Musculoskeletal evaluation in severe haemophilia A patients from Latin America

There is a paucity of literature on haemophilia treatment in Latin American countries, a region characterized by rapidly improving systems of care, but with substantial disparities in treatment between countries. The aim of this study was to evaluate the musculoskeletal status of haemophilia patients from Latin America and to examine the relationship between musculoskeletal status and treatment practices across countries. The Committee of Latin America on the Therapeutics of Inhibitor Groups conducted a survey of its member country representatives on key aspects of haemophilia treatment in 10 countries. Musculoskeletal status of patients was obtained during routine comprehensive evaluations between March 2009 and March 2011. Eligible patients had severe haemophilia A (factor VIII <1%) without inhibitors (<0.6 BU mL−1) and were ≥5 years of age. Musculoskeletal status was compared between three groups of countries, based primarily on differences in the availability of long‐term prophylaxis. Overall, 143 patients (5–66 years of age) were enrolled from nine countries. In countries where long‐term prophylaxis had been available for at least 10 years (Group A), patients aged 5–10 years had significantly better mean World Federation of Hemophilia clinical scores, fewer target joints and fewer affected joints than patients from countries where long‐term prophylaxis has been available for about 5 years (Group B) or was not available (Group C). In Latin America, the musculoskeletal status of patients with severe haemophilia without inhibitors has improved significantly in association with the provision of long‐term prophylaxis. As more countries in Latin America institute this practice, further improvements are anticipated

The influence of non-haematological factors on the development of ankle arthropathy in haemophilia

Haemophilia is an inherited condition in which circulating blood clotting factors are much reduced or absent resulting in the tendency to bleed into joint cavities where the ankle is the most commonly affected. Prophylactic replacement of clotting factors has much improved joint health in the majority of people with haemophilia however many continue to develop joint disease. Purpose. To explore the potential for non-haematological factors to influence the development of haemophilic arthropathy at the ankle. Methods. This study had two phases. Factors for investigation were determined using a Delphi process and subsequently preliminary clinical instrument testing occurred. Finally a case-control correlational study was carried out to investigate the presence of selected factors in a haemophilia cohort compared with normal volunteers. Results. Forty-two factors reached consensus from the Delphi Process of which 22 were selected for onward investigation comprising musculoskeletal, exercise, and haematological factors. In a case-control study with 90 participants, six factors successfully differentiated the Haemophilia Ankle group from the others. A further three factors separated people with haemophilia from normal volunteers representing musculoskeletal differences that cannot be attributed to arthropathy. A regression model was developed comprising: the Ankle Lunge Test, Foot and Ankle Ability Measure (FAAM), Duration of Exposure to a key sport and Subtalar joint inversion which correctly predicted 89.7% of cases with 86.7% sensitivity and 92.9% specificity. Conclusions. These results represent the first attempt to understand the interaction of factors that influence the arthropathy development. The FAAM sports subscale and Duration of Exposure to a key sport were identified as independent variables with the strongest association with haemophilic arthropathy at the ankle. Avenues for physiotherapeutic intervention have been identified with preventative screening tools and pre-habilitation programmes possible for young boys with haemophilia at risk of developing this debilitating condition

Haemarthrosis of the ankle in haemophilia A and B: prevalence, impact and intervention

Haemophilia is an X-linked recessive genetic disorder characterised by bleeding within soft tissue and joints. Multi-joint disease is a common feature of severe haemophilia where the ankle is prone to haemarthrosis and haemarthropathy, but little is known about the effect on individual joints, impact on health-related quality of life (HRQoL) and foot and ankle outcome measures. A multi-methods approach was used to improve the understanding of ankle haemarthrosis and resultant haemarthropathy. The prevalence of ankle haemarthrosis and incidence at individual joints with concurrent joint health in patients compliant with prophylaxis without an active inhibitor were investigated. Approximately 60% and 40% of people with haemophilia A and B respectively experienced a minimum of one haemarthrosis over the 12 month study period. Whilst haemarthrosis incidence at individual joints was similar, the ankle was the most affected by haemarthropathy. A multi-centre patient questionnaire of the impact of ankle haemarthrosis and haemarthropathy identified that HRQoL and foot and ankle outcome measures were poor regardless of haemophilia type, severity or treatment regime. A consultant survey identified adequate access to Musculoskeletal (MSK) services across the UK. However, only 12% and 49% of patients used footwear and foot orthoses respectively. Finally, a biomechanical study was established in a healthy cohort of males, the kinetic and kinematic effect of the Leeds Ankle Stabilising Enhanced Rocker intervention, a footwear and foot orthoses intervention used clinically in the management of haemophilia. Significant reductions in the primary outcome of ankle moment of force were reported when compared to a trainer, with a minimal effect on proximal joints. The work presented in this thesis improves the understanding of the current prevalence, incidence and impact of ankle haemarthrosis and haemarthropathy. Gaps in the access to MSK services have been identified and the mechanism of action of a targeted intervention has been established, providing a basis for future research in a pathological cohort with ankle haemarthropathy

FUNCTIONAL OUTCOME MEASURES IN HAEMOPHILIA –A SYSTEMATIC REVIEW

Background: Haemophilia is an inherited bleeding disorder that results in haemarthrosis leading to chronic arthropathy in those with severe forms of the disease. It causes significant disability and affects a patient’s quality of life. Functional outcome measures enable the healthcare professionals to assess the patients’ ability to carry out activities of daily living providing an important input to the assessment of joint disease. Objectives: This study aims to carry out a systematic review to identify the existing functional outcome measures used in the adult English speaking, haemophiliac population and evaluate these instruments based on their development methodology, measurement properties and other properties. Methods: Both PubMed and Scopus databases were searched to identify suitable outcome measures. Once the search identified the instruments, each instrument was searched to identify the relevant pilot and validation studies. Development methodology of each instrument was summarised. The measurement properties were evaluated using the COnsensus-based Standards for the selection of health Measurement INstruments (COSMIN) 4-point checklist. These measurement properties included internal consistency, reliability, measurement error, construct validity, criterion validity, content validity and responsiveness. The other properties that were assessed include interpretability, generalisability, precision, conceptual model, measurement model, acceptability, feasibility and burden. Results: There were three main outcome measures used to assess function in the adult haemophiliac population. These were the Haemophilia Activities List (HAL), the Functional Independence Score in Haemophilia (FISH) and the Haemophilia Exercise Project–Test- Questionnaire (HEP-Test-Q). Information on the development of instruments was only well provided in the HAL. However the COSMIN checklist proved that the HAL had not assessed all measurement properties. The FISH and the HEP-Test-Q, did not possess very good methodological quality of its measurement properties. With regards to the other properties, all three instruments were acceptable but interpretability was poor. The HAL and the HEP-Test- Q were precise. The conceptual model instruments assessed function in different forms, whereas the measurement model was treated as a reflective model in all three instruments. The HEP-Test-Q had the most amount of burden in comparison to the other instruments. The main limitation of this study was that the FISH, a performance based instrument was evaluated using the COSMIN checklist that was developed to assess patient reported outcomes. Conclusion: This systematic review suggests that the existing instruments produced to assess function in adult persons with haemophilia have not been adequately validated and that the methodology undertaken for this process consists of certain drawbacks. This suggests that there is scope for a new instrument to assess function in the English speaking adult haemophiliac population

Neural control of gait in people with haemophilic arthropathy

La hemofilia es un trastorno hemorrágico causado por una deficiencia de los factores VIII o IX de la coagulación. Las personas con hemofilia grave pueden tener hemorragias espontáneas o hemorragias en respuesta a traumatismos menores; la mayoría de los eventos ocurren en las articulaciones y los músculos. La manifestación clínica más frecuente es la artropatía hemofílica, que resulta del sangrado intraarticular repetitivo y de la membrana sinovial inflamada, lo que puede resultar en dolor crónico y deterioro articular. El objetivo general de mi tesis fue investigar el control neural de la marcha en personas con artropatía hemofílica (PCAH). La hipótesis de mi tesis fue que control neural de la marcha se ve afectado en PCAH, y los cambios en el control neural de la marcha están asociados con el daño articular y la cronicidad de la restricción articular. Se seleccionó la marcha, ya que las rodillas y los tobillos son las articulaciones que más se afectan en adultos PCAH. El núcleo de mi tesis fue investigar el control neural mediante el estudio de patrones de actividad de electromiografía (EMG) de músculos individuales y/o sinergias musculares, así como su interacción con la cinemática articular y evaluaciones clínicas. En el capítulo 1, ofrezco una perspectiva general sobre el impacto de la hemofilia en el sistema musculoesquelético, las lagunas actuales en el conocimiento sobre el control neural de la marcha en la artropatía hemofílica y cómo evaluar el control neural de la marcha. En los Capítulos 2 y 4, a través de las evaluaciones de los patrones de activación muscular de músculos individuales, la coordinación entre pares de músculos antagonistas y el análisis de sinergia muscular, confirmamos la hipótesis de que el control neural de la marcha se ve afectado en PCAH. En los capítulos 3 y 5, confirmamos que el control neural alterado de la marcha en PCAH está asociado con la gravedad del daño articular y la cronicidad de la restricción articular. En el capítulo 6, discutimos los resultados de los capítulos centrados en las perspectivas clínicas y fisiológicas del control neural alterado de la marcha en PCAH. Además, discutimos cómo la evaluación del control neuronal a través del índice dynamic motor control index during walking (Walk-DMC) puede ser una alternativa para monitorear el deterioro motor en PCAH. Con base en nuestros resultados, también discutimos cómo mejorar los resultados de la fisioterapia y las intervenciones quirúrgicas que tienen como objetivo mejorar la locomoción en PCAH. Mi tesis contribuye a comprender las consecuencias de la artropatía hemofílica, en especial en la neuromecánica de la marcha. Los hallazgos de mi tesis indican que el control neural de la marcha se ve afectado en PCAH, y los cambios en el control neural de la marcha están asociados con el daño articular, el dolor y cronicidad de la restricción articular. Desde una perspectiva científica, los cambios en el control neural de la marcha en PCAH implican patrones de actividad alterados de los músculos del tren inferior y una reorganización modular de la marcha. Desde una perspectiva clínica, mi tesis brinda una nueva mirada sobre cómo monitorear la progresión de la enfermedad en PCAH utilizando el índice Walk-DMC, brindando nuevas perspectivas para mejorar las intervenciones terapéuticas que apuntan a recuperar la marcha en PCAH.Haemophilia is a bleeding disorder caused by a deficiency of coagulation factors VIII or factor IX. People with severe haemophilia may have spontaneous bleeding events or bleeding in response to minor trauma; most of the events occur in the joints and muscles. The most frequent clinical manifestation is haemophilic arthropathy, which results from repetitive intraarticular bleeding and inflamed synovial membrane, which may result in chronic pain and joint impairment. The overall aim of my thesis was to investigate the neural control of gait in people with haemophilic arthropathy (PWHA). I hypothesized that neural gait control is affected in PWHA, and the changes in neural control of gait are associated with joint damage and chronicity of the joint constraint. Gait was selected because the knees and ankles are the most prevalent affected joints in adults PWHA. The core of my thesis is investigating neural control by studying electromyography (EMG) activity patterns of single muscles and/or muscle synergies, as well as their interaction with joint kinematics and clinical outcomes. In chapter 1, I provide a general perspective about the impact of haemophilia on the musculoskeletal system, the current gaps in knowledge in the neural control of gait in haemophilic arthropathy, and how to assess the neural control of gait. In Chapters 2 and 4, through the assessments of muscle activation patterns of single muscles, coordination between antagonistic muscle pairs, and muscle synergy analysis, we confirmed the hypothesis that the neural control of gait is affected in PWHA. In chapters 3 and 5, we confirm that the altered neural control of gait in PWHA is associated with the severity of joint damage and chronicity of joint constraint. In chapter 6, we discussed the results of chapters focused on clinical and physiological perspectives of the altered neural control of gait in PWHA. In addition, we discuss how the evaluation of neural control through the Walk-DMC index can be an alternative to monitoring the motor impairment in PWHA. Based on our results, we also discussed on how to improve the outcomes of physical therapy and surgical interventions that aimed to improve the locomotion in PWHA. My thesis contributes to understanding the consequences of haemophilic arthropathy for the neuromechanics of gait. The findings of my thesis indicate that neural control of gait is affected in PWHA, and the changes in the neural control of gait are associated with joint damage, pain and chronicity of the joint constraint. From a scientific perspective, the changes in the neural control of gait in PWHA implicate altered activity patterns of single leg muscles and a modular reorganization of gait. From a clinical perspective, my thesis gives a new perspective on how to monitor disease progression in PWHA using the Walk-DMC index—providing new perspectives to improve the therapeutic interventions that aim to recover gait in PWHA

Impacto da adoção da estratégia de profilaxia primária sobre os pacientes com hemofilia grave no Estado do Rio Grande do Sul : uma coorte de base populacional

Base teórica:O tratamento da hemofilia severa no Brasil apresentou avanços importantes nos últimos anos. Passamos de uma realidade de tratamento episódico, com quantitativos de fatores de coagulação insuficientes, para uma situação de programas de profilaxia primária, imunotolerância e fatores de coagulação recombinantes. A adoção destas modalidades terapêuticas pretende melhorar os desfechos de sangramentos, em especial musculoesqueléticos, nesta população de pacientes. Entretanto, estas estratégias possuem implicações clínicas, como o desenvolvimento de inibidores, além das relacionadas aos custos do tratamento. Objetivo: Avaliar os desfechos articulares e de inibidores, na população de pacientes do estado do Rio Grande do Sul com novo diagnóstico de Hemofilia A ou B severa, submetidos ao regime de tratamento com profilaxia primária. Métodos: Trata-se de uma coorte retrospectiva de base populacional, na qual foram incluídos todos os pacientes do estado do Rio Grande do Sul com novo diagnóstico de Hemofilia A ou B severa, que cumpriram os critérios do programa de profilaxia primária estabelecidos pelo Ministério da Saúde. Estes pacientes foram acompanhados desde a data de sua inclusão no programa, iniciado em 2012, até dezembro/2019, quando foi encerrado o seguimento. Os desfechos foram comparados, quando aplicável, aos encontrados em uma coorte histórica com a mesma base populacional, tratados na modalidade episódica, em um período anterior ao estabelecimento do programa de profilaxia primária. Resultados: O regime de profilaxia primária nos pacientes com novo diagnóstico de Hemofilia A ou B severa, no estado do Rio Grande do Sul, impactou em um menor número de inibidores, quando comparada ao regime prévio de terapia episódica. O desenvolvimento de artropatia, nesta modalidade terapêutica, foi inferior ao relatado em estudos prévios. Conclusão: Este trabalho, com um desenho original, acompanhou através de uma coorte retrospectiva a população de crianças com hemofilia severa do estado do Rio Grande do Sul, ao longo de 16 anos. Neste período, se deu a transição de um modelo de tratamento episódico com produtos plasmáticos, para a profilaxia primária com doses escalonadas, baseada em concentrados de fatores de origem recombinante. A profilaxia primária foi associada a um menor risco de desenvolvimento de inibidores quando comparada ao tratamento episódico, e a ocorrência de articulação alvo foi inferior à descrita em estudos prévios.Background: The treatment of people with severe hemophilia in Brazil had important advances in recent years. The reality of episodic treatment, with insufficient quantities of coagulation factors as recommended by the World Federation of Hemophilia, has undergone advances towards the implementation of primary prophylaxis, immunotolerance and recombinant coagulation factors programs. The adoption of these therapeutic modalities intends to improve bleeding outcomes, especially musculoskeletal, in this patient population. However, these strategies have clinical implications, such as the development of inhibitors, in addition to those related to treatment costs. Objective: The objective of this study is to evaluate joint and inhibitor outcomes in the population of patients in the state of Rio Grande do Sul with a new diagnosis of severe Hemophilia A or B, undergoing treatment with primary prophylaxis. Methods: This is a population-based study, which included all patients in the state of Rio Grande do Sul with a new diagnosis of severe Hemophilia A or B, who met the criteria of the primary prophylaxis program established by the Ministry of Health. These patients were followed in a retrospective cohort, from the date of their inclusion in the program, which started in 2012, until December/2019, when the follow-up ended. Outcomes were compared, when applicable, to those found in a historical cohort with the same population base, treated in the episodic modality, in a period prior to the establishment of the primary prophylaxis program. Results: The adoption of the primary prophylaxis regimen in patients with a new diagnosis of severe Hemophilia A or B, in the state of Rio Grande do Sul, resulted in a smaller number of inhibitors, when compared to the previous regimen of episodic therapy. The development of arthropathy in this therapeutic modality was lower than that reported in previous studies. Conclusion: This work, with an original design, followed through a retrospective cohort the population of children with severe hemophilia in the state of Rio Grande do Sul, over 16 years. During this period, there was a transition from a model of episodic treatment with plasma products to tailored primary prophylaxis, with concentrates of factors of recombinant origin. Primary prophylaxis was associated with a lower risk of developing inhibitors when compared to episodic treatment, and the occurrence of target joint was lower than described in previous studies

Pain, people, and ethnicity

Pain is an integral part of the life experience. Furthermore, the factors that influence the experience of pain are dynamic. Of the various influencing factors, ethnicity has a growing literature that is revealing how an individual’s subjectivity that stems from ancestral and geographic origins is affecting this process of pain perception. The actual perception of pain has been shown to be quite different among different ethnicities. Ethnically motivated dispositions, in terms of coping, has also led to more questions on how effectively patients can be treated for pain when medicine often attempts to mandate objectivity. Moreover, the interaction and feedback that patients and providers give to each other is a powerful indicator of how pain is experienced and how successful the outcomes of treatment will be

Clinicopathological profile of Patients Diagnosed with Congenital Disorder of Haemostasis

Except for menstrual bleeding, spontaneous bleeding is abnormal. The presence of normal blood vessels, platelets and coagulation factors ensure that bleeding occurs only after inciting stimuli such as trauma, ulcers, surgery etc. Common causes of acquired disorders of haemostasis are liver disease, drugs, thrombocytopenia etc. When patients develop spontaneous bleeding with no obvious identifiable cause or abnormal bleeding following a challenge, they are referred to the clinical pathology laboratory for a workup for haemostatic disease. Investigation of a bleeding patient begins with meticulous history taking, identifying the type of bleeding and a thorough clinical examination. This is followed by a sequential array of laboratory tests starting from first-line screening tests followed by specialized tests such as mixing tests, factor assays and platelet function tests. This was an observational study of data of patients who underwent investigations for abnormal bleeding between the periods January 2016 to May 2019. Of the 55 patients who underwent this examination process, 20 were diagnosed to have Congenital Disorder of Haemostasis. The ratio of males to females was 3: 1 and the age range was from 6 months to 41 years. 50% of them had Hemophilia. The ratio of Hemophilia A: B was 4:1. Rare inherited bleeding disorders included deficiencies of factor VII & X. Three patients had combined factor deficiencies. Of the 6 von Willebrand disease patients, 4 were of Type III. 60% had mucocutaneous bleeding while 40 % had major bleeding. There was no correlation between severity of factor VIII deficiency and clinical bleeding