleeding, but hemostasis was easily achieved after administrating a factor Ⅷ preparation. Upon admission to the intensive care unit, his factor Ⅷ clotting activity was slightly below the normal range. Therefore, in cases where a patient with remission stage hemophilia A resulting in liver transplantation undergoes open heart surgery, it is crucial to have coagulation factor medication readily available, regardless of normal preoperative factor Ⅷ levels.

The effect of HIV prevalence, CD4 counts and disease severity on the outcome of total knee arthroplasty for haemophilic arthropathy: a systematic review and meta-analysis.

PURPOSE: End-stage knee arthropathy is a recognised complication of haemophilia. It is often treated by total knee arthroplasty (TKA), which is more technically challenging in patients with haemophilia (PwH). It remains unclear what factors may predict implant survivorship and deep infection rate. Therefore, we systematically review the evidence regarding TKA survivorship and infection in PwH, compared to the general population, and determine the important factors influencing survivorship, particularly HIV and CD4 + count. METHODS: A systematic literature review was conducted using MEDLINE, EMBASE, and PubMed for studies reporting Kaplan-Meier survivorship for TKA in PwH (PROSPERO CRD42021284644). Meta-analysis was performed for survivorship, and the results compared to < 55-year-olds from the National Joint Registry (NJR). Meta-regression was performed to determine the impact of relevant variables on 10-year survivorship, with a sub-analysis focusing on HIV. RESULTS: Twenty-one studies were reviewed, totalling 1338 TKAs (average age 39 years). Implant survivorship for PwH at 5, 10, and 15 years was 94%, 86%, and 76% respectively. NJR-reported survivorship for males < 55 years was 94%, 90%, and 86%. Survivorship improved over time (1973-2018), and correlated inversely with HIV prevalence. Infection rate was 5%, compared to 0.5-1% in the NJR. Infection was not significantly increased with higher HIV prevalence, and CD4 + count had no effect. Complications were inconsistently reported. CONCLUSION: Survivorship was similar at 5 years but declined thereafter, and infection rate was six-fold higher. HIV was related to worse survivorship, but not increased infection. Meta-analysis was limited by inconsistent reporting, and standardised reporting is required in future studies.

Risk factors for increased perioperative blood loss during total knee arthroplasty in patients with haemophilia.

INTRODUCTION: Currently, there is a paucity of literature describing the risk factors for increased perioperative blood loss (PBL) during total knee arthroplasty (TKA) in haemophilia. Furthermore, no studies have analysed coagulation factor levels that affect PBL. AIM: To identify the risk factors for increased PBL by incorporating coagulation factor levels following TKA in patients with haemophilic arthropathy. METHODS: A total of 92 TKA (78 haemophilia A and 14 haemophilia B) were performed for haemophilic arthropathy. PBL was calculated using the haemoglobin (Hb) balance method, and patients were categorised into two groups: group H (higher blood loss than the mean PBL, n = 36) and group L (lower blood loss than the mean PBL, n = 56). Body mass index (BMI), operation day Hb, haematocrit and coagulation factor level (VIII or IX) were analysed, including demographic and laboratory data. RESULTS: The mean PBL volume during TKA for haemophilic arthropathy of the knee was 542.3 ± 361.7 mL. Multivariate analysis revealed that lower haematocrit on the operation day (odds ratio [OR], .633; 95% confidence interval [CI], .511-.786; p < .001) and coagulation factor level (OR .970, CI .941-.999; p = .046) were independent risk factors for increased PBL. Receiver-operating characteristic analysis identified these cutoff values for predicting increased PBL: operation day coagulation factor level 93.5% (sensitivity, 70.4%; specificity, 67.6%) and haematocrit level of 38.2% (sensitivity, 85.7%; specificity, 80.6%). CONCLUSIONS: The PBL increased as haematocrit and coagulation factor levels decreased on the operation day. A coagulation factor level <93.5% or haematocrit level of <38.2% may be a significant risk factor for increasing PBL. LEVEL OF EVIDENCE: Level IV, Case Series, Treatment Study.

Surgical outcomes in patients with haemophilia A or B receiving extended half-life recombinant factor VIII and IX Fc fusion proteins: Real-world experience in the Nordic countries.

INTRODUCTION: Perioperative dosing recommendations vary across Nordic haemophilia treatment centres (HTCs) for extended half-life (EHL) factor concentrates in haemophilia A/B (HA/HB) patients. AIM: To summarise Nordic real-world surgical experiences with EHL recombinant factor VIII/IX Fc (rFVIIIFc/rFIXFc) fusion proteins using retrospective data from clinical records at four HTCs in Finland, Sweden and Norway. METHODS: Factor dosing and surgical outcomes were recorded from HA/HB patients who underwent surgery and were treated with rFVIIIFc/rFIXFc. Perioperative factor dosing regimens were clinician-determined based on local practises. RESULTS: Twenty five surgeries were performed on 20 patients, all covered by bolus injections except one minor HA surgery; eight minor surgeries were in paediatric patients. Median preoperative rFVIIIFc dose for major HA surgeries (n = 8) was 48 IU/kg (range: 35-57), with total consumption up to Day 14 of 427 IU/kg (196-568). For the two major HB surgeries (in one patient), preoperative rFIXFc doses were 50 IU/kg and 20 IU/kg; total consumption up to Day 14 was 130 IU/kg and 40 IU/kg. Median preoperative rFVIIIFc/rFIXFc bolus doses for minor HA (n = 10) and HB (n = 4) surgeries were 50 IU/kg (24-79) and 47 IU/kg (40-71), with total consumption up to Day 5 of 138 IU/kg (49-404) and 100 IU/kg (43-125), respectively. Intraoperative and postoperative haemostatic responses were rated as at least good/excellent for 24/25 surgeries, with bleeding episodes reported in only three surgeries. CONCLUSION: Nordic real-world experiences suggest that EHL products can be used safely and effectively for peri-operative haemostasis. Further research is required to develop local dosing guidelines for optimised treatment schedules.

Total Hip Arthroplasty in Patients With Classic Hemophilia: A Matched Comparison of 90-Day Outcomes and 5-Year Implant Survival.

BACKGROUND: Patients with classic hemophilia can develop joint hemarthroses, degenerative changes, and eventually require total hip arthroplasty (THA). Little data exist concerning THA outcomes in this population, and evidence-based guidelines specifically addressing venous thromboembolism (VTE) prophylaxis in this population are lacking. METHODS: A retrospective study was conducted using the 2010-2020 PearlDiver MHip database. Patients undergoing primary THA were identified, and those with classic hemophilia were matched 1:10 with non-hemophilia patients based on age, gender, and Elixhauser Comorbidity Index. Ninety-day serious adverse events, minor adverse events, and any adverse events were compared with multivariate analysis. Reoperation at 5 years was assessed using Kaplan-Meier analysis. RESULTS: Five hundred eighteen classic hemophilia THA patients were matched 1:10 with 5,193 non-hemophilia patients. On multivariate analysis, those with classic hemophilia had greater odds of aggregated any adverse events (odds ratio [OR] 1.76), serious adverse events (OR 2.30), and minor adverse events (OR 1.52) (P < .001 for each). Patients with classic hemophilia had greater odds of bleeding issues (transfusion, OR 1.98; hematoma, OR 4.23; P < .001 for both), VTE (deep vein thrombosis, OR 2.67; pulmonary embolism, OR 4.01; P < .001 for both), and acute kidney injury (OR 1.63; P = .03). Five-year implant survival was lower in hemophilia patients (91.9%) relative to matched controls (95.3%; P = .009). CONCLUSION: Hemophilia patients undergoing THA had elevated risks of both 90-day bleeding complications (transfusion and hematoma) and VTE (deep vein thrombosis and pulmonary embolism) relative to matched controls. These findings emphasize the need to balance factor replacement and VTE prophylaxis. Although the 5-year implant survival was lower in hemophilia patients, this represented a difference of 3.4% at 5 years, suggesting that THA remains effective in this cohort.

Ankle arthrodesis in patients with haemophilia-associated ankle arthropathy - does the technique influence the outcome?

Management of symptomatic osteoarthritis (OA) of the ankle in patients with haemophilia can be challenging. Arthroscopic ankle arthrodesis has been shown in non-haemophiliac patients to provide similar or superior rates of fusion to open ankle fusion. However, the literature regarding ankle arthrodesis in patients with haemophilia is limited. Our aim was to compare the rate of successful fusion between open and arthroscopic assisted ankle arthrodesis in patients with haemophilia. A retrospective study was performed. All patients with haemophilia who underwent ankle arthrodesis at our centre were included. Outcomes including peri- and post-operative complications, and lengths of stay were extracted from patients' records. Radiographs were reviewed for signs of successful arthrodesis. Seventeen arthrodesis procedures were performed in 13 patients between 1980 and 2017. Nine procedures were performed arthroscopically and eight were open. Ten patients were diagnosed with haemophilia A and three with haemophilia B. The success rates of arthroscopic and open tibiotalar arthrodesis were 100% and 87.5% respectively. Four complications occurred. In the open technique group, there was one non-union. The same patient also developed subsequent haematoma after revision surgery. One patient developed a superficial wound infection which resolved with antibiotics. In the arthroscopic group, one patient developed a pseudoarthrosis of the distal tibiofibular joint which required a revision procedure. The results of this study suggest that arthroscopic ankle fusion for haemophilia- associated arthropathy is a viable option, with the rate of successful fusion being comparable to open procedures.

Total knee arthroplasty in patients with haemophilic arthropathy is effective and safe according to the outcomes at a mid-term follow-up.

BACKGROUND: Haemophilic arthropathy (HA), a common complication of haemophilia, is secondary to recurrent joint bleeding and increases the prevalence of end-stage osteoarthritis (OA). Total knee arthroplasty (TKA) is a reliable treatment for haemophilia patients. This study was performed to evaluate the mid-term outcomes of TKA for end-stage HA. We hypothesized that the rate of complications of TKA is higher for patients with haemophilia than for patients without haemophilia. METHODS: Patients with HA undergoing TKA from January 2015 to December 2016 in our centre were retrospectively reviewed. All patients were managed by a multidisciplinary team. The improvements in flexion contracture, range of motion (ROM), Knee Society Score (KSS; clinical and functional), Visual Analogue Scale (VAS) score, and satisfaction at final follow-up were analysed to evaluate the effectiveness of TKA in HA. The complications were analysed to evaluate the safety of TKA in HA. RESULTS: Twenty-eight patients (32 knees) were included in the study. The follow-up was 69.1 ± 5.1 months. Significant differences between the preoperative and final follow-up values of flexion contracture (which changed from 21.1 ± 6.5° to 14.3 ± 4.1°, P < 0.001), ROM (from 53.9 ± 15.0° to 70.3 ± 16.3°, P < 0.001), clinical KSS (from 33.5 ± 14.4° to 62.7 ± 9.5°, P < 0.001), functional KSS (from 46.1 ± 15.5° to 62.9 ± 9.7°, P < 0.001), and VAS score (from 6.8 ± 1.4 to 4.9 ± 1.3, P < 0.01) were observed. Importantly, the incidence of complications was 15.6% and the satisfaction was 100% in our mid-term study. CONCLUSION: Under elaborative and comprehensive management, TKA is effective and safe in patients with advanced HA on the basis of mid-term follow-up outcomes.

Cementless total hip arthroplasty in haemophilia patients through direct anterior approach.

INTRODUCTION: Total hip arthroplasty (THA) has become the treatment of choice for patients with severe haemophilic arthropathy of the hip. However, the intraoperative and postoperative complications, including blood loss and infection, are significant concerns. Direct Anterior Approach (DAA) might be beneficial in THA of patients with haemophilia. AIM: The present study was conducted to assess outcomes of THA using DAA in patients with haemophilia. METHODS: We retrospectively reviewed our joint replacement database. From January 2010 to December 2015, we had 12 patients with haemophilia who underwent 14 THAs by DAA and followed for an average of 69 months. RESULTS: All patients were male with a mean age of 36 ± 7 years at the time of THA. The mean Harris Hip Score improved from 46 preoperatively to 89 at the final follow-up visit. One dislocation and one infection occurred. Only one patient with simultaneous bilateral THA needed a transfusion. All components were radiologically well fixed at the final follow-up visit except one acetabular loosening that needed revision. All patients were satisfied with the outcome of the surgery at the final follow-up visit. CONCLUSION: In this study, it was observed that complications of cementless THA using DAA in haemophilia patients with hip arthropathy are comparable to other surgical approaches. However, the complication of bleeding in this approach might be less.

Results of a randomized phase III/IV trial comparing intermittent bolus versus continuous infusion of antihaemophilic factor (recombinant) in adults with severe or moderately severe haemophilia A undergoing major orthopaedic surgery.

INTRODUCTION: In patients with haemophilia A undergoing surgery, factor VIII (FVIII) replacement therapy by continuous infusion (CI) may offer an alternative to bolus infusion (BI). AIM: To compare the perioperative haemostatic efficacy and safety of antihaemophilic factor (recombinant) (ADVATE® ; Baxalta US Inc., a Takeda company, Lexington, MA, USA) CI or BI administration. METHODS: In this multicentre, phase III/IV, controlled study (NCT00357656), 60 previously treated adult patients with severe or moderately severe disease undergoing elective unilateral major orthopaedic surgery (knee replacement, n = 48; hip surgery, n = 4; other, n = 8) requiring drain placement were randomized to receive antihaemophilic factor (recombinant) CI (n = 29) or BI (n = 31) through postoperative day 7. Primary outcome measure was cumulative packed red blood cell (PRBC)/blood volume in the drainage fluid within 24 h after surgery, used to establish non-inferiority of CI to BI. RESULTS: CI:BI ratio of cumulative PRBC volume in the 24-h drainage fluid was 0.92 (p-value <.001 for non-inferiority; 95% confidence interval, 0.82-1.05). Total antihaemophilic factor (recombinant) dose per kg body weight received in the combined trans- and postoperative periods was similar with CI and BI to maintain targeted FVIII levels during/after surgery. Treatment-related adverse events (AEs) were reported in five patients treated by CI (eight events) and five treated by BI (six events), including two serious AEs in each arm. CONCLUSION: CI administration of antihaemophilic factor (recombinant) is a viable alternative to BI in patients with haemophilia A undergoing major orthopaedic surgery, providing comparable efficacy and safety.

Recombinant FVIIa in elective non-orthopaedic surgery of adults with haemophilia and inhibitors: A systematic literature review.

AIM: To assess available evidence on the use of rFVIIa in non-orthopaedic surgery including dental surgery in adult patients with congenital haemophilia with inhibitors (PWHI). METHODS: A systematic literature search was performed according to a prespecified search string; prespecified criteria were used to select applicable studies including PWHI ≥18 years of age who underwent any non-orthopaedic surgery using rFVIIa. RESULTS: Thirty-three publications met the eligibility criteria, of which 26 publications - including 46 procedures in 44 patients - were selected for the qualitative analysis. Most publications were case reports or case series (21/26). Primary authors assessed rFVIIa as effective in maintaining haemostasis during and after most major surgeries (22/32). rFVIIa dose was mainly on label, with higher doses used in 4 cases, and a lower dose in 1 case. Duration of treatment was mostly 5-10 days (range: 3 days to 1 month post-operatively). Adverse events related to rFVIIa were rare. CONCLUSIONS: Assessing non-orthopaedic surgery in this patient population is hampered by a paucity of published data; nevertheless, the current evidence indicates that rFVIIa is effective in achieving haemostasis in haemophilia patients with inhibitors undergoing elective non-orthopaedic or dental surgery. rFVIIa was generally well tolerated in these patients, with thrombotic events occurring rarely. These data, generated to help clinicians manage congenital haemophilia with inhibitors, highlight the need for more systematic reporting of rFVIIa and all other therapeutic agents in non-orthopaedic surgery and dental surgery in patients with congenital haemophilia and inhibitors.

The role of total ankle replacement in patients with haemophilia and end-stage ankle arthropathy: A review.

Haemophilia is the most common X-linked bleeding disorder, affecting over 1 million individuals throughout the world. Patients are subclassified into mild, moderate and severe disease based on per cent factor activity level. Nearly, all patients with haemophilia develop haemophilic arthropathy (HA) by age 30 and HA is known to have a negative impact on physical health subscores in Haem-A-QOL, a validated quality of life scoring system for patients with haemophilia. Unfortunately, many patients progress to end-stage HA of the ankle, which is characterized by pain, contractures, decreased range of motion and muscle atrophy. Ankle arthrodesis (AAD) has been the standard of care in the definitive surgical management of end-stage HA of the ankle. While AAD is a safe surgical procedure known to improve HA-related pain, it decreases functional mobility and has been associated with secondary hindfoot arthritis as well as subtalar degeneration. In recent years, total ankle replacement (TAR) has emerged as an alternative surgical procedure that strives to improve functional mobility, pain and quality of life in end-stage HA of the ankle. However, the safety, durability, and efficacy of this procedure in these patients are unknown. In this review, we analyse the clinical studies investigating TAR in patients with end-stage HA of the ankle. We also discuss important considerations in the perioperative management of patients with haemophilia and compare the risks and benefits of AAD and TAR for patients with end-stage HA of the ankle.

Clinical and patient reported outcome in total ankle replacement compared to ankle fusion in end-stage haemophilic arthropathy.

BACKGROUND: Ankle arthropathy is a frequent complication of haemophilia, reducing the patients' quality of life. Despite intensive conservative therapy, end-stage arthropathy requires surgical treatment, either by ankle fusion (AF) or total ankle replacement (TAR). METHODS: Eleven consecutive AFs were performed in nine patients and 11 TARs were implemented in 10 patients. Outcomes were assessed clinically by AOFAS score and radiologically by the Pettersson and Gilbert scores. RESULTS: The mean age of the patients in these groups were 35.7 years and 49.4 years, respectively. Of the 11 ankles that underwent fusion, 10 showed bony consolidation not later than 12 weeks after surgery, whereas one still showed non-union after 6 months. VAS pain scores decreased significantly in both groups. Mean AOFAS scores also improved significantly, from 28.1 before to 80.3 after AF and from 21.5 before to 68.0 after ankle replacement. No perioperative complications were observed in either group. Late deep infection was observed in two patients that underwent TAR, which required removal of the implant. CONCLUSION: Our data indicate that both AF and TAR result in significantly reduced pain in patients with haemophilia with end-stage haemophilic arthropathy. While TAR is associated with a higher risk of deep infection and minimal persistent pain, it preserves the pre-operative range of motion. AF on the other hand is associated with the risk of non-union and a longer post-operative recovery period but results in greater pain reduction.

Circumcision in Hemophilia: A Multicenter Experience.

BACKGROUND: Hemophiliac patients and their families have social pressure to undergo circumcision, despite the potential complications. The objective of this study was to report our experience in the circumcision of hemophilia patients. MATERIALS AND METHODS: We included 35 patients with hemophilia who had circumcision in 3 centers from January 2010 to August 2019. Their age ranged between 0.3 months and 8 years. Hemophilia a was classified as mild (n=3), moderate (n=4), and severe (n=28). Patients received 2 doses of factor VIII concentrate 50µ/kg, 1 hour before the procedure and 12 hours after it. RESULTS: Four neonates were diagnosed with hemophilia after circumcision because of prolonged bleeding. Two patients with severe hemophilia A had bleeding after hospital discharge (6.5%). They received additional factor concentrate, and 1 patient had an extra stitch. Two patients had wound gaping (6.5%), and 1 patient had a wound infection (3.2%). CONCLUSION: Hemophilia is not an absolute contraindication for circumcision. Circumcision of hemophilic children should be performed under appropriate conditions in hemophilia centers. Bleeding is not frequent but could be serious.