Hemarthrosis in hemophilia: new treatment methods and the effect of hemarthroses repetition on joints sensitivity

Intraarticular bleeding is a complication, that concerns almost every person with haemophilia. The number and heaviness of them depends on the grade of illness and on presence of inhibitor. Presence of blood inside joint cavity leads to destruction of joint cartilage and haemophilic artropathy occures. Consequent events are as follows: bleeding - synovial irritation - re-bleeding - chronic haemophilic synovitis - haemophilic artropathy. There are four main targets of this work: 1. to summarize the possibilities of treatment of chronic haemophilic artropathy with radionuclides and to rise indication criteria for that kind of treatment, 2. to evaluace retrospectively long term efficacy od radiation synovectomy with corelation to other methods of treatment, 3. to find out, if platelet-rich-plasma therapy is effective in chronic haemophilic artropathy and 4. to find out, what is the effect of repeated intraarticular bleedings on joints sensitivity. 4 hypothesis are pronounced and methodology of their confirmation or disprove is described. There are results presented of prospective study of radiation synovectomy including recommendation of treatment indication. Further, this method is compared to other ones, from the point of view of the long term efficacy in retrospective study. Beneficial effect of...Nitrokloubní krvácení je stav, se kterým se většina hemofiliků během života setká. Počet a tíže krvácivých epizod jsou závislé na stavu základní choroby a na případné přítomnosti inhibitorů koagulačních faktorů. Přítomnost krve v kloubní dutině vede k navození chemických procesů, které probíhají v synoviální vrstvě kloubního pouzdra a v kloubní chrupavce, a které ve svém důsledku vedou k destrukci kloubních ploch a ke vzniku hemofilické artropatie. Destrukce kloubu probíhá v řetězci: krvácení → iritace synoviální výstelky → recidiva krvácení → chronická synovialitida → artropatie. Jsou čtyři hlavní cíle této práce: 1. sumarizovat poznatky o možnostech léčby chronické hemofilické synovialitidy pomocí radionuklidů a pokusit se stanovit indikační kritéria k této léčbě, 2. retrospektivně zhodnotit dlouhodobý efekt radiační synovektomie v porovnání s jinými metodami léčby, 3. zjistit, je-li léčba pomocí plazmy bohaté na trombocyty účinná u chronické hemofilické synovialitidy a 4. zjistit jaký vliv mají recidivy krvácení na senzitivitu postižených kloubů. Jsou stanoveny čtyři hypotézy a je popsaná metodika, jak tyto hypotézy potvrdit nebo vyvrátit. Jsou prezentovány výsledky radiační synovektomie v prospektivní studii včetně doporučení indikace k tomuto výkonu, dále je tato metoda porovnána s jinými...Deparment of Gynaecology and Obstetrics - Division of Tumour BiologyGynekologicko-porodnická klinika - oddělení nádorové biologie3. lékařská fakultaThird Faculty of Medicin

Hemarthrosis in hemophilia: new treatment methods and the effect of hemarthroses repetition on joints sensitivity

Intraarticular bleeding is a complication, that concerns almost every person with haemophilia. The number and heaviness of them depends on the grade of illness and on presence of inhibitor. Presence of blood inside joint cavity leads to destruction of joint cartilage and haemophilic artropathy occures. Consequent events are as follows: bleeding - synovial irritation - re-bleeding - chronic haemophilic synovitis - haemophilic artropathy. There are four main targets of this work: 1. to summarize the possibilities of treatment of chronic haemophilic artropathy with radionuclides and to rise indication criteria for that kind of treatment, 2. to evaluace retrospectively long term efficacy od radiation synovectomy with corelation to other methods of treatment, 3. to find out, if platelet-rich-plasma therapy is effective in chronic haemophilic artropathy and 4. to find out, what is the effect of repeated intraarticular bleedings on joints sensitivity. 4 hypothesis are pronounced and methodology of their confirmation or disprove is described. There are results presented of prospective study of radiation synovectomy including recommendation of treatment indication. Further, this method is compared to other ones, from the point of view of the long term efficacy in retrospective study. Beneficial effect of..

Monitoring joint health in haemophilia : Factors associated with deterioration

Introduction: Joint bleeds in patients with haemophilia may result in haemophilic arthropathy. Monitoring joint health is essential for identifying early signs of deterioration and allows timely adjustment of treatment. Aim: The aim was to describe changes in joint health over 5-10 years follow-up and identify factors associated with joint health deterioration in patients with haemophilia. Methods: A post hoc analysis was performed from previous cohort studies in patients with moderate/severe haemophilia, ≥16 years. Joint health of ankles, knees and elbows was measured with the Haemophilia Joint Health Score (HJHS) from 2006-2008 (T0) to 2011-2016 (T1). Analyses were performed on patient level (ΔHJHS-total) and joint level (ΔHJHS-joint). Deterioration was defined as ΔHJHS-total ≥4 and ΔHJHS-joint ≥2. Results: Sixty-two patients (median age 25, 73% severe haemophilia, median [interquartile range] 0.0 [0.0;2.0] joint bleeds between T0 to T1) were included. After median 8 years, HJHS-total deteriorated in 37% and HJHS-joint in 17%. Ankle joints (31%) showed deterioration more often than elbows (19%) and knees (3%). Deterioration of HJHS-total was only associated with severe haemophilia. Deterioration of HJHS-joint was weakly associated with a lower HJHS at baseline and more self-reported limitations in activities, and strongly with more joint bleeds between T0 and T1 and presence of synovitis. Conclusion: In 37% of patients with moderate/severe haemophilia and low joint bleeding rates, joint health deteriorated over 5-10 years. Ankle and elbow joints showed deterioration most frequently. Factors found in this study help to identify which joints need frequent monitoring in patients with haemophilia with access to early prophylaxis

Inhibition of Fenton reaction is a novel mechanism to explain the therapeutic effect of intra-articular injection of PRP in patients with chronic haemophilic synovitis

Introduction and Aim: Haemarthroses cause major morbidity in haemophilia resulting in chronic haemophilic synovitis (CHS) and arthropathy. Oxidation of haemoglobin-coupled iron released in synovium after haemolysis induces chondrocytes death and cartilage damage, allowing postulate using iron-chelating drugs as potential therapeutic tool for haemophilic joint damage. Considering that albumin, the most abundant plasma protein, is a physiologic iron chelator, we aim to demonstrate that impediment of haemoglobin oxidation is exerted by plasma as a mechanism involved in the therapeutic effect of intra-articular injection of platelet-rich plasma in CHS. Methods: Oxidation of haemoglobin (Hb) to methaemoglobin (MeHb) through Fenton reaction was induced in vitro by addition of potassium ferricyanide in the presence or absence of peripheral blood-derived platelets-rich or platelets-poor plasma (PRP/ PPP) or albumin. The relevance of in vitro findings was analysed in synovial fluid (SF) samples from one patient with CHS obtained before and after 6 months of PRP intraarticular injection. Results: MeHb formation was completely impaired either by of PPP, PRP or albumin indicating that PRP exerts an anti-oxidative effect, probably due by plasma albumin. Analysis of SF samples revealed the presence of MeHb levels and haemosiderinladen macrophages in SF obtained before PRP treatment. Reduction of synovial MeHb, normalization of cellular composition and improvement of health joint haemophilic score, pain and bleeding episodes were registered after 6 months of PRP intra-articular injection. Conclusion: Inhibition of Fenton reaction and the consequent normalization of joint cellular composition is a noncanonical mechanism underlying the therapeutic effect of PRP intra-articular injection in CHS.Fil: Caviglia, Horacio. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Daffunchio, Carla. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Galatro, Gustavo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Cambiaggi, Guillermo. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Oneto, Paula. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; ArgentinaFil: Douglas Price, Ana Laura. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Landro, María Eulalia. Gobierno de la Ciudad de Buenos Aires. Hospital General de Agudos "Juan A. Fernández"; ArgentinaFil: Etulain, Julia. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Medicina Experimental. Academia Nacional de Medicina de Buenos Aires. Instituto de Medicina Experimental; Argentin