Thrombotic Thrombocytopenic Purpura (TTP) and Systemic Lupus Erythematosus (SLE): Distinct but Potentially Overlapping Syndromes.
Authors: Hunt Laura , Li Xiaoning , James Judith , Terrell Deirdra R. , Lammle Bernhard , Kremer-Hovinga Johanna , George James N. , Vesely Sara K. 
Published: October 2019

A systematic literature review suggests that SLE and TTP co-exist: we identified 51 articles reporting 87 patients who were diagnosed with both TTP and SLE. SLE was diagnosed prior to TTP in 53 (61%), subsequent to TTP in 11 (13%) and simultaneously with TTP in 23 (26%) patients. However a critical distinction is that TTP is a rapidly fatal disease without plasma exchange (PE) treatment while SLE is typically a more chronic disease with intermittent acute flares and PE is not an essential treatment. Therefore when TTP is suspected in a patient with an established diagnosis of SLE, the relative benefits and risks of PE are difficult to assess, since the diagnosis of TTP may be unclear and PE is a procedure with risk for major complications and death. The Oklahoma TTP-HUS Registry has collected serum samples on 185 of 206 (90%) of prospectively enrolled patients with a clinical diagnosis of TTP or HUS from 11/13/1995 to 12/31/2003; all patients have been followed to the present time. We compared presenting features and clinical outcomes of the first episode of TTP-HUS between the 14 (7%) patients in whom SLE had been previously diagnosed to the 22 patients in whom the diagnosis of TTP was supported by severely deficient (<5%) ADAMTS13. None of the 14 patients with a previous diagnosis of SLE had severe ADAMTS13 deficiency (range 7–100%, median 50%). SLE disease activity as measured by the SLEDAI score ranged from 3–32, median 10, indicating that SLE manifestations were severe in most patients. Only 2 patients had inactive lupus as indicated by a SLEDAI score <4. SLE was not considered at the time of diagnosis of the first episode of TTP in the 22 patients with severe ADAMTS13 deficiency. Only 1/22 patients has been subsequently diagnosed with SLE; at the time of an apparent relapse of TTP he had serositis and positive serologic tests; his ADAMTS13 activity at that time was 30%. This patient’s course documents the potential overlap of these two disorders.

SLE-TTP(n=14) TTP (n=22) p-value Median values are presented for continuous data. Laboratory data are most abnormal values at diagnosis of TTP-HUS ±7 days Age (years) 39 39 0.820 Race (% Black) 36% 45% 0.563 Gender (% female) 100% 82% 0.140 Obesity (BMI ≥ 30 kg/m²) 14% 55% 0.016 Severe neurologic abnormalities 71% 45% 0.126 Platelet count 21 9 0.010 Hematocrit 22 21 0.660 LDH 707 1431 0.043 Acute renal failure 64% 5% <0.001 Response to PE 36% 86% 0.003 Death 64% 23% 0.018 Relapse in 30 day survivors 0% 44% 0.031

Although the demographic (age, race, gender) and some presenting clinical features of patients with SLE and a clinical diagnosis of TTP-HUS were not different from patients with TTP and severe ADAMTS13 deficiency, other presenting features and the outcomes were different. Response to PE was poor, all cause mortality was high, and relapses of TTP have not occurred in patients with a previous diagnosis of SLE. These differences suggest that these 2 groups of patients in our Registry are distinct. Therefore in patients with an established diagnosis of SLE in whom the additional diagnosis of TTP-HUS is considered, more intensive immunosuppressive treatment for SLE is appropriate initial management in addition to considering the relative benefits and risks of PE.