Background
The worldwide pandemic spread of SARS‐CoV‐2 can lead to either respiratory infection or containment‐associated isolation with possible higher impact on chronic diseases such as inherited ...bleeding disorders (IBD). The aim of the study was to evaluate the impact of COVID‐19 on patients and caregivers of IBD patients regarding their concerns and worries related to own health, access to treatment and availability of factor concentrates and their experiences related to medical care.
Methods
Multicentre, cross‐sectional study evaluating the impact of COVID‐19 on mental health of IBD patients. An ad hoc questionnaire was developed and sent to 586 patients/caregivers with haemophilia A, haemophilia B and VWD type III. The survey included information on demographic and clinical data, needs, concerns and experiences regarding medical care during COVID‐19 pandemic.
Results
In total, 355 of the IBD‐Group (200 patients, 155 caregivers) completed the survey (61.7% response rate). Most patients suffered from haemophilia A (73.8%) and were severely affected (64.7%). Eleven patients were in quarantine due to suspected COVID‐19; none had symptoms. One quarter worried (very) strongly about getting the coronavirus, 71.3% asked themselves what will happen to them when they will get COVID‐19, 40.1% felt unchanged, and 18.9% worried about delivery difficulties of their IBD treatment product. In 52.8%, medical appointments were postponed. Significant differences between caregivers and patients were found in most aspects.
Discussion
The IBD patients affected by a chronic disorder have particular thoughts and worries regarding COVID‐19. Haemophilia specialists should be committed to address these concerns and guarantee treatment despite containment strategies.
Patients with Philadelphia-negative myeloproliferative neoplasms (MPNs), particularly those carrying the JAK2V617F mutation, are at increased risk of thrombosis. While an association of MPNs with ...autoimmune disorders has been established, the prevalence of inherited or acquired thrombophilias in JAK2V617F-positive patients remains obscure. We therefore investigated the coincidence of the JAK2V617F mutation with additional thrombogenic risk factors.
In a retrospective study, we analyzed all patients referred for thrombophilia work-up between 01/2011 and 08/2019, in whom additional JAK2V617F mutation analysis was performed because of thromboembolic events that were recurrent, atypically located and/or associated with abnormal blood counts.
Of 472 tested patients, 49 (10.4%) were JAK2V617F-positive. While the frequency of inherited thrombophilias (factor V Leiden and prothrombin G20210A mutation, deficiency of antithrombin, protein C, protein S) was not different between the two groups, the prevalence of definite antiphospholipid syndrome (APS), mostly associated with a moderate- or high-risk antibody profile, was significantly higher in patients with (22.4%) than in those without (8.4%) JAK2V617F mutation (p < 0.01). All evaluable JAK2V617F-positive patients with APS were subsequently diagnosed with MPN. In patients with JAK2V617F mutation, presence of concomitant APS was associated with a significantly younger age (49 ± 14 vs. 60 ± 15 years) at the time of thrombophilia work-up (p < 0.05).
We found a significant association between JAK2V617F-positive MPN and definite APS. The presence of concomitant APS in patients carrying the JAK2V617F mutation may lead to earlier manifestation of thromboembolic events and may warrant more aggressive antithrombotic treatment strategies to prevent recurrence.
•The JAK2V617F (JAK2) mutation confers an increased risk of thromboembolism (TE).•The role of additional thrombophilias in JAK2-positive (JAK2+) patients is unclear.•We retrospectively analyzed 472 TE patients, 49 of whom carried a JAK2 mutation.•Diagnosis of JAK2 was associated with definite antiphospholipid syndrome (APS).•JAK2+ patients with APS were significantly younger than JAK2+ patients without APS.
Introduction
Gene therapy (GT) is becoming a realistic treatment option for patients with haemophilia. Outside clinical trials, the complexity and potential complications of GT will pose ...unprecedented challenges to haemophilia care centres.
Aim
To explore the potential use of electronic tools to improve the delivery of GT under real‐world conditions.
Methods
Considering the hub‐and‐spoke model, the GTH working group on GT considered the entire patient pathway and reached consensus on requirements for an integrative software tool to secure documenting and sharing information between treaters, pharmacies and patients.
Results
Six steps of the gene therapy process were identified, each requiring completion of the previous step as a prerequisite for entry. The responsibilities of GT dosing and follow‐up treatment centres, read/write access rules, and the minimum data set were outlined. Data contributed by patients through mobile devices was also considered.
Conclusion
Important information needs to be shared between patients and treatment centres in a real‐world GT hub‐and‐spoke model. Collecting and sharing this information in well‐organised electronic applications will not only improve patient care but also enable national and international data collection in clinical registries.
Introduction
The development of inhibitory antibodies is a severe complication of clotting factor replacement therapy in patients with severe haemophilia A (HA). Current World Federation of ...Hemophilia (WFH) guidelines for haemophilia care indicate that eradication of inhibitors is best achieved through immune tolerance induction (ITI) therapy.
Aim
The European Collaborative Haemophilia Network conducted a survey to determine whether ITI is still used in the routine management of patients with HA, and whether the availability of emicizumab prophylaxis has influenced treatment decisions.
Methods
The survey was conducted in late 2020/early 2021 in 18 centres representing 17 countries in the Europe/Middle East region treating a total of 4955 patients, and included sections specific to patient and centre demographics, treatment protocols (both ITI and prophylactic), inhibitor development and initiation of ITI, treatment success, and the incidence of adverse events.
Results
While our results indicate that ITI can still be considered a mainstay of treatment for patients with HA with inhibitors, less than daily dosing of ITI in combination with emicizumab prophylaxis is becoming commonplace across the spectrum of disease severity, with initiation being guided by bleeding patterns. The most frequently cited reasons for not initiating emicizumab prophylaxis were availability or reimbursement issues.
Conclusion
ITI remains a mainstay for haemophilia treatment of patients with HA with inhibitors, but emicizumab has become a preferred first-line approach to protect against bleeds and represents an alternative to burdensome ITI in certain patient groups.
Introduction
The development of inhibitory antibodies is a severe complication of clotting factor replacement therapy in patients with severe haemophilia A (HA). Current World Federation of ...Hemophilia (WFH) guidelines for haemophilia care indicate that eradication of inhibitors is best achieved through immune tolerance induction (ITI) therapy.
Aim
The European Collaborative Haemophilia Network conducted a survey to determine whether ITI is still used in the routine management of patients with HA, and whether the availability of emicizumab prophylaxis has influenced treatment decisions.
Methods
The survey was conducted in late 2020/early 2021 in 18 centres representing 17 countries in the Europe/Middle East region treating a total of 4955 patients, and included sections specific to patient and centre demographics, treatment protocols (both ITI and prophylactic), inhibitor development and initiation of ITI, treatment success, and the incidence of adverse events.
Results
While our results indicate that ITI can still be considered a mainstay of treatment for patients with HA with inhibitors, less than daily dosing of ITI in combination with emicizumab prophylaxis is becoming commonplace across the spectrum of disease severity, with initiation being guided by bleeding patterns. The most frequently cited reasons for not initiating emicizumab prophylaxis were availability or reimbursement issues.
Conclusion
ITI remains a mainstay for haemophilia treatment of patients with HA with inhibitors, but emicizumab has become a preferred first‐line approach to protect against bleeds and represents an alternative to burdensome ITI in certain patient groups.
Chronic diseases, such as inherited bleeding disorders (IBD) are often associated with high costs of medical care. COVID-19 containment measures, including isolation and triage, led to restrictions ...in the health care of chronically ill patients. The aim of the present study was to investigate the effects of the COVID-19 pandemic on the health care of IBD patients.
In this multicentre cross-sectional study to evaluate the effects of COVID-19 on the mental health and quality of care of patients with inherited bleeding disorder, an ad hoc questionnaire was sent to 586 patients/parents of children with haemophilia A, B or von Willebrand syndrome type 3. In addition to demographic and clinical data, patients/parents of patients with inherited bleeding disorders were asked about their thoughts, concerns and experiences regarding their medical care during the COVID-19 pandemic. Differences between clinical subgroups were calculated.
Significant differences were found between subgroups (severity, type of therapy, product class, comorbidities) with regard to the transmission of COVID-19 through plasma products, the effects of COVID-19 positive test results, fear of getting COVID-19, delayed drug supply and physiotherapy treatment.
The medical care of patients with inherited bleeding disorders, who need a continuous supply of essential drugs, is a particular challenge in times of pandemics. Therefore, worries and fears of IBD patients should be taken seriously and innovative communication channels established to maintain therapy standards and quality of care.
Zusammenfassung
Fragestellung
Chronische Erkrankungen, wie z. B. angeborene
Blutungsneigungen (IBD: Inherited Bleeding Disorders), gehen häufig
mit einem erhöhten Versorgungsaufwand einher. Maßnahmen ...zur
Eindämmung der COVID-19 Pandemie, inklusive Isolation und
Triageierung, haben zu Einschränkungen in der Krankenversorgung von
chronisch kranken Patienten geführt. Ziel der vorliegenden Arbeit
ist es, die Auswirkungen der COVID-19 Pandemie auf die Krankenversorgung von
IBD-Patienten zu untersuchen.
Methodik
In dieser multizentrischen Querschnittsstudie zur Bewertung
der Auswirkungen von COVID-19 auf die psychische Gesundheit und
Versorgungsqualität von Patienten mit angeborener Blutungsneigung
wurde ein ad-hoc Fragebogen an 586 Patienten/Eltern von Kindern mit
Hämophilie A, B oder von Willebrand Syndrom Typ 3 verschickt. Neben
demografischen und klinischen Daten wurden IBD Patienten zu ihren Gedanken,
Sorgen und Erfahrungen in Bezug auf ihre medizinische Versorgung
während der COVID-19 Pandemie befragt. Unterschiede zwischen
klinischen Subgruppen wurden berechnet.
Ergebnisse
Signifikante Unterschiede zeigten sich zwischen Subgruppen
(Schweregrad, Art der Therapie, Produktklasse, Komorbiditäten)
bezüglich Übertragung von COVID-19 durch Plasmaprodukte,
Auswirkungen COVID-19 positiver Testergebnisse, Angst COVID-19 zu bekommen,
verzögerter Medikamentenversorgung und Physiotherapiebehandlung.
Diskussion
Die medizinische Versorgung von IBD-Patienten, die eine
kontinuierliche Versorgung mit lebensnotwendigen Medikamenten
benötigen, stellt in Pandemiezeiten eine besondere Herausforderung
dar. Daher sollten Sorgen und Ängste von IBD-Patienten ernst
genommen und innovative Kommunikationswege zur Aufrechterhaltung von
Therapiestandards und Versorgungsqualität etabliert werden.
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.
Introduction
Inhibitors develop less frequently in haemophilia B (HB) than haemophilia A (HA). However, when present, the success of tolerization by immune tolerance induction (ITI) therapy is lower ...and the risk of complications higher.
Aim
To evaluate the use and outcome of ITI in patients with HB and inhibitors.
Methods
Subjects include singletons or siblings with a current/history of inhibitors enrolled in B‐Natural—an observational study designed to increase understanding of clinical management of patients with HB. Patients were followed for 6 months and information on demographics, medical and social history, and treatment were recorded.
Results
Twenty‐nine patients with severe HB and inhibitors were enrolled in 24 centres. Twenty‐two underwent one or more courses of ITI with or without immune suppression. Eight patients (36.4%) were successfully tolerized after the first course of ITI. One of these successes (12.5%) experienced allergic manifestations, whereas the corresponding number for the 10 treatment failures was five (50%). One of seven (14.2%) patients with large deletions and three of eight (37.5%) with nonsense mutations were tolerized at the first attempt, and all patients experiencing nephrosis either failed or were on‐going. At study end, 11 (50%) were considered successfully tolerized after one or more ITI courses, three were unsuccessful, and eight were still undergoing treatment.
Conclusion
Our data underscore the possibilities and difficulties of achieving tolerization in patients with HB with inhibitors. The type of mutation and complications appear to correlate with ITI outcome, but more accurate definitions of successful ITI are warranted.
Dual platelet inhibition is commonly used for prevention of cardiovascular events in patients undergoing neuroendovascular procedures. Non-responsiveness to platelet inhibitors may be associated with ...adverse outcomes. The aim of this study was to evaluate the reliability of the platelet function analyzer PFA-100® in comparison to light transmittance aggregometry (LTA) for monitoring clopidogrel and acetylsalicylic acid (ASA) non-responsiveness in a cohort of patients treated for intracranial aneurysm or cranial artery stenosis.
Non-responsiveness to clopidogrel and ASA was assessed by LTA using adenosine diphosphate (ADP) and arachidonic acid and by PFA-100® with the ADP/prostaglandin E1 (PGE1) and collagen/epinephrine cartridges, respectively.
A total of 203 patients (145 females; median age, 57 years) were analyzed. Agreement between the two tests was poor for clopidogrel non-responsiveness (ƙ=0.19) and not better than chance for ASA non-responsiveness (ƙ=0.01). Clopidogrel non-responsiveness by LTA and PFA-100® was associated with higher von Willebrand factor antigen and activity levels. ADP-induced platelet disaggregation was lower in patients with clopidogrel non-responsiveness as assessed by PFA-100®. Clopidogrel non-responsiveness by LTA was associated with a higher prevalence of diabetes and a higher body mass index (BMI). Adverse outcomes (death, thromboembolism, or in-stent thrombosis) occurred in 13% (n=26) of all patients independently of ASA and clopidogrel non-responsiveness as assessed by both devices.
Our results show that LTA and PFA-100® are not interchangeable in the assessment of ASA and clopidogrel non-responsiveness in patients undergoing neuroendovascular interventions.
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