Managing Systemic Autoimmune Diseases Associated With Thrombotic Microangiopathy

anemia, red blood cells
Hemotransfusion in treatment of anemia, 3D illustration showing two populations of red blood cells, small hypochromic red blood cells and normal. A small lymphocyte is drawn for size comparison
Using data from the French National TMA registry, study authors evaluated the demographic and clinical characteristics of thrombotic microangiopathy in autoimmune diseases, and assessed therapeutic approaches.

The management of systemic autoimmune disease-associated thrombotic microangiopathy (SAID-TMA) requires a specific therapeutic approach, such as the early initiation of immunosuppression therapy for flares of the related SAID and/or systemic complications, according to an analysis published in the European Journal of Internal Medicine.

Using the French National TMA Registry, study authors aimed to provide a demographic and clinical picture of SAID-TMA, as well as assess therapeutic approaches.

Between October 2000 and 2019, the medical records of patients aged 18 years and older from the registry were used to identify patients with TMA who met the criteria for SAID. All individuals who fulfilled the SAID criteria and had detectable “ADAMTS13” (A Disintegrin and Metalloproteinase with ThromboSpondin-1 motifs; 13th member) activity were included in the current analysis. Clinical features of the patients were collected and compared with those from a historical cohort of patients with atypical hemolytic and uremic syndrome (aHUS).

A total of 41 patients with SAID-TMA were compared with 78 patients with aHUS. Among 10 patients with SAID-TMA, the diagnosis of SAID was made at the same time as the diagnosis of TMA or shortly thereafter. In the 31 remaining patients, the presence of preexisting SAID was known to the clinicians. Median time between the first appearance of SAID and TMA was 3.34 years (range, 13.5 days to 3.45 years). No diagnoses of SAID were made during the follow-up of individuals from the historical aHUS cohort.

The connective tissue diseases (CTD) reported among the 41 participants with SAID-TMA included systemic lupus erythematosus (n=18), primary Sjögren syndrome (n=7), systemic sclerosis (n=11), mixed CTD (n=2), and vasculitides (n=2), which included 7 overlapping forms of CTD and 8 cases of primary antiphospholipid syndromes. Patients with SAID-TMA vs uHUS commonly had preexisting chronic kidney failure (odds ratio [OR], 3.17; 95% CI, 1.204-7.923; P =.023), although creatinine levels in these individuals were statistically significantly lower (216 vs 368 µmol/L; P =.002)

More than half of patients with SAID-TMA were hospitalized in an intensive care unit, with 18 of the 41 individuals requiring renal replacement therapy. Overall, 6 patients received therapeutic plasma exchange (TPE), with a median of 4.5 procedures performed. Despite having features of aHUS, 22 patients were treated with TPE, receiving between 3 and 53 TPE procedures, which were usually followed by the use of immunosuppressive therapy.

Participants who needed renal replacement therapy at disease onset were significantly less likely to achieve complete remission of SAID-TMA (OR, 0.07; 95% CI, 0.02-0.34; P <.001). A total of 30 participants achieved a response to treatment with immunosuppressive medications, with 25 achieving complete remission. However, the use of TPE did not demonstrate a significant early effect on features of TMA on day 7 or 15 (P >.05).

Study limitations included the lack of centralized testing for immunologic markers and the fact that parameters for SAID activity, including complement fractions, were not reported.

Study authors concluded, “In the setting of such infrequent clinical entities, we believe in the implementation of prospective long-term patient registries to gain better knowledge of heterogeneous diseases such as SAID-TMA.”


Martis N, Jamme M, Bagnis-Isnard C, et al; French Reference Centre for Thrombotic Microangiopathies. Systemic autoimmune disorders associated with thrombotic microangiopathy: a cross-sectional analysis from the French National TMA registry: systemic autoimmune disease-associated TMA. Eur J Intern Med. Published online June 23, 2021. doi:10.1016/j.ejim.2021.05.040