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Aortitis is a classic manifestation of large vessel vasculitis. Antiphospholipid syndrome (APS), sometimes known as Hughes syndrome, is an acquired autoimmune disorder that manifests clinically as recurrent venous or arterial thrombosis. Patients with APS may also suffer from various underlying diseases, most frequently systemic lupus erythematosus (SLE). Catastrophic antiphospholipid syndrome (CAPS) is a rare but serious complication of APS characterized by failure of several organs due to diffuse microcirculatory thrombi. Its main manifestations involve the kidneys, lungs, heart and central nervous system, and require early diagnosis and rapid therapeutic management. While APS can affect virtually any blood vessel, aortitis is not a known symptom of APS. We report the case of a 36-year-old patient with APS and SLE who presented with CAPS during pregnancy, with no concomitant SLE flare. The first manifestation of CAPS was aortitis, preceding renal, cardiac and haematological manifestations. The outcome was favourable with combined treatment including corticosteroids, anticoagulants, plasma exchange and rituximab. We then carried out a literature search for papers describing the presence of aortitis in APS and/or SLE. In the cases of aortic involvement identified in the literature, including another case of CAPS, the occurrence of aortitis in SLE, often associated with the presence of antiphospholipid antibodies/APS, suggests that aortitis should be considered as an under-recognized manifestation and potential non-criterion feature of APS. [ABSTRACT FROM AUTHOR]

Purpose A new software release of the Fenwal Amicus device is now available for red blood cell (RBC) apheresis, offering RBC exchange, RBC depletion (RBCd)/RCB exchange, and RBCd procedures. The main goal of this study was to validate the new RBCd program through the accuracy of the patient's postprocedure hematocrit (HCT) (actual end HCT) to the HCT reported by the device at the end of the procedure (target end HCT). Secondary objectives were to assess the device‐related significant adverse events, the patient's cellular losses, and the degree of device induced hemolysis. Methods: The study was an open‐label, single‐center, prospective trial in adult patients eligible for RBCd. Patients were enrolled between October 2015 and June 2016. In all procedures, saline was used as replacement fluid. Blood samples were collected from the patient before and after the procedure. Device settings, adverse events, and procedure results were recorded. Results: Thirty‐nine patients were enrolled (34 treated for iron storage disease and 5 for polycythemia vera); only 36 were evaluable for the primary objective. The mean actual end HCT was 34.6 ± 2.79% and the mean target end HCT was 35.8 ± 2.25%. The ratio (actual end to target end HCT) was 0.97 ± 0.05 with a 95% CI demonstrating the accuracy of the target HCT. One patient experienced a vasovagal event not related to the device. Cellular losses were not clinically relevant. Conclusion: The RBCd Amicus program met all RBCd efficiency and safety requirements with high accuracy of the target HCT. [ABSTRACT FROM AUTHOR]

Aims: Gemcitabine has been associated with thrombotic microangiopathy (TMA). We conducted a national retrospective study of gemcitabine‐associated TMA (G‐TMA). Methods: From 1998 to 2015, all cases of G‐TMA reported to the French Pharmacovigilance Network and the French TMA Reference Center, and cases explored for complement alternative pathway abnormalities, were analysed. Results: G‐TMA was diagnosed in 120 patients (median age 61.5 years), after a median of 210 days of treatment, and a cumulative dose of 12 941 mg m–2. Gemcitabine indications were: pancreatic (52.9%), pulmonary (12.6%) and breast (7.6%) cancers, metastatic in 34.2% of cases. Main symptoms were oedema (56.7%) and new‐onset or exacerbated hypertension (62.2%). Most patients presented with haemolytic anaemia (95.6%) and thrombocytopenia (74.6%). Acute kidney injury was reported in 97.4% and dialysis was required in 27.8% of patients. Treatment consisted of: plasma exchange (PE; 39.8%), fresh frozen plasma (21.4%), corticosteroids (15.3%) and eculizumab (5.1%). A complete remission of TMA was obtained in 42.1% of patients and haematological remission in 23.1%, while 34.7% did not improve. The survival status was known for 52 patients, with 29 deaths (54.7%). Patients treated with PE, despite a more severe acute kidney injury, requiring dialysis more frequently, displayed comparable rates of remission, but with more adverse events. No abnormality in complement alternative pathway was documented in patients explored. Conclusion: This large cohort confirms the severity of G‐TMA, associated with severe renal failure and death. Oedema and hypertension could be monitored in patients treated with gemcitabine to detect early TMA. The benefit of PE or eculizumab deserves further investigation. [ABSTRACT FROM AUTHOR]

Background This study aims to compare in patients with sickle cell disease (SCD), the technical performance and packed red blood cell unit consumption between the automated depletion/Red Blood Cell exchange (RBCx) program (Spectra Optia Apheresis System) with the isovolemic hemodilution (IHD)/RBCx procedure (COBE Spectra Apheresis System) in a routine clinical setting. Methods We retrospectively reviewed the data of 23 patients treated between October 2010 and August 2013 who underwent repeated RBCx on both apheresis systems for preventive indications. Each patient was their own control and had undergone two procedures on each system, totaling 46 sessions per group. On Spectra Optia, we performed the automated depletion/RBCx program. For COBE Spectra, we used a modified IHD/RBCx protocol. All patients had an initial 250 mL depletion offset by a 5% albumin prior to the exchange procedure, for the respective device, with leucodepleted Rh/Kell compatible and cross-matched RBC packs. Results All procedures were well tolerated except three mild febrile nonhemolytic reactions. Postprocedure hemoglobin S (HbS), fraction of cells remaining (FCR), procedure duration and processed blood and anticoagulant volumes were comparable in the two groups. However, the RBCx volume was significantly higher for the Spectra Optia group (+71 mL, P = 0.01), with no significant difference in the number of RBC units used. Conclusions Technical performance and packed RBC unit consumption were not compromised when switching from the COBE Spectra IHD/RBCx protocol to the depletion/RBCx protocol on the Spectra Optia. Tolerability was equal for both protocols. J. Clin. Apheresis 31:429-433, 2016. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Le purpura thrombotique thrombocytopénique (PTT) est une microangiopathie thrombotique rare et sévère liée à un déficit en ADAMTS13. Néanmoins, ce déficit est une condition nécessaire mais non suffisante pour induire l'accumulation des multimères de facteur de von Willebrand (vWF) à l'origine des microthrombi. L'endothélium, qui est le lieu de stockage du vWF, est évoqué depuis longtemps comme participant à la physiopathologie. L'implication de l'activation endothéliale dans le déclenchement de la crise de PTT est étayée par des arguments cliniques (évolution par poussées à la faveur de facteurs déclenchants), histologiques et biologiques, avec des marqueurs d'agression endothéliale solubles et cellulaires élevés chez les patients. Cette hypothèse est confortée par différents arguments expérimentaux in vitro (mise en évidence d'une dégranulation endothéliale calcium-dépendante induite par les plasmas issus de patients PTT sur des cellules endothéliales en culture) et in vivo avec des modèles de souris et de zebrafish en faveur d'un modèle à "deux-coups". De plus, l'endothélium est à la fois la source et la cible de boucles d'amplification de l'activation endothéliale, qui impliquent notamment l'hème libérée lors de l'hémolyse, la voie alterne du complément pour laquelle les multimères de vWF constituent une plateforme d'activation, et les nucléosomes qui se trouvent au sein des "neutrophil extracellular traps". Étant donné l'accessibilité et la plasticité de l'endothélium, une modulation pharmacologique de la dégranulation endothéliale pourrait avantageusement trouver sa place dans l'arsenal thérapeutique pour traiter le PTT. [ABSTRACT FROM AUTHOR]

Severe ADAMTS13 deficiency occurs in 13% to 75% of thrombotic microangiopathies (TMA). In this context, the early identification of a severe, antibody-mediated, ADAMTS13 deficiency may allow to start targeted therapies such as Blymphocytes- depleting monoclonal antibodies. To date, assays exploring ADAMTS13 activity require skill and are limited to only some specialized reference laboratories, given the very low incidence of the disease. To identify clinical features which may allow to predict rapidly an acquired ADAMTS13 deficiency, we performed a cross-sectional analysis of our national registry from 2000 to 2007. The clinical presentation of 160 patients with TMA and acquired ADAMTS13 deficiency was compared with that of 54 patients with detectable ADAMTS13 activity. ADAMTS13 deficiency was associated with more relapses during treatment and with a good renal prognosis. Patients with acquired ADAMTS13 deficiency had platelet count <306109/L (adjusted odds ratio [OR] 9.1, 95% confidence interval [CI] 3.4-24.2, P<.001), serum creatinine level≤200 mmol/L (OR 23.4, 95% CI 8.8-62.5, P<.001), and detectable antinuclear antibodies (OR 2.8, 95% CI 1.0-8.0, P<.05). When at least 1 criteria was met, patients with a severe acquired ADAMTS13 deficiency were identified with positive predictive value of 85%, negative predictive value of 93.3%, sensitivity of 98.8%, and specificity of 48.1%. Our criteria should be useful to identify rapidly newly diagnosed patients with an acquired ADAMTS13 deficiency to better tailor treatment for different pathophysiological groups. [ABSTRACT FROM AUTHOR]

Introduction En 2016, la plateforme d’aphérèse AMICUS (Fresenius Kabi) a obtenu le marquage CE pour la réalisation d’échanges érythrocytaires automatisés. Cette nouvelle procédure a été évaluée en routine chez des patients drépanocytaires adultes et adolescents, au CHU de Marseille et au CHU de Montpellier. Nous rapportons les résultats en termes de mesure de la précision des pourcentages de fraction cellulaire restante (FCR) et d’hématocrite (Ht) de fin. Méthode Entre novembre 2016 et janvier 2017, 35 procédures concernant 31 patients (17H/14F, âge médian : 30 ans, poids médian : 65 kg) ont été réalisées avec le protocole déplétion/échange, en prévention de crises vaso-occlusives itératives ( n = 31) ou d’accidents vasculaires ( n = 4). Pendant la phase de déplétion, la substitution était réalisée par albumine, hydroxyéthylamidon (HEA) ou sérum physiologique. L’Ht moyen programmé des concentrés de GR était de 58 %. Un hémogramme et l’HbS étaient prélevés avant et trente minutes après chaque séance. Résultats L’HbS a diminué de 29,3 %, passant d’une valeur médiane initiale de 46,1 % (16,2–85,3) à 16,8 % (4,5–42,1) soit une FCR médiane de 33,3 % (21,8–63,1), comparé à la valeur médiane de FCR cible de 33 % (23–55). L’Ht médian de départ était à 27,1 % (22–40,6) et à 28 % en fin de procédure (24–36), strictement superposable à l’Ht ciblé. Ainsi, la différence constatée entre les valeurs d’Ht cible et les valeurs d’Ht réellement mesurées en fin de procédure est de 0,30 % (4,1–6,8). Conclusion Dans cette évaluation rétrospective, le séparateur AMICUS a permis une réduction effective et précise de l’HbS, en conformité avec les paramètres de FCR programmés, tout en atteignant les valeurs d’Ht de fin souhaitées. [ABSTRACT FROM AUTHOR]

Objectifs Les échanges érythrocytaires au long cours nécessitent souvent la pose de cathéters centraux fémoraux (KTC). L’identification de ce geste comme critique du fait du profil algique des patients drépanocytaires, nous a conduit à mettre en place une évaluation des pratiques professionnelles (EPP) sur la pose des KTC dans le but d’améliorer la prise en charge de la douleur et le ressenti des patients. Méthode Mise en œuvre d’une démarche d’EPP intégrée utilisant 3 méthodes validées : audit dossier, patient traceur et enquête de ressenti patients. Démarche structurée en 4 phases : – planification (création groupe projet multidisciplinaire, choix des méthodes et périmètre d’évaluation, fixation objectifs qualité, construction des outils d’évaluation) ; – évaluation initiale ; – mise en place d’un plan d’actions ; – évaluation de l’impact des actions mises en œuvre. Résultats L’analyse combinée des 3 évaluations (patient traceur, audit dossier, enquête ressenti patient) a permis d’identifier des points positifs, mais aussi des carences en termes de prise en charge de la douleur et de l’anxiété, de respect de l’intimité et d’informations sur le geste. Des actions d’amélioration ont été mises en place : optimisation de l’information, habilitation des médecins à la pose des KTC, personnalisation des protocoles de prise en charge de la douleur pendant la pose, communication thérapeutique, respect de l’intimité. Une évaluation de l’impact de ces actions est prévue dans 6 mois. Conclusion Dès à présent, les patients sont moins algiques et moins stressés. Cette EPP a permis en outre une meilleure cohésion des équipes et une appropriation des outils qualité par les professionnels. [ABSTRACT FROM AUTHOR]

In acquired thrombotic thrombocytopenic purpura (TTP), the persistence of severe ADAMTS13 deficiency (<10%) during remission is associated with more relapse. Preemptive (ie, after remission) administration of rituximab in these patients to prevent relapses remains controversial. We performed a cross-sectional analysis of 12-year follow-up data to compare the relapse incidence with or without preemptive rituximab infusion. Among 48 patients who experienced at least one episode of acquired TTP followed by severe ADAMTS13 deficiency during remission, 30 received preemptive rituximab (group 1); the other 18 did not (group 2). After a median of 17 months (interquartile range [IQR], 11 -29) following rituximab, the relapse incidence decreased from 0.57 episodes/year (IQR, 0.46-0.7) to 0 episodes/year (IQR, 0-0.81) (P< .01) in group 1. ADAMTS13 activity 3 months after the first rituximab infusion increased to 46% (IQR, 30%-68%). Nine patients required additional courses of rituximab. In 5 patients, ADAMTS13 activity failed to increase durably. Four patients experienced manageable adverse effects. In group 2, the relapse incidence was higher (0.5 relapses/year; IQR, 0.12-0.5; P< .01). Relapse-free survival was longer in group 1 (P = .049). A persistent severe ADAMTS13 deficiency during TTP remission should prompt consideration of preemptive rituximab to prevent relapses. [ABSTRACT FROM AUTHOR]