A Multinational Study of Thrombotic Microangiopathy in Macrophage Activation Syndrome: A Dreadful Condition Which Is Likely Underrecognized

Francesca Minoia¹, Jessica Tibaldi ², Valentina Muratore ³, Romina Gallizzi ⁴, Claudia Bracaglia ⁵, Alessia Arduini ⁶, Elif Comak ⁷, Olga Vougiouka ⁸, Ralf Trauzeddel ⁹, Giovanni Filocamo ¹⁰, Concetta Micalizzi ², Ozgur Kasapcopur ¹¹, Erbil Unsal ¹², Toshiyuki Kitoh ¹³, Elena Tsitsamis ¹⁴, Mikhail Kostik ¹⁵, Randy Cron ¹⁶, Jana Pachlopnik ¹⁷, Despoina Maritsi ¹⁸, Marija Jelusic ¹⁹, Susan Shenoi ²⁰ and Angelo Ravelli ², ¹Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milano, Italy, ²Istituto Giannina Gaslini, Genoa, Italy, ³IRCCS Policlinico San Matteo, Pavia, Italy, ⁴Università degli Studi di Messina, Messina, Italy, ⁵Division of Rheumatology, IRCCS Ospedale Pediatrico Bambino Gesu', Rome, Italy, ⁶IRCCS Ospedale Pediatrico Bambino Gesù, Rome, Italy, ⁷Akdeniz University, Antalya, Turkey, ⁸Second Department of Paediatrics, P. & A. Kyriakou Children’s Hospital, Athens, Greece, ⁹Helios Klinikum, Berlin, Germany, ¹⁰Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy, ¹¹Istanbul University-Cerrahpasa, Cerrahpasa Medical School, Cerrahpasa, Turkey, ¹²Dokuz Eylul University, Izmir, Turkey, ¹³Aichi Medical University, Nagakute, Japan, ¹⁴Children's Hospital Aghia Sophia, Athens, Greece, ¹⁵State Pediatric Medical Academy, Saint Petersburg, Russia, ¹⁶University of Alabama at Birmingham, Birmingham, ¹⁷Universitats-Kinderspital, Zurich, Switzerland, ¹⁸National and Kopdistrian University of Athens, Athens, Greece, ¹⁹Division of Paediatric Rheumatology and Immunology, University of Zagreb, Zagreb, Croatia, ²⁰Seattle Children's Hospital, Seattle

Meeting: 2020 Pediatric Rheumatology Symposium

Keywords: macrophage activation syndrome

Session Information

The 2020 Pediatric Rheumatology Symposium, originally scheduled for April 29 – May 2, was postponed due to COVID-19; therefore, abstracts were not presented as scheduled.

Date: Friday, May 1, 2020

Title: Poster Session 2

Session Type: ACR Abstract Session

Session Time: 5:00PM-6:00PM

Background/Purpose: Macrophage activation syndrome (MAS) is a severe complication of rheumatologic conditions, mainly systemic juvenile idiopathic arthritis (sJIA), and is classified among the secondary forms of hemophagocytic lymphohistiocytosis (HLH). Thrombotic microangiopathy (TMA) is a heterogeneous group of life-threating diseases characterized by microangiopathic hemolytic anemia, thrombocytopenia and organ injury. The association between TMA and HLH has been described only in single reports in adult renal transplant recipients and in two pediatric cases of virus-induced HLH. The aim of our study is to present the preliminary data from a multinational cohort of pediatric patients with MAS and TMA

Methods: The clinical charts of patients with MAS were retrospectively reviewed to identify the instances that were associated with TMA. Demographic, clinical and laboratory features at MAS and TMA onset, therapeutic interventions and outcome were collected

Results: A total of 27 patients, 66.7% females, with MAS and TMA were collected. An underlying rheumatologic disease was reported in 19/27 (14 sJIA or a sJIA-like illness, 2 systemic lupus erythematosus, 1 Kawasaki disease, 1 autoimmune hepatitis, 2 connective tissue diseases). The median age at MAS onset was 10.9 years. In 10 patients MAS and TMA occurred simultaneously, whereas in 4 TMA preceded and in 13 followed MAS. The main features at MAS and TMA onset are presented in Table 1. Low complement levels and reduced ADAMTS13 activity were observed in 70.6% and 50% of patients respectively. The parameters which significatively change in MAS patients complicated by TMA were platelet count, fibrinogen, LDH and AST. For MAS management, 92.6% of patients received high-dose corticosteroids and 59.3% cyclosporine; in 8 cases anakinra was added. TMA episodes were treated with plasma-exchange in 63% of patients; 18 patients were given biologics (6 rituximab and 12 eculizumab). Admission to the Intensive Care Unit was required in 92.6% of cases. Mortality rate was 15%.

Conclusion: The association of MAS and TMA is a dreadful complication, likely under-recognized. Clues to suspect TMA in a patient with MAS are the increase in LDH and AST and the decrease in platelet count and fibrinogen out of proportion of other laboratory abnormalities, the drop in haptoglobin level, the presence of schistocytes in blood smear and the new onset of kidney failure or hematuria. Biologics, particularly rituximab and eculizumab, may offer an adjunctive therapeutic option for refractory cases

Disclosure: F. Minoia, None; J. Tibaldi, None; V. Muratore, None; R. Gallizzi, None; C. Bracaglia, None; A. Arduini, None; E. Comak, None; O. Vougiouka, None; R. Trauzeddel, None; G. Filocamo, None; C. Micalizzi, None; O. Kasapcopur, None; E. Unsal, None; T. Kitoh, None; E. Tsitsamis, None; M. Kostik, None; R. Cron, SOBI, 1, Novartis, 1, SOBI, 1, Pfizer, 1; J. Pachlopnik, None; D. Maritsi, None; M. Jelusic, None; S. Shenoi, None; A. Ravelli, None.

To cite this abstract in AMA style:

Minoia F, Tibaldi J, Muratore V, Gallizzi R, Bracaglia C, Arduini A, Comak E, Vougiouka O, Trauzeddel R, Filocamo G, Micalizzi C, Kasapcopur O, Unsal E, Kitoh T, Tsitsamis E, Kostik M, Cron R, Pachlopnik J, Maritsi D, Jelusic M, Shenoi S, Ravelli A. A Multinational Study of Thrombotic Microangiopathy in Macrophage Activation Syndrome: A Dreadful Condition Which Is Likely Underrecognized [abstract]. Arthritis Rheumatol. 2020; 72 (suppl 4). https://acrabstracts.org/abstract/a-multinational-study-of-thrombotic-microangiopathy-in-macrophage-activation-syndrome-a-dreadful-condition-which-is-likely-underrecognized/. Accessed .

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