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Bortolati, Maria (2009) L’aferesi nel trattamento della Sindrome da Anticorpi Antifosfolipidi e del Blocco Cardiaco Congenito Autoimmune. [Tesi di dottorato]

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Abstract (inglese)

Introduction. Apheresis techniques can be a valuable treatment option for life-threatening autoimmune disorders. This study describes and discusses some apheresis protocols in the treatment of high risk Antiphospholipid Syndrome (APS) pregnancies, Catastrophic Antiphospholipid Syndrome (CAPS) and autoimmune Congenital Heart Block (CHB). Plasma exchange and immunoadsorption in high risk APS pregnancies. A second-line treatment protocol including apheresis in addition to the standard therapies was scheduled and utilized in our hospital with the intent of improving the outcome of high risk pregnancies of women with primary Antiphospholipid Syndrome (APS). Between April 1991 and January 2008, 159 pregnancies of patients with APS were followed by us. Thirteen pregnancies of 9 patients were thus followed using apheretic technique, which has undergone modification over the years. In the cases studied the outcome of pregnancy varied according to the different apheretic treatment conditions. This study suggests that prophylactic apheretic treatment administered along with full anticoagulation and intravenous immunoglobulins therapy could be a valuable therapeutic option in high risk pregnant APS women.
Plasma exchange in CAPS. CAPS is a rare, life-threatening variant of APS. It has been found that the recovery rate is best when the treatment protocol includes anticoagulants, steroids and therapeutic plasma-exchange (TPE). The treatment of CAPS with TPE is not, however, well defined as procedure modalities have not yet been standardized, and the best replacement fluid for TPE is still a controversial issue. Although the most commonly used one, fresh frozen plasma (FFP), contains natural anticoagulants, it is also made up of clotting factors, complement activation products and cytokines which could worsen CAPS’ “thrombotic storm”. The successful management of 4 CAPS patients, including TPE sessions initiated in the 1st week from diagnosis and using albumin solution as the replacement fluid, is described here. TPE was performed daily for the first 3 days, then tapered off, and withdrawn on the basis of patient's clinical condition. One of the patients was also treated with anticoagulants, while the others received anticoagulants plus high doses of steroids in addition to TPE. Our results indicate that, when initiated promptly and albumin solution is used as the replacement fluid, TPE can be considered an effective, safe treatment for CAPS.
Plasma exchange in autoimmune CHB. The features of 9 non-autoimmune and 36 autoimmune CHB fetuses were analyzed and compared. Among anti-SSA/SSB-negative cases only 3 blocks were complete in utero and 4 blocks were unstable. Death occurred in 3 cases, but never in utero; 6 infants were paced. Among anti-SSA/SSB-positive cases all except two had complete block in utero. Ten babies died; another developed severe dilated cardiomyopathy; 26 children were paced. Autoimmune blocks were more often stable and complete, with an overall worse prognosis. A case of autoimmune CHB treated with TPE in addition to steroid treatment has been described. Our experience, in agreement with some other reports, suggests that this treatment might counteract progression of the disease.
Conclusion. Our study emphasizes the benefits of apheresis in the treatment of high risk APS pregnancies, CAPS and autoimmune CHB. However the apheretic technique should be differentiated according to the clinical features of patients.

Abstract (italiano)

Introduzione. Le tecniche di aferesi rappresentano una valida scelta terapeutica nel trattamento di malattie autoimmuni gravate da una prognosi severa. In questo studio vengono descritti e discussi alcuni protocolli terapeutici di aferesi finalizzati al trattamento delle gravidanze ad alto rischio nelle pazienti con Sindrome da Antifosfolipidi (APS), della Sindrome da Antifosfolipidi Catastrofica (CAPS) e del Blocco Cardiaco Congenito (CHB) di tipo autoimmune.
La plasmaferesi e l’immunoadsorbimento nelle gravidanze di donne con APS ad alto rischio. Nel nostro studio è stato messo a punto e usato un protocollo di trattamento di secondo livello comprendente l’aferesi associata alle terapie convenzionali, nell’intento di prevenire le complicanze gravidiche nelle donne affette da APS primaria ad elevato rischio. Sono state seguite 159 gravidanze di donne affette da APS nel periodo aprile 1991-gennaio 2008. In 13 gravidanze di 9 pazienti sono state applicate tecniche di aferesi quali la plasmaferesi e l’immunoadsorbimento, secondo modalità che sono state modificate nel corso degli anni sulla base dell’esperienza acquisita nel trattamento dei singoli casi. I risultati ottenuti suggeriscono che un adeguato trattamento aferetico in associazione con anticoagulazione a dose terapeutica e immunoglobuline endovena potrebbe rappresentare una valida opzione terapeutica nella prevenzione e nel trattamento delle complicanze gravidiche in donne con APS ad alto rischio.
La plasmaferesi nel trattamento della CAPS. La CAPS è una variante rara dell’APS gravata da un’elevata mortalità. Il protocollo di trattamento più efficace comprende l’utilizzo di anticoagulanti, steroidi e plasmaferesi. Tuttavia le modalità del trattamento aferetico della CAPS non sono ben standardizzate; in particolare è controversa la scelta del liquido di sostituzione più adatto. Il plasma fresco congelato è attualmente il fluido di rimpiazzo maggiormente utilizzato; se da un lato esso contiene anticoagulanti naturali, dall’altro è però anche ricco di fattori della coagulazione, prodotti di attivazione del complemento e citochine che potrebbero aggravare lo stato trombofilico del paziente. Abbiamo trattato con risultato favorevole 4 casi di CAPS; le sedute aferetiche sono iniziate durante la prima settimana dalla diagnosi ed è stata utilizzata una soluzione di albumina come liquido di sostituzione. Il trattamento era eseguito giornalmente per 3 giorni e poi diradato e sospeso quando le condizioni cliniche del paziente lo consentivano. Una donna era trattata anche con anticoagulanti mentre le altre 3 ricevevano oltre agli anticoagulanti alte dosi di cortisone. I nostri risultati suggeriscono che la plasmaferesi, iniziata tempestivamente e con l’albumina come rimpiazzo, può essere considerata un trattamento efficace e sicuro nei pazienti con CAPS.
La plasmaferesi nel CHB autoimmune. La casistica dello studio comprendeva 9 casi di CHB non autoimmune e 36 di CHB autoimmune, le cui caratteristiche cliniche sono state tra loro confrontate. Nel gruppo di casi non correlati ad anticorpi anti-SSA/SSB materni erano presenti 3 blocchi completi in utero e 4 blocchi erano instabili. Il decesso si è verificato in 3 casi, sempre dopo la nascita; a 6 bambini è stato applicato il pace-maker. I casi associati ad anticorpi anti-SSA/SSB materni presentavano tutti un blocco cardiaco completo in utero, tranne 2. Sono deceduti 10 di questi bambini, uno ha sviluppato una miocardiopatia dilatativa e 26 sono stati sottoposti ad applicazione di pace-maker. Il blocco autoimmune è risultato più spesso stabile e completo e legato ad una prognosi complessivamente peggiore rispetto a quello non autoimmune. In considerazione della severità prognostica del CHB autoimmune la madre di un feto con blocco incompleto riscontrato alla 22^ settimana gestazionale è stata trattata con plasmaferesi in aggiunta alla terapia steroidea convenzionale, ottenendo un arresto dell’evoluzione del blocco e la nascita di una bambina con CHB incompleto e senza segni di scompenso cardiaco. La nostra esperienza, che concorda con quella di alcune segnalazioni in letteratura, suggerisce che il trattamento aferetico potrebbe contrastare la progressione della malattia.
Conclusioni. Il nostro studio mette in evidenza i benefici dell’aferesi nel trattamento delle gravidanze ad alto rischio nelle pazienti con APS, della CAPS e del CHB di tipo autoimmune. La modalità di esecuzione di tale terapia dovrebbe essere adeguata alle caratteristiche cliniche del singolo paziente.

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Tipo di EPrint:Tesi di dottorato
Relatore:Ruffatti, Amelia
Dottorato (corsi e scuole):Ciclo 21 > Scuole per il 21simo ciclo > SCIENZE MEDICHE, CLINICHE E SPERIMENTALI > SCIENZE REUMATOLOGICHE
Data di deposito della tesi:30 Gennaio 2009
Anno di Pubblicazione:30 Gennaio 2009
Parole chiave (italiano / inglese):plasmaferesi, immunoadsorbimento, Sindrome da Anticorpi Antifosfolipidi, Sindrome Catastrofica, gravidanza, Blocco Cardiaco Congenito autoimmune
Settori scientifico-disciplinari MIUR:Area 06 - Scienze mediche > MED/16 Reumatologia
Struttura di riferimento:Dipartimenti > Dipartimento di Medicina Clinica e Sperimentale
Codice ID:1314
Depositato il:30 Gen 2009
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