AIM:For people with haemophilia A (PwHA), bleeding in the joints leads to joint damage and haemophilia-related arthropathy, impacting range of motion and life expectancy. Existing guidelines for managing haemophilia A support healthcare professionals (HCPs) and PwHA in their efforts to preserve joint health. However, such guidance should be reviewed, considering emerging evidence and consensus as presented in this manuscript.METHODS:Fifteen HCPs experienced in the management of PwHA in the UK participated in a three-round Delphi panel. Consensus was defined at ≥70% of panellists agreeing or disagreeing for Likert-scale questions, and ≥70% selecting the same option for multiple- or single-choice questions. Questions not reaching consensus were revised for the next round.RESULTS:26.8% (11/41), 44.8% (13/29) and 93.3% (14/15) of statements reached consensus in Rounds 1, 2 and 3, respectively. HCPs agreed that prophylaxis should be offered to patients with a baseline factor VIII (FVIII) level of ≤5 IU/dL and that, where there is no treatment burden, the aim of prophylaxis should be to achieve a trough FVIII level ≥15 IU/dL and maintain a longer period with FVIII levels of ≥20-30 IU/dL to provide better bleed protection. The aspirational goal for PwHA is to prevent all joint bleeds, which may be achieved by maintaining normalised (50-150 IU/dL) FVIII levels.CONCLUSION:The panel of experts were largely aligned on approaches to preserving joint health in PwHA, and this consensus may help guide HCPs.

Silicone lymphadenopathy occurs following migration of silicone particles through the lymphatic system to regional nodes and more distal extranodal sites as a consequence of implant rupture or “gel bleed”. This silicone migration and tissue deposition with granulomatous reaction may cause systemic symptoms which can mimic lymphoma – fatigue, fever, and sweats. It is an important condition to be aware of and to consider in the context of bone marrow granulomatosis. The authors declare no conflicts of interest.

At the beginning of the COVID-19 (SARS-CoV-2) pandemic, it was not clear which patients would be most at risk, although it was soon realised that older age was a major risk factor and that there was a high incidence of coagulation disorders and thrombosis associated with COVID-19 infection.1 For clinicians managing PWH, and for the patients themselves, it was not known whether this would reduce, increase or have no impact in PWH. It soon became apparent that the risk of infection and severe disease in the general population was greater in older adults. Adults > 65 years of age represented 80% of hospitalizations and had a 23-fold greater risk of death than those < 65 years old.2 Published data regarding the incidence of COVID-19 infection in populations of people with haemophilia (PWH) is sparse (non-existent for populations of PWH B) and has only provided information for short time spans within the pandemic.3–5 Having suffered greatly from past viral infections (such as HIV and hepatitis C transmitted throughblood andbloodproducts), itwas speculated that the haemophilia community might be better prepared and willing to shield during the pandemic. The Age-related DeVelopments ANd Comorbidities in haemophilia (ADVANCE) Working Group is a European collaboration of over 20 Haemophilia Treatment Centres (HTCs) that focuses on the management of PWH aged ≥40 years. We conducted a survey within the ADVANCE HTC network that aimed to clarify the incidenceof serious adverseoutcomesofCOVID-19 inPWH aged≥40 years. A COVID-19 specific survey instrument was developed to record COVID-19 adverse outcomes (hospitalization, ICU admission and death) in PWH aged ≥40 years with haemophilia A or B at ADVANCE HTCs in Europe throughout the pandemic over a 24-month period (until 30April 2022). Patient numberswere recorded for themost serious outcome atmonth/year of first occurrence; for example, if patients died after being admitted the ICU, they were only included in the number of those who died from COVID-19. Information collected included date of hospital/ICU admission or death, age range, haemophilia type and severity, haemophilia treatment and major comorbidities linked to adverse COVID-19 outcomes. Aggregated data was provided by participating HTCs and therefore did not require Ethical Committee approval. Twenty ADVANCE HTCs participated in the study, comprising a total population of 3379 PWHA and 671 PWHB. Of the overall haemophilia A and B population, .9% (36/4050) suffered a serious outcome as a result of COVID-19 infection; .64% (27/4166) required hospital admission, .1% (5/4050) were admitted to the ICU and .1% (4/4050) died. Eleven of the participating 20 centres registered PWHAwith serious outcomes; serious outcomes for PWHBwere only reported in five centres. Overall, 22 (.6%) PWHA out of a total of 3379 PWHA treated at the ADVANCE HTCs required hospital admission for COVID-19; .1% (n = 5) required admission to the ICU; and < .1% (n=3) died due toCOVID-19, see Table 1.Of the 671PWHB treated at the ADVANCEHTCs, 5 (7.4%) required hospital admission, no patients were admitted to the ICU and one patient died. Of the patients with HA, 11 of the 22 who were hospitalised had ≥1 comorbidity associated with worse outcomes (eight patients had hypertension, two of whomalsohadobesity).Nearly all patientswithHAwhowereadmitted to the ICU or died had ≥1 comorbidity associated with worse outcomes; 4/5 patients admitted to the ICU and two of three patients who died had diabetes (Table 1). Most of the cases in people with either haemophilia A or B occurred early in the pandemic with no clear distinction according to haemophilia severity, age or geography (Table 2). The four reported deaths from a total population of 4050 patients cared for at the 20 participating HTCs (3/3379 for haemophilia A; 1/671 for haemophilia B) is low when compared with the total impact of the pandemic on the total population. Although there are not direct comparisons, in 2020, the WHO reported .6 million recorded deaths from COVID-19 (all ages) in Europe in 2020, resulting in a mortality rate of .13%.6,7 However, this is likely to be higher in the age group studies; US data to May 2020 showed an increase in the COVID-19 death rate from .4% in the 40–49 age group to 8.0% in the 70–79 age group.8 This is in accordance with a comprehensive review in which haemophilia was not identified as a condition presenting a high-risk for developing severe COVID-19.9 The World Federation of Hemophilia (WFH) concluded that there is no evidence to suggest that PWH, including those on prophylaxis with traditional replacement therapy or those with haemophilia A receiving emicizumab, are at increased risk for infection with COVID-19 or for more severe disease unless they have additional well-described comorbidities such as older age (> 65 years), pulmonary or cardiovascular disease, hypertension, obesity or diabetesmellitus.10 Whether the low rates of seriousCOVID-19 infection are due to some inherent degree of protection in PWH due to their coagulation state is beyond the remit of this study. However, the close interaction between PWH, their HTCs and organisations such as the WFH, the European Haemophilia Consortium (EHC), the

AIM:We aimed to compare the outcomes of total hip and knee arthroplasty (THA, TKA) in haemophilic patients compared to matched controls.METHODS:Through a literature search we identified all cohort studies comparing perioperative complications and other outcomes of THA and TKA in haemophilic patients and matched controls without haemophilia. Results of the same outcome measure assessed by two or more studies were pooled in meta-analyses; odds ratios (ORs) with 95% confidence intervals (CI) were calculated. The risk of bias in included studies and certainty of evidence of each result were assessed using the Newcastle-Ottawa scale and the GRADE tool respectively.RESULTS:A total of five retrospective studies with matched controls were included; four of them were of good and one of fair quality. Based on moderate certainty evidence, compared to matched controls, patients with haemophilia had a significantly higher incidence of the following complications after a) TKA: periprosthetic joint infection [PJI; OR 1.6 CI (1.3, 1.9)], 1-year revision/re-operation [OR 1.4 CI (1.2, 1.8)] and b) THA: major and minor 90-day complications [major OR 2.2 CI (1.7, 2.9); minor OR 1.4 CI (1.1, 1.8)], venous thromboembolism [OR 3.1 CI (2.1, 4.6)]. PJI incidence in THA was not different in haemophilia compared to controls [OR 1.5 CI (.9, 2.6)].CONCLUSION:Our results can be used by healthcare professionals counselling patients with haemophilia considering a THA or TKA as part of the informed consent process. We provide detailed clinical recommendations for the perioperative management of THA and TKA in haemophilic patients.

INTRODUCTION:As people with haemophilia (PWH) receive better treatment and live longer they are more likely to encounter cardiovascular disease (CVD) and other comorbidities. ESC guidelines for the acute management of patients presenting with acute coronary syndrome (ACS) are based on the non-haemophilia population.AIM:To review the guidelines and propose relevant adaptations for PWHA without inhibitors who are treated with prophylaxis and present with ACS.METHODS:As part of the ADVANCE Group, 20 European haemophilia experts used a modified Delphi approach to develop and gain consensus on proposed adaptations of the ESC guidelines for PWHA without inhibitors.RESULTS:Of the 32 Class I recommendations across both guidelines, adaptions were considered necessary and proposed for 15. The adaptions highlight the need to provide sufficient FVIII trough levels at the time of antithrombotic treatment in people with haemophilia A (HA) without inhibitors. Patients receiving emicizumab prophylaxis and requiring oral anticoagulation therapy or combined single antiplatelet plus oral anticoagulation therapy will require additional FVIII replacement therapy.CONCLUSION:In the absence of high-quality clinical evidence, the combined expert opinion used to develop these adaptions to the current ESC guidelines may help to guide clinicians in their treatment decisions when a PWHA presents with ACS.

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